Pubblicazioni - Nava Dott. Stefano

• Use of critical care resources during the first 2 weeks (February 24-March 8, 2020) of the Covid-19 outbreak in Italy.
  Ann Intensive Care

  2020 Oct;10(1):133. doi: 10.1186/s13613-020-00750-z.
  
  Tonetti Tommaso, Grasselli Giacomo, Zanella Alberto, Pizzilli Giacinto, Fumagalli Roberto, Piva Simone, Lorini Luca, Iotti Giorgio, Foti Giuseppe, Colombo Sergio, Vivona Luigi, Rossi Sandra, Girardis Massimo, Agnoletti Vanni, Campagna Anselmo, Gordini Giovanni, Navalesi Paolo, Boscolo Annalisa, Graziano Alessandro, Valeri Ilaria, Vianello Andrea, Cereda Danilo, Filippini Claudia, Cecconi Maurizio, Locatelli Franco, Bartoletti Michele, Giannella Maddalena, Viale Pierluigi, Antonelli Massimo, Nava Stefano, Pesenti Antonio, Ranieri V Marco,
  
  Abstract
  
  BACKGROUND:
  A Covid-19 outbreak developed in Lombardy, Veneto and Emilia-Romagna (Italy) at the end of February 2020. Fear of an imminent saturation of available ICU beds generated the notion that rationing of intensive care resources could have been necessary.
  
  RESULTS:
  In order to evaluate the impact of Covid-19 on the ICU capacity to manage critically ill patients, we performed a retrospective analysis of the first 2 weeks of the outbreak (February 24-March 8). Data were collected from regional registries and from a case report form sent to participating sites. ICU beds increased from 1545 to 1989 (28.7%), and patients receiving respiratory support outside the ICU increased from 4 (0.6%) to 260 (37.0%). Patients receiving respiratory support outside the ICU were significantly older [65 vs. 77 years], had more cerebrovascular (5.8 vs. 13.1%) and renal (5.3 vs. 10.0%) comorbidities and less obesity (31.4 vs. 15.5%) than patients admitted to the ICU. PaO/FiO ratio, respiratory rate and arterial pH were higher [165 vs. 244; 20 vs. 24 breath/min; 7.40 vs. 7.46] and PaCO and base excess were lower [34 vs. 42 mmHg; 0.60 vs. 1.30] in patients receiving respiratory support outside the ICU than in patients admitted to the ICU, respectively.
  
  CONCLUSIONS:
  Increase in ICU beds and use of out-of-ICU respiratory support allowed effective management of the first 14 days of the Covid-19 outbreak, avoiding resource rationing.
  
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• [A novel tool to monitor the individual functional status after COVID-19: the Post-COVID-19 Functional Status (PCFS) scale].
  G Ital Cardiol (Rome)

  2020 Oct;21(10):757. doi: 10.1714/3431.34198.
  
  Corsi Gabriele, Nava Stefano, Barco Stefano
  
  
  
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• Reply to: Spinelli E, et al and Jha.
  Am J Respir Crit Care Med

  2020 Sep;():. doi: 10.1164/rccm.202008-3049LE.
  
  Tonelli Roberto, Castaniere Ivana, Fantini Riccardo, Tabbì Luca, Busani Stefano, Pisani Lara, Nava Stefano, Clini Enrico, Marchioni Alessandro
  
  
  
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• Use of nasal high flow oxygen during acute respiratory failure.
  Intensive Care Med

  2020 Sep;():. doi: 10.1007/s00134-020-06228-7.
  
  Ricard Jean-Damien, Roca Oriol, Lemiale Virginie, Corley Amanda, Braunlich Jens, Jones Peter, Kang Byung Ju, Lellouche François, Nava Stefano, Rittayamai Nuttapol, Spoletini Giulia, Jaber Samir, Hernandez Gonzalo
  
  Abstract
  
  Nasal high flow (NHF) has gained popularity among intensivists to manage patients with acute respiratory failure. An important literature has accompanied this evolution. In this review, an international panel of experts assessed potential benefits of NHF in different areas of acute respiratory failure management. Analyses of the physiological effects of NHF indicate flow-dependent improvement in various respiratory function parameters. These beneficial effects allow some patients with severe acute hypoxemic respiratory failure to avoid intubation and improve their outcome. They require close monitoring to not delay intubation. Such a delay may worsen outcome. The ROX index may help clinicians decide when to intubate. In immunocompromised patients, NHF reduces the need for intubation but does not impact mortality. Beneficial physiological effects of NHF have also been reported in patients with chronic respiratory failure, suggesting a possible indication in acute hypercapnic respiratory failure. When intubation is required, NHF can be used to pre-oxygenate patients either alone or in combination with non-invasive ventilation (NIV). Similarly, NHF reduces reintubation alone in low-risk patients and in combination with NIV in high-risk patients. NHF may be used in the emergency department in patients who would not be offered intubation and can be better tolerated than NIV.
  
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• Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study.
  Lancet Respir Med

  2020 Aug;():. doi: S2213-2600(20)30370-2.
  
  Grasselli Giacomo, Tonetti Tommaso, Protti Alessandro, Langer Thomas, Girardis Massimo, Bellani Giacomo, Laffey John, Carrafiello Gianpaolo, Carsana Luca, Rizzuto Chiara, Zanella Alberto, Scaravilli Vittorio, Pizzilli Giacinto, Grieco Domenico Luca, Di Meglio Letizia, de Pascale Gennaro, Lanza Ezio, Monteduro Francesco, Zompatori Maurizio, Filippini Claudia, Locatelli Franco, Cecconi Maurizio, Fumagalli Roberto, Nava Stefano, Vincent Jean-Louis, Antonelli Massimo, Slutsky Arthur S, Pesenti Antonio, Ranieri V Marco,
  
  Abstract
  
  BACKGROUND:
  Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19.
  
  METHODS:
  This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed.
  
  FINDINGS:
  Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm HO (33-52), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm HO [25-43]; p<0·0001). 17 (6%) of 297 patients with COVID-19-associated ARDS had compliances greater than the 95th percentile of the classical ARDS cohort. Total lung weight did not differ between the two cohorts. CT pulmonary angiograms (obtained in 23 [8%] patients with COVID-19-related ARDS) showed that 15 (94%) of 16 patients with D-dimer concentrations greater than the median had bilateral areas of hypoperfusion, consistent with thromboembolic disease. Patients with D-dimer concentrations equal to or less than the median had ventilatory ratios lower than those of patients with D-dimer concentrations greater than the median (1·66 [1·32-1·95] vs 1·90 [1·50-2·33]; p=0·0001). Patients with static compliance equal to or less than the median and D-dimer concentrations greater than the median had markedly increased 28-day mortality compared with other patient subgroups (40 [56%] of 71 with high D-dimers and low compliance vs 18 [27%] of 67 with low D-dimers and high compliance, 13 [22%] of 60 with low D-dimers and low compliance, and 22 [35%] of 63 with high D-dimers and high compliance, all p=0·0001).
  
  INTERPRETATION:
  Patients with COVID-19-associated ARDS have a form of injury that, in many aspects, is similar to that of those with ARDS unrelated to COVID-19. Notably, patients with COVID-19-related ARDS who have a reduction in respiratory system compliance together with increased D-dimer concentrations have high mortality rates.
  
  FUNDING:
  None.
  
  Copyright © 2020 Elsevier Ltd. All rights reserved.
  
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• Late-sequalae of Kawasaki disease characterized by optical coherence tomography.
  J Cardiovasc Med (Hagerstown)

  2020 Aug;():. doi: 10.2459/JCM.0000000000001083.
  
  Soriano Francesco, Veas Nicolas, Nava Stefano, Piccinelli Enrico, Pedrotti Patrizia, Oreglia Jacopo, Vignati Gabriele, Winter José, Ammirati Enrico, Burns Jane C, Gordon John B
  
  
  
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• Extracorporeal CO removal (ECCOR) in patients with stable COPD with chronic hypercapnia: a proof-of-concept study.
  Thorax

  2020 Oct;75(10):897-900. doi: 10.1136/thoraxjnl-2020-214744.
  
  Pisani Lara, Nava Stefano, Desiderio Emilia, Polverino Mario, Tonetti Tommaso, Ranieri V Marco
  
  Abstract
  
  Domiciliary non-invasive ventilation (NIV) effectively reduces arterial carbon dioxide pressure (PaCO) in patients with stable hypercapnic chronic obstructive pulmonary disease, but a consistent percentage of them may remain hypercapnic. We hypothesised that extracorporeal CO removal (ECCOR) may lower their PaCO Ten patients hypercapnic despite ?6 months of NIV underwent a 24-hour trial of ECCOR. Six patients completed the ECCOR-trial with a PaCO drop ranging between 23% and 47%. Time to return to baseline after interruption ranged 48-96?hours. In four patients, mechanical events led to ECCOR premature interruption, despite a decreased in PaCO This time window 'free' from hypercapnia might allow to propose the concept of 'CO dialysis'.
  
  © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
  
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• Feasibility and clinical impact of out-of-ICU non-invasive respiratory support in patients with COVID-19 related pneumonia.
  Eur Respir J

  2020 Aug;():. doi: 2002130.
  
  Franco Cosimo, Facciolongo Nicola, Tonelli Roberto, Dongilli Roberto, Vianello Andrea, Pisani Lara, Scala Raffaele, Malerba Mario, Carlucci Annalisa, Negri Emanuele Alberto, Spoladore Greta, Arcaro Giovanna, Tillio Paolo Amedeo, Lastoria Cinzia, Schifino Gioachino, Tabbi' Luca, Guidelli Luca, Guaraldi Giovanni, Ranieri V Marco, Clini Enrico, Nava Stefano
  
  Abstract
  
  INTRODUCTION:
  The Coronavirus 2(SARS-CoV-2) outbreak spread rapidly in Italy and the lack of intensive care unit(ICU) beds soon became evident, forcing the application of noninvasive respiratory support(NRS) outside the ICU, raising concerns over staff contamination. We aimed to analyse the safety of the hospital staff, the feasibility, and outcomes of NRS applied to patients outside the ICU.
  
  METHODS:
  In this observational study, data from 670 consecutive patients with confirmed COVID-19 referred to the Pulmonology Units in nine hospitals between March 1st and May 10th,2020 were analysed. Data were collected including medication, mode and usage of the NRS ( high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), noninvasive ventilation(NIV)), length of stay in hospital, endotracheal intubation(ETI) and deaths.
  
  RESULTS:
  Forty-two health-care workers (11.4%) tested positive for infection, but only three of them required hospitalisation. Data are reported for all patients (69.3% male), whose mean age was 68 (sd 13) years. The PaO/FiO ratio at baseline was 152±79, and the majority of patients (49.3%) were treated with CPAP. The overall unadjusted 30-day mortality rate was 26.9% with 16%, 30%, and 30%, while the total ETI rate was 27% with 29%, 25% and 28%, for HFNC, CPAP, and NIV, respectively, and the relative probability to die was not related to the NRS used after adjustment for confounders. ETI and length of stay were not different among the groups. Mortality rate increased with age and comorbidity class progression.
  
  CONCLUSIONS:
  The application of NRS outside the ICU is feasible and associated with favourable outcomes. Nonetheless, it was associated with a risk of staff contamination.
  
  Copyright ©ERS 2020.
  
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• [Iliac-femoral lithoplasty for a transcatheter aortic valve implantation. Report of one case].
  Rev Med Chil

  2020 Apr;148(4):548-552. doi: S0034-98872020000400548.
  
  Veas NicolÁs, Soriano Francesco, Winter JosÉ, Nava Stefano, Hameau RenÉ, Lidefjeld Dante, Valdebenito MartÍn, MuÑoz Rodrigo, Oreglia Jacopo
  
  
  
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• Pulmonary Rehabilitation.
  Monaldi Arch Chest Dis

  2020 Jul;90(3):. doi: 10.4081/monaldi.2020.1526.
  
  Polastri Massimiliano, Nava Stefano
  
  Abstract
  
  Commenting on this book is a great privilege and an opportunity to share some emerging aspects regarding the development of pulmonary rehabilitation. Indeed, appreciating the therapeutic value of this modality is possible because of continuous research and tireless commitment of all professionals involved in the care of patients with respiratory diseases and pulmonary-related impairments....
  
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• High-Flow, Noninvasive Ventilation and Awake (Nonintubation) Proning in Patients With Coronavirus Disease 2019 With Respiratory Failure.
  Chest

  2020 Jul;():. doi: S0012-3692(20)31910-3.
  
  Raoof Suhail, Nava Stefano, Carpati Charles, Hill Nicholas S
  
  Abstract
  
  The coronavirus disease 2019 pandemic will be remembered for the rapidity with which it spread, the morbidity and mortality associated with it, and the paucity of evidence-based management guidelines. One of the major concerns of hospitals was to limit spread of infection to health-care workers. Because the virus is spread mainly by respiratory droplets and aerosolized particles, procedures that may potentially disperse viral particles, the so-called "aerosol-generating procedures" were avoided whenever possible. Included in this category were noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), and awake (nonintubated) proning. Accordingly, at many health-care facilities, patients who had increasing oxygen requirements were emergently intubated and mechanically ventilated to avoid exposure to aerosol-generating procedures. With experience, physicians realized that mortality of invasively ventilated patients was high and it was not easy to extubate many of these patients. This raised the concern that HFNC and NIV were being underutilized to avoid intubation and to facilitate extubation. In this article, we attempt to separate fact from fiction and perception from reality pertaining to the aerosol dispersion with NIV, HFNC, and awake proning. We describe precautions that hospitals and health-care providers must take to mitigate risks with these devices. Finally, we take a practical approach in describing how we use the three techniques, including the common indications, contraindications, and practical aspects of application.
  
  Copyright © 2020. Published by Elsevier Inc.
  
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• Thoracic radiotherapy as a risk factor for heart ischemia in subjects treated with chest irradiation and chemotherapy and without classic cardiovascular RISK factors.
  Radiother Oncol

  2020 Jul;():. doi: S0167-8140(20)30397-2.
  
  Vallerio Paola, Maloberti Alessandro, Palazzini Matteo, Occhi Lucia, Peretti Alessio, Nava Stefano, Soriano Francesco, Musca Francesco, De Chiara Benedetta, Belli Oriana, Moreo Antonella, Bisceglia Irma, Lestuzzi Chiara, Giannattasio Cristina
  
  Abstract
  
  BACKGROUND AND PURPOSE:
  Radiation Induced Heart Disease (RIHD) represents a late effect of chest irradiation, contributing in increasing mortality rate in oncological patients by affecting pericardium, myocardium, valvs and coronaries. Currently, regarding the risk of Coronary Artery Disease (CAD), a cardiological screening involving exercise stress electrocardiography after 5-10 years from radiotherapy is advised. We sought to determine the rate of ischemia at exercise stress electrocardiography in a population of patients without cardiovascular risk factors who sustained radiotherapy, using a cohort of patients presenting with at least one cardiovascular risk factor as control group.
  
  DESIGN AND METHODS:
  A population of 115 patients who sustained chest irradiation (and associated chemotherapy), presenting without classic cardiovascular risk factors or typical symptoms suggesting CAD, was evaluated with exercise stress electrocardiography. 135 patients with at least one risk factor for cardiovascular disease candidate to stress testing for primary prevention or for atypical symptoms served as control group.
  
  RESULTS:
  The cohort of irradiated patients without classical cardiovascular risk factors is younger (48.7 ± 10.1 vs 60.5 ± 10.8 years, p < 0.001) and presents a lower percentage of males when compared with the control group. In this latter group 25.9% of subjects has diabetes, 62.9% dyslipidaemia, 67.4% hypertension and 19.2% actively smoke. Despite this important differences regarding classic cardiovascular risk factors, no significant differences were found in the number of positive exercise stress electrocardiography (10.4 vs 5.9%, p = ns).
  
  CONCLUSIONS:
  Chest irradiation represents a strong cardiovascular risk factor. In fact, prevalence of positive ECG-stress test is not different (nor higher and nor lower) in irradiated subjects without cardiovascular risk and not irradiated patients with classic cardiovascular risk.
  
  Copyright © 2020 Elsevier B.V. All rights reserved.
  
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• COVID-19 and pulmonary rehabilitation: preparing for phase three.
  Eur Respir J

  2020 Jun;55(6):. doi: 2001822.
  
  Polastri Massimiliano, Nava Stefano, Clini Enrico, Vitacca Michele, Gosselink Rik
  
  
  
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• Reply to Tuffet and to Michard and Shelley.
  Am J Respir Crit Care Med

  2020 Sep;202(5):771-772. doi: 10.1164/rccm.202005-1730LE.
  
  Tonelli Roberto, Tabbì Luca, Fantini Riccardo, Castaniere Ivana, Gozzi Filippo, Busani Stefano, Nava Stefano, Clini Enrico, Marchioni Alessandro
  
  
  
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• Careful consideration of the bleeding caused by transbronchial lung cryobiopsies.
  Eur Respir J

  2020 May;55(5):. doi: 1902415.
  
  Bourdin Arnaud, Romagnoli Micaela, Gamez Anne Sophie, Hireche Kheira, Berthet Jean Philippe, Mallet Jean Pierre, Vachier Isabelle, Nava Stefano, Reynaud Paul, Molinari Nicolas, Suehs Carey
  
  
  
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• An Italian sacrifice to the COVID-19 epidemic.
  Eur Respir J

  2020 06;55(6):. doi: 2001445.
  
  Nava Stefano, Tonelli Roberto, Clini Enrico M
  
  
  
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• One ventilator for two patients: feasibility and considerations of a last resort solution in case of equipment shortage.
  Thorax

  2020 06;75(6):517-519. doi: 10.1136/thoraxjnl-2020-214895.
  
  Tonetti Tommaso, Zanella Alberto, Pizzilli Giacinto, Irvin Babcock Charlene, Venturi Sergio, Nava Stefano, Pesenti Antonio, Ranieri V Marco
  
  
  
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• Early Inspiratory Effort Assessment by Esophageal Manometry Predicts Noninvasive Ventilation Outcome in Respiratory Failure. A Pilot Study.
  Am J Respir Crit Care Med

  2020 Aug;202(4):558-567. doi: 10.1164/rccm.201912-2512OC.
  
  Tonelli Roberto, Fantini Riccardo, Tabbì Luca, Castaniere Ivana, Pisani Lara, Pellegrino Maria Rosaria, Della Casa Giovanni, D'Amico Roberto, Girardis Massimo, Nava Stefano, Clini Enrico M, Marchioni Alessandro
  
  Abstract
  
  The role of inspiratory effort still has to be determined as a potential predictor of noninvasive mechanical ventilation (NIV) failure in acute hypoxic respiratory failure. To explore the hypothesis that inspiratory effort might be a major determinant of NIV failure in these patients. Thirty consecutive patients with acute hypoxic respiratory failure admitted to a single center and candidates for a 24-hour NIV trial were enrolled. Clinical features, tidal change in esophageal pressure (?Pes), tidal change in dynamic transpulmonary pressure (?Pl), expiratory Vt, and respiratory rate were recorded on admission and 2-4 to 12-24 hours after NIV start and were tested for correlation with outcomes. ?Pes and ?Pes/?Pl ratio were significantly lower 2 hours after NIV start in patients who successfully completed the NIV trial (?=?18) compared with those who needed endotracheal intubation (?=?12) (median [interquartile range], 11 [8-15] cm HO vs. 31.5 [30-36] cm HO; ?
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• Early consensus management for non-ICU acute respiratory failure SARS-CoV-2 emergency in Italy: from ward to trenches.
  Eur Respir J

  2020 05;55(5):. doi: 2000632.
  
  Vitacca Michele, Nava Stefano, Santus Pierachille, Harari Sergio
  
  
  
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• Protecting healthcare workers from SARS-CoV-2 infection: practical indications.
  Eur Respir Rev

  2020 Mar;29(155):. doi: 200068.
  
  Ferioli Martina, Cisternino Cecilia, Leo Valentina, Pisani Lara, Palange Paolo, Nava Stefano
  
  Abstract
  
  The World Health Organization has recently defined the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection a pandemic. The infection, that may cause a potentially very severe respiratory disease, now called coronavirus disease 2019 (COVID-19), has airborne transmission droplets. The rate of transmission is quite high, higher than common influenza. Healthcare workers are at high risk of contracting the infection particularly when applying respiratory devices such as oxygen cannulas or noninvasive ventilation. The aim of this article is to provide evidence-based recommendations for the correct use of "respiratory devices" in the COVID-19 emergency and protect healthcare workers from contracting the SARS-CoV-2 infection.
  
  Copyright ©ERS 2020.
  
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• [Concomitant deployment of MitraClip devices and left atrial appendage closure. Report of one case].
  Rev Med Chil

  2019 Oct;147(10):1350-1354. doi: S0034-98872019001001350.
  
  Veas Nicolás, Hameau René, Nava Stefano, Winter José, Soriano Francesco, Oreglia Jacopo
  
  Abstract
  
  We report a 65-years old woman with a history of permanent atrial fibrillation with high risk for ischemic and bleeding events. She developed a heart failure with severely impaired left ventricular ejection fraction and severe secondary mitral regurgitation. Given her high surgical risk, using transesophageal echocardiography guidance, a concomitant deployment of two MitraClip devices using a high-posterior septal puncture and a left atrial appendage closure with an Amplatzer Amulet occluder were performed through the same access.
  
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• Colon Sarcoidosis Mimicking Cancer at 18F-FDG PET/CT.
  Clin Nucl Med

  2020 May;45(5):387-388. doi: 10.1097/RLU.0000000000002996.
  
  Mei Riccardo, Prediletto Irene, Nava Stefano, Fanti Stefano, Ambrosini Valentina
  
  Abstract
  
  This 68-year-old woman with a 9-year history of skin sarcoidosis presented with abdominal pain, bloating, and diarrhea. Following positive occult fecal blood, a diagnosis of ascending colon sarcoidosis was pathologically confirmed after colonoscopy. FDG PET/CT was performed for sarcoid staging, and the ascending colon demonstrated the only focal site of active sarcoidosis (SUVmax = 10).
  
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• Extracorporeal Membrane Oxygenation for Respiratory Failure.
  Anesthesiology

  2020 05;132(5):1257-1276. doi: 10.1097/ALN.0000000000003221.
  
  Quintel Michael, Bartlett Robert H, Grocott Michael P W, Combes Alain, Ranieri Marco V, Baiocchi Massimo, Nava Stefano, Brodie Daniel, Camporota Luigi, Vasques Francesco, Busana Mattia, Marini John J, Gattinoni Luciano
  
  Abstract
  
  This review focuses on the use of veno-venous extracorporeal membrane oxygenation for respiratory failure across all blood flow ranges. Starting with a short overview of historical development, aspects of the physiology of gas exchange (i.e., oxygenation and decarboxylation) during extracorporeal circulation are discussed. The mechanisms of phenomena such as recirculation and shunt playing an important role in daily clinical practice are explained.Treatment of refractory and symptomatic hypoxemic respiratory failure (e.g., acute respiratory distress syndrome [ARDS]) currently represents the main indication for high-flow veno-venous-extracorporeal membrane oxygenation. On the other hand, lower-flow extracorporeal carbon dioxide removal might potentially help to avoid or attenuate ventilator-induced lung injury by allowing reduction of the energy load (i.e., driving pressure, mechanical power) transmitted to the lungs during mechanical ventilation or spontaneous ventilation. In the latter context, extracorporeal carbon dioxide removal plays an emerging role in the treatment of chronic obstructive pulmonary disease patients during acute exacerbations. Both applications of extracorporeal lung support raise important ethical considerations, such as likelihood of ultimate futility and end-of-life decision-making. The review concludes with a brief overview of potential technical developments and persistent challenges.
  
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• The authors reply.
  Crit Care Med

  2020 01;48(1):e76-e77. doi: 10.1097/CCM.0000000000004085.
  
  Longhini Federico, Pisani Lara, Nava Stefano, Navalesi Paolo
  
  
  
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• Respiratory Mechanics and Diaphragmatic Dysfunction in COPD Patients Who Failed Non-Invasive Mechanical Ventilation.
  Int J Chron Obstruct Pulmon Dis

  2019 ;14():2575-2585. doi: 10.2147/COPD.S219125.
  
  Marchioni Alessandro, Tonelli Roberto, Fantini Riccardo, Tabbì Luca, Castaniere Ivana, Livrieri Francesco, Bedogni Sabrina, Ruggieri Valentina, Pisani Lara, Nava Stefano, Clini Enrico
  
  Abstract
  
  Background:
  Although non-invasive mechanical ventilation (NIV) is the gold standard treatment for patients with acute exacerbation of COPD (AECOPD) developing respiratory acidosis, failure rates still range from 5% to 40%. Recent studies have shown that the onset of severe diaphragmatic dysfunction (DD) during AECOPD increases risk of NIV failure and mortality in this subset of patients. Although the imbalance between the load and the contractile capacity of inspiratory muscles seems the main cause of AECOPD-induced hypercapnic respiratory failure, data regarding the influence of mechanical derangement on DD in this acute phase are lacking. With this study, we investigate the impact of respiratory mechanics on diaphragm function in AECOPD patients experiencing NIV failure.
  
  Methods:
  Twelve AECOPD patients with respiratory acidosis admitted to the Respiratory ICU of the University Hospital of Modena from 2017 to 2018 undergoing mechanical ventilation (MV) due to NIV failure were enrolled. Static respiratory mechanics and end-expiratory lung volume (EELV) were measured after 30 mins of volume control mode MV. Subsequently, transdiaphragmatic pressure (Pdi) was calculated by means of a sniff maneuver (Pdisniff) after 30 mins of spontaneous breathing trial. Linear regression analysis and Pearson's correlation coefficient served to assess associations.
  
  Results:
  Average Pdisniff was 23.3 cmHO (standard deviation 29 cmHO) with 3 patients presenting bilateral diaphragm palsy. Pdisniff was directly correlated with static lung elastance (r=0.69, p=0.001) while inverse correlation was found with dynamic intrinsic PEEP (r=-0.73, p=0.007). No significant correlation was found with static intrinsic PEEP (r=-0.55, p=0.06), EELV (r=-0.4, p=0.3), airway resistance (r=-0.2, p=0.54), chest wall, and total elastance (r=-0-01, p=0.96 and r=0.3, p=0.36, respectively). Significant linear inverse correlation was found between Pdisniff and the ratio between Pdi assessed at tidal volume and Pdi sniff (r=-0.82, p=0.02).
  
  Conclusion:
  The causes of extreme DD in AECOPD patients who experienced NIV failure might be predominantly mechanical, driven by a severe dynamic hyperinflation that overlaps on an elastic lung substrate favoring volume overload.
  
  © 2019 Marchioni et al.
  
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• An integrative review on the positive expiratory pressure (PEP)-bottle therapy for patients with pulmonary diseases.
  Physiother Res Int

  2020 Jan;25(1):e1823. doi: 10.1002/pri.1823.
  
  Liverani Benedetta, Nava Stefano, Polastri Massimiliano
  
  Abstract
  
  BACKGROUND AND PURPOSE:
  Positive expiratory pressure (PEP)-bottle device delivers a PEP within a range of 10-20 cmH O. PEP treatment is applied to different pathological conditions also in combination with other physiotherapeutic techniques. The primary aim of the present review was to investigate the effects of PEP-bottle therapy in patients with pulmonary diseases and, secondarily, to provide a physiological analysis of its use.
  
  METHODS:
  The databases PubMed, Scopus, Web of Science, Cinahl, and Cochrane Library were searched for citations published from their inception until May 2019. Adult participants (>18 years) with pulmonary disease who underwent PEP-bottle treatment, with no restriction on gender, were included in the study. There were no restrictions about the therapeutic settings and the condition of the disease (either acute or chronic).
  
  RESULTS:
  The literature review returned 97 citations. After duplicates removal, the remaining 77 articles have been screened: 66 have been assessed as not eligible at first because the abstract did not meet the inclusion criteria. Eleven articles were left after the first two steps of selection: four have been excluded after full-text reading.
  
  CONCLUSION:
  PEP-bottle therapy has been proved to improve lung volume, to reduce hyperinflation, and to remove secretions. The device delivers a pressure equal to the water column only if the inner diameter of the tubing and the width of the air escape orifice are equal or greater than 8 mm, and the length of tubing ranges between 20 and 80 cm. The cost of a PEP-bottle device is significantly lower if compared with other commercially available devices having the same therapeutic purposes.
  
  © 2019 John Wiley & Sons, Ltd.
  
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• Precision medicine is coming to town: personalising home ventilatory equipment in COPD patients with chronic hypercapnic respiratory failure.
  Eur Respir Rev

  2019 Dec;28(154):. doi: 190043.
  
  Gonzalez-Bermejo Jesus, Nava Stefano, Rabec Claudio, Vega Maria Laura
  
  Abstract
  
  Discharging a chronic critically ill patient is a risky procedure if the clinician does not have full control of his prescription. This is even more important when applying a machine to replace a failing organ, as is the case for home ventilation. Even if modern home ventilators fulfil quality and safety criteria and, 'on paper', ventilators and masks look very similar, performance and scenarios of applicability are not always equivalent. In the case of ventilators, the type of circuit, accessories provided and available modes vary between devices. Bench studies comparing ventilators have shown large differences in triggering, rise time, pressurisation capacities, maximal flow provided, cycling and level of authorised expiratory positive airway pressure. Automated algorithms to deal with leaks also vary and have not been sufficiently evaluated. In the case of interfaces, the choice of mask requires careful evaluation of the underlying disease and of the type of ventilator and circuit, which could have a potentially major impact on patient compliance and clinical effectiveness. This could explain different results in the same clinical situation. The choice of ventilator and type of mask represents a medical prescription and should be respected by the provider and not subject to financial constraints.
  
  Copyright ©ERS 2019.
  
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• Real-life comparison of pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis: A 24-month assessment.
  Respir Med

  2019 11;159():105803. doi: S0954-6111(19)30310-5.
  
  Cerri Stefania, Monari Matteo, Guerrieri Aldo, Donatelli Pierluigi, Bassi Ilaria, Garuti Martina, Luppi Fabrizio, Betti Sara, Bandelli Gianpiero, Carpano Marco, Bacchi Reggiani Maria Letizia, Tonelli Roberto, Clini Enrico, Nava Stefano
  
  Abstract
  
  BACKGROUND:
  Real-life data on the use of pirfenidone and nintedanib to treat patients with idiopathic pulmonary fibrosis (IPF) are still scarce.
  
  METHODS:
  We compared the efficacy of either pirfenidone (n?=?78) or nintedanib (n?=?28) delivered over a 24-month period in patients with IPF, followed at two regional clinic centers in Italy, with a group of patients who refused the treatment (n?=?36), and who were considered to be controls. All patients completed regular visits at 1- to 3-month intervals, where primary [forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO)] and secondary outcomes (side effects, treatment compliance, and mortality) were recorded.
  
  RESULTS:
  Over time, the decline in FVC and DLCO was significantly higher (p?=?0.0053 and p?=?0.037, respectively) in controls when compared with the combined treated group, with no significant difference between the two treated groups. Compared to patients with less advanced disease (GAP (Gender, Age, Physiology) stage I), those in GAP stages II and III showed a significantly higher decline in both FVC and DLCO irrespective of the drug taken. Side effects were similarly reported in patients receiving pirfenidone and nintedanib (5% and 7%, respectively), whereas mortality did not differ among the three groups.
  
  CONCLUSION:
  This real-life study demonstrated that both pirfenidone and nintedanib were equally effective in reducing the decline of FVC and DLCO versus non-treated patients after 24 months of treatment; however, patients with more advanced disease were likely to show a more rapid decline in respiratory function.
  
  Copyright © 2019 Elsevier Ltd. All rights reserved.
  
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• The authors reply.
  Crit Care Med

  2019 10;47(10):e847-e848. doi: 10.1097/CCM.0000000000003936.
  
  Longhini Federico, Pisani Lara, Nava Stefano, Navalesi Paolo
  
  
  
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• Noninvasive ventilation during weaning from prolonged mechanical ventilation.
  Pulmonology

  ;25(6):328-333. doi: S2531-0437(19)30137-0.
  
  Ceriana Piero, Nava Stefano, Vitacca Michele, Carlucci Annalisa, Paneroni Mara, Schreiber Annia, Pisani Lara, Ambrosino Nicolino
  
  Abstract
  
  BACKGROUND AND OBJECTIVE:
  Non invasive ventilation (NIV) is currently employed for weaning from invasive ventilation (IMV) in the acute setting but its use for weaning from prolonged ventilation is still occasional and not standardized. We wanted to evaluate whether a combined protocol of NIV and decannulation in tracheostomized patients needing prolonged mechanical ventilation was feasible and what would be the one-year outcome.
  
  METHODS:
  We studied patients still dependent from invasive mechanical ventilation with the following inclusion criteria: a) tolerance of at least 8h of unsupported breathing, b) progressive hypercapnia/acidosis after invasive ventilation discontinuation, c) good adaptation to NIV, d) favorable criteria for decannulation. These patients were switched from IMV to NIV and decannulated; then they were discharged on home NIV and followed-up for one year in order to evaluate survival and complications rate.
  
  RESULTS:
  Data from patients consecutively admitted to a weaning unit were prospectively collected between 2005 and 2018. Out of 587 patients admitted over that period, 341 were liberated from prolonged mechanical ventilation. Fifty-one out of 147 unweaned patients (35%) were eligible for the protocol but only 46 were enrolled. After a mean length of stay of 35 days they were decannulated and discharged on domiciliary NIV. After one year, 38 patients were still alive (survival rate 82%) and 37 were using NIV with good adherence (only one patient was switched again to invasive ventilation).
  
  CONCLUSIONS:
  NIV applied to patients with failed weaning from prolonged IMV is feasible and can facilitate the decannulation process. Patients successfully completing this process show good survival rates and few complications.
  
  Copyright © 2019 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.
  
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• European Respiratory Society guidelines on long-term home non-invasive ventilation for management of COPD.
  Eur Respir J

  2019 09;54(3):. doi: 1901003.
  
  Ergan Begum, Oczkowski Simon, Rochwerg Bram, Carlucci Annalisa, Chatwin Michelle, Clini Enrico, Elliott Mark, Gonzalez-Bermejo Jesus, Hart Nicholas, Lujan Manel, Nasilowski Jacek, Nava Stefano, Pepin Jean Louis, Pisani Lara, Storre Jan Hendrik, Wijkstra Peter, Tonia Thomy, Boyd Jeanette, Scala Raffaele, Windisch Wolfram
  
  Abstract
  
  BACKGROUND:
  While the role of acute non-invasive ventilation (NIV) has been shown to improve outcome in acute life-threatening hypercapnic respiratory failure in COPD, the evidence of clinical efficacy of long-term home NIV (LTH-NIV) for management of COPD is less. This document provides evidence-based recommendations for the clinical application of LTH-NIV in chronic hypercapnic COPD patients.
  
  MATERIALS AND METHODS:
  The European Respiratory Society task force committee was composed of clinicians, methodologists and experts in the field of LTH-NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology. The GRADE Evidence to Decision framework was used to formulate recommendations. A number of topics were addressed under a narrative format which provides a useful context for clinicians and patients.
  
  RESULTS:
  The task force committee delivered conditional recommendations for four actionable PICO (target population-intervention-comparator-outcome) questions, 1) suggesting for the use of LTH-NIV in stable hypercapnic COPD; 2) suggesting for the use of LTH-NIV in COPD patients following a COPD exacerbation requiring acute NIV 3) suggesting for the use of NIV settings targeting a reduction in carbon dioxide and 4) suggesting for using fixed pressure support as first choice ventilator mode.
  
  CONCLUSIONS:
  Managing hypercapnia may be an important intervention for improving the health outcome of COPD patients with chronic respiratory failure. The task force conditionally supports the application of LTH-NIV to improve health outcome by targeting a reduction in carbon dioxide in COPD patients with persistent hypercapnic respiratory failure. These recommendations should be applied in clinical practice by practitioners that routinely care for chronic hypercapnic COPD patients.
  
  Copyright ©ERS 2019.
  
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• High-flow nasal therapy versus noninvasive ventilation in COPD patients with mild-to-moderate hypercapnic acute respiratory failure: study protocol for a noninferiority randomized clinical trial.
  Trials

  2019 Jul;20(1):450. doi: 10.1186/s13063-019-3514-1.
  
  Cortegiani Andrea, Longhini Federico, Carlucci Annalisa, Scala Raffaele, Groff Paolo, Bruni Andrea, Garofalo Eugenio, Taliani Maria Rita, Maccari Uberto, Vetrugno Luigi, Lupia Enrico, Misseri Giovanni, Comellini Vittoria, Giarratano Antonino, Nava Stefano, Navalesi Paolo, Gregoretti Cesare
  
  Abstract
  
  BACKGROUND:
  Noninvasive ventilation (NIV) is indicated to treat respiratory acidosis due to exacerbation of chronic obstructive pulmonary disease (COPD). Recent nonrandomized studies also demonstrated some physiological effects of high-flow nasal therapy (HFNT) in COPD patients. We designed a prospective, unblinded, multicenter, randomized controlled trial to assess the noninferiority of HFNT compared to NIV with respect to the reduction of arterial partial pressure of carbon dioxide (PaCO) in patients with hypercapnic acute respiratory failure with mild-to-moderate respiratory acidosis.
  
  METHODS:
  We will enroll adult patients with acute hypercapnic respiratory failure, as defined by arterial pH between 7.25 and 7.35 and PaCO???55?mmHg. Patients will be randomly assigned 1:1 to receive NIV or HFNT. NIV will be applied through a mask with a dedicated ventilator in pressure support mode. Positive end-expiratory pressure will be set at 3-5 cmHO with inspiratory support to obtain a tidal volume between 6 and 8?ml/kg of ideal body weight. HFNT will be initially set at a temperature of 37?°C and a flow of 60?L/min. At 2 and 6?h we will assess arterial blood gases, vital parameters, respiratory rate, treatment intolerance and failure, need for endotracheal intubation, time spent under mechanical ventilation (both invasive and NIV), intensive care unit and hospital length of stay, and hospital mortality. Based on an ? error of 5% and a ? error of 80%, with a standard deviation for PaCO equal to 15?mmHg and a noninferiority limit of 10?mmHg, we computed a sample size of 56 patients. Considering potential drop-outs and nonparametric analysis, the final computed sample size was 80 patients (40 per group).
  
  DISCUSSION:
  HFNT is more comfortable than NIV in COPD patients recovering from an episode of exacerbation. If HFNT would not be inferior to NIV, HFNT could be considered as an alternative to NIV to treat COPD patients with mild-to-moderate respiratory acidosis.
  
  TRIAL REGISTRATION:
  ClinicalTrials.gov, NCT03370666 . Registered on December 12, 2017.
  
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• Manual Massage Therapy for Patients with COPD: A Scoping Review.
  Medicina (Kaunas)

  2019 May;55(5):. doi: E151.
  
  Polastri Massimiliano, Clini Enrico Maria, Nava Stefano, Ambrosino Nicolino
  
  Abstract
  
  Manual massage therapy is a therapeutic option for the treatment of several pathological conditions affecting the musculoskeletal system. It has been pointed out that massage might be beneficial for chronic obstructive pulmonary disease (COPD) patients thanks to therapeutic effects primarily related to hyperemia (increased skin temperature and blood flow), and activation of the lymphatic system. The present study reports current evidence on the systemic effects of manual massage in patients with COPD. A scoping review was conducted on five major databases. The search went through all databases since their inception until December 2018. Seventy-eight citations were retrieved; after the selection process was completed, seven articles were considered eligible. In patients receiving manual massage, improvements were observed in Forced Expiratory Volume in 1 s, dyspnea perception, and in the 6-min walking test. To date, the use of manual massage in patients with COPD is not supported by substantial evidence in the literature: indeed, it is proposed as a therapeutic option in association with other interventions such as physical exercise.
  
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• Acute myocardial infarction complicating ischemic stroke: is there room for cangrelor?
  Platelets

  2020 ;31(1):120-123. doi: 10.1080/09537104.2019.1609663.
  
  Morici Nuccia, Nava Stefano, Sacco Alice, Viola Giovanna, Oreglia Jacopo, Meani Paolo, Oliva Fabrizio, Ranucci Marco, Leonardi Sergio, Rossini Roberta
  
  Abstract
  
  Acute myocardial infarction (AMI) complicating ischemic stroke is a well known and undertreated event. A conservative management is not infrequent in these settings, due to the fear of hemorrhagic complications related to antithrombotic therapy. Notably, an invasive approach with a primary percutaneous coronary intervention (PCI) has been shown to be associated with a lower in-hospital mortality in patients with concomitant ischemic stroke and AMI. The optimal antiplatelet regimen in these cases has been not clearly defined, yet. We report two cases of patients with AMI complicating ischemic stroke, successfully treated with cangrelor infusion, which was started during PCI and maintained up to 48 h at bridge therapy dosage (0.75 mcg/kg/min). Both patients underwent successful PCI in the acute phase, and neither ischemic nor hemorrhagic complications occurred during in-hospital stay.
  
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• Noninvasive ventilation and renal replacement therapy in do-not-intubate order critically ill patients: A brief report.
  Clin Respir J

  2019 Jun;13(6):400-403. doi: 10.1111/crj.13023.
  
  Catalanotti Vito, Pisani Lara, Betti Sara, Bensai Serena, Prediletto Irene, Fasano Luca, Nava Stefano
  
  Abstract
  
  INTRODUCTION:
  Multiple organ failure has been considered a contraindication for noninvasive ventilation (NIV).
  
  MATERIALS AND METHODS:
  We described the outcome of Do-not-Intubate (DNI) patients with acute respiratory failure, treated with NIV and, subsequently, necessitating renal replacement therapy (RRT).
  
  RESULTS AND DISCUSSION:
  Seven patients admitted to our Respiratory Intensive Care Unit, developed Acute Kidney Injury (AKI) during NIV treatment and received RRT for 12.8 ± 8 days together with NIV. All the patients but one, discontinued renal support because they regained a satisfactory urinary output; nevertheless mortality rate was high (71%).
  
  CONCLUSION:
  Our data suggest that RRT could be feasible together with NIV. RRT was associated with an acute improvement in renal function but did not modify the mortality rate.
  
  © 2019 John Wiley & Sons Ltd.
  
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• Patient-Clinician Alliance during Prolonged Mechanical Ventilation. "Never Give Up on a Dream".
  Am J Respir Crit Care Med

  2019 Jun;199(12):1453-1454. doi: 10.1164/rccm.201901-0032ED.
  
  Nava Stefano, Pisani Lara
  
  
  
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• Use of Symptoms Scores, Spirometry, and Other Pulmonary Function Testing for Asthma Monitoring.
  Front Pediatr

  2019 ;7():54. doi: 10.3389/fped.2019.00054.
  
  Gallucci Marcella, Carbonara Paolo, Pacilli Angela Maria Grazia, di Palmo Emanuela, Ricci Giampaolo, Nava Stefano
  
  Abstract
  
  Asthma is a global problem affecting millions of people all over the world. Monitoring of asthma both in children and in adulthood is an indispensable tool for the optimal disease management and for the maintenance of clinical stability. To date, several resources are available to assess the asthma control, first is the monitoring of symptoms, both through periodic follow-up visits and through specific quality of life measures addressed to the patient in first person or to parents. Clinical monitoring is not always sufficient to predict the risk of future exacerbations, which is why further instrumental examinations are available including lung function tests, the assessment of bronchial hyper-reactivity and bronchial inflammation. All these tools may help in quantifying the future risk for each patient and therefore they potentially may change the natural history of asthmatic disease. The monitoring of asthma in children as in adults is certainly linked by many aspects, however the asthmatic child is a future asthmatic adult and it is precisely during childhood and adolescence that we should implement all the efforts and strategies to prevent the progression of the disease and the subsequent impairment of lung function. For these reasons, asthma monitoring plays a crucial role and must be particularly close and careful. In this paper, we evaluate several tools currently available for asthma monitoring, focusing on current recommendations emerging from various guidelines and especially on the differences between the monitoring in pediatric age and adulthood.
  
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• High-Flow Oxygen Therapy After Noninvasive Ventilation Interruption in Patients Recovering From Hypercapnic Acute Respiratory Failure: A Physiological Crossover Trial.
  Crit Care Med

  2019 06;47(6):e506-e511. doi: 10.1097/CCM.0000000000003740.
  
  Longhini Federico, Pisani Lara, Lungu Ramona, Comellini Vittoria, Bruni Andrea, Garofalo Eugenio, Laura Vega Maria, Cammarota Gianmaria, Nava Stefano, Navalesi Paolo
  
  Abstract
  
  OBJECTIVES:
  Assessing gas exchange, diaphragm function, respiratory rate, and patient comfort during high-flow oxygen therapy and standard oxygen at the time of noninvasive ventilation discontinuation.
  
  DESIGN:
  Randomized crossover physiologic study.
  
  SETTING:
  Two ICUs.
  
  PATIENTS:
  Thirty chronic obstructive pulmonary disease patients with hypercapnic acute respiratory failure receiving noninvasive ventilation greater than 24 hours.
  
  INTERVENTIONS:
  All patients underwent five 30-minute trials, the first, third, and fifth trial in noninvasive ventilation, whereas the second and fourth were randomly conducted with either standard oxygen and high-flow oxygen therapy.
  
  MEASUREMENTS AND MAIN RESULTS:
  Diaphragm displacement and thickening fraction were determined by sonographic evaluation at the end of each trial. Arterial blood gases, respiratory rate, and patient comfort were also assessed. PaCO2 (p = 0.153) and pH (p = 0.114) were not different among trials, while PaO2 was greater in noninvasive ventilation than with both standard oxygen (p ? 0.005) and high-flow oxygen therapy (p ? 0.001). The diaphragm displacement was no different among trials (p = 0.875), while its thickening fraction was greater with standard oxygen, compared with high-flow oxygen therapy and all noninvasive ventilation trials (p < 0.001 for all comparisons), without differences between high-flow oxygen therapy and noninvasive ventilation. Respiratory rate also increased with standard oxygen, compared with both high-flow oxygen therapy (p < 0.001) and noninvasive ventilation (p < 0.01). High-flow oxygen therapy improved comfort, compared with standard oxygen (p = 0.004) and noninvasive ventilation (p < 0.001).
  
  CONCLUSIONS:
  At the time of noninvasive ventilation interruption, PaCO2 and diaphragm displacement remained unchanged regardless of the modality of oxygen administration. However, although standard oxygen resulted in a remarkable increase in diaphragm thickening fraction, high-flow oxygen therapy allowed maintaining it unchanged, while improving patient comfort.
  
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• Pulmonary rehabilitation, physical activity, respiratory failure and palliative respiratory care.
  Thorax

  2019 07;74(7):693-699. doi: 10.1136/thoraxjnl-2018-212044.
  
  Spruit Martijn A, Rochester Carolyn L, Pitta Fabio, Kenn Klaus, Schols Annemie M W J, Hart Nicholas, Wouters Emiel F M, Nava Stefano, Dreher Michael, Janssen Daisy J A, Johnson Miriam J, Curtis Randall J, Sastry Manuel, Franssen Frits M E
  
  Abstract
  
  The CIRO Academy in Horn (the Netherlands) organised a 2-day meeting to present and discuss the studies published in 2017 pertaining to key priority areas of respiratory and critical care medicine. This review summarises studies focussing on pulmonary rehabilitation and exercise training, physical activity, chronic respiratory failure and palliative respiratory care published in 2017.
  
  © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
  
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• Poor Concordance between Sequential Transbronchial Lung Cryobiopsy and Surgical Lung Biopsy in the Diagnosis of Diffuse Interstitial Lung Diseases.
  Am J Respir Crit Care Med

  2019 05;199(10):1249-1256. doi: 10.1164/rccm.201810-1947OC.
  
  Romagnoli Micaela, Colby Thomas V, Berthet Jean-Philippe, Gamez Anne Sophie, Mallet Jean-Pierre, Serre Isabelle, Cancellieri Alessandra, Cavazza Alberto, Solovei Laurence, Dell'Amore Andrea, Dolci Giampiero, Guerrieri Aldo, Reynaud Paul, Bommart Sébastien, Zompatori Maurizio, Dalpiaz Giorgia, Nava Stefano, Trisolini Rocco, Suehs Carey M, Vachier Isabelle, Molinari Nicolas, Bourdin Arnaud
  
  Abstract
  
  The diagnostic concordance between transbronchial lung cryobiopsy (TBLC)-versus surgical lung biopsy (SLB) as the current gold standard-in interstitial lung disease (ILD) cases requiring histology remains controversial. To assess diagnostic concordance between TBLC and SLB sequentially performed in the same patients, the diagnostic yield of both techniques, and subsequent changes in multidisciplinary assessment (MDA) decisions. A two-center prospective study included patients with ILD with a nondefinite usual interstitial pneumonia pattern (on high-resolution computed tomography scan) confirmed at a first MDA. Patients underwent TBLC immediately followed by video-assisted thoracoscopy for SLB at the same anatomical locations. After open reading of both sample types by local pathologists and final diagnosis at a second MDA (MDA2), anonymized TBLC and SLB slides were blindly assessed by an external expert pathologist (T.V.C.). Kappa-concordance coefficients and percentage agreement were computed for: TBLC versus SLB, MDA2 versus TBLC, MDA2 versus SLB, and blinded pathology versus routine pathology. Twenty-one patients were included. The median TBLC biopsy size (longest axis) was 7 mm (interquartile range, 5-8 mm). SLB biopsy sizes averaged 46.1?±?13.8 mm. Concordance coefficients and percentage agreement were: TBLC versus SLB: ??=?0.22 (95% confidence interval [CI], 0.01-0.44), percentage agreement?=?38% (95% CI, 18-62%); MDA2 versus TBLC: ??=?0.31 (95% CI, 0.06-0.56), percentage agreement?=?48% (95% CI, 26-70)%; MDA2 versus SLB: ??=?0.51 (95% CI, 0.27-0.75), percentage agreement?=?62% (95% CI, 38-82%); two pneumothoraces (9.5%) were recorded during TBLC. TBLC would have led to a different treatment if SLB was not performed in 11 of 21 (52%) of cases. Pathological results from TBLC and SLB were poorly concordant in the assessment of ILD. SLBs were more frequently concordant with the final diagnosis retained at MDA.
  
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• Noninvasive Ventilation in Unplanned Endotracheal Extubation: Just a Little Help From My Friend?
  Respir Care

  2019 03;64(3):352-354. doi: 10.4187/respcare.06886.
  
  Nava Stefano, Prediletto Irene, Pisani Lara
  
  
  
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• Benefits of non-invasive ventilation in acute hypercapnic respiratory failure.
  Respirology

  2019 04;24(4):308-317. doi: 10.1111/resp.13469.
  
  Comellini Vittoria, Pacilli Angela Maria Grazia, Nava Stefano
  
  Abstract
  
  Non-invasive ventilation (NIV) with bilevel positive airway pressure is a non-invasive technique, which refers to the provision of ventilatory support through the patient's upper airway using a mask or similar device. This technique is successful in correcting hypoventilation. It has become widely accepted as the standard treatment for patients with hypercapnic respiratory failure (HRF). Since the 1980s, NIV has been used in intensive care units and, after initial anecdotal reports and larger series, a number of randomized trials have been conducted. Data from these trials have shown that NIV is a valuable treatment for HRF. This review aims to explore the principal areas in which NIV can be useful, focusing particularly on patients with acute HRF (AHRF). We will update the evidence base with the goal of supporting clinical practice. We provide a practical description of the main indications for NIV in AHRF and identify the group of patients with hypercapnic failure who will benefit most from the application of NIV.
  
  © 2019 Asian Pacific Society of Respirology.
  
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• Elastic Band Exercises for Patients with Intensive Care Unit-Acquired Weakness: A Case Report.
  Tanaffos

  2018 Feb;17(2):132-137.
  
  Polastri Massimiliano, Oldani Stefano, Pisani Lara, Nava Stefano
  
  Abstract
  
  Intensive care unit-acquired weakness is characterised by severe impairment of muscle function that often arises after prolonged mechanical ventilation, difficult weaning, and severe sepsis. Elastic band exercises constitute an inexpensive and simple technique that is quite appealing for implementation in a "protected environment" such as the intensive care unit; however, elastic band application in the intensive care unit and in critical patients has not yet been described. A 72-year-old male was referred to the respiratory intensive care unit for hypoxemic respiratory failure due to acute respiratory distress syndrome. Upper limb active exercises were performed using an elastic band exploring three main movement rays: abduction, forward flexion, and external rotation. At discharge, major improvements were observed for upper limb activities. The patient was also able to maintain a sitting position at the edge of the bed starting from day 27. We found that an elastic band exercise program in a critical ill patient recovering from intensive care unit-acquired weakness was a suitable, safe, viable, and inexpensive therapeutic option to preserve residual upper limb motor activities and improve trunk control.
  
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• High-flow nasal therapy vs standard oxygen during breaks off noninvasive ventilation for acute respiratory failure: A pilot randomized controlled trial.
  J Crit Care

  2018 12;48():418-425. doi: S0883-9441(18)31068-2.
  
  Spoletini Giulia, Mega Chiara, Pisani Lara, Alotaibi Mona, Khoja Alia, Price Lori Lyn, Blasi Francesco, Nava Stefano, Hill Nicholas S
  
  Abstract
  
  PURPOSE:
  To assess the role of high-flow nasal therapy (HFNT) compared to standard oxygen (SO) as complementary therapy to non-invasive ventilation (NIV).
  
  METHODS:
  Multicenter trial including patients (n?=?54) anticipated to receive NIV for ?24?h due to acute or acute-on-chronic respiratory failure. Subjects were randomized (1:1) to SO or HFNT during breaks off NIV. Primary outcome was total time on and off NIV. Secondary outcomes were comfort and dyspnea, respiratory rate (RR), oxygen saturation (SO), tolerance and side effects.
  
  RESULTS:
  Total time per patient on NIV (1315 vs 1441?min) and breaks (1362 vs 1196?min), and mean duration of each break (520 vs 370?min) were similar in the HFNT and SO arms (p?>?.05). Comfort score was higher on HFNT than on SO (8.3?±?2.7 vs 6.9?±?2.3, p?=?.001). Dyspnea, RR and SO were similar in the two arms, but the increase in RR and dyspnea seen with SO during breaks did not occur with HFNT.
  
  CONCLUSION:
  Compared to SO, HFNT did not reduce time on NIV. However, it was more comfortable and the increase in RR and dyspnea seen with SO did not occur with HFNT. Therefore, HFNT could be a suitable alternative to SO during breaks off NIV.
  
  Copyright © 2018. Published by Elsevier Inc.
  
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• Response.
  Chest

  2018 10;154(4):992. doi: S0012-3692(18)31070-5.
  
  Pisani Lara, Hill Nicholas S, Pacilli Angela Maria Grazia, Polastri Massimiliano, Nava Stefano
  
  
  
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• Physiotherapy and Weaning From Prolonged Mechanical Ventilation.
  Respir Care

  2019 Jan;64(1):17-25. doi: 10.4187/respcare.06280.
  
  Schreiber Annia F, Ceriana Piero, Ambrosino Nicolino, Malovini Alberto, Nava Stefano
  
  Abstract
  
  BACKGROUND:
  Patients undergoing prolonged mechanical ventilation represent up to 15% of all patients requiring weaning from mechanical ventilation. Although recent guidelines have recommended including physiotherapy early during mechanical ventilation to speed the process of weaning, only indirect evidence supporting the use of physiotherapy is available for patients receiving prolonged mechanical ventilation. The aim of our study was to evaluate the effects of a physiotherapy program in subjects requiring prolonged mechanical ventilation and the correlates of successful weaning.
  
  METHODS:
  A retrospective analysis was performed on 1,313 consecutive patients admitted to a weaning unit over a 15-y period to be liberated from prolonged mechanical ventilation. Subjects underwent a program of intensive physiotherapy organized in 4 incremental steps (1-4) and were analyzed according to the steps achieved (> 2 steps or ? 2 steps). The rate of successful weaning was recorded, and possible predictors were considered. The 15-y period of observation was divided into 3 consecutive 5-y intervals.
  
  RESULTS:
  Out of 560 subjects undergoing final analysis, 349 (62.3%) were successfully weaned. The weaning success rate was significantly greater in subjects attaining > 2 steps than in subjects who attained ? 2 steps (72.1% vs 55.9%, respectively, odds ratio = 2.04, 95% CI = 1.42-2.96, < .001). Stepwise logistic regression analysis showed that achievement of > 2 physiotherapy steps was the main predictor of successful weaning (odds ratio = 2.17, 95% CI = 1.48-3.23, < .001). Underlying disease was also a predictor of successful weaning. The overall rate of successful weaning decreased, and the median duration of weaning increased, during the period of observation.
  
  CONCLUSIONS:
  Our data support the inclusion of physiotherapy in the management of patients requiring prolonged mechanical ventilation.
  
  Copyright © 2019 by Daedalus Enterprises.
  
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• Tai Chi Recreational Exercise Is Not Rehabilitation.
  Chest

  2018 09;154(3):730-731. doi: S0012-3692(18)30817-1.
  
  Ambrosino Nicolino, Polastri Massimiliano, Vitacca Michele, Nava Stefano, Clini Enrico M
  
  
  
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• Pharmacological approach and adherence to treatment recommendations in frequently and non-frequently exacerbating COPD patients from Italy: MISTRAL - The prospective cohort, observational study.
  Pulm Pharmacol Ther

  2018 12;53():68-77. doi: S1094-5539(18)30149-4.
  
  Scalone Gino, Nava Stefano, Ventrella Francesco, Bussoli Guglielmo, Catapano Giosuè Angelo, Pennisi Alfio, Dadduzio Francesco, Schino Pietro, Pela Riccardo, Bartezaghi Marta, Morini Paolo, Porpiglia Pasquale Alberto, Muscianisi Elisa,
  
  Abstract
  
  BACKGROUND:
  Several documents and guidelines provide recommendations for effective management of COPD patients. However, there is often a significant imbalance between recommended treatment of COPD patients and the actual care provided both in primary care and specialty setting. This imbalance could result in a significant negative impact on patients' health status and quality of life, leading to increased hospitalisations and health resource utilisation in COPD patients METHODS: MISTRAL was an observational, longitudinal, prospective cohort study, designed to assess the overall pharmacological approach of COPD in routine clinical practice in Italy. Eligible patients were divided into two cohorts based on their exacerbation history in the year prior to the enrolment, frequent exacerbators (FEs; ?2 exacerbations), and non-frequent exacerbators (NFEs; ?1 exacerbation). The primary objective was to assess adherence to Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 treatment recommendations in FEs and NFEs at baseline and follow-up visits RESULTS: Of the 1489 enrolled patients, 1468 (98.6%; FEs, 526; NFEs, 942) were considered evaluable for analyses. At baseline, 57.8% of patients were treated according to GOLD 2011 recommendations; a greater proportion of FEs were treated according to GOLD recommendations, compared with NFEs patients at baseline (77.1% versus 46.7%; P < 0.0001), and all study visits. At baseline, GOLD group D patients were the most adherent (81.2%) to treatment recommendations, while group A patients were the least adherent (30.3%) at baseline, attributed mainly to overuse of inhaled corticosteroids in less severe GOLD groups. Triple therapy with long-acting muscarinic antagonist (LAMA) + long-acting ?-agonist/inhaled corticosteroid (LABA/ICS) was the most frequent prescribed treatment at all study visits, irrespective of patient's exacerbation history. Changes in treatment were more frequent in FEs versus NFEs CONCLUSIONS: The Mistral study reports a scarce adherence to the GOLD 2011 treatment recommendations in routine clinical practice in Italy. The adherence was particularly low in less severe, non-frequent exacerbating patients mostly for ICS overuse, and was higher in high-risk, frequent exacerbating COPD patients.
  
  Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
  
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• Extracorporeal Lung Support for Hypercapnic Ventilatory Failure.
  Respir Care

  2018 Sep;63(9):1174-1179. doi: 10.4187/respcare.06277.
  
  Pisani Lara, Polastri Massimiliano, Pacilli Angela Maria Grazia, Nava Stefano
  
  Abstract
  
  Extracorporeal lung support can be achieved using extracorporeal membrane oxygenation (ECMO) and extracorporeal CO removal. The ECMO systems allow a total lung support, providing both blood oxygenation and CO removal. Unlike ECMO, extracorporeal CO removal refers to an extracorporeal circuit that provides a partial lung support and selectively extracts CO from blood. The concept of partial extracorporeal lung support by removing only CO without effect on oxygenation was first proposed in 1977 by Kolobow and Gattinoni, with the aim to reduce breathing frequency, ventilator tidal volumes, and inspiratory pressures, facilitating lung-protective ventilation. Patients with end-stage chronic lung disease can survive, while waiting for lung transplantation, only if treated with mechanical ventilation or extracorporeal lung support. ECMO has been considered a suitable approach as a bridge to lung transplantation for patients with advanced respiratory failure waiting for lung transplantation. Extracorporeal CO removal has been proposed for the treatment of COPD patients suffering from exacerbation to avoid invasive mechanical ventilation. The rationale is to combine the improvement of alveolar ventilation by using noninvasive ventilation with muscle unload provided by removing CO directly from the blood, using an extracorporeal device. Increasing attention has been given to the possibility of patients performing a variety of physical activities while receiving extracorporeal lung support. This is possible thanks to the continuous development of technology together with the customization of sedative protocols. Awake extracorporeal support is a specific approach in which the patient is awake and potentially cooperative while receiving ECMO. The present analysis aims to synthesize the main results obtained by using extracorporeal circuits in patients with respiratory failure, particularly in those patients with hypercapnia.
  
  Copyright © 2018 by Daedalus Enterprises.
  
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• The use of bronchoscopy in critically ill patients: considerations and complications.
  Expert Rev Respir Med

  2018 08;12(8):651-663. doi: 10.1080/17476348.2018.1494576.
  
  Ergan Begum, Nava Stefano
  
  Abstract
  
  INTRODUCTION:
  Flexible bronchoscopy has been well established for diagnostic and therapeutic purposes in critically ill patients. Areas covered: This review outlines the clinical evidence of the utility and safety of flexible bronchoscopy in the intensive care unit, as well as specific considerations, including practical points and potential complications, in critically ill patients. Expert commentary: Its ease to learn and perform and its capacity for bedside application with relatively few complications make flexible bronchoscopy an indispensable tool in the intensive care unit setting. The main indications for flexible bronchoscopy in the intensive care unit are the visualization of the airways, sampling for diagnostic purposes and management of the artificial airways. The decision to perform flexible bronchoscopy can only be made by trade-offs between potential risks and benefits because of the fragile nature of the critically ill. Flexible bronchoscopy-associated serious adverse events are inevitable in cases of a lack of expertise or appropriate precautions.
  
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• Should I stay or should I go? COPD and air travel.
  Eur Respir Rev

  2018 Jun;27(148):. doi: 180030.
  
  Ergan Begum, Akgun Metin, Pacilli Angela Maria Grazia, Nava Stefano
  
  Abstract
  
  Chronic obstructive pulmonary disease (COPD) is a challenging respiratory problem throughout the world. Although survival is prolonged with new therapies and better management, the magnitude of the burden resulting from moderate-to-severe disease is increasing. One of the major aims of the disease management is to try to break the vicious cycle of patients being homebound and to promote an active lifestyle. A fundamental component of active daily life is, of course, travelling. Today, the world is getting smaller with the option of travelling by air. Air travel is usually the most preferred choice as it is easy, time saving, and relatively inexpensive. Although it is a safe choice for many passengers, the environment inside the aeroplane may sometimes have adverse effects on health. Hypobaric hypoxaemia due to cabin altitude may cause health risks in COPD patients who have limited cardiopulmonary reserve. Addressing the potential risks of air travel, promoting proactive strategies including pre-flight assessment, and education of COPD patients about the "fitness to fly" concept are essential. Thus, in this narrative review, we evaluated the current evidence for potential risks of air travel in COPD and tried to give a perspective for how to plan safe air travel for COPD patients.
  
  Copyright ©ERS 2018.
  
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• Management of Dyspnea in the Terminally Ill.
  Chest

  2018 10;154(4):925-934. doi: S0012-3692(18)30566-X.
  
  Pisani Lara, Hill Nicholas S, Pacilli Angela Maria Grazia, Polastri Massimiliano, Nava Stefano
  
  Abstract
  
  The genesis of dyspnea involves the activation of several mechanisms that are mediated and perceived depending on previous experiences, values, emotions, and beliefs. Breathlessness may become unbearable, especially in patients who are terminally ill, whether afflicted by respiratory-, cardiac-, or cancer-related disorders, because of a final stage of a chronic process, an acute event, or both. Compared with pain, palliation of dyspnea has received relatively little attention in clinical practice and the medical literature. This is particularly true when the breathlessness is associated with acute respiratory failure because most of the studies on pharmacologic and nonpharmacologic treatments of respiratory distress have excluded such patients. Assessments of the quality of dying for patients in an ICU consistently show that few patients are considered by family members to breathe comfortably at the end of their life. This review focuses on the management of dyspnea in patients with advanced terminal illness, summarizing clinical trial evidence on pharmacologic and nonpharmacologic interventions available for these patients.
  
  Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
  
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• Magnetic Stimulation Therapy in Patients with COPD: A Systematic Review.
  COPD

  2018 04;15(2):165-170. doi: 10.1080/15412555.2018.1439910.
  
  Polastri Massimiliano, Comellini Vittoria, Pacilli Angela Maria Grazia, Nava Stefano
  
  Abstract
  
  Magnetotherapy (MT) is a therapeutic treatment based on the use of magnetic fields (MF) that can have an anti-inflammatory and analgesic effect. MT represents a possible treatment or an ancillary therapeutic intervention for a wide range of diseases and it is often used in the field of physiotherapeutic practices. A crucial point in the treatment of chronic obstructive pulmonary disease (COPD) patients, to counteract muscular depletion and respiratory symptoms, is represented by physiotherapy. Nevertheless, the knowledge about the application of MF as a therapeutic option in COPD patients is very limited. The purpose of the present study was to define what is currently known about the use of MF in patients with COPD. A systematic review of the literature was conducted during the month of October 2017, searching three main databases. Only those citations providing detailed informations about the use of MF to treat COPD symptoms either during an acute or a chronic phase of the disease, were selected. Following the selection process three articles were included in the final analysis. The present review focused on a total of thirty-six patients with COPD, and on the effects of the application of MF. In the majority of cases, the treatment sessions with MF were carried-out in an outpatient setting, and they differed with regard to the duration; frequency of application; dosage; intensity of the applied MF. Basing on the available informations, it seems that MF is a feasible, well tolerated, safe therapeutic option, for the treatment of motor-related COPD symptoms.
  
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• A New Ultrasound Method for Estimating Dynamic Intrinsic Positive Airway Pressure: A Prospective Clinical Trial.
  Am J Respir Crit Care Med

  2018 08;198(3):392-396. doi: 10.1164/rccm.201706-1292LE.
  
  Bernardi Emanuele, Pisani Lara, Fasano Luca, Lauria Giuseppe, Comellini Vittoria, Appendini Lorenzo, Conti Giorgio, Tosello Francesco, Pizzolato Elisa, Nava Stefano
  
  
  
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• Assessing Risk and Treatment Responsiveness in ARDS. Beyond Physiology.
  Am J Respir Crit Care Med

  2018 06;197(12):1516-1518. doi: 10.1164/rccm.201802-0273ED.
  
  Del Sorbo Lorenzo, Nava Stefano, Rubenfeld Gordon, Thompson Taylor, Ranieri V Marco
  
  
  
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• Revolving door respiratory patients: A rehabilitative perspective.
  Monaldi Arch Chest Dis

  2017 09;87(3):857. doi: 10.4081/monaldi.2017.857.
  
  Polastri Massimiliano, Pisani Lara, Dell'Amore Andrea, Nava Stefano
  
  Abstract
  
  Rehabilitation is an integral component of care for patients affected by either acute or chronic pulmonary diseases. The key elements of rehabilitation treatment for critical respiratory patients are as follows: weaning from mechanical ventilation, respiratory therapy, physical reconditioning, and occupational therapy. It should be noted that patients affected by pulmonary diseases are prone to hospital re-admission due to frequent exacerbations, especially in cases with more severe stages of chronic obstructive pulmonary disease. A periodical worsening of clinical conditions is common in asthma, acute respiratory distress syndrome survivors, obstructive sleep apnea syndrome, and pulmonary fibrosis, as well as in patients with severe neuromuscular diseases. These patients are often identified as "revolving door patients". Pulmonary patients are typically forced to maintain bed rest, or at least spend most of their waking hours dealing with mobility limitations, due to various pathological conditions including dyspnea, fatigue, and poor tolerance of movements. Alterations in mood are common in pulmonary patients who experience a decreased quality of life and limited social interactions. These negative emotional and cognitive aspects can be a major limitation to the provision of care, because to enhance and facilitate a degree of autonomy, the patient must be cooperative and pro-active.
  
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• Efficacy of ventilator waveform observation for detection of patient-ventilator asynchrony during NIV: a multicentre study.
  ERJ Open Res

  2017 Oct;3(4):. doi: 00075-2017.
  
  Longhini Federico, Colombo Davide, Pisani Lara, Idone Francesco, Chun Pan, Doorduin Jonne, Ling Liu, Alemani Moreno, Bruni Andrea, Zhaochen Jin, Tao Yu, Lu Weihua, Garofalo Eugenio, Carenzo Luca, Maggiore Salvatore Maurizio, Qiu Haibo, Heunks Leo, Antonelli Massimo, Nava Stefano, Navalesi Paolo
  
  Abstract
  
  The objective of this study was to assess ability to identify asynchronies during noninvasive ventilation (NIV) through ventilator waveforms according to experience and interface, and to ascertain the influence of breathing pattern and respiratory drive on sensitivity and prevalence of asynchronies. 35 expert and 35 nonexpert physicians evaluated 40 5-min NIV reports displaying flow-time and airway pressure-time tracings; identified asynchronies were compared with those ascertained by three examiners who evaluated the same reports displaying, additionally, tracings of diaphragm electrical activity. We determined: 1) sensitivity, specificity, and positive and negative predictive values; 2) the correlation between the double true index (DTI) of each report ( the ratio between the sum of true positives and true negatives, and the overall breath count) and the corresponding asynchrony index (AI); and 3) the influence of breathing pattern and respiratory drive on both AI and sensitivity. Sensitivities to detect asynchronies were low either according to experience (0.20 (95% CI 0.14-0.29) for expert 0.21 (95% CI 0.12-0.30) for nonexpert, p=0.837) or interface (0.28 (95% CI 0.17-0.37) for mask 0.10 (95% CI 0.05-0.16) for helmet, p<0.0001). DTI inversely correlated with the AI (r=0.67, p<0.0001). Breathing pattern and respiratory drive did not affect prevalence of asynchronies and sensitivity. Patient-ventilator asynchrony during NIV is difficult to recognise solely by visual inspection of ventilator waveforms.
  
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• Sex-related relationships between uric acid and target organ damage in hypertension.
  J Clin Hypertens (Greenwich)

  2018 01;20(1):193-200. doi: 10.1111/jch.13136.
  
  Maloberti Alessandro, Maggioni Simone, Occhi Lucia, Triglione Nicola, Panzeri Francesco, Nava Stefano, Signorini Stefano, Falbo Rosanna, Casati Marco, Grassi Guido, Giannattasio Cristina
  
  Abstract
  
  Heterogeneous results have been obtained in the relationship between serum uric acid (SUA) and target organ damage (TOD) in patients with hypertension. Clinic blood pressure, SUA, and cardiac, arterial (carotid and aortic), and renal TOD were assessed in 762 consecutive patients with hypertension. Hyperuricemia was defined as an SUA >7.0 in men and >6.0 mg/dL in women. Men with hyperuricemia compared with those with normal SUA showed lower estimated glomerular filtration rates and E/A ratios and a higher prevalence of carotid plaques. Women with hyperuricemia showed lower estimated glomerular filtration rates and E/A ratios and a higher intima-media thickness. Except for pulse wave velocity, all TODs significantly correlated with SUA. However, at multivariate analysis, only estimated glomerular filtration rate was significantly determined by SUA. Our data provide evidence on the role of SUA in the development of TOD only in the case of renal alteration. It is likely that SUA may indirectly act on the other TODs through the increase in blood pressure and the decrease in glomerular filtration rate.
  
  ©2017 Wiley Periodicals, Inc.
  
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• Intensive care unit patients with lower respiratory tract nosocomial infections: the ENIRRIs project.
  ERJ Open Res

  2017 Oct;3(4):. doi: 00092-2017.
  
  De Pascale Gennaro, Ranzani Otavio T, Nseir Saad, Chastre Jean, Welte Tobias, Antonelli Massimo, Navalesi Paolo, Garofalo Eugenio, Bruni Andrea, Coelho Luis Miguel, Skoczynski Szymon, Longhini Federico, Taccone Fabio Silvio, Grimaldi David, Salzer Helmut J F, Lange Christoph, Froes Filipe, Artigas Antoni, Díaz Emili, Vallés Jordi, Rodríguez Alejandro, Panigada Mauro, Comellini Vittoria, Fasano Luca, Soave Paolo M, Spinazzola Giorgia, Luyt Charles-Edouard, Alvarez-Lerma Francisco, Marin Judith, Masclans Joan Ramon, Chiumello Davide, Pezzi Angelo, Schultz Marcus, Mohamed Hafiz, Van Der Eerden Menno, Hoek Roger A S, Gommers D A M P J, Pasquale Marta Di, Civljak Rok, Kutle?a Marko, Bassetti Matteo, Dimopoulos George, Nava Stefano, Rios Fernando, Zampieri Fernando G, Povoa Pedro, Bos Lieuwe D, Aliberti Stefano, Torres Antoni, Martín-Loeches Ignacio
  
  Abstract
  
  The clinical course of intensive care unit (ICU) patients may be complicated by a large spectrum of lower respiratory tract infections (LRTI), defined by specific epidemiological, clinical and microbiological aspects. A European network for ICU-related respiratory infections (ENIRRIs), supported by the European Respiratory Society, has been recently established, with the aim at studying all respiratory tract infective episodes except community-acquired ones. A multicentre, observational study is in progress, enrolling more than 1000 patients fulfilling the clinical, biochemical and radiological findings consistent with a LRTI. This article describes the methodology of this study. A specific interest is the clinical impact of non-ICU-acquired nosocomial pneumonia requiring ICU admission, non-ventilator-associated LRTIs occurring in the ICU, and ventilator-associated tracheobronchitis. The clinical meaning of microbiologically negative infectious episodes and specific details on antibiotic administration modalities, dosages and duration are also highlighted. Recently released guidelines address many unresolved questions which might be answered by such large-scale observational investigations. In light of the paucity of data regarding such topics, new interesting information is expected to be obtained from our network research activities, contributing to optimisation of care for critically ill patients in the ICU.
  
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• Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure.
  Eur Respir J

  2017 08;50(2):. doi: 1602426.
  
  Rochwerg Bram, Brochard Laurent, Elliott Mark W, Hess Dean, Hill Nicholas S, Nava Stefano, Navalesi Paolo, Antonelli Massimo, Brozek Jan, Conti Giorgio, Ferrer Miquel, Guntupalli Kalpalatha, Jaber Samir, Keenan Sean, Mancebo Jordi, Mehta Sangeeta, Raoof Suhail
  
  Abstract
  
  Noninvasive mechanical ventilation (NIV) is widely used in the acute care setting for acute respiratory failure (ARF) across a variety of aetiologies. This document provides European Respiratory Society/American Thoracic Society recommendations for the clinical application of NIV based on the most current literature.The guideline committee was composed of clinicians, methodologists and experts in the field of NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology for each actionable question. The GRADE Evidence to Decision framework in the guideline development tool was used to generate recommendations. A number of topics were addressed using technical summaries without recommendations and these are discussed in the supplementary material.This guideline committee developed recommendations for 11 actionable questions in a PICO (population-intervention-comparison-outcome) format, all addressing the use of NIV for various aetiologies of ARF. The specific conditions where recommendations were made include exacerbation of chronic obstructive pulmonary disease, cardiogenic pulmonary oedema, hypoxaemic respiratory failure, immunocompromised patients, chest trauma, palliation, post-operative care, weaning and post-extubation.This document summarises the current state of knowledge regarding the role of NIV in ARF. Evidence-based recommendations provide guidance to relevant stakeholders.
  
  Copyright ©ERS 2017.
  
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• Pulmonary involvement in adult Still's disease: Case report and brief review of literature.
  Respir Med Case Rep

  2017 ;22():91-94. doi: 10.1016/j.rmcr.2017.07.001.
  
  Guerrieri Aldo, Angeletti Giulia, Mazzolini Massimiliano, Bassi Ilaria, Nava Stefano
  
  Abstract
  
  BACKGROUND:
  Adult onset Still disease (AOSD) is a rare condition characterized by elevated fever along with arthritic symptoms, elevated polymorphonuclear neutrophil count, evanescent rash, and hyperferritinemia. Diagnosis can be made only after have ruled out more frequent conditions, and Yamagouchi or Fautrel criteria should be applied. Parenchimal lung involvement (PLI) is present in less than 5% of AOSD cases and ranges from aspecific reticular interstitial opacities to life threatening conditions, such as acute respiratory distress syndrome (ARDS).
  
  CASE:
  We report the case of a 59 years old man who was referred to our ward because of high fever treated as a pneumonia with antibiotic but not responding to medical treatment, and findings suggestive of interstitial lung disease prevalent in the lower zone on high resolution computed tomography (HRCT). AOSD was diagnosed when the diagnostic Yamaguchi criteria were fulfilled and our suspect was confirmed by the rheumatologist; the patient was then successfully treated with corticosteroids.
  
  CONCLUSIONS:
  PLI in AOSD is very rare but must be considered among differential diagnosis in patients with high fever and aspecific interstial parenchimal lung involvement.
  
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• I want to break free: liberation from noninvasive ventilation.
  Eur Respir J

  2017 07;50(1):. doi: 1700674.
  
  Nava Stefano, Ergan Begum
  
  
  
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• Invited Review Series Introduction.
  COPD

  2017 06;14(3):344-345. doi: 10.1080/15412555.2017.1320542.
  
  Nava Stefano
  
  
  
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• Long-Term Oxygen Therapy in COPD Patients Who Do Not Meet the Actual Recommendations.
  COPD

  2017 Jun;14(3):351-366. doi: 10.1080/15412555.2017.1319918.
  
  Ergan Begum, Nava Stefano
  
  Abstract
  
  Chronic respiratory failure due to chronic obstructive pulmonary disease (COPD) is an increasing problem worldwide. Many patients with severe COPD develop hypoxemic respiratory failure during the natural progression of disease. Long-term oxygen therapy (LTOT) is a well-established supportive treatment for COPD and has been shown to improve survival in patients who develop chronic hypoxemic respiratory failure. The degree of hypoxemia is severe when partial pressure of oxygen in arterial blood (PaO) is ?55 mmHg and moderate if PaO is between 56 and 69 mmHg. Although current guidelines consider LTOT only in patients with severe resting hypoxemia, many COPD patients with moderate to severe disease experience moderate hypoxemia at rest or during special circumstances, such as while sleeping or exercising. The efficacy of LTOT in these patients who do not meet the actual recommendations is still a matter of debate, and extensive research is still ongoing to understand the possible benefits of LTOT for survival and/or functional outcomes such as the sensation of dyspnea, exacerbation frequency, hospitalizations, exercise capacity, and quality of life. Despite its frequent use, the administration of "palliative" oxygen does not seem to improve dyspnea except for delivery with high-flow humidified oxygen. This narrative review will focus on current evidence for the effects of LTOT in the presence of moderate hypoxemia at rest, during sleep, or during exercise in COPD.
  
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• Portico Sheathless Transcatheter Aortic Valve Implantation via Distal Axillary Artery.
  Ann Thorac Surg

  2017 Feb;103(2):e175-e177. doi: S0003-4975(16)30974-2.
  
  Bruschi Giuseppe, Colombo Paola, Botta Luca, Nava Stefano, Merlanti Bruno, Belli Oriana, Musca Francesco, Soriano Francesco, Russo Claudio F, Oliva Fabrizio
  
  Abstract
  
  Transcatheter aortic valve implantation has been designed to treat older patients affected by severe aortic stenosis who are considered high-risk surgical candidates because of multiple comorbidities. The least invasive approach for transcatheter aortic valves implantation should be considered the transfemoral retrograde route, because it is minimally invasive and is feasible with local anesthesia and mild sedation. Despite significant technical improvements in recent years, the transfemoral approach is contraindicated in cases of severe peripheral artery disease. We describe the first case of a Portico transcatheter aortic valve implantation system (St. Jude Medical, Minneapolis, MN) made through the distal axillary artery in a 90-year-old patient affected by severe aortic stenosis.
  
  Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
  
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• Change in pulmonary mechanics and the effect on breathing pattern of high flow oxygen therapy in stable hypercapnic COPD.
  Thorax

  2017 Apr;72(4):373-375. doi: 10.1136/thoraxjnl-2016-209673.
  
  Pisani Lara, Fasano Luca, Corcione Nadia, Comellini Vittoria, Musti Muriel Assunta, Brandao Maria, Bottone Damiano, Calderini Edoardo, Navalesi Paolo, Nava Stefano
  
  Abstract
  
  : We studied the effects of high flow oxygen therapy (HFOT) versus non-invasive ventilation (NIV) on inspiratory effort, as assessed by measuring transdiaphragmatic pressure, breathing pattern and gas exchange. Fourteen patients with hypercapnic COPD underwent five 30-min trials: HFOT at two flow rates, both with open and closed mouth, and NIV, applied in random order. After each trial standard oxygen therapy was reinstituted for 10?min. Compared with baseline, HFOT and NIV significantly improved breathing pattern, although to different extents, and reduced inspiratory effort; however, arterial carbon dioxide oxygen tension decreased but not significantly. These results indicate a possible role for HFOT in the long-term management of patients with stable hypercapnic COPD.
  
  TRIAL REGISTRATION NUMBER:
  NCT02363920.
  
  Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
  
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• Arterial Stiffness in Aortic Stenosis: Relationship with Severity and Echocardiographic Procedures Response.
  High Blood Press Cardiovasc Prev

  2017 Mar;24(1):19-27. doi: 10.1007/s40292-016-0176-x.
  
  Bruschi Giuseppe, Maloberti Alessandro, Sormani Paola, Colombo Giulia, Nava Stefano, Vallerio Paola, Casadei Francesca, Bruno Jolie, Moreo Antonella, Merlanti Bruno, Russo Claudio, Oliva Fabrizio, Klugmann Silvio, Giannattasio Cristina
  
  Abstract
  
  INTRODUCTION:
  Aortic stenosis (AS) is more than only a degenerative disease, it could be also an atherosclerotic-like process involving the valve instead of the vessels. Little is known about the relation of arterial stiffness and AS.
  
  AIM:
  We sought to determine wether pulse wave velocity (PWV), is related to AS severity and to the procedures response, both as surgical aortic-valve-replacement (AVR) and trascatheter-aortic-valve-implantation (TAVI).
  
  METHODS:
  30 patients with severe AS were treated (15 AVR, 15 TAVI). Before the procedures (t0) and after 1 week (t1) echocardiography and PWV were evaluated.
  
  RESULTS:
  On the whole population, subjects with higher PWV showed higher transvalvular pressure gradient at baseline (mean: 56.5 ± 15.1 vs 45.4 ± 9.5; peak: 93.3 ± 26.4 vs 73.3 ± 14.9, p = 0.02) and, a significantly greater response to the procedures (mean: -42.9 ± 17.2 vs -27.9 ± 10.1, peak: -68.7 ± 29.2 vs -42.8 ± 16.4, p = 0.02). When the two different procedures groups were separated, data were confirmed only in the TAVI subgroup.
  
  CONCLUSIONS:
  In patients undergoing procedures for AS, PWV is correlated with transvalvular gradient and, in TAVI subjects, is able to predict the echocardiographic response. Baseline evaluation of PWV in patients candidates to TAVI can help the selection of subjects, even if larger and longer studies are needed before definitive conclusion can be drawn.
  
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• Changes of Respiratory Mechanics in COPD Patients from Stable State to Acute Exacerbations with Respiratory Failure.
  COPD

  2017 Apr;14(2):150-155. doi: 10.1080/15412555.2016.1254173.
  
  Ceriana Piero, Vitacca Michele, Carlucci Annalisa, Paneroni Mara, Pisani Lara, Nava Stefano
  
  Abstract
  
  Symptoms, clinical course, functional and biological data during an exacerbation of chronic obstructive pulmonary disease (EXCOPD) have been investigated, but data on physiological changes of respiratory mechanics during a severe exacerbation with respiratory acidosis requiring noninvasive mechanical ventilation (NIMV) are scant. The aim of this study was to evaluate changes of respiratory mechanics in COPD patients comparing data observed during EXCOPD with those observed during stable state in the recovery phase. In 18 COPD patients having severe EXCOPD requiring NIMV for global respiratory failure, we measured respiratory mechanics during both EXCOPD (T0) and once the patients achieved a stable state (T1). The diaphragm and inspiratory muscles effort was significantly increased under relapse, as well as the pressure-time product of the diaphragm and the inspiratory muscle (PTPdi and PTPes). The resistive loads to breathe (i.e., PEEPi,dyn, compliance and inspiratory resistances) were also markedly increased, while the maximal pressures generated by the diaphragm and the inspiratory muscles, together with forced expired volumes were decreased. All these indices statistically improved but with a great intrasubject variability in stable condition. Moreover, tension-time index (TTdi) significantly improved from the EXCOPD state to the condition of clinical stability (0.156 ± 0.04 at T0 vs. 0.082 ± 0.02 at T1 p < 0.001). During an EXCOPD, the load/capacity of the respiratory pump is impaired, and although the patients exhibit a rapid shallow breathing pattern, this does not necessarily correlate with a TTdi ? 0.15. These changes are reverted once they recover from the EXCOPD, despite a large variability between patients.
  
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• Evolut R Implantation to Treat Severe Pure Aortic Regurgitation in a Patient With Mitral Bioprosthesis.
  Ann Thorac Surg

  2016 Dec;102(6):e521-e524. doi: S0003-4975(16)30549-5.
  
  Bruschi Giuseppe, Colombo Paola, Nava Stefano, Musca Francesco, Merlanti Bruno, Belli Oriana, Soriano Francesco, Botta Luca, De Caria Danile, Giannattasio Cristina, Russo Claudio F
  
  Abstract
  
  Transcatheter aortic valves have been designed to treat high-risk surgical candidates affected by severe aortic stenosis, but little is known about the use of transcatheter valves in patients with severe pure aortic regurgitation. We describe the implantation of Medtronic CoreValve Evolut R (Medtronic, Minneapolis, MN) to treat an 82-year-old patient affected by severe pure aortic regurgitation who underwent prior mitral valve replacement with a biological valve protruding into the left ventricular outflow tract.
  
  Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
  
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• ECCOR in COPD exacerbation only for the right patients and with the right strategy.
  Intensive Care Med

  2016 Nov;42(11):1830-1831.
  
  Del Sorbo Lorenzo, Fan Eddy, Nava Stefano, Ranieri V Marco
  
  
  
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• Early Noninvasive Neurally Adjusted Ventilatory Assist Versus Noninvasive Flow-Triggered Pressure Support Ventilation in Pediatric Acute Respiratory Failure: A Physiologic Randomized Controlled Trial.
  Pediatr Crit Care Med

  2016 11;17(11):e487-e495.
  
  Chidini Giovanna, De Luca Daniele, Conti Giorgio, Pelosi Paolo, Nava Stefano, Calderini Edoardo
  
  Abstract
  
  OBJECTIVE:
  Neurally adjusted ventilatory assist has been shown to improve patient-ventilator interaction in children with acute respiratory failure. Objective of this study was to compare the effect of noninvasive neurally adjusted ventilatory assist versus noninvasive flow-triggered pressure support on patient-ventilator interaction in children with acute respiratory failure, when delivered as a first-line respiratory support.
  
  DESIGN:
  Prospective randomized crossover physiologic study.
  
  SETTING:
  Pediatric six-bed third-level PICU.
  
  PATIENTS:
  Eighteen children with acute respiratory failure needing noninvasive ventilation were enrolled at PICU admission.
  
  INTERVENTIONS:
  Enrolled children were allocated to receive two 60-minutes noninvasive flow-triggered pressure support and noninvasive neurally adjusted ventilatory assist trials in a crossover randomized sequence.
  
  MEASUREMENTS AND MAIN RESULTS:
  Primary endpoint was the asynchrony index. Parameters describing patient-ventilator interaction and gas exchange were also considered as secondary endpoints. Noninvasive neurally adjusted ventilatory assist compared to noninvasive flow-triggered pressure support: 1) reduced asynchrony index (p = 0.001) and the number of asynchronies per minute for each type of asynchrony; 2) it increased the neuroventilatory efficiency index (p = 0.001), suggesting better neuroventilatory coupling; 3) reduced inspiratory and expiratory delay times (p = 0.001) as well as lower peak and mean airway pressure (p = 0.006 and p = 0.038, respectively); 4) lowered oxygenation index (p = 0.043). No adverse event was reported.
  
  CONCLUSIONS:
  In children with mild early acute respiratory failure, noninvasive neurally adjusted ventilatory assist was feasible and safe. Noninvasive neurally adjusted ventilatory assist compared to noninvasive flow-triggered pressure support improved patient-ventilator interaction.
  
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• A new access for transcatheter aortic valve implantation: Distal axillary artery.
  Int J Cardiol

  2016 Nov;223():810-812. doi: S0167-5273(16)32008-3.
  
  Bruschi Giuseppe, Colombo Paola, Merlanti Bruno, Nava Stefano, Belli Oriana, Musca Francesco, Soriano Francesco, Botta Luca, Calini Angelo, De Caria Daniele F, Oliva Fabrizio, Russo Claudio F
  
  
  
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• Ventilator associated pneumonia following liver transplantation: Etiology, risk factors and outcome.
  World J Transplant

  2016 Jun;6(2):389-95. doi: 10.5500/wjt.v6.i2.389.
  
  Siniscalchi Antonio, Aurini Lucia, Benini Beatrice, Gamberini Lorenzo, Nava Stefano, Viale Pierluigi, Faenza Stefano
  
  Abstract
  
  AIM:
  To determine the incidence, etiology, risk factors and outcome of ventilator-associated pneumonia (VAP) in patients undergoing orthotopic liver transplantation (OLT).
  
  METHODS:
  This retrospective study considered 242 patients undergoing deceased donor OLT. VAP was diagnosed according to clinical and microbiological criteria.
  
  RESULTS:
  VAP occurred in 18 (7.4%) patients, with an incidence of 10 per 1000 d of mechanical ventilation (MV). Isolated bacterial etiologic agents were mainly Enterobacteriaceae (79%). Univariate logistic analysis showed that model for end-stage liver disease (MELD) score, pre-operative hospitalization, treatment with terlipressin, Child-Turcotte-Pugh score, days of MV and red cell transfusion were risk factors for VAP. Multivariate analysis, considering significant risk factors in univariate analysis, demonstrated that pneumonia was strongly associated with terlipressin usage, pre-operative hospitalization, days of MV and red cell transfusion. Mortality rate was 22% in the VAP group vs 4% in the group without VAP.
  
  CONCLUSION:
  Our data suggest that VAP is an important cause of nosocomial infection during postoperative period in OLT patients. MELD score was a significant risk factor in univariate analysis. Multiple transfusions, treatment with terlipressin, preoperative hospitalization rather than called to the hospital while at home and days of MV constitute important risk factors for VAP development.
  
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• Can fiberoptic bronchoscopy be applied to critically ill patients treated with noninvasive ventilation for acute respiratory distress syndrome? Prospective observational study.
  BMC Pulm Med

  2016 May;16(1):89. doi: 10.1186/s12890-016-0236-y.
  
  Korkmaz Ekren Pervin, Basarik Aydogan Burcu, Gurgun Alev, Tasbakan Mehmet Sezai, Bacakoglu Feza, Nava Stefano
  
  Abstract
  
  BACKGROUND:
  Noninvasive ventilation (NIV) is a cornerstone for the treatment of acute respiratory failure of various etiologies. Using NIV is discussed in mild-to-moderate acute respiratory distress syndrome (ARDS) patients (PaO2/FiO2?>?150). These patients often have comorbidities that increase the risk for bronchoscopy related complications. The primary outcome of this prospective observational study was to evaluate the feasibility, safety and contribution in diagnosis and/or modification of the ongoing treatment of fiberoptic bronchoscopy (FOB) in patients with ARDS treated with NIV.
  
  METHODS:
  ARDS patients treated with NIV and who require FOB as the diagnostic or therapeutic procedure were included the study. Intensive care ventilators or other dedicated NIV ventilators were used. NIV was applied via simple oro-nasal mask or full-face mask. Pressure support or inspiratory positive airway pressure (IPAP), external positive end expiratory pressure (PEEP) or expiratory positive airway pressure (EPAP) levels were titrated to achieve an expiratory tidal volume of 8 to 10 ml/kg according to ideal body weight, SpO2?>?90 % and respiratory rate below 25/min.
  
  RESULTS:
  Twenty eight subjects (mean age 63.3?±?15.9 years, 15 men, 13 women, PaO2/FiO2 rate 145?±?50.1 at admission) were included the study. Overall the procedure was well tolerated with only 5 (17.9 %) patients showing minor complications. There was no impairment in arterial blood gas and cardiopulmonary parameters after FOB. PaO2/FiO2 rate increased from 132.2?±?49.8 to 172.9?±?63.2 (p?=?0.001). No patient was intubated within 2 h after the bronchoscopy. 10.7, 32.1 and 39.3 % of the patients required invasive mechanical ventilation after 8 h, 24 h and 48 h, respectively. Bronchoscopy provided diagnosis in 27 (96.4 %) patients. Appropriate treatment was decided according to the results of the bronchoscopic sampling in 20 (71.4 %) patients.
  
  CONCLUSION:
  FOB under NIV could be considered as a feasible tool for diagnosis and guide for treatment of patients with ARDS treated via NIV in intensive care units. However, FOB-correlated life-treathening complications in severe hypoxemia should not be forgotten. Furthermore, further controlled studies involving a larger series of homogeneous ARDS patients undergoing FOB under NIV are needed to confirm these preliminary findings.
  
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• Preoperative physiotherapy in subjects with idiopathic pulmonary fibrosis qualified for lung transplantation: implications on hospital length of stay and clinical outcomes.
  J Thorac Dis

  2016 May;8(5):E264-8. doi: 10.21037/jtd.2016.03.52.
  
  Polastri Massimiliano, Dell'Amore Andrea, Zagnoni Giulia, Nava Stefano
  
  Abstract
  
  BACKGROUND:
  Lung transplantation (LTx) candidates with chronic disease are more prone to exercise limitations. Preoperative physiotherapy (PP) can improve exercise tolerance, which in some patients, is severely impaired, often leaving them housebound. The aim of this study was to answer this question: In patients with idiopathic pulmonary fibrosis (IPF) qualifying for LTx, is PP effective in improving postoperative outcomes and reducing length of stay (LOS) after transplantation?
  
  METHODS:
  Six major databases were searched up to December 2015. We did not apply limits to publication date, date, gender, or language. Citations were accepted if they discussed preoperative physiotherapeutic treatment in patients with IPF waiting for LTx.
  
  RESULTS:
  After the full texts were read, three papers met the inclusion criteria and were included. All of these papers had an observational design. In total, 55 subjects with IPF and awaiting LTx were observed.
  
  CONCLUSIONS:
  The effectiveness of PP in improving postoperative outcomes and reducing LOS following LTx remains unclear, although it appears to benefit IPF patients who qualify for LTx by improving their health status, physical activity levels, and respiratory-related symptoms.
  
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• Noninvasive ventilation versus oxygen therapy for the treatment of acute respiratory failure.
  Expert Rev Respir Med

  2016 07;10(7):813-21. doi: 10.1080/17476348.2016.1184977.
  
  Pisani Iara, Comellini Vittoria, Nava Stefano
  
  Abstract
  
  INTRODUCTION:
  There is an ongoing discussion on whether oxygen therapy or noninvasive ventilation (NIV) should be used in patient with acute respiratory failure. While respiratory acidosis, especially in case of COPD exacerbation, is a clear indication for NIV, data available in patients with acute hypoxemic respiratory failure (AHRF) are ambiguous. In addition, recently the use of nasal high flow (NHF) has been increased. Despite that NHF has been studied as an alternative to NIV, the clinical advantages of NHF need to be confirmed.
  
  AREAS COVERED:
  The purpose of this review is to enhance our understanding about the management of AHRF in specific settings, focusing on recent papers in which NIV and standard oxygen or NHF have been compared. Expert commentary: The choice of the most appropriate strategy for AHRF treatment should be made based upon patient's clinical status, underlying diseases, level of required respiratory support and patient's tolerance and comfort.
  
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• End-of-Life Discussion, Patient Understanding and Determinants of Preferences in Very Severe COPD Patients: A Multicentric Study.
  COPD

  2016 10;13(5):632-8. doi: 10.3109/15412555.2016.1154034.
  
  Carlucci Annalisa, Vitacca Michele, Malovini Alberto, Pierucci Paola, Guerrieri Aldo, Barbano Luca, Ceriana Piero, Balestrino Antonella, Santoro Carmen, Pisani Lara, Corcione Nadia, Nava Stefano
  
  Abstract
  
  Discussion about patients' end-of-life (E-o-L) preferences should be part of the routine practice. Using a semi-structured interview with a scenario-based decision, we performed a prospective multicentre study to elicit the patients' E-o-L preferences in very severe chronic obstructive pulmonary disease (COPD). We also checked their ability to retain this information and the respect of their decisions when they die. Forty-three out of ninety-one of the eligible patients completed the study. The choice of E-o-L practice was equally distributed among the three proposed options: endotracheal intubation (ETI), 'ceiling' non-invasive ventilation (NIV), and palliation of symptoms with oxygen and morphine. NIV and ETI were more frequently chosen by patients who already experienced them. ETI preference was also associated with the use of anti-depressant drugs and a low educational level, while a higher educational level and a previous discussion with a pneumologist significantly correlated with the preference for oxygen and morphine. Less than 50% of the patients retained a full comprehension of the options at 24 hours. About half of the patients who died in the follow-up period were not treated according to their wishes. In conclusion, in end-stage COPD more efforts are needed to improve communication, patients' knowledge of the disease and E-o-L practice.
  
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• Use of high-flow nasal cannula oxygenation in ICU adults: a narrative review.
  Intensive Care Med

  2016 Sep;42(9):1336-49. doi: 10.1007/s00134-016-4277-8.
  
  Papazian Laurent, Corley Amanda, Hess Dean, Fraser John F, Frat Jean-Pierre, Guitton Christophe, Jaber Samir, Maggiore Salvatore M, Nava Stefano, Rello Jordi, Ricard Jean-Damien, Stephan François, Trisolini Rocco, Azoulay Elie
  
  Abstract
  
  Oxygen therapy can be delivered using low-flow, intermediate-flow (air entrainment mask), or high-flow devices. Low/intermediate-flow oxygen devices have several drawbacks that cause critically ill patients discomfort and translate into suboptimal clinical results. These include limitation of the FiO2 (due to the high inspiratory flow often observed in patients with respiratory failure), and insufficient humidification and warming of the inspired gas. High-flow nasal cannula oxygenation (HFNCO) delivers oxygen flow rates of up to 60 L/min and over the last decade its effect on clinical outcomes has widely been evaluated, such as in the improvement of respiratory distress, the need for intubation, and mortality. Mechanisms of action of HFNCO are complex and not limited to the increased oxygen flow rate. The main aim of this review is to guide clinicians towards evidence-based clinical practice guidelines. It summarizes current knowledge about HFNCO use in ICU patients and the potential areas of uncertainties. For instance, it has been recently suggested that HFNCO could improve the outcome of patients with hypoxemic acute respiratory failure. In other settings, research is ongoing and additional evidence is needed. For instance, if intubation is required, studies suggest that HFNCO may help to improve preoxygenation and can be used after extubation. Likewise, HFNCO might be used in obese patients, or to prevent respiratory deterioration in hypoxemic patients requiring bronchoscopy, or for the delivery of aerosol therapy. However, areas for which conclusive data exist are limited and interventions using standardized HFNCO protocols, comparators, and relevant clinical outcomes are warranted.
  
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• Direct Flow Implantation in a Patient With Mechanical Mitral Prostheses.
  Ann Thorac Surg

  2016 Feb;101(2):753-6. doi: 10.1016/j.athoracsur.2015.02.139.
  
  Bruschi Giuseppe, Barosi Alberto, Colombo Paola, Montorsi Emanuela, Nava Stefano, Soriano Francesco, Botta Luca, Fratto Pasquale, Klugmann Silvio, de Marco Federico
  
  Abstract
  
  We describe a case of Direct Flow (Direct Flow Medical Inc, Santa Rosa, CA) transcatheter aortic valve implantation in a patient with a mechanical valve in a mitral position.
  
  Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
  
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• Prospective Multicenter Evaluation of the Direct Flow Medical Transcatheter Aortic Valve System: 12-Month Outcomes of the Evaluation of the Direct Flow Medical Percutaneous Aortic Valve 18F System for the Treatment of Patients With Severe Aortic Stenosis (DISCOVER) Study.
  JACC Cardiovasc Interv

  2016 Jan;9(1):68-75. doi: S1936-8798(15)01581-2.
  
  Lefèvre Thierry, Colombo Antonio, Tchétché Didier, Latib Azeem, Klugmann Silvio, Fajadet Jean, De Marco Federico, Maisano Francesco, Bruschi Giuseppe, Bijuklic Klaudija, Nava Stefano, Weissman Neil, Low Reginald, Thomas Martyn, Young Christopher, Redwood Simon, Mullen Michael, Yap John, Grube Eberhard, Nickenig Georg, Sinning Jan-Malte, Hauptmann Karl Eugen, Friedrich Ivar, Lauterbach Michael, Schmoeckel Michael, Davidson Charles, Schofer Joachim
  
  Abstract
  
  OBJECTIVES:
  The aim of this study was to assess the 1-year outcome after transcatheter aortic valve replacement (TAVR) of the Direct Flow Medical (DFM) valve in patients with severe symptomatic aortic stenosis who were contraindicated or high risk for surgery.
  
  BACKGROUND:
  The DFM transcatheter heart valve is a new-generation, nonmetallic aortic valve with a pressurized support structure and conformable double-ring annular sealing delivered through an 18-F sheath. The device allows repositioning, retrieval, and assessment of valve performance before permanent implantation.
  
  METHODS:
  A prospective multicenter European registry was set up to determine the safety and performance of the valve in 100 consecutive patients (10 centers). Echocardiographic and angiographic data were evaluated by an independent core laboratory, and adverse events were adjudicated by a clinical events committee using Valve Academic Research Consortium criteria.
  
  RESULTS:
  Patients were 83.1 ± 5.9 years of age and had a logistic EuroSCORE of 22.5 ± 11.3% and a Society of Thoracic Surgeons score of 9.7 ± 8.7%. Correct valve positioning was obtained in 99% of cases with a combined 30-day safety endpoint at 10%, including major stroke in 5.0%, major vascular complications in 2.0%, and death in 1%. At 12 months, 95% of patients were in New York Heart Association functional class I or II. Freedom from any death was 90%, and freedom from any death or major stroke was 85%. Echocardiography demonstrated none/trace to mild aortic regurgitation in 100% of patients and an unchanged mean aortic gradient of 12.2 ± 6.6 mm Hg and effective orifice area of 1.6 ± 0.4 cm(2).
  
  CONCLUSIONS:
  At 1 year, the DFM transcatheter heart valve had durable hemodynamics. This study demonstrates that the low rate of early complications and the low risk of significant aortic regurgitation translated into midterm clinical benefit.
  
  Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
  
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• Domiciliary Non-invasive Ventilation in COPD: An International Survey of Indications and Practices.
  COPD

  2016 08;13(4):483-90. doi: 10.3109/15412555.2015.1108960.
  
  Crimi Claudia, Noto Alberto, Princi Pietro, Cuvelier Antoine, Masa Juan F, Simonds Anita, Elliott Mark W, Wijkstra Peter, Windisch Wolfram, Nava Stefano
  
  Abstract
  
  Despite the fact that metanalyses and clinical guidelines do not recommend the routine use of domiciliary non-invasive ventilation (NIV) for patients diagnosed with severe stable Chronic Obstructive Pulmonary Disease (COPD) and with chronic respiratory failure, it is common practice in some countries. We conducted an international web-survey of physicians involved in provision of long-term NIV to examine patterns of domiciliary NIV use in patients diagnosed with COPD. The response rate was 41.6%. A reduction of hospital admissions, improvements in quality of life and dyspnea relief were considered as the main expected benefits for patients. Nocturnal oxygen saturation assessment was the principal procedure performed before NIV prescription. Recurrent exacerbations (>3) requiring NIV and failed weaning from in hospital NIV were the most important reasons for starting domiciliary NIV. Pressure support ventilation (PSV) was the most common mode, with "low" intensity settings (PSV-low) the most popular (44.4 ± 30.1%) compared with "high" intensity (PSV-high) strategies (26.9 ± 25.9%), with different geographical preferences. COPD is confirmed to be a common indication for domiciliary NIV. Recurrent exacerbations and failed weaning from in-hospital NIV were the main reasons for its prescription.
  
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• Evaluation of a systematic approach to weaning of tracheotomized neurological patients: an early interrupted randomized controlled trial.
  Ann Intensive Care

  2015 Dec;5(1):54. doi: 10.1186/s13613-015-0098-0.
  
  Vaschetto Rosanna, Frigerio Pamela, Sommariva Maurizio, Boggero Arianna, Rondi Valentina, Grossi Francesca, Cavuto Silvio, Nava Stefano, Corte Francesco Della, Navalesi Paolo
  
  Abstract
  
  BACKGROUND:
  While a systematic approach to weaning reduces the rate of extubation failure in intubated brain-injured patients, no data are available on the weaning outcome of these patients after tracheotomy. We aimed to assess whether a systematic approach to disconnect tracheotomized neurological and neurosurgical patients off the ventilator (intervention) is superior to the sole physician's judgment (control). Based on previous work in intubated patients, we hypothesized a reduction of the rate of failure within 48 h from 15 to 5 %. Secondary endpoints were duration of mechanical ventilation, ICU length of stay and mortality.
  
  METHODS:
  We designed a single center randomized controlled study. Since no data are available on tracheotomized patients, we based our a priori power analysis on results derived from intubated patients and calculated an overall sample size of 280 patients.
  
  RESULTS:
  After inclusion of 168 consecutive patients, the trial was interrupted because the attending physicians judged the observed rate of reconnection to be much greater than expected. The overall rate of failure was 29 %, confirming the physicians' judgment. Twenty-one patients (24 %) in the intervention group and 27 (33 %) controls were reconnected to the ventilator within 48 h (p = 0.222). The main reasons for failure were respiratory distress (80 and 88 % in the treatment and control group, respectively), hemodynamic impairment (15 and 4 % in the treatment and control group, respectively), neurological deterioration (4 % in the control group only). The duration of mechanical ventilation was of 412 ± 202 h and 402 ± 189 h, in the control and intervention group, respectively. ICU length of stay was on average of 23 days for both groups. ICU mortality was 6 % in the control and 2 % in the intervention group without significant differences.
  
  CONCLUSION:
  We found no difference between the two groups under evaluation, with a rate of failure much higher than expected. Consequent to the early interruption, our study results to be underpowered. Based on the results of the present study, a further trial should overall enroll 790 patients.
  
  TRIAL REGISTRATION:
  ACTRN12612000372886.
  
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• Management of acute hypercapnic respiratory failure.
  Curr Opin Crit Care

  2016 Feb;22(1):45-52. doi: 10.1097/MCC.0000000000000269.
  
  Pisani Lara, Corcione Nadia, Nava Stefano
  
  Abstract
  
  PURPOSE OF REVIEW:
  The objective of this article is to review the most recent literature regarding the management of acute hypercapnic respiratory failure (AHRF).
  
  RECENT FINDINGS:
  In the field of AHRF management, noninvasive ventilation (NIV) has become the standard method of providing primary mechanical ventilator support. Recently, extracorporeal carbon dioxide removal (ECCO2R) devices have been proposed as new therapeutic option.
  
  SUMMARY:
  NIV is an effective strategy in specific settings and in selected population with AHRF. To date, evidence on ECCO2R is based only on case reports and case-control trials. Although the preliminary results using ECCO2R to decrease the rate of NIV failure and to wean hypercapnic patients from invasive ventilation are remarkable; further randomized studies are needed to assess the effects of this technique on both short-term and long-term clinical outcomes.
  
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• Effects of Extracorporeal CO2 Removal on Inspiratory Effort and Respiratory Pattern in Patients Who Fail Weaning from Mechanical Ventilation.
  Am J Respir Crit Care Med

  2015 Dec;192(11):1392-4. doi: 10.1164/rccm.201505-0930LE.
  
  Pisani Lara, Fasano Luca, Corcione Nadia, Comellini Vittoria, Guerrieri Aldo, Ranieri Marco V, Nava Stefano
  
  
  
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• Erratum to: Effects of Renal Sympathetic Denervation on Arterial Stiffness and Blood Pressure Control in Resistant Hypertensive Patients: A Single Centre Prospective Study.
  High Blood Press Cardiovasc Prev

  2015 Dec;22(4):451. doi: 10.1007/s40292-015-0124-1.
  
  Baroni Matteo, Nava Stefano, Giupponi Luca, Meani Paolo, Panzeri Francesco, Varrenti Marisa, Maloberti Alessandro, Soriano Francesco, Agrati Antonio Maria, Ferraro Giovanni, Colombo Fabrizio, Rampoldi Antonio, Mancia Giuseppe, Colombo Paola, Klugmann Silvio, Giannattasio Cristina
  
  
  
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• Short-term effects of a nicotine-free e-cigarette compared to a traditional cigarette in smokers and non-smokers.
  BMC Pulm Med

  2015 Oct;15():120. doi: 10.1186/s12890-015-0106-z.
  
  Ferrari Marco, Zanasi Alessandro, Nardi Elena, Morselli Labate Antonio Maria, Ceriana Piero, Balestrino Antonella, Pisani Lara, Corcione Nadia, Nava Stefano
  
  Abstract
  
  BACKGROUND:
  A few studies have assessed the short-term effects of low-dose nicotine e-cigarettes, while data about nicotine-free e-cigarettes (NF e-cigarettes) are scanty. Concerns have been expressed about the use of NF e-cigarettes, because of the high concentrations of propylene glycol and other compounds in the e-cigarette vapor.
  
  METHODS:
  This laboratory-based study was aimed to compare the effects of ad libitum use of a NF e-cigarette or and a traditional cigarette for 5 min in healthy adult smokers (n = 10) and non-smokers (n = 10). The main outcome measures were pulmonary function tests, fraction of exhaled nitric oxide (FeNO) and fractional concentration of carbon monoxide (FeCO) in exhaled breath.
  
  RESULTS:
  The traditional cigarette induced statistically significant increases in FeCO in both smokers and non-smokers, while no significant changes were observed in FeNO. In non-smokers, the traditional cigarette induced a significant decrease from baseline in FEF75 (81 % ± 35 % vs 70.2 % ± 28.2 %, P = 0.013), while in smokers significant decreases were observed in FEF25 (101.3 % ± 16.4 % vs 93.5 % ± 31.7 %, P = 0.037), FEV1 (102.2 % ± 9.5 % vs 98.3 % ± 10 %, P = 0.037) and PEF (109.5 % ± 14.6 % vs 99.2 % ± 17.5 %, P = 0.009). In contrast, the only statistically significant effects induced by the NF e-cigarette in smokers were reductions in FEV1 (102.2 % ± 9.5 % vs 99.5 ± 7.6 %, P = 0.041) and FEF25 (103.4 % ± 16.4 % vs 94.2 % ± 16.2 %, P =? .014).
  
  DISCUSSION:
  The present study demonstrated that the specific brand of NF e-cigarette utilized did not induce any majoracute effects. In contrast, several studies have shown that both traditional cigarettes and nicotine-containing e-cigarettes have acute effects on lung function. Our study expands on previous observations on the effects of NF e-cigarettes, but also for the first time describes the changes induced by smoking one traditional cigarette in a group of never smokers.
  
  CONCLUSIONS:
  The short-term use of the specific brand of NF e-cigarette assessed in this study had no immediate adverse effects on non-smokers and only small effects on FEV1 and FEF25 in smokers. The long-term health effects of NF e-cigarette use are unknown but worthy of further investigations.
  
  TRIAL REGISTRATION:
  Clinicaltrials.gov: NCT02102191.
  
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• Effects of Renal Sympathetic Denervation on Arterial Stiffness and Blood Pressure Control in Resistant Hypertensive Patients: A Single Centre Prospective Study.
  High Blood Press Cardiovasc Prev

  2015 Dec;22(4):411-6. doi: 10.1007/s40292-015-0121-4.
  
  Baroni Matteo, Nava Stefano, Giupponi Luca, Meani Paolo, Panzeri Francesco, Varrenti Marisa, Maloberti Alessandro, Soriano Francesco, Agrati Antonio Maria, Ferraro Giovanni, Colombo Fabrizio, Rampoldi Antonio, Mancia Giuseppe, Colombo Paola, Klugmann Silvio, Giannattasio Cristina
  
  Abstract
  
  Renal denervation (RD) is an intriguing treatment strategy for resistant hypertension. However, limited data are available about its long time efficacy as well as its effects on intermediate phenotypes like arterial stiffness and carotid IMT. 12 patients (9 males, mean 69 years) with resistant hypertension underwent bilateral RDN (Medtronic System) since April 2012 in Niguarda Ca' Granda Hospital (Milan). Patients were studied before intervention, and at 1, 3, 6 and 12 months after RD. Carotid intima media thickness (Esaote Mylab) and carotid-femoral pulse wave velocity (Complior, Alam medical) were assessed at each step. Compared to baseline, patients showed a marked reduction of office systolic blood pressure at each follow-up step (p < 0.05 versus baseline for all steps) as well as pulse wave velocity (p < 0.01 at 1 year versus baseline). Moreover, reduction in pulse wave velocity was higher than the expected value obtained only considering blood pressure drop. Conversely, no significant effect was observed on diastolic blood pressure as well as carotid intima-media thickness. In our study, renal denervation was a safe and effective procedure. The BP lowering effect was maintained during follow-up and a beneficial effect on arterial stiffness was observed, which implies that this effect can't passively originate from the BP fall but rather from an improvement of arterial mechanical properties, possibly related to a reduced sympathetic arterial drive.
  
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• CoreValve Evolut R implantation as valve-in-valve in an Edwards SAPIEN 3 to treat paravalvular regurgitation.
  EuroIntervention

  2015 Sep;11(5):e1. doi: 10.4244/EIJV11I5A116.
  
  Bruschi Giuseppe, Soriano Francesco, Musca Francesco, Nava Stefano, Einaudi Arturo, Garascia Andrea, Belli Oriana, Barosi Alberto, Fratto Pasquale, Colombo Paola, Russo Claudio Francesco, Gagliardone Maria Pia, Klugmann Silvio
  
  
  
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• The authors reply.
  Crit Care Med

  2015 Sep;43(9):e391. doi: 10.1097/CCM.0000000000001154.
  
  Del Sorbo Lorenzo, Nava Stefano, Ranieri V Marco
  
  
  
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• Physiotherapy for Patients on Awake Extracorporeal Membrane Oxygenation: A Systematic Review.
  Physiother Res Int

  2016 Dec;21(4):203-209. doi: 10.1002/pri.1644.
  
  Polastri Massimiliano, Loforte Antonino, Dell'Amore Andrea, Nava Stefano
  
  Abstract
  
  BACKGROUND AND PURPOSE:
  Extracorporeal membrane oxygenation (ECMO) is used as temporary life support in subjects with potentially reversible respiratory/cardiac failure. The principal purpose of this review was to assess the characteristics and potential advantages of physiotherapeutic interventions in subjects on awake ECMO support.
  
  METHODS:
  Seven databases were interrogated: we searched titles, abstracts and keywords using the Medical Subject Headings terms 'extracorporeal membrane oxygenation' and 'rehabilitation' linked with the Boolean operator 'AND'.
  
  RESULTS AND CONCLUSION:
  In total, 216 citations were retrieved. Nine citations satisfied our inclusion criteria and were subjected to full-text analysis. The numbers of patients enrolled in the included studies (most of which were case series) were low (n?=?52). We found no prospective studies or randomized controlled trials. Overall, subjects on awake ECMO usually received a combination of passive and active physiotherapy, and most achieved an acceptable degree of autonomy after treatment. Emerging research in the field affords preliminary evidence supporting the safety of early mobilization and ambulation in patients on awake veno-venous ECMO support. Copyright © 2015 John Wiley & Sons, Ltd.
  
  Copyright © 2015 John Wiley & Sons, Ltd.
  
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• Direct Flow valve-in-valve implantation in a degenerated mitral bioprosthesis.
  EuroIntervention

  2016 Apr;11(13):1549-53. doi: 10.4244/EIJY15M07_05.
  
  Bruschi Giuseppe, Cannata Aldo, Barosi Alberto, Colombo Paola, Soriano Francesco, Nava Stefano, Montrasio Elisa, Botta Luca, Gagliardone Maria Pia, Klugmann Silvio, De Marco Federico
  
  Abstract
  
  AIMS:
  Mitral valve reoperations due to failing bioprostheses, in patients affected by multiple comorbidities, are associated with high morbidity and mortality. Transcatheter techniques may evolve as complementary approaches to surgery in these patients at high risk for surgery.
  
  METHODS AND RESULTS:
  We describe a case of Direct Flow 25 mm transcatheter valve implantation as valve-in-valve in a degenerated mitral bioprosthesis through a transapical approach in a 63-year-old man affected by dilated cardiomyopathy. The patient was affected by Carpentier-Edwards 29 mm severe regurgitation. The 25 mm Direct Flow bioprosthesis was advanced through the mitral bioprosthesis into the left atrium and then positioned using the three independent positioning wires. Transoesophageal echocardiography evidenced normal Direct Flow function with no paravalvular regurgitation and a low transmitral gradient of 4 mmHg.
  
  CONCLUSIONS:
  Our successful experience, characterised by a Heart Team approach and multidisciplinary patient care, demonstrated the technical feasibility and procedural safety of Direct Flow valve-in-valve mitral implantation.
  
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• Is sedation safe and beneficial in patients receiving NIV? No.
  Intensive Care Med

  2015 Sep;41(9):1692-5. doi: 10.1007/s00134-015-3915-x.
  
  Conti Giorgio, Hill Nicholas S, Nava Stefano
  
  
  
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• The authors reply.
  Crit Care Med

  2015 Jul;43(7):e261-2. doi: 10.1097/CCM.0000000000000994.
  
  Del Sorbo Lorenzo, Nava Stefano, Ranieri V Marco
  
  
  
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• [A matter of perspective: multimodality imaging of a giant cardiac mass].
  G Ital Cardiol (Rome)

  2015 Mar;16(3):186-7. doi: 10.1714/1820.19830.
  
  Baroni Matteo, Nava Stefano, Vignati Gabriele, Marianeschi Stefano Maria, Giannattasio Cristina, Pedrotti Patrizia
  
  Abstract
  
  A newborn was suspected of having situs inversus with levocardia based on chest X-ray. Echocardiography ruled out this hypothesis but revealed a giant cardiac mass that was confirmed by magnetic resonance imaging. Coronary angiography showed that the right coronary artery ran on the surface of the mass, and only partial debulking surgery was performed to relieve right heart compression. Histological examination classified the mass as cardiac fibroma. Complex diagnostic work-up allowed correct anatomic definition of the mass as well as its relationship with adjacent structures, and helped guide surgical planning.
  
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• Direct aortic Direct Flow implantation via right anterior thoracotomy in a patient with patent bilateral mammary artery coronary grafts.
  Int J Cardiol

  2015 Apr;185():22-4. doi: 10.1016/j.ijcard.2015.03.083.
  
  Bruschi Giuseppe, Merlanti Bruno, Barosi Alberto, Colombo Paola, Fratto Pasquale, Nava Stefano, Soriano Francesco, Montrasio Elisa, Klugmann Silvio, de Marco Federico
  
  
  
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• The authors reply.
  Crit Care Med

  2015 Mar;43(3):e103-4. doi: 10.1097/CCM.0000000000000811.
  
  Del Sorbo Lorenzo, Nava Stefano, Ranieri V Marco
  
  
  
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• Neurally adjusted non-invasive ventilation in patients with chronic obstructive pulmonary disease: does patient-ventilator synchrony matter?
  Crit Care

  2014 Nov;18(6):670. doi: 10.1186/s13054-014-0670-2.
  
  Nava Stefano, Pisani Lara
  
  Abstract
  
  Patient-ventilator interaction represents an important clinical challenge during non-invasive ventilation (NIV). Doorduin and colleagues' study shows that non-invasive neurally adjusted ventilatory assist (NAVA) improves patient-ventilator interaction compared with pressure support ventilation in patients with chronic obstructive pulmonary disease. There is no doubt nowadays that NAVA is the most effective mode of improving the synchrony between patient and machine, but the key question for the clinicians is whether or not this will make a difference to the patient's outcome. The results of the study still do not clarify this issue because of the very low clinically important dyssynchrony, like wasted efforts, in the population studied. Air leaks play an important role in determining patient-ventilator interaction and therefore NIV success or failure. Apart from the use of a dedicated NIV ventilator or specific modes of ventilation like NAVA, the clinicians should be aware that the choice of interface, the humidification system and the appropriate sedation are key factors in improving patient-ventilator synchrony.
  
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• A systematic review on tracheostomy decannulation: a proposal of a quantitative semiquantitative clinical score.
  BMC Pulm Med

  2014 Dec;14():201. doi: 10.1186/1471-2466-14-201.
  
  Santus Pierachille, Gramegna Andrea, Radovanovic Dejan, Raccanelli Rita, Valenti Vincenzo, Rabbiosi Dimitri, Vitacca Michele, Nava Stefano
  
  Abstract
  
  BACKGROUND:
  Tracheostomy is one of the most common surgical procedures performed in critical care patient management; more specifically, ventilation through tracheal cannula allows removal of the endotracheal tube (ETT). Available literature about tracheostomy care and decannulation is mainly represented by expert opinions and no certain knowledge arises from it.
  
  METHODS:
  In lack of statistical requirements, a systematic and critical review of literature regarding tracheostomy tube removal was performed in order to assess predictor factors of successful decannulation and to propose a predictive score. We combined 3 terms and a literature search has been performed using the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE via Ovid SP; EMBASE via Ovid SP; EBSCO. Abstracts were independently reviewed: for those studies fitting the inclusion criteria on the basis of the title and abstract, full-text was achieved. We included studies published from January 1, 1995 until March 31, 2014; any sort of review and expert opinion has been excluded by our survey. English language restriction was applied. Ten studies have been considered eligible for inclusion in the review and were analysed further.
  
  RESULTS:
  Cough effectiveness and ability to tolerate tracheostomy tube capping are the most considered parameters in clinical practice; other parameters are taken into different consideration by many authors in order to proceed to decannulation. Among them, we distinguished between objective quantitative parameters and semi-quantitative parameters more dependent from clinician's opinion. We then built a score (the Quantitative semi Quantitative score: QsQ score) based on selected parameters coming from literature.
  
  CONCLUSIONS:
  On our knowledge, this review provides the first proposal of decannulation score system based on current literature that is hypothetical and requires to be validated in daily practice. The key point of our proposal is to give a higher value to the objective parameters coming from literature compared to less quantifiable clinical ones.
  
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• Oronasal mask versus helmet in acute hypercapnic respiratory failure.
  Eur Respir J

  2015 Mar;45(3):691-9. doi: 10.1183/09031936.00053814.
  
  Pisani Lara, Mega Chiara, Vaschetto Rosanna, Bellone Andrea, Scala Raffaele, Cosentini Roberto, Musti Muriel, Del Forno Manuela, Grassi Mario, Fasano Luca, Navalesi Paolo, Nava Stefano
  
  Abstract
  
  The choice of the interface for noninvasive ventilation (NIV) is a key factor in NIV success. We hypothesised that a new helmet specifically design to improve performance in hypercapnic patients would be clinically equivalent to a standard oronasal mask. In a multicentre, short-term, physiological, randomised trial in chronic obstructive pulmonary disease patients facing an acute hypercapnic respiratory failure episode, we compared the changes in arterial blood gases (ABGs) and tolerance score obtained using the helmet or mask, and, as secondary end-points, dyspnoea, vital signs, early NIV discontinuation and rate of intubation. 80 patients were randomly assigned to receive NIV either with the helmet (n=39) or mask (n=41), using an intensive care unit ventilator. Compared with baseline, in the first 6 h, NIV improved ABGs, dyspnoea and respiratory rate (p<0.05) in both groups. Changes in ABGs and discomfort were similar with the two groups, while dyspnoea decreased more (p<0.005) using the mask. The rate of intubation and the need for interface change during the whole period of NIV were very low and not different between groups. The new helmet may be a valid alternative to a mask in improving ABGs and achieving a good tolerance during an episode of acute hypercapnic respiratory failure.
  
  Copyright ©ERS 2015.
  
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• Regular versus as-needed budesonide and formoterol combination treatment for moderate asthma: a non-inferiority, randomised, double-blind clinical trial.
  Lancet Respir Med

  2015 Feb;3(2):109-119. doi: S2213-2600(14)70266-8.
  
  Papi Alberto, Marku Brunilda, Scichilone Nicola, Maestrelli Piero, Paggiaro Pierluigi, Saetta Marina, Nava Stefano, Folletti Ilenia, Bertorelli Giuseppina, Bertacco Stefano, Contoli Marco, Plebani Mario, Barbaro Maria Pia Foschino, Spanevello Antonio, Aliani Maria, Pannacci Marco, Morelli Paolo, Beghé Bianca, Fabbri Leonardo M,
  
  Abstract
  
  BACKGROUND:
  Treatment guidelines for patients with moderate persistent asthma recommend regular therapy with a combination of an inhaled corticosteroid and a longacting ?2 agonist plus as-needed rapid-acting bronchodilators. We investigated whether symptom-driven budesonide and formoterol combination therapy administered as needed would be as effective as regular treatment with this combination plus as-needed symptom-driven terbutaline for patients with moderate asthma.
  
  METHODS:
  In this non-inferiority randomised clinical trial, we recruited adult patients (18-65 years of age) with stable moderate persistent asthma, according to 2006 Global Initiative for Asthma guidelines. Patients were recruited from outpatient clinics of secondary and tertiary referral hospitals and university centres. After a 6-week run-in period of inhaled regular budesonide and formoterol plus as-needed terbutaline, the patients were randomly assigned in a 1:1 ratio to receive placebo twice daily plus as-needed treatment with inhaled 160 ?g budesonide and 4·5 ?g formoterol (as-needed budesonide and formoterol therapy) or twice-daily 160 ?g budesonide and 4·5 ?g formoterol combination plus symptom-driven 500 ?g terbutaline (regular budesonide/formoterol therapy) for 1 year. Randomisation was done according to a list prepared with the use of a random number generator and a balanced-block design stratified by centre. Patients and investigators were masked to treatment assignment. The primary outcome was time to first treatment failure measured after 1 year of treatment using Kaplan-Meier estimates, and the power of the study was calculated based on the rate of treatment failure. Analyses were done on the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00849095.
  
  FINDINGS:
  Between April 20, 2009, and March 31, 2012, we screened 1010 patients with moderate asthma and randomly assigned 866 eligible patients to the two treatment groups (424 to as-needed budesonide and formoterol therapy and 442 to regular budenoside and formoterol therapy). Compared with regular budesonide and formoterol therapy, as-needed budesonide and formoterol treatment was associated with a lower probability of patients having no treatment failure at 1 year (Kaplan-Meier estimates 53·6% for as-needed treatment vs 64·0% for regular treatment; difference 10·3% [95% CI 3·2-17·4], at a predefined non-inferiority limit of 9%). Patients in the as-needed budesonide and formoterol group had shorter time to first treatment failure than those in the regular therapy group (11·86 weeks vs 28·00 weeks for the first quartile [ie, the time until the first 25% of patients experienced treatment failure]). The difference in treatment failures was largely attributable to nocturnal awakenings (82 patients in the as-needed treatment group vs 44 in the regular treatment group). Both treatment regimens were well tolerated.
  
  INTERPRETATION:
  In patients with moderate stable asthma, as-needed budesonide and formoterol therapy is less effective than is the guideline-recommended regular budesonide and formoterol treatment, even though the differences are small.
  
  FUNDING:
  Italian Medicines Agency.
  
  Copyright © 2015 Elsevier Ltd. All rights reserved.
  
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• Extracorporeal Co2 removal in hypercapnic patients at risk of noninvasive ventilation failure: a matched cohort study with historical control.
  Crit Care Med

  2015 Jan;43(1):120-7. doi: 10.1097/CCM.0000000000000607.
  
  Del Sorbo Lorenzo, Pisani Lara, Filippini Claudia, Fanelli Vito, Fasano Luca, Terragni Pierpaolo, Dell'Amore Andrea, Urbino Rosario, Mascia Luciana, Evangelista Andrea, Antro Camillo, D'Amato Raffaele, Sucre Maria José, Simonetti Umberto, Persico Pietro, Nava Stefano, Ranieri V Marco
  
  Abstract
  
  OBJECTIVES:
  To assess efficacy and safety of noninvasive ventilation-plus-extracorporeal Co2 removal in comparison to noninvasive ventilation-only to prevent endotracheal intubation patients with acute hypercapnic respiratory failure at risk of failing noninvasive ventilation.
  
  DESIGN:
  Matched cohort study with historical control.
  
  SETTING:
  Two academic Italian ICUs.
  
  PATIENTS:
  Patients treated with noninvasive ventilation for acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease (May 2011 to November 2013).
  
  INTERVENTIONS:
  Extracorporeal CO2 removal was added to noninvasive ventilation when noninvasive ventilation was at risk of failure (arterial pH ? 7.30 with arterial PCO2 > 20% of baseline, and respiratory rate ? 30 breaths/min or use of accessory muscles/paradoxical abdominal movements). The noninvasive ventilation-only group was created applying the genetic matching technique (GenMatch) on a dataset including patients enrolled in two previous studies. Exclusion criteria for both groups were mean arterial pressure less than 60 mm Hg, contraindications to anticoagulation, body weight greater than 120 kg, contraindication to continuation of active treatment, and failure to obtain consent.
  
  MEASUREMENTS AND MAIN RESULTS:
  Primary endpoint was the cumulative prevalence of endotracheal intubation. Twenty-five patients were included in the noninvasive ventilation-plus-extracorporeal CO2 removal group. The GenMatch identified 21 patients for the noninvasive ventilation-only group. Risk of being intubated was three times higher in patients treated with noninvasive ventilation-only than in patients treated with noninvasive ventilation-plus-extracorporeal CO2 removal (hazard ratio, 0.27; 95% CI, 0.07-0.98; p = 0.047). Intubation rate in noninvasive ventilation-plus-extracorporeal CO2 removal was 12% (95% CI, 2.5-31.2) and in noninvasive ventilation-only was 33% (95% CI, 14.6-57.0), but the difference was not statistically different (p = 0.1495). Thirteen patients (52%) experienced adverse events related to extracorporeal CO2 removal. Bleeding episodes were observed in three patients, and one patient experienced vein perforation. Malfunctioning of the system caused all other adverse events.
  
  CONCLUSIONS:
  These data provide the rationale for future randomized clinical trials that are required to validate extracorporeal CO2 removal in patients with hypercapnic respiratory failure and respiratory acidosis nonresponsive to noninvasive ventilation.
  
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• First case of trans-axillary direct flow implantation.
  Int J Cardiol

  2014 Dec;177(3):e176-8. doi: 10.1016/j.ijcard.2014.08.097.
  
  Bruschi Giuseppe, Botta Luca, Cannata Aldo, Colombo Paola, Barosi Alberto, Soriano Francesco, Bottiroli Maurizio, Nava Stefano, Klugmann Silvio, De Marco Federico
  
  
  
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• Defining a training framework for clinicians in respiratory critical care.
  Eur Respir J

  2014 Sep;44(3):572-7. doi: 10.1183/09031936.00104914.
  
  Artigas Antonio, Noël Julie-Lyn, Brochard Laurent, Busari Jamiu O, Dellweg Dominic, Ferrer Miguel, Geiseler Jens, Larsson Anders, Nava Stefano, Navalesi Paolo, Orfanos Stylianos, Palange Paolo, Pelosi Paolo, Rohde Gernot, Schoenhofer Bernd, Vassilakopoulos Theodoros, Simonds Anita K
  
  
  
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• A randomized, placebo-controlled, double-blind trial on the management of post-infective cough by inhaled ipratropium and salbutamol administered in combination.
  Pulm Pharmacol Ther

  2014 Dec;29(2):224-32. doi: 10.1016/j.pupt.2014.07.008.
  
  Zanasi Alessandro, Lecchi Marzia, Del Forno Manuela, Fabbri Elisa, Mastroroberto Marianna, Mazzolini Massimiliano, Pisani Lara, Pandolfi Paolo, Nava Stefano, Morselli-Labate Antonio Maria
  
  Abstract
  
  Post-viral cough is a type of cough originating from upper respiratory tract infections that persists after the infection is resolved. Although it was hypothesized that bronchodilators might have a role in the management of post-viral cough, a clear demonstration of their efficacy is missing. Therefore, we tested the efficacy of a combination of a ?-agonist and an anticholinergic agent in reducing post-viral cough with a randomized, double blind, placebo controlled clinical trial. Patients were treated for 10 days with either a nebulized combination of salbutamol 1.875 mg/0.5 mL and ipratropium bromide 0.375 mg/0.5 mL, or a placebo, and followed up for another 10 days. Daytime and nighttime cough severity and spirometry testing were assessed before starting treatment, after 10 and 20 days. Ninety-two patients were randomized to receive placebo (n = 46) or the active treatment (n = 46); nine of them (4 in the placebo group, 5 in the active treatment group) dropped out from the study. Daytime and nighttime cough severity were significantly reduced in both groups during the study period, but the reduction was more prominent in the active treatment group vs. placebo after 10 days of treatment (P = 0.003 for day cough; P = 0.061 for night cough), whereas at the end of follow-up period cough severity was comparable between the two groups. Small but significant increases in spirometric parameters were observed in the active treatment vs. placebo group, although at the end of follow-up these values returned to be comparable to placebo. The frequency of adverse events was not significantly different between the two groups of patients. We concluded that a combination of a ?-agonist and an anticholinergic agent can effectively reduce post-viral cough, and can thus represent a valid option for this type of cough.
  
  Copyright © 2014 Elsevier Ltd. All rights reserved.
  
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• Noninvasive ventilation in acute hypercapnic respiratory failure.
  Semin Respir Crit Care Med

  2014 Aug;35(4):501-6. doi: 10.1055/s-0034-1383864.
  
  Pisani Lara, Nava Stefano
  
  Abstract
  
  Noninvasive mechanical ventilation (NIV) improves gas exchange and clinical outcome in various types of acute respiratory failure. Acute exacerbation of chronic obstructive pulmonary disease is a frequent cause of acute hypercapnic respiratory failure (AHRF). According to several randomized controlled trials, the addition of NIV to standard medical therapy reduces mortality, intubation rate, and hospital length of stay in these patients. Indications for the use of NIV have expanded over the past decade. In this article, we discuss the clinical indications and goals of NIV in the management of AHRF.
  
  Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
  
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• Non-invasive positive pressure ventilation for the treatment of severe stable chronic obstructive pulmonary disease: a prospective, multicentre, randomised, controlled clinical trial.
  Lancet Respir Med

  2014 Sep;2(9):698-705. doi: 10.1016/S2213-2600(14)70153-5.
  
  Köhnlein Thomas, Windisch Wolfram, Köhler Dieter, Drabik Anna, Geiseler Jens, Hartl Sylvia, Karg Ortrud, Laier-Groeneveld Gerhard, Nava Stefano, Schönhofer Bernd, Schucher Bernd, Wegscheider Karl, Criée Carl P, Welte Tobias
  
  Abstract
  
  BACKGROUND:
  Evidence is weak for the ability of long-term non-invasive positive pressure ventilation (NPPV) to improve survival in patients with stable hypercapnic chronic obstructive pulmonary disease (COPD). Previous prospective studies did not target a reduction in hypercapnia when adjusting ventilator settings. This study investigated the effect of long-term NPPV, targeted to markedly reduce hypercapnia, on survival in patients with advanced, stable hypercapnic COPD.
  
  METHODS:
  This investigator-initiated, prospective, multicentre, randomised, controlled clinical trial enrolled patients with stable GOLD stage IV COPD and a partial carbon dioxide pressure (PaCO2) of 7 kPa (51.9 mm Hg) or higher and pH higher than 7.35. NPPV was targeted to reduce baseline PaCO2 by at least 20% or to achieve PaCO2 values lower than 6.5 kPa (48.1 mm Hg). Patients were randomly assigned (in a 1:1 ratio) via a computer-generated randomisation sequence with a block size of four, to continue optimised standard treatment (control group) or to receive additional NPPV for at least 12 months (intervention group). The primary outcome was 1-year all-cause mortality. Analysis was by intention to treat. The intervention was unblinded, but outcome assessment was blinded to treatment assignment. This study is registered with ClinicalTrials.gov, number NCT00710541.
  
  FINDINGS:
  Patients were recruited from 36 respiratory units in Germany and Austria, starting on Oct 29, 2004, and terminated with a record of the vital status on July 31, 2011. 195 patients were randomly assigned to the NPPV group (n=102) or to the control group (n=93). All patients from the control group and the NPPV group were included in the primary analysis. 1-year mortality was 12% (12 of 102 patients) in the intervention group and 33% (31 of 93 patients) in the control group; hazard ratio 0.24 (95% CI 0.11-0.49; p=0.0004). 14 (14%) patients reported facial skin rash, which could be managed by changing the type of the mask. No other intervention-related adverse events were reported.
  
  INTERPRETATION:
  The addition of long-term NPPV to standard treatment improves survival of patients with hypercapnic, stable COPD when NPPV is targeted to greatly reduce hypercapnia.
  
  FUNDING:
  German Lung Foundation; ResMed, Germany; Tyco Healthcare, Germany; and Weinmann, Germany.
  
  Copyright © 2014 Elsevier Ltd. All rights reserved.
  
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• Topics in acute respiratory distress syndrome: the patient needs our tender loving and care.
  Eur Respir Rev

  2014 Jun;23(132):157-60. doi: 10.1183/09059180.00002814.
  
  Wort S John, Price Laura, Nava Stefano
  
  
  
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• Helmet CPAP vs. oxygen therapy in severe hypoxemic respiratory failure due to pneumonia.
  Intensive Care Med

  2014 Jul;40(7):942-9. doi: 10.1007/s00134-014-3325-5.
  
  Brambilla Anna Maria, Aliberti Stefano, Prina Elena, Nicoli Francesco, Del Forno Manuela, Nava Stefano, Ferrari Giovanni, Corradi Francesco, Pelosi Paolo, Bignamini Angelo, Tarsia Paolo, Cosentini Roberto
  
  Abstract
  
  PURPOSE:
  The efficacy of noninvasive continuous positive airway pressure (CPAP) to improve outcomes in severe hypoxemic acute respiratory failure (hARF) due to pneumonia has not been clearly established. The aim of this study was to compare CPAP vs. oxygen therapy to reduce the risk of meeting criteria for endotracheal intubation (ETI).
  
  METHODS:
  In a multicenter randomized controlled trial conducted in four Italian centers patients with severe hARF due to pneumonia were randomized to receive helmet CPAP (CPAP group) or oxygen delivered with a Venturi mask (control group). The primary endpoint was the percentage of patients meeting criteria for ETI, including either one or more major criteria (respiratory arrest, respiratory pauses with unconsciousness, severe hemodynamic instability, intolerance) or at least two minor criteria (reduction of at least 30% of basal PaO2/FiO2 ratio, increase of 20% of PaCO2, worsening of alertness, respiratory distress, SpO2 less than 90%, exhaustion).
  
  RESULTS:
  Between February 2010 and 2013, 40 patients were randomized to CPAP and 41 to Venturi mask. The proportion of patients meeting ETI criteria in the CPAP group was significantly lower compared to those in the control group (6/40 = 15% vs. 26/41 = 63%, respectively, p < 0.001; relative risk 0.24, 95% CI 0.11-0.51; number needed to treat, 2) two patients were intubated in the CPAP group and one in the control group. The CPAP group showed a faster and greater improvement in oxygenation in comparison to controls (p < 0.001). In either study group, no relevant adverse events were detected.
  
  CONCLUSIONS:
  Helmet CPAP reduces the risk of meeting ETI criteria compared to oxygen therapy in patients with severe hARF due to pneumonia.
  
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• Extracorporeal lung support for COPD reaches a crossroad.
  Lancet Respir Med

  2014 May;2(5):350-2. doi: 10.1016/S2213-2600(14)70099-2.
  
  Nava Stefano, Ranieri V Marco
  
  
  
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• Cardiac magnetic resonance imaging of left ventricular apical hypoplasia in two complex congenital clinical syndromes.
  Circ J

  2014 ;78(6):1507-9.
  
  Baroni Matteo, Pedrotti Patrizia, Nava Stefano, Giannattasio Cristina, Roghi Alberto
  
  
  
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• Determinants of noninvasive ventilation outcomes during an episode of acute hypercapnic respiratory failure in chronic obstructive pulmonary disease: the effects of comorbidities and causes of respiratory failure.
  Biomed Res Int

  2014 ;2014():976783. doi: 10.1155/2014/976783.
  
  Pacilli Angela Maria Grazia, Valentini Ilaria, Carbonara Paolo, Marchetti Antonio, Nava Stefano
  
  Abstract
  
  OBJECTIVES:
  To investigate the effect of the cause of acute respiratory failure and the role of comorbidities both acute and chronic on the outcome of COPD patients admitted to Respiratory Intensive Care Unit (RICU) with acute respiratory failure and treated with NIV.
  
  DESIGN:
  Observational prospective study.
  
  PATIENTS AND METHODS:
  176 COPD patients consecutively admitted to our RICU over a period of 3 years and treated with NIV were evaluated. In all patients demographic, clinical, and functional parameters were recorded including the cause of acute respiratory failure, SAPS II score, Charlson comorbidity index, and further comorbidities not listed in the Charlson index. NIV success was defined as clinical improvement leading to discharge to regular ward, while exitus or need for endotracheal intubation was considered failure.
  
  RESULTS:
  NIV outcome was successful in 134 patients while 42 underwent failure. Univariate analysis showed significantly higher SAP II score, Charlson index, prevalence of pneumonia, and lower serum albumin level in the failure group. Multivariate analysis confirmed a significant predictive value for pneumonia and albumin.
  
  CONCLUSIONS:
  The most important determinants of NIV outcome in COPD patients are the presence of pneumonia and the level of serum albumin as an indicator of the patient nutritional status.
  
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• Timing of noninvasive ventilation failure: causes, risk factors, and potential remedies.
  BMC Pulm Med

  2014 Feb;14():19. doi: 10.1186/1471-2466-14-19.
  
  Ozyilmaz Ezgi, Ugurlu Aylin Ozsancak, Nava Stefano
  
  Abstract
  
  BACKGROUND:
  Identifying the predictors of noninvasive ventilation (NIV) failure has attracted significant interest because of the strong link between failure and poor outcomes. However, very little attention has been paid to the timing of the failure. This narrative review focuses on the causes of NIV failure and risk factors and potential remedies for NIV failure, based on the timing factor.
  
  RESULTS:
  The possible causes of immediate failure (within minutes to <1 h) are a weak cough reflex, excessive secretions, hypercapnic encephalopathy, intolerance, agitation, and patient-ventilator asynchrony. The major potential interventions include chest physiotherapeutic techniques, early fiberoptic bronchoscopy, changing ventilator settings, and judicious sedation. The risk factors for early failure (within 1 to 48 h) may differ for hypercapnic and hypoxemic respiratory failure. However, most cases of early failure are due to poor arterial blood gas (ABGs) and an inability to promptly correct them, increased severity of illness, and the persistence of a high respiratory rate. Despite a satisfactory initial response, late failure (48 h after NIV) can occur and may be related to sleep disturbance.
  
  CONCLUSIONS:
  Every clinician dealing with NIV should be aware of these risk factors and the predicted parameters of NIV failure that may change during the application of NIV. Close monitoring is required to detect early and late signs of deterioration, thereby preventing unavoidable delays in intubation.
  
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• The application of esophageal pressure measurement in patients with respiratory failure.
  Am J Respir Crit Care Med

  2014 Mar;189(5):520-31. doi: 10.1164/rccm.201312-2193CI.
  
  Akoumianaki Evangelia, Maggiore Salvatore M, Valenza Franco, Bellani Giacomo, Jubran Amal, Loring Stephen H, Pelosi Paolo, Talmor Daniel, Grasso Salvatore, Chiumello Davide, Guérin Claude, Patroniti Nicolo, Ranieri V Marco, Gattinoni Luciano, Nava Stefano, Terragni Pietro-Paolo, Pesenti Antonio, Tobin Martin, Mancebo Jordi, Brochard Laurent,
  
  Abstract
  
  This report summarizes current physiological and technical knowledge on esophageal pressure (Pes) measurements in patients receiving mechanical ventilation. The respiratory changes in Pes are representative of changes in pleural pressure. The difference between airway pressure (Paw) and Pes is a valid estimate of transpulmonary pressure. Pes helps determine what fraction of Paw is applied to overcome lung and chest wall elastance. Pes is usually measured via a catheter with an air-filled thin-walled latex balloon inserted nasally or orally. To validate Pes measurement, a dynamic occlusion test measures the ratio of change in Pes to change in Paw during inspiratory efforts against a closed airway. A ratio close to unity indicates that the system provides a valid measurement. Provided transpulmonary pressure is the lung-distending pressure, and that chest wall elastance may vary among individuals, a physiologically based ventilator strategy should take the transpulmonary pressure into account. For monitoring purposes, clinicians rely mostly on Paw and flow waveforms. However, these measurements may mask profound patient-ventilator asynchrony and do not allow respiratory muscle effort assessment. Pes also permits the measurement of transmural vascular pressures during both passive and active breathing. Pes measurements have enhanced our understanding of the pathophysiology of acute lung injury, patient-ventilator interaction, and weaning failure. The use of Pes for positive end-expiratory pressure titration may help improve oxygenation and compliance. Pes measurements make it feasible to individualize the level of muscle effort during mechanical ventilation and weaning. The time is now right to apply the knowledge obtained with Pes to improve the management of critically ill and ventilator-dependent patients.
  
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• Metabolic syndrome in human immunodeficiency virus-positive subjects: prevalence, phenotype, and related alterations in arterial structure and function.
  Metab Syndr Relat Disord

  2013 Dec;11(6):403-11. doi: 10.1089/met.2013.0008.
  
  Maloberti Alessandro, Giannattasio Christina, Dozio Dario, Betelli Mauro, Villa Paulo, Nava Stefano, Cesana Francesca, Facchetti Rita, Giupponi Luca, Castagna Francesco, Sabbatini Francesca, Bandera Alessandra, Gori Andre, Grassi Guido, Mancia Giuseppe
  
  Abstract
  
  BACKGROUND:
  Human immunodeficiency virus (HIV) infection itself and highly active antiretroviral treatment (HAART) have been proposed to be associated with a higher prevalence of metabolic syndrome, but, to date, prevalence and phenotype of metabolic syndrome among HIV subjects and the related structural and functional vascular alterations are not conclusively defined.
  
  METHODS:
  We analyzed the data of 108 HIV-infected subjects without known cardiovascular risk factors: 72 were on HAART (group A, age 46.5±7.5 years, clinical blood pressure 125.7/74.9±11.6/7.8?mmHg) and there 36 in a naïve group (group B, age 40.7±7.9 years, blood pressure 126/75.8±9.8/7.7?mmHg). A total of 224 healthy subjects served as controls (group C, age 44.9±6.9 years, blood pressure 123.7/75.7±9.8/7.1?mmHg). Arterial stiffness was measured by aorto-femoral pulse wave velocity (PWV, sfigmocor), and carotid intima media thickness (IMT) was measured by a semiautomatic echotracking system (Esaote-WTS).
  
  RESULTS:
  Metabolic syndrome was more frequent in HIV-positive subjects than in controls (19.4%, 13.8%, 4.5% for groups A, B, and C; P<0.001), with no significant difference between HAART and naïve. In metabolic syndrome subjects, group A displayed lipid profile alterations more frequently (91%, 50%, 57% for groups A, B, and C; P<0.05), whereas others metabolic syndrome components were equally represented in the three groups. In metabolic syndrome subjects, IMT was similar [556±108, 542±164, and 564±110.4 ?m for groups A, B, and C; P=not significant (NS)], whereas PWV was significantly greater in HAART subjects when compared with controls (10.8±1.8, 9.±1.1, 9.3±1?cm/sec for groups A, B, and C; P=0.02 for A vs. C). Moreover, in this group (metabolic syndrome+HAART), PWV was higher than in subjects on HAART but without metabolic syndrome.
  
  CONCLUSIONS:
  HIV subjects showed a higher prevalence and a different pattern of metabolic syndrome components. HAART, more than HIV infection per se, appeared to be responsible for the increased prevalence of metabolic syndrome and arterial function derangement.
  
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• Behind a mask: tricks, pitfalls, and prejudices for noninvasive ventilation.
  Respir Care

  2013 Aug;58(8):1367-76. doi: 10.4187/respcare.02457.
  
  Nava Stefano
  
  Abstract
  
  It is difficult to exactly date the beginning of mechanical ventilation, but there are no doubts that noninvasive ventilation (NIV) was the first method of ventilatory support in clinical practice. The technique had a sudden increase in popularity, so that it is now considered, according to criteria of evidence-based medicine, the first-line treatment for an episode of acute respiratory failure in 4 pathologies (the Fabulous Four): COPD exacerbation, cardiogenic pulmonary edema, pulmonary infiltrates in immunocompromised patients, and in the weaning of extubated COPD patients. The so-called emerging applications are those for which the evidence has not achieved level A, mainly because the number or sample size of the published studies does not allow conclusive meta-analysis. These emerging applications are the post-surgical period, palliation of dyspnea, asthma attack, obesity hypoventilation syndrome, and to prevent extubation failure. Potentially "risky business" uses include for respiratory failure from pandemic diseases and ARDS, where probably the "secret" for success is early use. Healthcare is rich in evidence-based innovations, yet even when such innovations are implemented successfully in one location, they often disseminate slowly, if at all, so their clinical use remains limited and heterogeneous. The low rate of NIV use in some hospitals relates to lack of knowledge about or experience with NIV, insufficient confidence in the technique, lack of NIV equipment, and inadequate funding. But NIV use has been increasing around the world, thanks partly to improved technologies. The skill and confidence of clinicians in NIV have improved with time and experience, but NIV is and should remain a team effort, rather than the property of a single local "champion," because, overall, NIV is beautiful!
  
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• Impact of blood glucose variability on carotid artery intima media thickness and distensibility in type 1 diabetes mellitus.
  Blood Press

  2013 Dec;22(6):355-61. doi: 10.3109/08037051.2013.791413.
  
  Cesana Francesca, Giannattasio Cristina, Nava Stefano, Soriano Francesco, Brambilla Gianmaria, Baroni Matteo, Meani Paolo, Varrenti Marisa, Paleari Felice, Gamba Pierluigi, Facchetti Rita, Alloni Marta, Grassi Guido, Mancia Giuseppe
  
  Abstract
  
  AIMS:
  Diabetes mellitus is characterized by structural and functional alterations of the large- and medium-size arteries. Whether blood glucose variability, i.e. the glycemic oscillations occurring during the 24-h period, represents a risk factor for vascular alterations additional to and independent on HbA1c in type 1 diabetes mellitus is still undefined. The present study was carried out with the aim at investigating the impact of different measures of blood glucose variability on arterial structure and function. We studied 17 non-complicated type 1 diabetic patients (11 males, six females) with an age of 40.8 ± 7.6 years (mean ± SD). In each patient, 24-h glucose profile was obtained by continuous glucose monitoring system and glucose variability was expressed as mean ± SD of 24-h blood glucose levels, mean amplitude of glycemic excursions and postprandial hyperglycemic spikes. Arterial structure and function was measured as carotid IMT and stiffness.
  
  MAJOR FINDINGS:
  The different approaches to assessing blood glucose variability well correlated between and with HbA1c. Carotid IMT and stiffness showed significant correlations with age, blood pressure, heart rate and daily insulin intake but a non- significant correlation with blood glucose variability.
  
  PRINCIPAL CONCLUSION:
  Thus, in type 1 diabetes mellitus, measures of glycemic variability are useful in predicting both actual and long-lasting glycemic control. In absence of diabetes-related complications and of any intima-media thickness alterations, the major predictors of arterial distensibility are represented by traditional risk factors beside glycemic 24-h control.
  
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• Influence of the admission pattern on the outcome of patients admitted to a respiratory intensive care unit: does a step-down admission differ from a step-up one?
  Respir Care

  2013 Dec;58(12):2053-60. doi: 10.4187/respcare.02225.
  
  Valentini Ilaria, Pacilli Angela Maria Grazia, Carbonara Paolo, Fasano Luca, Vitale Rita, Zenesini Corrado, Melotti Rita Maria, Faenza Stefano, Nava Stefano
  
  Abstract
  
  BACKGROUND:
  The outcomes of patients admitted to a respiratory ICU (RICU) have been evaluated in the past, but no study has considered the influence of location prior to RICU admission.
  
  METHODS:
  We analyzed prospectively collected data from 326 consecutive patients admitted to a 7-bed RICU. The primary end points were survival and severity of morbidity-related complications, evaluated according to the patient's location prior to RICU admission. Three admission pathways were considered: step-down for patients transferred from the ICUs of our hospital; step-up for patients coming from our respiratory wards or other medical wards; and directly for patients coming from the emergency department. The secondary end point was the potential influence of several risk factors for morbidity and mortality.
  
  RESULTS:
  Of the 326 subjects, 92 (28%) died. Overall, subjects admitted in a step-up process had a significantly higher mortality (P < .001) than subjects in the other groups. The mortality rate was 64% for subjects admitted from respiratory ward, 43% for those from medical wards, and 18% for subjects from both ICU and emergency department (respiratory ward vs medical ward P = .04, respiratory ward vs emergency department P < .001, respiratory ward vs ICU P < .001, medical ward vs emergency department P < .001, and medical ward vs ICU P < .001). Subjects admitted from a respiratory ward had a lower albumin level, and Simplified Acute Physiology Score II was significantly higher in subjects following a step-up admission. About 30% of the subjects admitted from a respiratory ward received noninvasive ventilation as a "ceiling treatment." The highest odds ratios related to survival were subject location prior to RICU admission and female sex. Lack of use of noninvasive ventilation, younger age, female sex, higher albumin level, lower Simplified Acute Physiology Score II, higher Barthel score, and absence of chronic heart failure were also statistically associated with a lower risk of death.
  
  CONCLUSIONS:
  The pathway of admission to a RICU is a determinant of outcome. Patients following a step-up pattern are more likely to die. Other major determinants of survival are age, nutritional status and female sex.
  
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• Non-invasive ventilation for end-of-life oncology patients--authors' reply.
  Lancet Oncol

  2013 May;14(6):e201. doi: 10.1016/S1470-2045(13)70155-4.
  
  Nava Stefano,
  
  
  
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• First use of noninvasive ventilation during urgent coronary stenting in acute myocardial infarction complicated by pulmonary edema.
  Intensive Care Med

  2013 Jun;39(6):1166-7. doi: 10.1007/s00134-013-2916-x.
  
  Rucci Giuliano, Casale Tommasina, Nava Stefano
  
  
  
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• Patient-ventilator asynchronies: may the respiratory mechanics play a role?
  Crit Care

  2013 Mar;17(2):R54. doi: 10.1186/cc12580.
  
  Carlucci Annalisa, Pisani Lara, Ceriana Piero, Malovini Alberto, Nava Stefano
  
  Abstract
  
  INTRODUCTION:
  The mechanisms leading to patient/ventilator asynchrony has never been systematically assessed. We studied the possible association between asynchrony and respiratory mechanics in patients ready to be enrolled for a home non-invasive ventilatory program. Secondarily, we looked for possible differences in the amount of asynchronies between obstructive and restrictive patients and a possible role of asynchrony in influencing the tolerance of non-invasive ventilation (NIV).
  
  METHODS:
  The respiratory pattern and mechanics of 69 consecutive patients with chronic respiratory failure were recorded during spontaneous breathing. After that patients underwent non-invasive ventilation for 60 minutes with a "dedicated" NIV platform in a pressure support mode during the day. In the last 15 minutes of this period, asynchrony events were detected and classified as ineffective effort (IE), double triggering (DT) and auto-triggering (AT).
  
  RESULTS:
  The overall number of asynchronies was not influenced by any variable of respiratory mechanics or by the underlying pathologies (that is, obstructive vs restrictive patients). There was a high prevalence of asynchrony events (58% of patients). IEs were the most frequent asynchronous events (45% of patients) and were associated with a higher level of pressure support. A high incidence of asynchrony events and IE were associated with a poor tolerance of NIV.
  
  CONCLUSIONS:
  Our study suggests that in non-invasively ventilated patients for a chronic respiratory failure, the incidence of patient-ventilator asynchronies was relatively high, but did not correlate with any parameters of respiratory mechanics or underlying disease.
  
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• Inspiratory pressure during noninvasive ventilation in stable COPD: help the lungs, but do not forget the heart.
  Eur Respir J

  2013 Mar;41(3):765-6. doi: 10.1183/09031936.00173212.
  
  Lukácsovits József, Nava Stefano
  
  
  
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• Does the 9p region affect arterial stiffness? Results from a cohort of hypertensive individuals.
  Blood Press

  2013 Oct;22(5):302-6. doi: 10.3109/08037051.2013.765627.
  
  Cesana Francesca, Nava Stefano, Menni Cristina, Boffi Lucia, Varrenti Marisa, Meani Paolo, Maloberti Alessandro, Grassi Guido, Giannattasio Cristina, Mancia Giuseppe
  
  Abstract
  
  OBJECTIVE:
  Evidence exists that arterial stiffness, i.e. an independent predictor of cardiovascular and all-causes mortality, has a genetic component. The 9p21 region is associated with a greater susceptibility to coronary disease. Whether this can be ascribed to the fact that genes located on chromosome 9p may also regulate arterial stiffness is largely unknown, however. We evaluate the influence of single nucleotide polymorphisms (SNPs) from 9p on carotid-femoral pulse wave velocity (C-F PWV), measured via the Complior method, in a cohort of 821 hypertensive subjects.
  
  DESIGN:
  The selected tagSNPs were screened with a custom-designed 384-plex VeraCode GoldenGate Genotyping assay on Illumina BeadXpress Reader platform. Association analysis was done using PLINK considering C-F PWV as a quantitative trait (linear regression assuming an additive model) adjusting for sex, age, systolic blood pressure and body mass index (BMI). We used false discovery rate (FDR) to account for multiple testing.
  
  RESULTS:
  Although none of the 384 SNPs was significant after adjusting for multiple testing, probably due to the small sample size of the study population, a trend of association with C-F PWV was observed for rs300622 and rs2381640.
  
  CONCLUSIONS:
  These data suggest that SNPs located on chromosome 9p may affect arterial stiffness. Further studies are needed to confirm our finding on a larger sample and define the physiopathological link of the present results.
  
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• (18)F-FDG PET/CT for the assessment of disease extension and activity in patients with sarcoidosis: results of a preliminary prospective study.
  Clin Nucl Med

  2013 Apr;38(4):e171-7. doi: 10.1097/RLU.0b013e31827a27df.
  
  Ambrosini Valentina, Zompatori Maurizio, Fasano Luca, Nanni Cristina, Nava Stefano, Rubello Domenico, Fanti Stefano
  
  Abstract
  
  PURPOSE:
  This study aimed to prospectively investigate F-FDG PET/CT role for the assessment of sarcoidosis activity and extension in comparison with thoracic high-resolution CT (HRCT) and to evaluate the potential clinical impact of PET/CT findings. Secondary aim was to investigate the changes in cardiac FDG uptake related to the specific preparation before PET/CT.
  
  METHODS:
  We prospectively enrolled biopsy proven sarcoidosis patients consecutively referred for F-FDG PET/CT since January 2010. PET/CT was performed after a fat meal followed by 12-hour fasting and compared with thoracic HRCT results obtained in supine position and clinical follow-up. The impact on the clinical management was recorded.Patterns of cardiac FDG uptake of the study group were compared with a historical population in which PET/CT was performed following standard preparation.
  
  RESULTS:
  A total of 28 patients were enrolled, and 35 PET/CT scans were reviewed. On a scan basis, PET/CT was concordant with HRCT in 16 (45.7%), detecting active disease in 10/16 and no signs of activity in 4/16. PET/CT data had a direct impact on management in 4/16.In 19 (54.3%) discordant scans, PET/CT finding was positive in 14 and negative in 5. PET/CT findings influenced the clinical management in 18/19 cases.Considering all scans, PET/CT information influenced the clinical management of 22 (63%) of 35.Our data suggest that cardiac FDG uptake may vary regardless of the preparation before PET/CT.
  
  CONCLUSIONS:
  F-FDG PET/CT was useful to assess sarcoidosis activity and extension and provided valuable information for the clinical management in a single-step examination. Additional data are needed to better ascertain the optimal patient preparation before image acquisition to improve sensitivity of heart lesions.
  
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• Palliative use of non-invasive ventilation in end-of-life patients with solid tumours: a randomised feasibility trial.
  Lancet Oncol

  2013 Mar;14(3):219-27. doi: 10.1016/S1470-2045(13)70009-3.
  
  Nava Stefano, Ferrer Miguel, Esquinas Antonio, Scala Raffaele, Groff Paolo, Cosentini Roberto, Guido Davide, Lin Ching-Hsiung, Cuomo Anna Maria, Grassi Mario
  
  Abstract
  
  BACKGROUND:
  Despite best-possible medical management, many patients with end-stage cancer experience breathlessness, especially towards the end of their lives. We assessed the acceptability and effectiveness of non-invasive mechanical ventilation (NIV) versus oxygen therapy in decreasing dyspnoea and the amount of opiates needed.
  
  METHODS:
  In this randomised feasibility study, we recruited patients from seven centres in Italy, Spain, and Taiwan, who had solid tumours and acute respiratory failure and had a life expectancy of less than 6 months. We randomly allocated patients to receive either NIV (using the Pressure Support mode and scheduled on patients' request and mask comfort) or oxygen therapy (using a Venturi or a reservoir mask). We used a computer-generated sequence for randomisation, stratified on the basis of patients' hypercapnic status (PaCO2 >45 mm Hg or PaCO2 ?45 mm Hg), and assigned treatment allocation using opaque, sealed envelopes. Patients in both groups were given sufficient subcutaneous morphine to reduce their dyspnoea score by at least one point on the Borg scale. Our primary endpoints were to assess the acceptability of NIV used solely as a palliative measure and to assess its effectiveness in reducing dyspnoea and the amount of opiates needed compared with oxygen therapy. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00533143.
  
  FINDINGS:
  We recruited patients between Jan 15, 2008, and March 9, 2011. Of 234 patients eligible for recruitment, we randomly allocated 200 (85%) to treatment: 99 to NIV and 101 to oxygen. 11 (11%) patients in the NIV group discontinued treatment; no patients in the oxygen group discontinued treatment. Dyspnoea decreased more rapidly in the NIV group compared with the oxygen group (average change in Borg scale -0·58, 95% CI -0·92 to -0·23, p=0·0012), with most benefit seen after the first hour of treatment and in hypercapnic patients. The total dose of morphine during the first 48 h was lower in the NIV group than it was in the oxygen group (26·9 mg [37·3] for NIV vs 59·4 mg [SD 67·1] for oxygen; mean difference -32·4 mg, 95% CI -47·5 to -17·4). Adverse events leading to NIV discontinuation were mainly related to mask intolerance and anxiety. Morphine was suspended because of severe vomiting and nausea (one patient in each group), sudden respiratory arrest (one patient in the NIV group), and myocardial infarction (one patient in the oxygen group).
  
  INTERPRETATION:
  Our findings suggest that NIV is more effective compared with oxygen in reducing dyspnoea and decreasing the doses of morphine needed in patients with end-stage cancer. Further studies are needed to confirm our findings and to assess the effectiveness of NIV on other outcomes such as survival. The use of NIV is, however, restricted to centres with NIV equipment, our findings are not generalisable to all cancer or palliative care units.
  
  FUNDING:
  None.
  
  Copyright © 2013 Elsevier Ltd. All rights reserved.
  
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• Incomplete network for survivors of catastrophic illness after release from ICUs.
  Respir Care

  2013 Feb;58(2):383-5. doi: 10.4187/respcare.02262.
  
  Vitacca Michele, Nava Stefano
  
  
  
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• Palliative care in COPD patients: is it only an end-of-life issue?
  Eur Respir Rev

  2012 Dec;21(126):347-54. doi: 10.1183/09059180.00001512.
  
  Carlucci Annalisa, Guerrieri Aldo, Nava Stefano
  
  Abstract
  
  The presence of acute or chronic respiratory failure is often seen as a terminal phase of chronic obstructive pulmonary disease. A great variability in end-of-life practice is observed in these patients mainly because physicians are not always able to correctly predict survival. There is a need for a clear discussion about decision making earlier than when acute respiratory failure ensues. Indeed, a perceived poor quality of life does not necessarily correlate with a clear willingness to refuse invasive or noninvasive mechanical ventilation. It has been suggested to start palliative care earlier, together with curative and restorative care, when there is an increased intensity of symptoms. The patients eligible for palliative care are those complaining of breathlessness, pain, fatigue and depression, which in some studies accounted for a prevalence much higher than 50%. Among comfort measures for palliation, oxygen is frequently prescribed even when the criteria for long-term home oxygen therapy are not met; however, when compared with air, no benefits on dyspnoea have been found. The only drug with a proven effect on dyspnoea is morphine, but not when it is delivered with a nebuliser. Finally, noninvasive ventilation may be used only as a comfort measure for palliation to maximise comfort by minimising adverse effects.
  
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• Idiopathic pulmonary fibrosis and polymorphisms of the folate pathway genes.
  Clin Biochem

  2013 Jan;46(1-2):85-8. doi: 10.1016/j.clinbiochem.2012.10.009.
  
  Martinelli Marcella, Scapoli Luca, Carbonara Paolo, Valentini Ilaria, Girardi Ambra, Farinella Francesca, Mattei Gabriella, Pacilli Angela Maria Grazia, Fasano Luca, Nava Stefano, Solmi Rossella
  
  Abstract
  
  OBJECTIVES:
  This study aims to determine the possible association between folate pathway gene polymorphisms and idiopathic pulmonary fibrosis. This represents the first study carried out on folate pathway gene polymorphisms as possible risk factors in this kind of pathology. The premise is that several polymorphisms mapping on genes responsible for folate uptake are associated with the risk of numerous diseases occurring between pregnancy and old age, and that too little is currently known about idiopathic pulmonary fibrosis.
  
  DESIGN AND METHODS:
  We genotyped 9 single nucleotide polymorphisms and 1 polymorphic insertion in 7 essential genes belonging to the folate pathway in 32 Italian idiopathic pulmonary fibrosis patients and 81 control subjects. This was done by PCR and restriction analysis.
  
  RESULTS:
  Allelic and genotypic association tests indicated that for all the analysed polymorphisms there were no significant differences between patients and controls. Nevertheless, the haplotype association analysis revealed a significant association between idiopathic pulmonary fibrosis and transcobalamin II gene polymorphisms: specifically the haplotype 776G (rs1801198)-c.1026-394G (rs7286680)-444C (rs10418) (OR=2.84; 95% C.I. 1.36-5.93, P value=0.004).
  
  CONCLUSIONS:
  This small-scale preliminary study would suggest the importance of further research focusing on the role of folate in the onset of idiopathic pulmonary fibrosis.
  
  Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
  
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• Variant on chromosome 9p is associated with left ventricular mass: results from two cohorts of essential hypertensive individuals.
  J Hypertens

  2012 Nov;30(11):2144-50. doi: 10.1097/HJH.0b013e3283581f7e.
  
  Menni Cristina, Boffi Lucia, Cesana Francesca, Viviani Anselmi Chiara, Nava Stefano, Bertola Francesca, Blasio Anna M Di, Roncarati Roberta, Trimarco Valentina, Marino Marina, Trimarco Bruno, Grassi Guido, Giannattasio Cristina, Mancia Giuseppe
  
  Abstract
  
  OBJECTIVES:
  It is well known that among hypertensive patients, an increased left ventricular mass (LVM) is a powerful predictor of cardiovascular morbidity and mortality. However, the mechanisms underlying LVM in hypertension are not completely understood, as the absolute value of blood pressure and other risk factors associated do not predict alone a definite LVM progression. Recently, the 9p21 chromosomal region has been consistently associated with coronary heart disease.
  
  METHODS AND RESULTS:
  We examined the association of 384 single nucleotide polymorphisms (SNPs) in the short arm of chromosome 9 with LVM in 821 hypertensive individuals from northern Italy. We identified a SNP (rs894379) in the intronic region of the centlein, centrosomal protein (CNTLN) gene on chromosome 9p22, whose minor allele G is associated with an increased LVM. We performed a follow-up validation analysis for the top SNP in 1038 hypertensive individuals from southern Italy. We then combined the results and found a nominal association for rs894379 (? ?= ?2.46, P ?=? 0.0026).
  
  CONCLUSION:
  We describe a new variant associated with echocardiography LVM. This result, though it needs to be further investigated, may improve our understanding of the genetic determination of this prognostically relevant trait.
  
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• The use of non-invasive ventilation during acute respiratory failure due to pneumonia.
  Eur J Intern Med

  2012 Jul;23(5):420-8. doi: 10.1016/j.ejim.2012.02.011.
  
  Ferrer Miquel, Cosentini Roberto, Nava Stefano
  
  Abstract
  
  The use of non-invasive ventilation in patients with community-acquired pneumonia is controversial since this is associated with high rates of treatment failure, compared with other causes of severe acute respiratory failure. The populations of patients with community-acquired pneumonia who have demonstrated better response to non-invasive ventilation are those with previous cardiac or respiratory disease, particularly chronic obstructive pulmonary disease. By contrast, the use of non-invasive ventilation in patients with community-acquired pneumonia without these pre-existing diseases should be very cautious and under strict monitoring conditions, since there are increasing evidences that the unnecessary delay in intubation of those patients who fail treatment with non-invasive ventilation is associated with lower survival. Pulmonary complications of immunosuppressed patients are associated with high rates of intubation and mortality. The use of non-invasive ventilation in these patients may decrease the need for intubation and improve the poor outcome associated with these complications. Continuous positive airway pressure has been used to treat acute respiratory failure in several conditions characterised by alveolar collapse. While this is extremely useful in patients with acute cardiogenic pulmonary oedema, the efficacy in pneumonia seems limited to immunosuppressed patients with pulmonary complications. Conversely, there are no sufficient evidences on the efficacy of continuous positive airway pressure in immunocompetent patients with pneumonia and severe acute respiratory failure.
  
  Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
  
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• Respiratory critical care HERMES syllabus: defining competencies for respiratory doctors.
  Eur Respir J

  2012 Jun;39(6):1294-7. doi: 10.1183/09031936.00056212.
  
  Artigas Antonio, Pelosi Paolo, Dellweg Dominic, Brochard Laurent, Ferrer Miguel, Geiseler Jens, Larsson Anders, Nava Stefano, Navalesi Paolo, Noël Julie-Lyn, Orfanos Stylianos, Palange Paolo, Schoenhofer Bernd, Vassilakopoulos Theodoros, Simonds Anita,
  
  
  
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• Different tracheotomy tube diameters influence diaphragmatic effort and indices of weanability in difficult to wean patients.
  Respir Care

  2012 Dec;57(12):2012-8. doi: 10.4187/respcare.01747.
  
  Valentini Ilaria, Tonveronachi Eva, Gregoretti Cesare, Mega Chiara, Fasano Luca, Pisani Lara, Nava Stefano
  
  Abstract
  
  OBJECTIVE:
  To determine the effects of different tracheotomy tube sizes on diaphragm effort and weanability indices.
  
  METHODS:
  Ten tracheotomized and difficult to wean subjects were randomized to 2 T-piece trials, with different tracheotomy tube diameters: inner diameters 8 mm and 6.5 mm. Diaphragm pressure-time product per min. (PTP(di/min)), lung compliance and resistance (C(L) and R(L)), breathing pattern, tension-time index of the diaphragm (TT(di)), and the ratio of breathing frequency to tidal volume (f/V(T)) were recorded. In an in vitro model, the flow-pressure relationship was measured using the 2 tracheotomy tubes and 2 endotracheal tubes of the same diameter.
  
  RESULTS:
  The use of a smaller diameter resulted in an increase of PTP(di) (337.63 ± 194.35 cm H(2)O · s/min vs 263.28 ± 156.23 cm H(2)O · s/min for 6.5 mm and 8 mm, respectively, P = .004) and R(L) (16.74 ± 8.10 cm H(2)O · s/min vs 11.72 ± 7.88 cm H(2)O · s/min, respectively, P = .008). Both weanability indices were also significantly higher using the smaller tube: f/V(T) 93.32 ± 20.91 vs 77.06 ± 19.26 for 6.5 mm and 8 mm, respectively, P < .02; TT(di) 0.09 ± 0.052 vs 0.08 ± 0.04, respectively, P < .02. In vitro measurements confirmed that the resistances were higher with the smaller diameter and similar between the tracheotomy tubes and the endotracheal tubes of the same diameters.
  
  CONCLUSIONS:
  In tracheotomized difficult to wean subjects the decrease of the tracheotomy tube size was associated with an increased PTP(di), f/V(T), and TT(di), that were otherwise normal, using a higher diameter. The in vitro study showed that the resistances increased similarly for tracheotomy tube and endotracheal tube, decreasing the diameter and increasing the flows.
  
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• Volume assured pressure support ventilation--induced arousals.
  Sleep Med

  2012 Jun;13(6):767-8. doi: 10.1016/j.sleep.2012.02.006.
  
  Carlucci Annalisa, Fanfulla Francesco, Mancini Marco, Nava Stefano
  
  
  
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• Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease: "Don't think twice, it's alright!".
  Am J Respir Crit Care Med

  2012 Jan;185(2):121-3. doi: 10.1164/rccm.201111-1933ED.
  
  Elliott M W, Nava Stefano
  
  
  
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• Noninvasive mechanical ventilation.
  Curr Opin Crit Care

  2012 Feb;18(1):48-53. doi: 10.1097/MCC.0b013e32834ebd71.
  
  Boldrini Rossella, Fasano Luca, Nava Stefano
  
  Abstract
  
  PURPOSE OF REVIEW:
  A critical review of the most recent literature regarding use and clinical indications of noninvasive mechanical ventilation (NIV).
  
  RECENT FINDINGS:
  According to several randomized controlled trials, NIV has gained acceptance as the preferred ventilatory modality to treat acute respiratory failure (ARF) due to chronic obstructive pulmonary disease exacerbations, cardiogenic pulmonary edema, respiratory failure in immunocompromised patients, and to decrease the intubation length and to improve weaning results in patients recovering from a hypercapnic respiratory failure. Observational studies suggest that NIV may also be used to treat other conditions like severe pneumonia (including H1N1 virus), severe asthma attack, cystic fibrosis, obesity hypoventilation, and to improve the respiratory outcome in postsurgical patients.
  
  SUMMARY:
  NIV has radically changed the management of ARF. Recently the possible applications of NIV have increased, both in the hospital and extrahospital setting. NIV is no longer confined to the ICU, but has crossed over into the regular ward, Emergency Department and 'out-of-hospital' environment. Current research is focusing on improving the quality and safety of the devices and establishing new ventilatory modes in order to extend even further the indications to NIV as well as its rate of success.
  
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• Critical care rationing: international comparisons.
  Chest

  2011 Dec;140(6):1618-1624. doi: S0012-3692(11)60661-2.
  
  Evans Timothy W, Nava Stefano, Mata Guillermo Vazquez, Guidet Bertrand, Estenssoro Elisa, Fowler Robert, Scheunemann Leslie P, White Douglas, Manthous Constantine A
  
  Abstract
  
  Every country has finite resources that are expended to provide citizens with social "goods," including education, protection, infrastructure, and health care. Rationing-of any resource-refers to distribution of an allotted amount and may involve withholding some goods that would benefit some citizens. Health-care rationing is controversial because good health complements so many human endeavors. We explored (perceptions regarding) critical care rationing in seven industrialized countries. Academic physicians from England, Spain, Italy, France, Argentina, Canada, and the United States wrote essays that addressed specific questions including: (1) What historical, cultural, and medical institutional features inform my country's approach to rationing of health care? (2) What is known about formal rationing, especially in critical care, in my country? (3) How does rationing occur in my ICU? Responses suggest that critical care is rationed, by varying mechanisms, in all seven countries. We speculate that while no single "best" method of rationing is likely to be acceptable or optimal for all countries, professional societies could serve international health by developing evidence-based guidelines for just and effective rationing of critical care.
  
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• Oxygen: the kiss of life.
  Respir Care

  2011 Dec;56(12):1975-6. doi: 10.4187/respcare.01586.
  
  Nava Stefano
  
  
  
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• Optimization of ventilator setting by flow and pressure waveforms analysis during noninvasive ventilation for acute exacerbations of COPD: a multicentric randomized controlled trial.
  Crit Care

  2011 ;15(6):R283. doi: 10.1186/cc10567.
  
  Di Marco Fabiano, Centanni Stefano, Bellone Andrea, Messinesi Grazia, Pesci Alberto, Scala Raffaele, Perren Andreas, Nava Stefano
  
  Abstract
  
  INTRODUCTION:
  The analysis of flow and pressure waveforms generated by ventilators can be useful in the optimization of patient-ventilator interactions, notably in chronic obstructive pulmonary disease (COPD) patients. To date, however, a real clinical benefit of this approach has not been proven.
  
  METHODS:
  The aim of the present randomized, multi-centric, controlled study was to compare optimized ventilation, driven by the analysis of flow and pressure waveforms, to standard ventilation (same physician, same initial ventilator setting, same time spent at the bedside while the ventilator screen was obscured with numerical data always available). The primary aim was the rate of pH normalization at two hours, while secondary aims were changes in PaCO2, respiratory rate and the patient's tolerance to ventilation (all parameters evaluated at baseline, 30, 120, 360 minutes and 24 hours after the beginning of ventilation). Seventy patients (35 for each group) with acute exacerbation of COPD were enrolled.
  
  RESULTS:
  Optimized ventilation led to a more rapid normalization of pH at two hours (51 vs. 26% of patients), to a significant improvement of the patient's tolerance to ventilation at two hours, and to a higher decrease of PaCO2 at two and six hours. Optimized ventilation induced physicians to use higher levels of external positive end-expiratory pressure, more sensitive inspiratory triggers and a faster speed of pressurization.
  
  CONCLUSIONS:
  The analysis of the waveforms generated by ventilators has a significant positive effect on physiological and patient-centered outcomes during acute exacerbation of COPD. The acquisition of specific skills in this field should be encouraged.
  
  TRIAL REGISTRATION:
  ClinicalTrials.gov NCT01291303.
  
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• Comparison of echotracking and magnetic resonance assessment of abdominal aorta distensibility and relationships with pulse wave velocity.
  Ultrasound Med Biol

  2011 Dec;37(12):1970-6. doi: 10.1016/j.ultrasmedbio.2011.09.009.
  
  Giannattasio Cristina, Cesana Francesca, Maestroni Silvia, Salvioni Alessandra, Maloberti Alessandro, Nava Stefano, Cairo Matteo, Madotto Fabiana, Zerboni Filippo, Sironi Sandro, Grassi Guido, Mancia Giuseppe
  
  Abstract
  
  Arterial distensibility can be measured either by echotracking or by nuclear magnetic resonance (MRI). Little information, however, is available on the comparison between the two methods and on the relationships between the results obtained with the two approaches and the arterial stiffness gold standard measurement, i.e., pulse wave velocity (PWV). In 28 normotensive subjects (age 33.0 ± 10.4 years, mean ± SD) we measured aortic diameter 1 cm above iliac bifurcation, aortic pulse pressure by tonometry and calculated arterial distensibility via the Reneman formulae for both methods. Aortic diameter and aortic distensibility were not superimposable and higher values were systematically detected with the MRI approach than with the ultrasound one. However, PWV showed a significant correlation with aortic distensibility values obtained by both methods (r = 0.50 and r = 0.49, p < 0.05). These data provide evidence that MRI-measured distensibility value is higher than that obtained via echotracking. The significant correlation with PWV, however, suggests that both methods can be regarded as valuable approaches. Considering the greater economic cost and the lower availability in daily clinical and research practice of MRI, echotracking ultrasonography can be regarded as a reliable and feasible method to assess aortic distensibility.
  
  Copyright © 2011. Published by Elsevier Inc.
  
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• Physiologic determinants of prolonged mechanical ventilation in patients after major surgery.
  J Crit Care

  2012 Apr;27(2):221.e9-16. doi: 10.1016/j.jcrc.2011.08.009.
  
  Karakurt Zuhal, Fanfulla Francesco, Ceriana Piero, Carlucci Annalisa, Grassi Mario, Colombo Roberto, Karakurt Sait, Nava Stefano
  
  Abstract
  
  PURPOSE:
  The aim of the study was to evaluate the physiologic determinants of ventilator dependency in patients who underwent major surgery.
  
  MATERIALS AND METHODS:
  In this observational study, 43 stable tracheostomized patients undergoing prolonged ventilation (>14 days) were evaluated. Diaphragmatic muscle function was assessed invasively by the tension-time index of the diaphragm (TTdi), an indicator of diaphragm endurance time. The TTdi was calculated as transdiaphragmatic pressure/maximum transdiaphragmatic pressure × inspiratory time/total respiratory time and was recorded either when weaning from mechanical ventilation had finally been successful (n = 28 patients) or at the end of the fifth week in those patients in whom weaning failed (FW) (n = 15). Furthermore, the characteristics of survivors (n = 33) were compared with those of nonsurvivors (n = 10).
  
  RESULTS:
  Successfully weaned patients had a lower breathing frequency/tidal volume or rapid shallow breathing index compared with FW patients (93.9 ± 45.5 vs 142.4 ± 60.3, respectively; P < .005). The TTdi was significantly higher in FW than in successfully weaned patients (0.107 ± 0.050 vs 0.148 ± 0.059; P < .023) and in nonsurvivors than in survivors (0.106 ± 0.046 vs 0.174 ± 0.058, P < .0001, respectively). A transdiaphragmatic pressure/maximum transdiaphragmatic pressure ratio of more than 40% was an independent predictor of mortality, whereas an increased frequency/tidal volume ratio and TTdi were independent predictors of weaning failure.
  
  CONCLUSIONS:
  Difficult-to-wean patients after major surgery have overall a limited diaphragm endurance time, in particular, FW breathe very close to the fatigue threshold, and they adopt a rapid shallow breathing respiratory pattern to avoid crossing this threshold.
  
  Copyright © 2012 Elsevier Inc. All rights reserved.
  
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• Noninvasive ventilation for patients with acute lung injury or acute respiratory distress syndrome.
  Respir Care

  2011 Oct;56(10):1583-8. doi: 10.4187/respcare.01209.
  
  Nava Stefano, Schreiber Ania, Domenighetti Guido
  
  Abstract
  
  Few studies have been performed on noninvasive ventilation (NIV) to treat hypoxic acute respiratory failure in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). The outcomes of these patients, for whom endotracheal intubation is not mandatory, depend on the degree of hypoxia, the presence of comorbidities and complications, and their illness severity. The use of NIV as an alternative to invasive ventilation in severely hypoxemic patients with ARDS (ie, P(aO(2))/F(IO(2)) < 200) is not generally advisable and should be limited to hemodynamically stable patients who can be closely monitored in an intensive care unit by highly skilled staff. Early NIV application may be extremely helpful in immunocompromised patients with pulmonary infiltrates, in whom intubation dramatically increases the risk of infection, pneumonia, and death. The use of NIV in patients with severe acute respiratory syndrome and other airborne diseases has generated debate, despite encouraging clinical results, mainly because of safety issues. Overall, the high rate of NIV failure suggests a cautious approach to NIV use in patients with ALI/ARDS, including early initiation, intensive monitoring, and prompt intubation if signs of NIV failure emerge.
  
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• Respiratory care year in review 2010: part 2. Invasive mechanical ventilation, noninvasive ventilation, pediatric mechanical ventilation, aerosol therapy.
  Respir Care

  2011 May;56(5):667-80. doi: 10.4187/respcare.01310.
  
  Macintyre Neil R, Nava Stefano, Diblasi Robert M, Restrepo Ruben D, Hess Dean R
  
  Abstract
  
  The purpose of this paper is to review the recent literature related to invasive mechanical ventilation, NIV, pediatric mechanical ventilation, and aerosol therapy. Topics covered related to invasive mechanical ventilation topics include the role of PEEP in providing lung protection during mechanical ventilation, unconventional modes for severe hypoxemia, and strategies to improve patient-ventilator interactions. Topics covered related to NIV include real-life NIV use, NIV and extubation failure, and NIV and pandemics. For pediatric mechanical ventilation, the topics addressed are NIV, invasive respiratory support, and inhaled nitric oxide. Topics covered related to aerosol therapy include short-acting ?-adrenergic agents, long-acting ?-adrenergic agents, long-acting antimuscarinic agents, inhaled corticosteroid therapy, phosphodiesterase type 4 (PDE4) inhibitors, long-acting ?-adrenergic plus inhaled corticosteroid, long-acting antimuscarinic plus inhaled corticosteroid, nebulized hypertonic saline, inhaled mannitol, and inhaled antibiotic therapy. These topics were chosen and reviewed in a manner that is most likely to have interest to the readers of Respiratory Care.
  
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• Persistence of arterial functional abnormalities after successful coronary revascularization.
  J Hypertens

  2011 Jul;29(7):1374-9. doi: 10.1097/HJH.0b013e328347a0e3.
  
  Giannattasio Cristina, Capra Anna C M, Calchera Ivan, Colombo Virgilio, Cesana Francesca, Nava Stefano, Maloberti Alessandro, Alloni Marta, Facchetti Rita, Trocino Giuseppe, Grassi Guido, Paolini Giovanni, Mancia Giuseppe
  
  Abstract
  
  BACKGROUND:
  In patients with myocardial ischemia and coronary atherosclerosis, arterial stiffness and endothelial function are impaired. Whether these alterations can be favorably affected by successful coronary revascularization is debated.
  
  METHODS:
  We studied 39 hospitalized patients 59.3 ± 3.2 years old (mean ± SEM). In 21 patients with angiographic evidence of significant coronary artery stenosis, revascularization procedures were performed (stenting n = 11 and bypass surgery n = 10). The remaining patients had no significant stenosis and thus served as controls. Prerevascularization measurements included carotido-femoral pulse wave velocity (PWV), radial artery flow-mediated vasodilatation and a complete echocardiographic examination. The same measurements were performed 6 months later. Pharmacological treatment consisted of different cardiovascular drugs and remained substantially unchanged over the 6-month follow-up period.
  
  RESULTS:
  With the exception of an increased left ventricular mass index (LVMI; 130 ± 5.3 versus 105.8 ± 7.2 g/m(2), P < 0.05) and a lower Em/Am (0.6 ± 0.01 and 0.8 ± 0.01 respectively, P < 0.05) observed in patients with coronary stenosis, all other hemodynamic, cardiac and vascular variables were similar in the two groups. Following the 6-month follow-up period, all variables remained substantially unchanged, with the exception, in revascularized patients, of a significant reduction in LVMI (-12%, P < 0.05) and an improvement in Tissue Doppler Imaging-measured diastolic function (Em/Am + 30%, P < 0.05). This was not associated, however, with any significant change in PWV and in flow-mediated vasodilatation.
  
  CONCLUSION:
  Cardiac revascularization has no effect on arterial function, assessed either as arterial stiffness or as flow-mediated vasodilatation. On the contrary, the improvement in coronary blood flow triggers local cardiac changes, namely, a reduction in LVMI and an improvement in diastolic function.
  
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• 18F-FDG PET/CT detects systemic involvement in sarcoidosis.
  Eur J Nucl Med Mol Imaging

  2011 Nov;38(11):2102. doi: 10.1007/s00259-011-1823-z.
  
  Ambrosini Valentina, Fasano Luca, Zompatori Maurizio, Nanni Cristina, Allegri Vincenzo, Nava Stefano, Fanti Stefano
  
  
  
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• Inspiratory muscle training in difficult to wean patients: work it harder, make it better, do it faster, makes us stronger.
  Crit Care

  2011 ;15(2):153. doi: 10.1186/cc10125.
  
  Nava Stefano, Fasano Luca
  
  Abstract
  
  Weaning from prolonged mechanical ventilation is a complex, time-consuming process that involves the loss of force/generating capacity of the inspiratory muscle. In their study 'Inspiratory muscle strength training improves the outcome in failure to wean patients: a randomized trial', Martin and colleagues showed that the use of an inspiratory muscle strength program increased the maximal inspiratory pressure and improved weaning success compared to a control group. The study was performed mainly in post-surgical patients, however, and the results, therefore, may not be generalizable to other subsets of patients, such as those with chronic obstructive pulmonary disease or congestive heart failure. Indeed, the study applied so-called 'strength training' and not 'endurance training', which may be more appropriate in certain circumstances.
  
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• An unusual case of rapid nasal skin breakdown during noninvasive ventilation.
  Intensive Care Med

  2011 Jul;37(7):1220. doi: 10.1007/s00134-011-2199-z.
  
  Anagnostopoulou Georgia, Pacilli Angela Maria Grazia, Nava Stefano
  
  
  
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• Sleep disturbances in patients admitted to a step-down unit after ICU discharge: the role of mechanical ventilation.
  Sleep

  2011 Mar;34(3):355-62.
  
  Fanfulla Francesco, Ceriana Piero, D'Artavilla Lupo Nadia, Trentin Rossella, Frigerio Francesco, Nava Stefano
  
  Abstract
  
  BACKGROUND:
  Severe sleep disruption is a well-documented problem in mechanically ventilated, critically ill patients during their time in the intensive care unit (ICU), but little attention has been paid to the period when these patients become clinically stable and are transferred to a step-down unit (SDU). We monitored the 24-h sleep pattern in 2 groups of patients, one on mechanical ventilation and the other breathing spontaneously, admitted to our SDU to assess the presence of sleep abnormalities and their association with mechanical ventilation.
  
  METHODS:
  Twenty-two patients admitted to an SDU underwent 24-h polysomnography with monitoring of noise and light.
  
  RESULTS:
  One patient did not complete the study. At night, 10 patients showed reduced sleep efficiency, 6 had reduced percentage of REM sleep, and 3 had reduced percentage of slow wave sleep (SWS). Sleep amount and quality did not differ between patients breathing spontaneously and those on mechanical ventilation. Clinical severity (SAPS(II) score) was significantly correlated with daytime total sleep time and efficiency (r = 0.51 and 0.5, P < 0.05, respectively); higher pH was correlated with reduced sleep quantity and quality; and higher PaO(2) was correlated with increased SWS (r = 0.49; P = 0.02).
  
  CONCLUSIONS:
  Patients admitted to an SDU after discharge from an ICU still have a wide range of sleep abnormalities. These abnormalities are mainly associated with a high severity score and alkalosis. Mechanical ventilation does not appear to be a primary cause of sleep impairment.
  
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• Non-invasive ventilation in elderly patients with acute hypercapnic respiratory failure: a randomised controlled trial.
  Age Ageing

  2011 Jul;40(4):444-50. doi: 10.1093/ageing/afr003.
  
  Nava Stefano, Grassi Mario, Fanfulla Francesco, Domenighetti Guido, Carlucci Annalisa, Perren Andreas, Dell'Orso Daniela, Vitacca Michele, Ceriana Piero, Karakurt Zuhal, Clini Enrico
  
  Abstract
  
  OBJECTIVE:
  older patients usually receive less invasive and costly hospital care, even if they meet the criteria for Intensive Care Unit admission or have a 'do not intubate'(DNI) order. The aim of this randomised, controlled trial was to assess the effectiveness of non-invasive mechanical ventilation (NIV) versus the standard medical therapy (SMT) in reducing the need of intubation, improving survival and reducing respiratory distress in very old patients with acute hypercapnic respiratory failure (AHRF).
  
  PARTICIPANTS AND DESIGN:
  eighty-two patients aged >75 years (mean age 81.3 ± 3.5 years) were randomised to receive NIV or SMT.
  
  SETTINGS:
  three respiratory units.
  
  MEASUREMENTS:
  the primary outcome was the rate of meeting the endotracheal intubation (ETI) criteria. Secondary outcomes were the mortality rate, the respiratory rate, dyspnoea score, arterial blood gases.
  
  RESULTS:
  the rate of meeting the ETI criteria was lower in the NIV group compared with the SMT group (7.3 versus 63.4%, respectively; P < 0.001), as was the mortality rate [(odds ratios) OR = 0.40; 95% CI: 0.19-0.83; P = 0.014]. Twenty-two of 41 SMT patients with DNI orders received NIV as a rescue therapy. The mortality rate in this subgroup was comparable with the NIV group and significantly lower compared with patients receiving ETI (OR = 0.60, 95% CI: 0.18-1.92 versus 4.03, 95% CI: 2.35-6.94, respectively; P = 0.009). Arterial blood gases, respiratory rate and dyspnoea improved significantly faster with NIV than with SMT.
  
  CONCLUSIONS:
  compared with SMT, NIV decreased the rate of meeting the ETI criteria and the mortality rate of very old patients with AHRF. NIV should be offered as an alternative to patients considered poor candidates for intubation and those with a DNI order.
  
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• Pilot study of a new device to titrate oxygen flow in hypoxic patients on long-term oxygen therapy.
  Respir Care

  2011 Apr;56(4):429-34. doi: 10.4187/respcare.00983.
  
  Cirio Serena, Nava Stefano
  
  Abstract
  
  BACKGROUND:
  The O(2) Flow Regulator (Dima, Bologna, Italy) is a new automated oxygen regulator that titrates the oxygen flow based on a pulse-oximetry signal to maintain a target S(pO(2)). We tested the device's safety and efficacy.
  
  METHODS:
  We enrolled 18 subjects with chronic lung disease, exercise-induced desaturation, and on long-term oxygen therapy, in a randomized crossover study with 2 constant-work-load 15-min cycling exercise tests, starting with the patient's previously prescribed usual oxygen flow. In one test the oxygen flow was titrated manually by the respiratory therapist, and in the other test the oxygen flow was titrated by the O(2) Flow Regulator, to maintain an S(pO(2)) of 94%. We measured S(pO(2)) throughout each test, the time spent by the respiratory therapist to set the device or to manually regulate the oxygen flow, and the total number of respiratory-therapist titration interventions during the trial.
  
  RESULTS:
  There were no differences in symptoms or heart rate between the exercise tests. Compared to the respiratory-therapist-controlled tests, during the O(2) Flow Regulator tests S(pO(2)) was significantly higher (95 ± 2% vs 93 ± 3%, P = .04), significantly less time was spent below the target S(pO(2)) (171 ± 187 s vs 340 ± 220 s, P < .001), and the O(2) Flow Regulator tests required significantly less respiratory therapist time (5.6 ± 3.7 min vs 2.0 ± 0.1 min, P = .005).
  
  CONCLUSIONS:
  The O(2) Flow Regulator may be a safe and effective alternative to manual oxygen titration during exercise in hypoxic patients. It provided stable S(pO(2)) and avoided desaturations in our subjects.
  
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• Functional recovery following physical training in tracheotomized and chronically ventilated patients.
  Respir Care

  2011 Mar;56(3):306-13. doi: 10.4187/respcare.00956.
  
  Clini Enrico M, Crisafulli Ernesto, Antoni Francesca Degli, Beneventi Claudio, Trianni Ludovico, Costi Stefania, Fabbri Leonardo M, Nava Stefano
  
  Abstract
  
  BACKGROUND:
  Rehabilitation is a non-pharmacologic therapy that can restore health and reverse the patient's disability, but the efficacy of rehabilitation in critically ill patients is not well documented.
  
  METHODS:
  In a prospective cohort study, we assessed whether the degree of change in functional status after comprehensive rehabilitation influenced clinical outcomes in 77 tracheotomized patients (mean ± SD age 75 ± 7 y) admitted for difficult weaning to our regional weaning center. The care plan, including peripheral muscle training, was delivered daily. We recorded admission demographic, anthropometric, and functional characteristics. We measured the change in basic activities of daily living score (?BADL), survival, and weaning success rate as clinical outcomes. We performed the Pearson correlation analysis and linear regression, with ?BADL as the dependent variable, to test the predictive power of the baseline measurements.
  
  RESULTS:
  Sixty-seven patients (87%) survived, and 55 of them (74%) succeeded in weaning during their stay in the weaning center. The mean ± SD ?BADL improvement was 2.5 ± 2.0 points (median 2 points). Baseline performance of the latissimus dorsi predicted ?BADL (? = 0.388, 95% CI 0.111-1,664, P = .03). The probability of remaining ventilator-free (P = .043) and survival (P = .001) differed across the 4 ?BADL categories (0 = no change, 1-2 = least improvement, and > 2 = improvement above median change).
  
  CONCLUSIONS:
  Mortality rate and weaning success differ according to ?BADL following active rehabilitation/training in tracheotomized, ventilated, difficult-to-wean patients. The performance of the latissimus dorsi was the only significant predictor of change.
  
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• Helmet continuous positive airway pressure vs oxygen therapy to improve oxygenation in community-acquired pneumonia: a randomized, controlled trial.
  Chest

  2010 Jul;138(1):114-20. doi: 10.1378/chest.09-2290.
  
  Cosentini Roberto, Brambilla Anna Maria, Aliberti Stefano, Bignamini Angelo, Nava Stefano, Maffei Antonino, Martinotti Renato, Tarsia Paolo, Monzani Valter, Pelosi Paolo
  
  Abstract
  
  OBJECTIVE:
  Our objective was to evaluate the efficacy of noninvasive continuous positive airway pressure (CPAP) delivered by helmet in improving oxygenation in comparison with oxygen therapy in community-acquired pneumonia (CAP).
  
  METHODS:
  This was a multicenter, randomized, controlled trial enrolling patients with CAP admitted to an ED with moderate hypoxemic acute respiratory failure (ARF) (Pa(O(2))/Fi(O(2)) ratio > or = 210 and < or = 285). Patients were randomized to helmet CPAP or standard oxygen therapy (control group). The primary end point was the time to reach a Pa(O(2))/Fi(O(2)) ratio > 315. After reaching this value, patients randomized to CPAP were switched to oxygen, and the proportion of subjects who could maintain a Pa(O(2))/Fi(O(2)) ratio > 315 at 1 h was recorded.
  
  RESULTS:
  Forty-seven patients were recruited: 20 randomized to CPAP and 27 to controls. Patients randomized to CPAP reached the end point in a median of 1.5 h, whereas controls reached the end point in 48 h (P < .001). The proportion of patients who reached the primary end point was 95% (19/20) among the CPAP group and 30% (8/27) among controls (P < .001). One hour after reaching the primary end point, 2/14 patients in the CPAP group maintained a Pa(O(2))/Fi(O(2)) value > 315.
  
  CONCLUSIONS:
  CPAP delivered by helmet rapidly improves oxygenation in patients with CAP suffering from a moderate hypoxemic ARF. This trial represents a proof-of-concept evaluation of the potential usefulness of CPAP in patients with CAP.
  
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• Automated detection of asynchrony in patient-ventilator interaction.
  Annu Int Conf IEEE Eng Med Biol Soc

  2009 ;2009():5324-7. doi: 10.1109/IEMBS.2009.5332684.
  
  Mulqueeny Qestra, Redmond Stephen J, Tassaux Didier, Vignaux Laurence, Jolliet Philippe, Ceriana Piero, Nava Stefano, Schindhelm Klaus, Lovell Nigel H
  
  Abstract
  
  An automated classification algorithm for the detection of expiratory ineffective efforts in patient-ventilator interaction is developed and validated. Using this algorithm, 5624 breaths from 23 patients in a pulmonary ward were examined. The participants (N = 23) underwent both conventional and non-invasive ventilation. Tracings of patient flow, pressure at the airway, and transdiaphragmatic pressure were manually labeled by an expert. Overall accuracy of 94.5% was achieved with sensitivity 58.7% and specificity 98.7%. The results demonstrate the viability of using pattern classification techniques to automatically detect the presence of asynchrony between a patient and their ventilator.
  
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• Molecular epidemiology of KI and WU polyomaviruses in infants with acute respiratory disease and in adult hematopoietic stem cell transplant recipients.
  J Med Virol

  2010 Jan;82(1):153-6. doi: 10.1002/jmv.21659.
  
  Debiaggi Maurizia, Canducci Filippo, Brerra Roberto, Sampaolo Michela, Marinozzi Maria Chiara, Parea Maurizio, Arghittu Milena, Alessandrino Emilio Paolo, Nava Stefano, Nucleo Elisabetta, Romero Egidio, Clementi Massimo
  
  Abstract
  
  Polyomaviruses KI (KIPyV) and WU (WUPyV) were described recently in children with acute respiratory disease. The pathogenic potential of these human viruses has not been determined completely, but a correlation between immunosuppression and virus reactivation has been suggested. In the present study, the association between KI/WUPyV infection and immunosuppression was investigated using sequential nasopharyngeal aspirates from asymptomatic adult hematopoietic stem cell transplant recipients. In parallel, an investigation on the WU/KIPyV prevalence in children with acute respiratory disease was also carried out. Two of the 126 samples obtained from the 31 hematopoietic transplant recipients were positive for KIPyV (1 sample, 0.79%) and WUPyV (1 sample, 0.79%). Both samples were obtained 15 days after allogeneic transplantation and virus persistence was not observed in subsequent samples. In symptomatic children, 7 of the 486 nasopharyngeal aspirates were positive for WUPyV (1.4%) and 1 for KIPyV (0.2%). Single polyomavirus infection was detected in four patients, whereas the remaining patients were co-infected with respiratory syncityal virus (three patients) or adenovirus (one patient). The results suggest that WU/KIPyVs have a limited circulation in Italy and a low pathogenic potential in young children. Brief and asymptomatic infection can occur in hematopoietic transplant recipients.
  
  (c) 2009 Wiley-Liss, Inc.
  
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• Patients' characterization, hospital course and clinical outcomes in five Italian respiratory intensive care units.
  Intensive Care Med

  2010 Jan;36(1):137-42. doi: 10.1007/s00134-009-1658-2.
  
  Polverino Eva, Nava Stefano, Ferrer Miquel, Ceriana Piero, Clini Enrico, Spada Elisa, Zanotti Ercole, Trianni Ludovico, Barbano Luca, Fracchia Claudio, Balbi Bruno, Vitacca Michele
  
  Abstract
  
  BACKGROUND:
  Respiratory intensive care units (RICU) dedicated to weaning could be suitable facilities for clinical management of "post-ICU" patients.
  
  METHODS:
  We retrospectively analyzed the time course of patients' characteristics, clinical outcomes and medical staff utilization in five Italian RICUs by comparing three periods of 5 consecutive years (from 1991 to 2005).
  
  RESULTS:
  A total of 3,106 patients (age 76 +/- 4 years; 72% males) were analyzed. The number of co-morbidities per patient (from 1.8 to 3.0, p = 0.05) and the previous intensive care unit (ICU) stay (from 25 to 32 days, p = 0.002) increased over time. The doctor-to-patient ratio significantly decreased over time (from 1:3 to 1:5, p < 0.01), whereas the physiotherapist-to-patient ratio mildly increased (from 1:6 to 1:4.5, p < 0.05). The overall weaning success rate decreased (from 87 to 66%, p < 0.001), and the discharge destination changed (p < 0.001) over time; fewer patients were discharged to home (from 22 to 10%), and more patients to nursing home (from 3 to 6%), acute hospitals (from 6 to 10%) and rehabilitative units (from 70 to 75%). The mortality rate increased over time (from 9 to 15%). Significant correlations between the doctor-to-patient ratio and the rates of weaning success (r = 0.679, p = 0.005), home discharge (r = 0.722, p = 0.002) and the RICU length of stay (LOS) (r = -0.683, p = 0.005) were observed.
  
  CONCLUSIONS:
  The clinical outcomes of our units worsened over 15 years, likely as consequence of admitting more severely ill patients. The potential further negative influence of reduced medical staff availability on weaning success, home discharge and LOS warrants future prospective investigations.
  
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• Delirium in patients admitted to a step-down unit: analysis of incidence and risk factors.
  J Crit Care

  2010 Mar;25(1):136-43. doi: 10.1016/j.jcrc.2009.07.004.
  
  Ceriana Piero, Fanfulla Francesco, Mazzacane Fulvio, Santoro Carmen, Nava Stefano
  
  Abstract
  
  BACKGROUND:
  Delirium is a rather common complication among patients admitted in intensive care units (ICUs), and rather than a single entity, it can be considered a spectrum of diseases where, besides overt cases, there are also many subsyndromal forms. Although there are many data about ICU delirium, there are few data concerning this complication in patients transferred from the ICU to a step-down unit (SDU) once clinically stable.
  
  OBJECTIVES:
  With the present study, we wanted to assess the incidence of and risk factors for delirium and subsyndromal forms and their impact on clinical outcome in a group of patients transferred from an ICU to an SDU.
  
  METHODS:
  All patients transferred from an ICU to our SDU over a 2-year period were screened for delirium and subsyndromal delirious forms using the Intensive Care Delirium Screening Checklist, a simple tool already validated in the ICU. The following data were also recorded: demographic data, severity score (SAPS II), reason for admission to the SDU, length of stay, death rate, use of sedatives, impact of delirium on weaning from mechanical ventilation (MV).
  
  RESULTS:
  Among the 234 patients, the incidence of delirium and subsyndromal forms was 7.6% and 20%, respectively. Subsyndromal forms diagnosed at admission represented a risk factor for the subsequent development of delirium (odds ratio [OR], P < .0001). A previous episode of brain failure during ICU stay and older age were risks factors for the development of subsyndromal forms, whereas not needing MV was a protective factor. Delirium significantly prolonged the stay in the SDU but did not influence survival and the process of weaning from MV. Overall, the percentage of patients with an abnormal Intensive Care Delirium Screening Checklist score at discharge (5%) was reduced compared with that recorded at admission (18%).
  
  CONCLUSIONS:
  Delirium may still occur after discharge from an ICU in patients who are transferred to an SDU. The strategy of care adopted in the SDU seems to positively affect the recovery from a delirious state. Patients with subsyndromal forms should be promptly recognized and treated because of the risk of developing delirium. Weaning from MV is not hindered by delirium.
  
  Copyright 2010 Elsevier Inc. All rights reserved.
  
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• Non-invasive ventilation in acute respiratory failure.
  Lancet

  2009 Jul;374(9685):250-9. doi: 10.1016/S0140-6736(09)60496-7.
  
  Nava Stefano, Hill Nicholas
  
  Abstract
  
  Non-invasive mechanical ventilation has been increasingly used to avoid or serve as an alternative to intubation. Compared with medical therapy, and in some instances with invasive mechanical ventilation, it improves survival and reduces complications in selected patients with acute respiratory failure. The main indications are exacerbation of chronic obstructive pulmonary disease, cardiogenic pulmonary oedema, pulmonary infiltrates in immunocompromised patients, and weaning of previously intubated stable patients with chronic obstructive pulmonary disease. Furthermore, this technique can be used in postoperative patients or those with neurological diseases, to palliate symptoms in terminally ill patients, or to help with bronchoscopy; however further studies are needed in these situations before it can be regarded as first-line treatment. Non-invasive ventilation implemented as an alternative to intubation should be provided in an intensive care or high-dependency unit. When used to prevent intubation in otherwise stable patients it can be safely administered in an adequately staffed and monitored ward.
  
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• Determinants of weaning success in patients with prolonged mechanical ventilation.
  Crit Care

  2009 ;13(3):R97. doi: 10.1186/cc7927.
  
  Carlucci Annalisa, Ceriana Piero, Prinianakis Georgios, Fanfulla Francesco, Colombo Roberto, Nava Stefano
  
  Abstract
  
  INTRODUCTION:
  Physiological determinants of weaning success and failure are usually studied in ventilator-supported patients, comparing those who failed a trial of spontaneous breathing with those who tolerated such a trial and were successfully extubated. A major limitation of these studies was that the two groups may be not comparable concerning the severity of the underlying disease and the presence of comorbidities. In this physiological study, we assessed the determinants of weaning success in patients acting as their own control, once they are eventually liberated from the ventilator.
  
  METHODS:
  In 30 stable tracheotomised ventilator-dependent patients admitted to a weaning center inside a respiratory intensive care unit, we recorded the breathing pattern, respiratory mechanics, inspiratory muscle function, and tension-time index of diaphragm (TTdi = Pdisw/Pdimax [that is, tidal transdiaphragmatic pressure over maximum transdiaphragmatic pressure] x Ti/Ttot [that is, the inspiratory time over the total breath duration]) at the time of weaning failure (T0). The measurements were repeated in all the patients (T1) either during a successful weaning trial (successful weaning [SW] group, n = 16) or 5 weeks later, in the case of repeated weaning failure (failed weaning [FW] group, n = 14).
  
  RESULTS:
  Compared to T0, in the FW group at T1, significant differences were observed only for a reduction in spontaneous breathing frequency and in TTdi (0.21 +/- 0.122 versus 0.14 +/- 0.054, P = 0.008). SW patients showed a significant increase in Pdimax (34.9 +/- 18.9 cm H2O versus 43.0 +/- 20.0, P = 0.02) and decrease in Pdisw/Pdimax (36.0% +/- 15.8% versus 23.1% +/- 7.9%, P = 0.004).
  
  CONCLUSIONS:
  The recovery of an inadequate inspiratory muscle force could be the major determinant of 'late' weaning success, since this allows the patients to breathe far below the diaphragm fatigue threshold.
  
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• Helmet to deliver noninvasive ventilation: "Handle with care".
  Crit Care Med

  2009 Jun;37(6):2111-3. doi: 10.1097/CCM.0b013e3181a5e6b5.
  
  Nava Stefano, Navalesi Paolo
  
  
  
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• Interfaces and humidification for noninvasive mechanical ventilation.
  Respir Care

  2009 Jan;54(1):71-84.
  
  Nava Stefano, Navalesi Paolo, Gregoretti Cesare
  
  Abstract
  
  During noninvasive ventilation (NIV) for acute respiratory failure, the patient's comfort may be less important than the efficacy of the treatment. However, mask fit and care are needed to prevent skin damage and air leaks that can dramatically reduce patient tolerance and the efficacy of NIV. Choice of interface is a major determinant of NIV success or failure. The number and types of NIV interface has increased and new types are in development. Oronasal mask is the most commonly used interface in acute respiratory failure, followed by nasal mask, helmet, and mouthpiece. There is no perfect NIV interface, and interface choice requires careful evaluation of the patient's characteristics, ventilation modes, and type of acute respiratory failure. Every effort should be made to minimize air leaks, maximize patient comfort, and optimize patient-ventilator interaction. Technological issues to consider when choosing the NIV interface include dead space (dynamic, apparatus, and physiologic), the site and type of exhalation port, and the functioning of the ventilator algorithm with different masks. Heating and humidification may be needed to prevent adverse effects from cool dry gas. Heated humidifier provides better CO(2) clearance and lower work of breathing than does heat-and-moisture exchanger, because heated humidifier adds less dead space.
  
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• Tracheostomy and related host-pathogen interaction are associated with airway inflammation as characterized by tracheal aspirate analysis.
  Respir Med

  2009 Feb;103(2):201-8. doi: 10.1016/j.rmed.2008.09.008.
  
  Pignatti Patrizia, Balestrino Antonella, Herr Christian, Bals Robert, Moretto Dania, Corradi Massimo, Alinovi Rossella, Delmastro Monica, Vogelmeier Claus, Nava Stefano, Moscato Gianna, Balbi Bruno
  
  Abstract
  
  In the last years an increasing number of subjects experienced respiratory failure and underwent tracheostomy. The aim of the present study was to analyze tracheal aspirates from the inflammatory point of view. Samples were collected from 38 consecutive tracheostomized patients: 13 COPD, 6 with neurologic disorders and 19 with other different causes of respiratory failure. We analyzed cells and soluble mediators related to inflammation and/or infection. We also compared results obtained in the tracheal aspirate of COPD patients with the same determination in the sputum of another group of non-tracheostomized COPD patients (n=41). Regardless of the underlying diagnosis, most of the samples were Pseudomonas aeruginosa positive and cells and soluble mediator did not differ. Treatment with steroids was associated with lower amount of total cells, neutrophils and lymphocytes, whereas treatment with antibiotics was not. Tracheal aspirate neutrophils correlated with PaCO(2) values; neutrophils and eosinophils correlated with their percentages in blood. As compared with sputa obtained from another group of culture-positive non-tracheostomized COPDs, tracheal aspirates showed similar cell count, proportions of inflammatory cells, and infection/inflammatory mediators. In conclusion tracheal aspirates presented high amounts of viable cells and soluble mediators independently to the cause of respiratory failure leading to tracheotomy and they represent suitable specimens to study infection/inflammation interactions.
  
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• Comparison between exhaled and bronchoalveolar lavage levels of hydrogen peroxide in patients with diffuse interstitial lung diseases.
  Acta Biomed

  2008 ;79 Suppl 1():73-8.
  
  Corradi Massimo, Pignatti Patrizia, Brunetti Giuseppe, Goldoni Matteo, Caglieri Andrea, Nava Stefano, Moscato Gianna, Balbi Bruno
  
  Abstract
  
  The aim of the present study was to compare hydrogen peroxide (H2O2) levels resulting from oxidative stress in exhaled breath condensate (EBC) and bronchoalveolar lavage (BAL) supernatants of subjects with different diffuse interstitial lung diseases (DILDs). Twenty-one patients who underwent BAL procedure for various DILDs were studied. EBC, which was collected the day before bronchoscopy, was obtained by cooling exhaled breath; BAL was processed for differential cellular count and supernatant was stored. H2O2 in both fluids was measured using a commercial fluorimetric kit with a limit of detection of 0.01 microM. No difference in H2O2 levels in EBC and in BAL was observed [median (range), 0.07 microM (0.01-0.6) and 0.08 microM (0.01-0.8), respectively]. No correlation was observed between BAL and EBC levels. H2O2 in BAL did not correlate with differential cellular count, whereas H2O2 EBC did correlate positively with the percentage of epithelial cells (r = 0.5, p = 0.007) and negatively with the number of macrophages (r = -0.4, p = 0.03). No correlation was observed between H2O2 levels either in EBC or BAL and lung function data. The data show that in DILDs H2O2 can be detected in both EBC and supernatants of BAL and that their relative concentrations are similar but not correlated with each other. The positive correlation between H2O2 levels in EBC and percentage of epithelial cells leads to the speculation that airway epithelia may play a relevant contribution in H2O2 production in the airway lumen.
  
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• The influence of the media on COPD patients' knowledge regarding cardiopulmonary resuscitation.
  Int J Chron Obstruct Pulmon Dis

  2008 ;3(2):295-300.
  
  Nava Stefano, Santoro Carmen, Grassi Mario, Hill Nicholas
  
  Abstract
  
  BACKGROUND:
  The decision whether or not to undertake cardiopulmonary resuscitation (CPR) is a major ethical challenge. Patient preferences may be influenced by multiple factors, including information given by the media.
  
  OBJECTIVES:
  We wanted to assess whether patients' knowledge about CPR survival and outcomes was related to presentation by the media.
  
  METHODS:
  100 consecutive patients with COPD and chronic respiratory failure (CRF) and 100 patients at their first hospital admission for respiratory problems were enrolled. A questionnaire was administered to the patients seeking to ascertain their exposure to health information from the media, and to obtain their opinions on 1) the probability of survival after CPR, 2) the maximal length of time from collapse to CPR that allows a reasonable chance of survival, and 3) long-term outcomes of CPR survivors.
  
  RESULTS:
  The patients overestimated the success rate of CPR (63% of them estimated a hospital survival > 40%), while the estimate of long-term outcome and timing of the procedure were more realistic. Bivariate correlations analysis showed significant correlation between the rate of correct responses and the viewing of educational television programs (p = 0.039), but not medical stories, reading of health-oriented newspapers, use of the internet, age, educational level, and the presence of CRF.
  
  CONCLUSIONS:
  In conclusion, we have shown that both COPD and "newly admitted" patients' estimate of survival after CPR is much higher than reported by the current literature. A correct knowledge of CPR procedures and outcomes is significantly correlated with the exposure to "educational" medical TV programs, but not medical stories, newspapers, or internet sources.
  
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• Noninvasive versus conventional ventilation to treat hypercapnic encephalopathy in chronic obstructive pulmonary disease.
  Intensive Care Med

  2007 Dec;33(12):2101-8.
  
  Scala Raffaele, Nava Stefano, Conti Giorgio, Antonelli Massimo, Naldi Mario, Archinucci Ivano, Coniglio Giovanni, Hill Nicholas S
  
  Abstract
  
  OBJECTIVE:
  We recently reported a high success rate using noninvasive positive pressure ventilation (NPPV) to treat COPD exacerbations with hypercapnic encephalopathy. This study compared the hospital outcomes of NPPV vs. conventional mechanical ventilation (CMV) in COPD exacerbations with moderate to severe hypercapnic encephalopathy, defined by a Kelly score of 3 or higher.
  
  DESIGN AND SETTING:
  A 3-year prospective matched case-control study in a respiratory semi-intensive care unit (RSICU) and intensive care unit (ICU).
  
  PATIENTS AND PARTICIPANTS:
  From 103 consecutive patients the study included 20 undergoing NPPV and 20 CMV, matched for age, simplified acute physiology score II, and baseline arterial blood gases.
  
  MEASUREMENTS AND RESULTS:
  ABG significantly improved in both groups after 2 h. The rate of complications was lower in the NPPV group than in the CMV group due to fewer cases of nosocomial pneumonia and sepsis. In-hospital mortality, 1-year mortality, and tracheostomy rates were similar in the two groups. Fewer patients remained on ventilation after 30 days in NPPV group. The NPPV group showed a shorter duration of ventilation.
  
  CONCLUSIONS:
  In COPD exacerbations with moderate to severe hypercapnic encephalopathy, the use of NPPV performed by an experienced team compared to CMV leads to similar short and long-term survivals with a reduced nosocomial infection rate and duration of ventilation.
  
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• Noninvasive ventilation in acute respiratory failure.
  Crit Care Med

  2007 Oct;35(10):2402-7.
  
  Hill Nicholas S, Brennan John, Garpestad Erik, Nava Stefano
  
  Abstract
  
  BACKGROUND:
  Noninvasive ventilation has assumed an important role in the management of respiratory failure in critical care units, but it must be used selectively depending on the patient's diagnosis and clinical characteristics.
  
  DATA:
  We review the strong evidence supporting the use of noninvasive ventilation for acute respiratory failure to prevent intubation in patients with chronic obstructive pulmonary disease exacerbations or acute cardiogenic pulmonary edema, and in immunocompromised patients, as well as to facilitate extubation in patients with chronic obstructive pulmonary disease who require initial intubation. Weaker evidence supports consideration of noninvasive ventilation for chronic obstructive pulmonary disease patients with postoperative or postextubation respiratory failure; patients with acute respiratory failure due to asthma exacerbations, pneumonia, acute lung injury, or acute respiratory distress syndrome; during bronchoscopy; or as a means of preoxygenation before intubation in critically ill patients with severe hypoxemia.
  
  CONCLUSION:
  Noninvasive ventilation has assumed an important role in managing patients with acute respiratory failure. Patients should be monitored closely for signs of noninvasive ventilation failure and promptly intubated before a crisis develops. The application of noninvasive ventilation by a trained and experienced intensive care unit team, with careful patient selection, should optimize patient outcomes.
  
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• Survey of sedation practices during noninvasive positive-pressure ventilation to treat acute respiratory failure.
  Crit Care Med

  2007 Oct;35(10):2298-302.
  
  Devlin John W, Nava Stefano, Fong Jeffrey J, Bahhady Imad, Hill Nicholas S
  
  Abstract
  
  OBJECTIVES:
  Noninvasive positive-pressure ventilation (NPPV) is increasingly used in patients with acute respiratory failure, but few data exist regarding current sedation practices during NPPV. We sought to characterize current practices and attitudes regarding sedation during NPPV.
  
  DESIGN:
  Cross-sectional Web-based survey.
  
  SETTING:
  Medical institutions.
  
  PARTICIPANTS:
  Physician members of the American College of Chest Physician's Critical Care Network (n = 2,656) and the European Respiratory Society's Assembly of Critical Care (n = 339).
  
  INTERVENTIONS:
  Survey.
  
  MEASUREMENTS AND MAIN RESULTS:
  Of the 790 of 2,985 (27%) of physicians who responded, 15%, 6%, and 28% never used sedation, analgesia, or hand restraints any of the time for NPPV patients, respectively, and the large majority reported using these interventions in < or =25% of patients. Sedation, analgesia, and hand restraints were more commonly used by North Americans than Europeans (41% vs. 24% for sedation, 48% vs. 35% for analgesia, and 27% vs. 16% for hand restraints, all p < .01) and critical care vs. noncritical care physicians (42% vs. 24% for sedation and 50% vs. 34% for analgesia, all p < .01). A benzodiazepine alone was the most preferred (33%), followed by an opioid alone (29%). Europeans were less likely to use a benzodiazepine alone (25% vs. 39%, p < .001) but more likely to use an opioid alone (37% vs. 26%, p < .009). Sedation was usually administered as an intermittent intravenous bolus, outside of a protocol, and was assessed by nurses using clinical end points rather than a sedation scale.
  
  CONCLUSIONS:
  Most physicians infrequently use sedation and analgesic therapy for NPPV to treat acute respiratory failure, but practices vary widely within and between specialties and geographic regions.
  
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• Automatic detection of ineffective triggering and double triggering during mechanical ventilation.
  Intensive Care Med

  2007 Nov;33(11):2014-8.
  
  Mulqueeny Qestra, Ceriana Piero, Carlucci Annalisa, Fanfulla Francesco, Delmastro Monica, Nava Stefano
  
  Abstract
  
  OBJECTIVE:
  Imperfect patient-ventilator interaction is common during assisted ventilation, and the detection of clinically relevant mismatching requires visual monitoring of the ventilator screen. We have assessed the feasibility, sensitivity and specificity of an algorithm embedded in a ventilator system that is able to automatically detect the occurrence of ineffective triggering and double triggering in real time.
  
  DESIGN:
  Prospective study.
  
  SETTING:
  Respiratory intensive care unit.
  
  METHODS:
  Twenty patients undergoing pressure-support ventilation, either non-invasively (NIV, n=10) or conventionally ventilated (n=10), were studied.
  
  MEASUREMENTS:
  The detection of ineffective triggering and double triggering from the algorithm was compared by two operators with the "real" occurrence of the phenomena as assessed using the transdiaphragmatic pressure (Pdi).
  
  RESULTS:
  Seven of the 20 patients exhibited gross mismatching, while in the remaining patients patient-ventilator mismatching was artificially induced using a pressure control, with a low respiratory rate. Ineffective triggering and double triggering were identified by the operators in 507 and 19 of the 3343 analyzed breaths, respectively. False positives were significantly more frequent in the NIV group than with conventional ventilation. The algorithm had an overall sensitivity of 91% and specificity of 97%. Specificity was statistically higher in the conventional ventilated group than with NIV (99% vs. 95%, p<0.05).
  
  CONCLUSIONS:
  We have demonstrated the feasibility and efficacy of a new algorithm to detect the occurrence of impaired patient-ventilator interaction during mechanical ventilation in real time. This software may help the clinician in the identification of this problem, which has been shown to have important clinical consequences.
  
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• Effect of sleep on patient/ventilator asynchrony in patients undergoing chronic non-invasive mechanical ventilation.
  Respir Med

  2007 Aug;101(8):1702-7.
  
  Fanfulla Francesco, Taurino Anna Eugenia, Lupo Nadia D'Artavilla, Trentin Rossella, D'Ambrosio Carolyn, Nava Stefano
  
  Abstract
  
  BACKGROUND:
  Patients who require home non-invasive ventilation (NIV) during sleep normally have the ventilation settings adjusted empirically during daytime wakefulness. However, patient-ventilator asynchrony may occur during sleep. To detect the incidence of ineffective efforts (IE) during the sleep compared to wakefulness, we studied 48 patients already enrolled in a long-term home NIV programme.
  
  METHODS:
  We evaluated arterial blood gases, breathing pattern during spontaneous breathing (SB) and ventilation during wakefulness. In addition, we assessed the breathing pattern and oxygen gas exchange during night-time NIV.
  
  RESULTS:
  Daytime NIV significantly improved blood gases compared to SB (PaO2 NIV 10.2 +/- 1.95 kPa vs PaO2 SB 8 +/- 1.37, p < 0.001; PaCO2 NIV 5.75 +/- 1.08 kPa, vs PaCO2 SB 6.5 +/- 1.25, p < 0.001). The IE index was higher during sleep compared to wakefulness (48 +/- 39.5 events/h versus 0 +/- 0). The IE index was correlated with the time spent with SaO2 < 90% (r = 0.39, p < 0.01), but not with ventilator parameters, underlying disease, ventilation mode or type of mask. Eight patients had an IE index >100 events/h; these patients had a faster respiratory rate, required a higher level of inspiratory assistance and had poor gas exchange during sleep.
  
  CONCLUSIONS:
  We conclude that IE to breath are common during nocturnal NIV and that they may be associated with desaturations even in patients who are considered compliant and effectively treated.
  
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• Year in Review in Intensive Care Medicine, 2006. III. Circulation, ethics, cancer, outcome, education, nutrition, and pediatric and neonatal critical care.
  Intensive Care Med

  2007 Mar;33(3):414-22.
  
  Andrews Peter, Azoulay Elie, Antonelli Massimo, Brochard Laurent, Brun-Buisson Christian, De Backer Daniel, Dobb Geoffrey, Fagon Jean-Yves, Gerlach Herwig, Groeneveld Johan, Macrae Duncan, Mancebo Jordi, Metnitz Philipp, Nava Stefano, Pugin Jerôme, Pinsky Michael, Radermacher Peter, Richard Christian
  
  
  
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• Preoperative inspiratory muscle training and postoperative complications.
  JAMA

  2007 Feb;297(7):697; author reply 698-9.
  
  Nava Stefano
  
  
  
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• Year in review in Intensive Care Medicine, 2006. II. Infections and sepsis, haemodynamics, elderly, invasive and noninvasive mechanical ventilation, weaning, ARDS.
  Intensive Care Med

  2007 Feb;33(2):214-29.
  
  Andrews Peter, Azoulay Elie, Antonelli Massimo, Brochard Laurent, Brun-Buisson Christian, De Backer Daniel, Dobb Geoffrey, Fagon Jean-Yves, Gerlach Herwig, Groeneveld Johan, Macrae Duncan, Mancebo Jordi, Metnitz Philipp, Nava Stefano, Pugin Jerôme, Pinsky Michael, Radermacher Peter, Richard Christian
  
  
  
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• Year in review in Intensive Care Medicine, 2006. I. Experimental studies. Clinical studies: brain injury, renal failure and endocrinology.
  Intensive Care Med

  2007 Jan;33(1):49-57.
  
  Andrews Peter, Azoulay Elie, Antonelli Massimo, Brochard Laurent, Brun-Buisson Christian, De Backer Daniel, Dobb Geoffrey, Fagon Jean-Yves, Gerlach Herwig, Groeneveld Johan, Macrae Duncan, Mancebo Jordi, Metnitz Philipp, Nava Stefano, Pugin Jerôme, Pinsky Michael, Radermacher Peter, Richard Christian
  
  
  
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• Risk factors for extubation failure in patients following a successful spontaneous breathing trial.
  Chest

  2006 Dec;130(6):1664-71.
  
  Frutos-Vivar Fernando, Ferguson Niall D, Esteban Andrés, Epstein Scott K, Arabi Yaseen, Apezteguía Carlos, González Marco, Hill Nicholas S, Nava Stefano, D'Empaire Gabriel, Anzueto Antonio
  
  Abstract
  
  BACKGROUND:
  To assess the factors associated with reintubation in patients who had successfully passed a spontaneous breathing trial.
  
  METHODS:
  We used logistic regression and recursive partitioning analyses of prospectively collected clinical data from adults admitted to ICUs of 37 hospitals in eight countries, who had undergone invasive mechanical ventilation for > 48 h and were deemed ready for extubation.
  
  RESULTS:
  Extubation failure occurred in 121 of the 900 patients (13.4%). The logistic regression analysis identified the following associations with reintubation: rapid shallow breathing index (RSBI) [odds ratio (OR), 1.009 per unit; 95% confidence interval (CI), 1.003 to 1.015]; positive fluid balance (OR, 1.70; 95% CI, 1.15 to 2.53); and pneumonia as the reason for initiating mechanical ventilation (OR, 1.77; 95% CI, 1.10 to 2.84). The recursive partitioning analysis allowed the separation of patients into different risk groups for extubation failure: (1) RSBI of > 57 breaths/L/min and positive fluid balance (OR, 3.0; 95% CI, 1.8 to 4.8); (2) RSBI of < 57 breaths/L/min and pneumonia as reason for mechanical ventilation (OR, 2.0; 95% CI, 1.1 to 3.6); (3) RSBI of > 57 breaths/L/min and negative fluid balance (OR, 1.4; 95% CI, 0.8 to 2.5); and (4) RSBI of < 57 breaths/L/min (OR, 1 [reference value]).
  
  CONCLUSIONS:
  Among routinely measured clinical variables, RSBI, positive fluid balance 24 h prior to extubation, and pneumonia at the initiation of ventilation were the best predictors of extubation failure. However, the combined predictive ability of these variables was weak.
  
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• Non-invasive ventilation in chronic obstructive pulmonary disease patients: helmet versus facial mask.
  Intensive Care Med

  2007 Jan;33(1):74-81.
  
  Navalesi Paolo, Costa Roberta, Ceriana Piero, Carlucci Annalisa, Prinianakis George, Antonelli Massimo, Conti Giorgio, Nava Stefano
  
  Abstract
  
  RATIONALE:
  The helmet is a new interface with the potential of increasing the success rate of non-invasive ventilation by improving tolerance.
  
  OBJECTIVES:
  To perform a physiological comparison between the helmet and the conventional facial mask in delivering non-invasive ventilation in hypercapnic patients with chronic obstructive pulmonary disease.
  
  METHODS:
  Prospective, controlled, randomized study with cross-over design. In 10 patients we evaluated gas exchange, inspiratory effort, patient-ventilator synchrony and patient tolerance after 30 min of non-invasive ventilation delivered either by helmet or facial mask; both trials were preceded by periods of spontaneous unassisted breathing.
  
  MEASUREMENTS:
  Arterial blood gases, inspiratory effort, duration of diaphragm contraction and ventilator assistance, effort-to-support delays (at the beginning and at the end of inspiration), number of ineffective efforts, and patient comfort.
  
  MAIN RESULTS:
  Non-invasive ventilation improved gas exchange (p<0.05) and inspiratory effort (p<0.01) with both interfaces. The helmet, however, was less efficient than the mask in reducing inspiratory effort (p<0.05) and worsened the patient-ventilator synchrony, as indicated by the longer delays to trigger on (p<0.05) and cycle off (p<0.05) the mechanical assistance and by the number of ineffective efforts (p<0.005). Patient comfort was no different with the two interfaces.
  
  CONCLUSIONS:
  Helmet and facial mask were equally tolerated and both were effective in ameliorating gas exchange and decreasing inspiratory effort. The helmet, however, was less efficient in decreasing inspiratory effort and worsened the patient-ventilator interaction.
  
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• Physiological responses during a T-piece weaning trial with a deflated tube.
  Intensive Care Med

  2006 Sep;32(9):1399-403.
  
  Ceriana Piero, Carlucci Annalisa, Navalesi Paolo, Prinianakis Georgios, Fanfulla Francesco, Delmastro Monica, Nava Stefano
  
  Abstract
  
  RATIONALE:
  T-piece trials and spontaneous breathing trials through the tracheostomy tube are often used as weaning techniques. They are usually performed with the cuff inflated, which may increase the inspiratory load and/or influence the tidal volume generated by the patient. We assessed diaphragmatic effort during T-piece trials with or without cuff inflation.
  
  SETTINGS:
  Respiratory intensive care unit
  
  METHODS:
  We measured breathing pattern, transdiaphragmatic pressure (Pdi), the pressure-time product of the diaphragm, per minute (PTPdi/min) and per breath (PTPdi/b), and lung mechanics (lung compliance and resistance) in 13 tracheotomized patients ready for a weaning trial. V(T) was recorded with respiratory inductive plethysmography (RIP-V(T)) or pneumotachography PT-V(T)). Patients completed two T-piece trials of 30[Symbol: see text]min each with or without the cuff inflated.
  
  RESULTS:
  RIP-V(T) and PT-V(T) values were similar with the cuff inflated, but PT-V(T) significantly underestimated RIP-V(T) when the cuff was deflated, and therefore the RIP-V(T) was chosen as the reference method. The RIP-V(T) was significantly greater and the Pdi and PTPdi/min significantly lower when the cuff was deflated than when it was inflated. The efficiency of the diaphragm, calculated by the ratio of PTPdi/b over RIP-V(T), was also improved, while no changes were observed in lung mechanics.
  
  CONCLUSIONS:
  Diaphragmatic effort is significantly lower during a T-piece trial with a deflated cuff than when the cuff is inflated, while RIP-V(T) is higher, so that the diaphragm's efficiency in generating tidal volume is also improved.
  
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• Noninvasive ventilation and dyspnea in palliative medicine.
  Chest

  2006 May;129(5):1391-2.
  
  Nava Stefano, Cuomo Annamaria, Maugeri Fondazione S
  
  
  
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• Physiological response to intrapulmonary percussive ventilation in stable COPD patients.
  Respir Med

  2006 Sep;100(9):1526-33.
  
  Nava Stefano, Barbarito Nicola, Piaggi Giancarlo, De Mattia Elisa, Cirio Serena
  
  Abstract
  
  Intrapulmonary percussive ventilation (IPV) is a ventilatory technique that delivers bursts of high-flow respiratory gas into the lung at high rates, intended for treating acute respiratory failure and for mobilization of secretions. We performed a study, aimed at assessing the physiological response to IPV, on patients' breathing pattern, inspiratory effort, lung mechanics and tolerance to ventilation. Ten COPD patients underwent randomized trials of IPV through a face mask at different pressure/frequency combinations (1.2 bar/250 cycles/min; 1.8/250; 1.2/350; 1.8/350), separated by return to baseline (SB), using the IMP2 ventilator. In 5 patients we have also compared the physiological changes of IPV with those obtained during pressure support ventilation (PSV). Minute ventilation did not vary among the trials, but tidal volumes (VT) were significantly greater during 1.2/250, 1.2/350 and 1.8/350 compared to SB. The pressure time product of the diaphragm per minute (PTPdi/min) estimate of the diaphragm oxygen expenditure was also significantly reduced during 1.2/250 and 1.8/250 (209 cmH2O x s/min for SB vs. 143 and 125 for 1.2/250 and 1.8/250, respectively P < 0.05), as well as dynamic intrinsic end-expiratory pressure (PEEPi,dyn). Similar reduction in PTPdi/min were obtained also during PSV. Tolerance to ventilation and oxygen saturation were satisfactory and did not change during the different trials. In 5 normal subjects a prolonged apnea trial lasting > 2 min was also performed, without any significant decrease in SaO2 or subjective discomfort. In conclusion, IPV was able to guarantee an adequate ventilation, while inducing a significant unloading of the diaphragm during the "low-frequency" trials.
  
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• Year in review in intensive care medicine, 2005. III. Nutrition, pediatric and neonatal critical care, and experimental.
  Intensive Care Med

  2006 Apr;32(4):490-500.
  
  Andrews Peter, Azoulay Elie, Antonelli Massimo, Brochard Laurent, Brun-Buisson Christian, Dobb Geoffrey, Fagon Jean-Yves, Gerlach Herwig, Groeneveld Johan, Mancebo Jordi, Metnitz Philipp, Nava Stefano, Pugin Jerome, Pinsky Michael, Radermacher Peter, Richard Christian, Tasker Robert
  
  
  
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• Year in review in intensive care medicine, 2005. II. Infection and sepsis, ventilator-associated pneumonia, ethics, haematology and haemostasis, ICU organisation and scoring, brain injury.
  Intensive Care Med

  2006 Mar;32(3):380-90.
  
  Andrews Peter, Azoulay Elie, Antonelli Massimo, Brochard Laurent, Brun-Buisson Christian, Dobb Geoffrey, Fagon Jean-Yves, Gerlach Herwig, Groeneveld Johan, Mancebo Jordi, Metnitz Philipp, Nava Stefano, Pugin Jerome, Pinsky Michael, Radermacher Peter, Richard Christian, Tasker Robert
  
  
  
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• Time of non-invasive ventilation.
  Intensive Care Med

  2006 Mar;32(3):361-70.
  
  Nava Stefano, Navalesi Paolo, Conti Giorgio
  
  Abstract
  
  Non-invasive ventilation (NIV) is a safe, versatile and effective technique that can avert side effects and complications associated with endotracheal intubation. The success of NIV relies on several factors, including the type and severity of acute respiratory failure, the underlying disease, the location of treatment, and the experience of the team. The time factor is also important. NIV is primarily used to avert the need for endotracheal intubation in patients with early-stage acute respiratory failure and post-extubation respiratory failure. It can also be used as an alternative to invasive ventilation at a more advanced stage of acute respiratory failure or to facilitate the process of weaning from mechanical ventilation. NIV has been used to prevent development of acute respiratory failure or post-extubation respiratory failure. The number of days of NIV and hours of daily use differ, depending on the severity and course of the acute respiratory failure and the timing of application. In this review article, we analyse, compare and discuss the results of studies in which NIV was applied at various times during the evolution of acute respiratory failure.
  
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• Year in review in intensive care medicine. 2005. I. Acute respiratory failure and acute lung injury, ventilation, hemodynamics, education, renal failure.
  Intensive Care Med

  2006 Feb;32(2):207-216. doi: 10.1007/s00134-005-0027-z.
  
  Andrews Peter, Azoulay Elie, Antonelli Massimo, Brochard Laurent, Brun-Buisson Christian, de Backer Daniel, Dobb Geoffrey, Fagon Jean-Yves, Gerlach Herwig, Groeneveld Johan, Mancebo Jordi, Metnitz Philipp, Nava Stefano, Pugin Jerome, Pinsky Michael, Radermacher Peter, Richard Christian, Tasker Robert
  
  
  
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• Noninvasive ventilation to prevent respiratory failure after extubation in high-risk patients.
  Crit Care Med

  2005 Nov;33(11):2465-70.
  
  Nava Stefano, Gregoretti Cesare, Fanfulla Francesco, Squadrone Enzo, Grassi Mario, Carlucci Annalisa, Beltrame Fabio, Navalesi Paolo
  
  Abstract
  
  OBJECTIVE:
  Compared with standard medical therapy (SMT), noninvasive ventilation (NIV) does not reduce the need for reintubation in unselected patients who develop respiratory failure after extubation. The goal of this study was to assess whether early application of NIV, immediately after extubation, is effective in preventing postextubation respiratory failure in an at-risk population.
  
  DESIGN:
  Multiple-center, randomized controlled study.
  
  SETTING:
  Multiple hospitals.
  
  PATIENTS:
  Ninety-seven consecutive patients with similar baseline characteristics, requiring >48 hrs of mechanical ventilation and considered at risk of developing postextubation respiratory failure (i.e., patients who had hypercapnia, congestive heart failure, ineffective cough and excessive tracheobronchial secretions, more than one failure of a weaning trial, more than one comorbid condition, and upper airway obstruction).
  
  INTERVENTIONS:
  After a successful weaning trial, the patients were randomized to receive NIV for > or = 8 hrs a day in the first 48 hrs or SMT. Primary outcome was the need for reintubation according to standardized criteria. Secondary outcomes were intensive care unit and hospital mortality, as well as time spent in the intensive care unit and in hospital.
  
  MEASUREMENTS AND MAIN RESULTS:
  Compared with the SMT group, the NIV group had a lower rate of reintubation (four of 48 vs. 12 of 49; p = .027). The need for reintubation was associated with a higher risk of mortality (p < .01). The use of NIV resulted in a reduction of risk of intensive care unit mortality (-10%, p < .01), mediated by the reduction for the need of reintubation.
  
  CONCLUSIONS:
  NIV was more effective than SMT in preventing postextubation respiratory failure in a population considered at risk of developing this complication.
  
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• Role of the chemokine receptors CXCR3 and CCR4 in human pulmonary fibrosis.
  Am J Respir Crit Care Med

  2006 Feb;173(3):310-7.
  
  Pignatti Patrizia, Brunetti Giuseppe, Moretto Dania, Yacoub Mona-Rita, Fiori Marco, Balbi Bruno, Balestrino Antonella, Cervio Gabriella, Nava Stefano, Moscato Gianna
  
  Abstract
  
  RATIONALE:
  The chemokine receptors CXCR3 and CCR4 have recently been described as playing a pivotal role in the mouse model of bleomycin-induced fibrosis.
  
  OBJECTIVES:
  To evaluate the role of these receptors in human idiopathic pulmonary fibrosis (IPF).
  
  METHODS:
  We studied 57 patients: 18 with IPF, 17 with non-IPF (nIPF), 12 with sarcoidosis, and 10 healthy control subjects.
  
  MEASUREMENTS:
  We evaluated the expression of CXCR3 and CCR4 in blood and bronchoalveolar lavage (BAL) T lymphocytes by flow cytometry and the chemokine CXCL10, CXCL11 and CCL17 BAL concentration by singular immunoassay.
  
  MAIN RESULTS:
  Patients with IPF had a significantly lower CXCR3 and a higher CCR4 expression on BAL CD4 T cells compared with the other groups. Among patients with IPF, those treated with corticosteroids exhibited higher CXCR3 and lower CCR4 expression compared with untreated patients. CXCR3 expression correlated with BAL lymphocytes and CCR4 with BAL neutrophils and eosinophils. CXCL10 levels correlated with the expression of CXCR3 on BAL CD4 cells. CXCL11 was undetectable in almost all patients, whereas CCL17 was primarily detectable in patients with IPF. The percentage of BAL CCR4CD4 cells negatively correlated with DL(CO). The changes in the total lung capacity, VC, and of the alveolar-arterial PO2 gradient in patients with IPF and those with nIPF 6 to 12 mo after the first evaluation were associated with CD4CXCR3 percentage on BAL cells.
  
  CONCLUSIONS:
  We found an imbalance in CXCR3/CCR4 expression on BAL CD4 lymphocytes and reduced CXCL10 BAL levels in patients with IPF, suggesting a pivotal role of these molecules in IPF.
  
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• Noninvasive positive pressure ventilation in patients with acute exacerbations of COPD and varying levels of consciousness.
  Chest

  2005 Sep;128(3):1657-66.
  
  Scala Raffaele, Naldi Mario, Archinucci Ivano, Coniglio Giovanni, Nava Stefano
  
  Abstract
  
  STUDY OBJECTIVES:
  A severely altered level of consciousness (ALC) has been considered a contraindication to noninvasive positive pressure ventilation (NPPV). We compared the clinical outcome of patients with acute respiratory failure (ARF) due to COPD exacerbations and different degrees of ALC.
  
  DESIGN:
  A 5-year case-control study with a prospective data collection.
  
  SETTING:
  Respiratory Monitoring Unit.
  
  PATIENTS:
  Eighty of 153 consecutive COPD patients requiring NPPV for ARF were divided into four groups, which were carefully matched for the main physiologic variables, according to the level of consciousness assessed with the Kelly-Matthay Score, in which 1 is normal (control subjects) and 6 is severely impaired.
  
  MEASUREMENT AND RESULTS:
  Changes from baseline in arterial blood gas (ABG) levels and Kelly score, the rate and causes of NPPV failure, the rate of nosocomial pneumonia, and the 90-day mortality rate were compared. NPPV significantly improved ABG levels and Kelly score in all groups after 1 to 2 h. NPPV failure (Kelly score 1 = 15%; Kelly score 2 = 25%; Kelly score 3 = 30%; Kelly score > 3 = 45%) and 90-day mortality rate (Kelly score 1 = 20%; Kelly score 2 = 35%; Kelly score 3 = 35%; Kelly score > 3 = 50%) significantly increased with the worsening of the level of consciousness. Using a multivariate analysis, the acute nonrespiratory component of the acute physiology and chronic health evaluation (APACHE) III score, and baseline pH independently predicted baseline Kelly score. After 1 to 2 h of NPPV, changes in the Kelly score were associated with those in pH. No correlation was found with Pa(CO2).
  
  CONCLUSIONS:
  This study confirms that NPPV may be successfully applied to patients experiencing COPD exacerbations with milder ALCs, whereas the rate of failure in patients with severely ALCs (ie, Kelly score > 3) is higher, even though better than expected, so that an initial and cautious attempt with NPPV may be performed even in this latter group. Changes in the level of consciousness induced by NPPV are not correlated with those in Pa(CO2).
  
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• Effects of different ventilator settings on sleep and inspiratory effort in patients with neuromuscular disease.
  Am J Respir Crit Care Med

  2005 Sep;172(5):619-24.
  
  Fanfulla Francesco, Delmastro Monica, Berardinelli Angela, Lupo Nadia D'Artavilla, Nava Stefano
  
  Abstract
  
  Patients with neuromuscular disease (NMD) who require long-term ventilation normally have the ventilation set using empirical daytime parameters. We evaluated arterial blood gases (ABG), breathing pattern, respiratory muscle function, and sleep architecture during ventilation with two noninvasive Pressure Support Ventilation (nPSV) settings in nine patients with NMD. The two settings were randomly applied: the usual (US), with the nPSV setting titrated on simple clinical parameters, and the physiological (PHYS), tailored to the patient's respiratory effort. During wakefulness, nPSV significantly improved ABG and minute ventilation and reduced the diaphragmatic pressure-time product (PTPdi/breath), independently of the type of setting (PTPdi/breath spontaneous breathing 5.7 +/- 2.4, US 3.2 +/- 2, PHYS 3.6 +/- 1.6 cm H2O . seconds(-1), p < 0.001). However, during sleep, PHY nPSV resulted in a significant improvement of gas exchange, sleep efficiency (71.7% +/- 14 US vs. 80.6% +/- 8.3 PHYS, p < 0.01) and % of REM sleep (9.1% +/- 7 US vs. 17.3% +/- 5.4 PHYS, p < 0.01). This improvement was significantly correlated with the reduction in ineffective efforts. In NMD, nPSV is effective in improving daytime ABG and in unloading inspiratory muscles independently of whether it is set on the basis of the patient's comfort or the patient's respiratory mechanics. However, PHYS was associated with better sleep architecture and nighttime gas exchange.
  
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• Patient-ventilator interaction during noninvasive positive pressure ventilation.
  Respir Care Clin N Am

  2005 Jun;11(2):281-93.
  
  Nava Stefano, Ceriana Piero
  
  Abstract
  
  The interaction between the patient and the ventilator is complex,especially in a "semi-open" system as for noninvasive ventilation(NIV). Air leaks around the mask are likely to occur, and they affect patient-ventilator synchrony. Several variables may be responsible for the mismatch between the start of the neural output and that of ventilatory aid during NIV. The most common mode of ventilation is pressure support ventilation (PSV), which may result in a number of inspiratory efforts not being followed by ventilator aid. New modes of ventilation, such as proportional assist ventilation, maybe useful in improving patient tolerance to ventilation without affecting clinical outcome. The ventilatory settings are important during PSV to determine the synchrony. The inspiratory trigger function may be influenced by the amount of leaks, whereas a better synchrony may be achieved if the termination of the inspiratory phase is time cycled instead of flow cycled. A high pressurization rate results in poor compliance. Care should be paid in the choice of the interfaces because leaks in the system are associated with a substantial breath-to-breath inspiratory variation independent from the patient effort. Last, NIV should be delivered with turbine- or piston-based ventilators that are able to compensate for air leaks. With respect to the problem of sedation, we point out the importance of optimizing the environmental conditions, avoiding excessive light and noise, assuring patient comfort, and providing reassurance. When sedation is needed, we suggest the use of low doses of analgesics and neuroleptic agents in selected cases.
  
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• Identification of a novel alpha1-antitrypsin null variant (Q0Cairo).
  Diagn Mol Pathol

  2005 Jun;14(2):121-4.
  
  Zorzetto Michele, Ferrarotti Ilaria, Campo Ilaria, Balestrino Antonella, Nava Stefano, Gorrini Marina, Scabini Roberta, Mazzola Paola, Luisetti Maurizio
  
  Abstract
  
  Alpha1-antitrypsin deficiency (AATD) is a common hereditary disorder associated with high risk of developing pulmonary emphysema early in life and, to a lesser extent, chronic liver disease and cirrhosis. Among Northern Europeans and Northern Americans, more than 95% of individuals with emphysema associated with AATD carry the most frequent AAT deficient gene variants, PI*Z and PI*S. Rare AAT deficient variants account for 2-4% of AATD individuals. We extend the sequence data on AAT by characterizing a novel Null allele detected in 3 subjects: a carrier belonging to an Italian/Egyptian family and 2 members of a family originating from Southern Italy. The mutation raised on a M1 (Ala213) base allele and it is characterized by an A-->T transversion at exon III, nt 218, codon 259 (AAA-->TAA) (GeneBank accession number AY 256958). The transversion results in a premature stop codon (Lys259AAA-->Stop259TAA). The proposed nomenclature of Q0cairo is from the birthplace of the father of first recognized subject. Serum levels and isoelectric focusing of AAT were consistent with the presence of the Null variant.
  
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• Mask ventilation and cardiogenic pulmonary edema: "another brick in the wall".
  Intensive Care Med

  2005 Jun;31(6):757-9.
  
  Mehta Sangeeta, Nava Stefano
  
  
  
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• Year in review in intensive care medicine, 2004. III. Outcome, ICU organisation, scoring, quality of life, ethics, psychological problems and communication in the ICU, immunity and hemodynamics during sepsis, pediatric and neonatal critical care, experimental studies.
  Intensive Care Med

  2005 Mar;31(3):356-72.
  
  Andrews Peter, Azoulay Elie, Antonelli Massimo, Brochard Laurent, Brun-Buisson Christian, Dobb Geoffrey, Fagon Jean-Yves, Gerlach Herwig, Groeneveld Johan, Mancebo Jordi, Metnitz Philipp, Nava Stefano, Pugin Jerome, Pinsky Michael, Radermacher Peter, Richard Christian, Tasker Robert, Vallet Benoit
  
  
  
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• Getting dark, too dark to see.
  Crit Care Med

  2005 Feb;33(2):468-9; author reply 469-70.
  
  Nava Stefano
  
  
  
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• Year in review in intensive care medicine, 2004. II. Brain injury, hemodynamic monitoring and treatment, pulmonary embolism, gastrointestinal tract, and renal failure.
  Intensive Care Med

  2005 Feb;31(2):177-88.
  
  Andrews Peter, Azoulay Elie, Antonelli Massimo, Brochard Laurent, Brun-Buisson Christian, Dobb Geoffrey, Fagon Jean-Yves, Gerlach Herwig, Groeneveld Johan, Mancebo Jordi, Metnitz Philipp, Nava Stefano, Pugin Jerome, Pinsky Michael, Radermacher Peter, Richard Christian, Tasker Robert, Vallet Benoit
  
  
  
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• Year in review in intensive care medicine, 2004. I. Respiratory failure, infection, and sepsis.
  Intensive Care Med

  2005 Jan;31(1):28-40.
  
  Andrews Peter, Azoulay Elie, Antonelli Massimo, Brochard Laurent, Brun-Buisson Christian, Dobb Geoffrey, Fagon Jean-Yves, Gerlach Herwig, Groeneveld Johan, Mancebo Jordi, Metnitz Philipp, Nava Stefano, Pugin Jerome, Pinsky Michael, Radermacher Peter, Richard Christian, Tasker Robert, Vallet Benoit
  
  
  
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• Noninvasive mechanical ventilation as a palliative treatment of acute respiratory failure in patients with end-stage solid cancer.
  Palliat Med

  2004 Oct;18(7):602-10.
  
  Cuomo Annamaria, Delmastro Monica, Ceriana Piero, Nava Stefano, Conti Giorgio, Antonelli Massimo, Iacobone Emanuele
  
  Abstract
  
  Noninvasive ventilation (NIV) is widely used in the treatment of acute respiratory failure (ARF), but not in patients with end-stage solid cancer in whom any form of mechanical ventilation tends to be avoided. In a prospective study, we investigated the use of NIV in 23 patients with solid malignancies receiving palliative care and who were affected by severe hypoxic or hypercapnic ARF. The most frequent causes of ARF were exacerbations of pre-existing pulmonary diseases and pneumonia. After one hour, NIV significantly improved PaO2/FiO2 (from 154+/-48 to 187+/-55) and the Borg dyspnoea score (from 5.5+/-1.2 to 2.3+/-0.3). NIV also improved pH, but only in the subset of hypercapnic patients. Thirteen of 23 (57%) patients were successfully ventilated and discharged alive, while 10/23 patients (43%) met the criteria for intubation or died after an initial trial of NIV. Only two of these patients accepted invasive ventilation. The mortality rate in this subgroup was 9/10 (90%). A higher Simplified Acute Physiology Score (SAPS II) and a lower PaO2/FiO2 on admission were associated with a lower probability of survival. Patients with ARF and end-stage solid malignancies have an overall ICU and 1-year mortality rate of 39% and 87%, respectively, but despite this, a consistent subset of patients may still be successfully treated with NIV, if the cause of ARF is reversible.
  
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• Year in review in intensive care medicine-2003. Part 3: intensive care unit organization, scoring, quality of life, ethics, neonatal and pediatrics, and experimental.
  Intensive Care Med

  2004 Aug;30(8):1514-25.
  
  Abraham Edward, Andrews Peter, Antonelli Massimo, Brochard Laurent, Brun-Buisson Christian, Dobb Geoffrey, Fagon Jean-Yves, Groeneveld Johan, Mancebo Jordi, Metnitz Philipp, Nava Stefano, Pinsky Michael, Radermacher Peter, Ranieri Marco, Richard Christian, Tasker Robert, Vallet Benoit
  
  
  
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• Acute respiratory failure in the cancer patient: the role of non-invasive mechanical ventilation.
  Crit Rev Oncol Hematol

  2004 Aug;51(2):91-103.
  
  Nava Stefano, Cuomo Anna Maria
  
  Abstract
  
  The most common cause of ICU admission in patients affected by a hematologic or solid cancer is acute respiratory failure, often associated with a respiratory infection. The prognosis of these critically ill patients is disappointingly low especially if they require endotracheal intubation. In the last 10 years, non-invasive mechanical ventilation (NIV), delivered through a face or nose mask, has been increasingly used as an alternative to invasive ventilation. There is good evidence that, compared to the standard medical therapy alone or with invasive mechanical ventilation, NIV may improve survival and reduce the rate of infectious complications in patients affected by hematologic cancers. Patients with a solid tumor and "reversible" acute respiratory failure are also likely to benefit from NIV, while the use of NIV in palliative care of terminally ill patients still needs to be elucidated. The success of NIV is strictly dependent on its "early" use and on the experience of the staff involved.
  
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• Year in review in intensive care medicine: 2003. II. Brain injury, hemodynamics, gastrointestinal tract, renal failure, metabolism, trauma, and postoperative.
  Intensive Care Med

  2004 Jul;30(7):1266-75.
  
  Abraham Edward, Andrews Peter, Antonelli Massimo, Brochard Laurent, Brun-Buisson Christian, Dobb Geoffrey, Fagon Jean-Yves, Groeneveld Johan, Mancebo Jordi, Metnitz Philipp, Nava Stefano, Pinsky Michael, Radermacher Peter, Ranieri Marco, Richard Christian, Tasker Robert, Vallet Benoit
  
  
  
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• Noninvasive positive-pressure ventilation for respiratory failure after extubation.
  N Engl J Med

  2004 Jun;350(24):2452-60.
  
  Esteban Andrés, Frutos-Vivar Fernando, Ferguson Niall D, Arabi Yaseen, Apezteguía Carlos, González Marco, Epstein Scott K, Hill Nicholas S, Nava Stefano, Soares Marco-Antonio, D'Empaire Gabriel, Alía Inmaculada, Anzueto Antonio
  
  Abstract
  
  BACKGROUND:
  The need for reintubation after extubation and discontinuation of mechanical ventilation is not uncommon and is associated with increased mortality. Noninvasive positive-pressure ventilation has been suggested as a promising therapy for patients with respiratory failure after extubation, but a single-center, randomized trial recently found no benefit. We conducted a multicenter, randomized trial to evaluate the effect of noninvasive positive-pressure ventilation on mortality in this clinical setting.
  
  METHODS:
  Patients in 37 centers in eight countries who were electively extubated after at least 48 hours of mechanical ventilation and who had respiratory failure within the subsequent 48 hours were randomly assigned to either noninvasive positive-pressure ventilation by face mask or standard medical therapy.
  
  RESULTS:
  A total of 221 patients with similar baseline characteristics had been randomly assigned to either noninvasive ventilation (114 patients) or standard medical therapy (107 patients) when the trial was stopped early, after an interim analysis. There was no difference between the noninvasive-ventilation group and the standard-therapy group in the need for reintubation (rate of reintubation, 48 percent in both groups; relative risk in the noninvasive-ventilation group, 0.99; 95 percent confidence interval, 0.76 to 1.30). The rate of death in the intensive care unit was higher in the noninvasive-ventilation group than in the standard-therapy group (25 percent vs. 14 percent; relative risk, 1.78; 95 percent confidence interval, 1.03 to 3.20; P=0.048), and the median time from respiratory failure to reintubation was longer in the noninvasive-ventilation group (12 hours vs. 2 hours 30 minutes, P=0.02).
  
  CONCLUSIONS:
  Noninvasive positive-pressure ventilation does not prevent the need for reintubation or reduce mortality in unselected patients who have respiratory failure after extubation.
  
  Copyright 2004 Massachusetts Medical Society
  
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• Year in review in Intensive Care Medicine-2003. Part 1: Respiratory failure, infection and sepsis.
  Intensive Care Med

  2004 Jun;30(6):1017-31.
  
  Abraham Edward, Andrews Peter, Antonelli Massimo, Brochard Laurent, Brun-Buisson Christian, Dobb Geoffrey, Fagon Jean-Yves, Groeneveld Johan, Mancebo Jordi, Metnitz Philipp, Nava Stefano, Pinsky Michael, Radermacher Peter, Ranieri Marco, Richard Christian, Tasker Robert, Vallet Benoît
  
  
  
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• Causes of failure of noninvasive mechanical ventilation.
  Respir Care

  2004 Mar;49(3):295-303.
  
  Nava Stefano, Ceriana Piero
  
  Abstract
  
  With selected patients noninvasive positive-pressure ventilation (NPPV) can obviate endotracheal intubation and thus avoid the airway trauma and infection associated with intubation. With patients who can cooperate, NPPV is the first-line treatment for mild-to-severe acute hypercapnic respiratory failure. NPPV is also used for hypercapnic ventilatory failure and to assist weaning from mechanical ventilation, by allowing earlier extubation. Some patients do not obtain adequate ventilation with NPPV and therefore require intubation. Also, some patients will initially benefit from NPPV (for one-to-several days) but will then deteriorate and require intubation. It is not always apparent which patients will initially benefit from NPPV, so researchers have been looking for variables that predict NPPV success/failure. The reported NPPV failure rate is 5-40%, so the necessary staff and equipment for prompt intubation should be readily available. Absolute contraindications to NPPV are: cardiac or respiratory arrest; nonrespiratory organ failure (eg, severe encephalopathy, severe gastrointestinal bleeding, hemodynamic instability with or without unstable cardiac angina); facial surgery or trauma; upper-airway obstruction; inability to protect the airway and/or high risk of aspiration; and inability to clear secretions. The NPPV training and experience of the clinician team partly determines whether the patient will succeed with NPPV or, instead, require intubation. Greater clinician-team NPPV experience and expertise are associated with a higher percentage of patients succeeding on NPPV and with NPPV success with sicker patients (than will succeed with a less-experienced clinician team). With patients suffering hypercapnic respiratory failure the best NPPV success/failure predictor is the degree of acidosis/acidemia (pH and P(aCO(2)) at admission and after 1 hour on NPPV), whereas mental status and severity of illness are less reliable predictors. With patients suffering hypoxic respiratory failure the likelihood of NPPV success seems to be related to the underlying disease rather than to the degree of hypoxia. For example, the presence of acute respiratory distress syndrome or community-acquired pneumonia portends NPPV failure, as does lack of oxygenation improvement after an hour on NPPV. All the proposed NPPV success/failure predictors should be used cautiously and need further study. We predict that further study and team experience will improve the NPPV success rate and allow successful NPPV-treatment of sicker patients.
  
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• Noninvasive ventilation in cardiogenic pulmonary edema: a multicenter randomized trial.
  Am J Respir Crit Care Med

  2003 Dec;168(12):1432-7.
  
  Nava Stefano, Carbone Giorgio, DiBattista Nicola, Bellone Andrea, Baiardi Paola, Cosentini Roberto, Marenco Mauro, Giostra Fabrizio, Borasi Guido, Groff Paolo
  
  Abstract
  
  Studies employing noninvasive pressure support ventilation in cardiogenic pulmonary edema have been performed in the intensive care unit when overt respiratory failure is already present and in small groups of patients. In this multicenter study, performed in emergency departments, 130 patients with acute respiratory failure were randomized to receive medical therapy plus O2 (65 patients) or noninvasive pressure support ventilation (65 patients). The primary end point was the need for intubation; secondary end points were in-hospital mortality and changes in some physiological variables. Noninvasive pressure support ventilation improved PaO2/FIO2, respiratory rate, and dyspnea significantly faster. Intubation rate, hospital mortality, and duration of hospital stay were similar in the two groups. In the subgroup of hypercapnic patients noninvasive pressure support ventilation improved PaCO2 significantly faster and reduced the intubation rate compared with medical therapy (2 of 33 versus 9 of 31; p=0.015). Adverse events, including myocardial infarction, were evenly distributed in the two groups. We conclude that during acute respiratory failure due to cardiogenic pulmonary edema the early use of noninvasive pressure support ventilation accelerates the improvement in PaO2/FIO2, PaCO2, dyspnea, and respiratory rate, but does not affect the overall clinical outcome. Noninvasive pressure support ventilation does, however, reduce the intubation rate in the subgroup of hypercapnic patients.
  
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• Demographics and clinical outcomes of patients admitted to a respiratory intensive care unit located in a rehabilitation center.
  Respir Care

  2003 Jul;48(7):670-6.
  
  Ceriana Piero, Delmastro Monica, Rampulla Ciro, Nava Stefano
  
  Abstract
  
  INTRODUCTION:
  A recent survey of respiratory intensive care units (RICU) in Italy showed that RICUs in Italy are mainly (85%) located in acute care hospitals. Forty-seven percent of the patients are admitted from emergency departments, and only 18% are admitted from intensive care units (ICU), so the percentage of patients admitted for difficulty in weaning is low (8%). Patient demographics and admission patterns in RICUs located outside acute care hospitals have not been previously described.
  
  METHODS:
  We analyzed admission patterns, demographics, treatment, and outcomes of patients during the first year of operation of a 7-bed RICU located in a rehabilitation center that does not have an emergency department.
  
  RESULTS:
  In the 1-year study period, 96 RICU patients were admitted for acute or chronic respiratory failure. The patients' mean Simplified Acute Physiology Score II was 28.9 +/- 3.6. Sixty-five percent of the patients were transferred from the ICU, 17% from medical wards of other hospitals, 7% and 5%, respectively, from the medical and surgical wards of our hospital, and 6% came directly from home for a periodic check. Difficulty in weaning from mechanical ventilation was the main reason for admission (42%), followed by simple monitoring (37%) and need for acute ventilatory invasive or noninvasive support (21%). Thirty-one patients had COPD, 23 had acute hypoxemic respiratory failure, 30 had post-surgical complications, and 12 had neuromuscular disease. Twenty-seven of 40 patients admitted for difficulty in weaning were liberated from ventilation. Intrahospital mortality was 13%. Fifty percent of patients were discharged directly to home; those patients' mean Dependence Nursing Scale score (which measures the degree of patient independence) improved during hospital stay (decreased from 23 to 12 [p < 0.05]), whereas the remaining patients were transferred to long-term facilities or an acute care hospital.
  
  CONCLUSIONS:
  The admission pattern at our RICU in a rehabilitation center is quite different from that of an RICU in an acute care hospital. Most of our patients are admitted from ICU because of difficulty with weaning. This may be the consequence of the institutional philosophy of rehabilitation centers, which strive to achieve greater patient independence.
  
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• Weaning from tracheotomy in long-term mechanically ventilated patients: feasibility of a decisional flowchart and clinical outcome.
  Intensive Care Med

  2003 May;29(5):845-8.
  
  Ceriana Piero, Carlucci Annalisa, Navalesi Paolo, Rampulla Ciro, Delmastro Monica, Piaggi GianCarlo, De Mattia Elisa, Nava Stefano
  
  Abstract
  
  OBJECTIVE:
  To assess the feasibility of following a decisional flowchart to decide whether to remove tracheotomy in long-term mechanically ventilated patients.
  
  DESIGN AND SETTING:
  Prospective study in a respiratory intensive care unit, with beds dedicated to weaning from prolonged mechanical ventilation.
  
  PATIENTS AND PARTICIPANTS:
  108 tracheotomized patients with respiratory failure of different causes (chronic obstructive pulmonary disease, postsurgical complications, recovery from hypoxemic respiratory failure, neuromuscular disorders), 36 of whom died or could not be weaned from mechanical ventilation.
  
  INTERVENTIONS:
  We applied a decisional flowchart based on some simple clinical and physiological parameters aimed at assessing the patient's ability to remove secretions, swallowing function, absence of psychiatric diseases, possibility of reaching spontaneous breathing, and amount of respiratory space.
  
  MEASUREMENTS AND RESULTS:
  Following our flowchart 56 of the remaining patients were successfully weaned from the tracheotomy cannula, with a reintubation rate at 3 months of 3%. The main reasons for not proceeding to decannulation were inability to remove secretions and severe glottic stenosis. No statistical differences were found between patients who received a surgical or percutaneous tracheotomy.
  
  CONCLUSIONS:
  Using a simple decisional flowchart we were able to remove tracheotomy cannula in almost 80% of the patients with spontaneous breathing autonomy without major clinical complications. Further larger prospective studies are needed to confirm this clinical approach in larger and different populations.
  
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• Changes in the practice of non-invasive ventilation in treating COPD patients over 8 years.
  Intensive Care Med

  2003 Mar;29(3):419-25.
  
  Carlucci Annalisa, Delmastro Monica, Rubini Fiorenzo, Fracchia Claudio, Nava Stefano
  
  Abstract
  
  OBJECTIVE:
  We reviewed data of 208 episodes of acute respiratory failure due to chronic obstructive pulmonary disease treated by non-invasive ventilation (NIV) in our Respiratory Intensive Care Unit (RICU) from its opening in 1992 to 1999.
  
  MATERIAL AND METHODS:
  We assessed whether the rate of NIV success, the severity of the disease, and the associated costs changed in this period during which the staff and the equipment did not change.
  
  RESULTS:
  The failure rate was constant over the years (17.2% on average). The severity of the episodes of ARF, defined by pH and APACHE II at admission, worsened during the years. The statistical change point test allowed us to identify 1997 as the year of a significant change in the severity of admission pH and therefore to identify two different periods: 1992-1996 (mean pH = 7.25+/-0.07) and 1997-1999 (7.20+/-0.08; P<0.001). In this latter period the risk of failure for a patient with a pH <7.25 was threefold lower than in 1992-1996. In 1997-1999 an increasing number of episodes of ARF with a pH >7.28 were treated in the Medical Ward (20% vs 60%). This allowed a significant reduction of daily cost per patient treated with NIV (558+/-8 Euros vs 470+/-14 Euros, respectively; P<0.01).
  
  CONCLUSIONS:
  We conclude that, over time, experience with NIV may progressively allow more severely ill patients to be treated without changing the rate of success. The daily cost of NIV per patient can be reduced by treating less severely ill patients outside the RICU.
  
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• Non-invasive pressure support ventilation in acute hypoxemic respiratory failure: common strategy for different pathologies?
  Intensive Care Med

  2002 Sep;28(9):1205-7.
  
  Nava Stefano, Carlucci Annalisa
  
  
  
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• Short-term effects of expiration under positive pressure in patients with acute exacerbation of chronic obstructive pulmonary disease and mild acidosis requiring non-invasive positive pressure ventilation.
  Intensive Care Med

  2002 May;28(5):581-5.
  
  Bellone Andrea, Spagnolatti Liliana, Massobrio Monica, Bellei Elena, Vinciguerra Rossana, Barbieri Andrea, Iori Emilio, Bendinelli Stefano, Nava Stefano
  
  Abstract
  
  OBJECTIVE:
  To investigate the feasibility and the efficacy of expiration under positive pressure (PEP mask) as a chest physiotherapy in patients with exacerbation of chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure (AHRF) requiring non-invasive positive pressure ventilation (NIPPV).
  
  DESIGN:
  A prospective, randomised, controlled study.
  
  SETTING:
  A respiratory intensive care unit.
  
  PATIENTS AND INTERVENTIONS:
  Twenty-seven patients with large amounts of bronchial secretions on clinical examination due to exacerbation of COPD and mild acidosis were randomly divided into two groups. Group A (13 patients) received PEP mask plus assisted coughing. The controls (group B, 14 patients) received assisted coughing alone.
  
  OUTCOME MEASURES:
  The primary end point was to compare total sputum wet weight and to assess the feasibility of the PEP mask. Secondary outcomes were: (a) the time required for weaning patients from NIPPV, (b) treatment failure expressed as mortality within 2 months after discharge from the respiratory intensive care unit (RICU) or the need for endotracheal intubation (ETI).
  
  RESULTS:
  The amount of sputum production at the end of physiotherapy was significantly ( p<0.01) higher in group A (9.6+/-3.9 g) compared with group B (4.7+/-2.5 g). The total length of weaning time was significantly lower in group A (4.9+/-0.8 days) versus group B (7.0+/-0.7 days), p<0.01. Mortality and ETI were not significantly different in the two groups of patients (0 versus 1 and 0 versus 1, respectively).
  
  CONCLUSIONS:
  Expiration under positive pressure was effective in acutely removing secretions in patients with exacerbation of COPD and mild acidosis requiring NIPPV. In conclusion, we suggest that this chest physiotherapy technique represents a useful therapeutic option for such patients and it should often be performed in addition to NIPPV.
  
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• Evaluation of patient skin breakdown and comfort with a new face mask for non-invasive ventilation: a multi-center study.
  Intensive Care Med

  2002 Mar;28(3):278-84.
  
  Gregoretti Cesare, Confalonieri Marco, Navalesi Paolo, Squadrone Vincenzo, Frigerio Pamela, Beltrame Fabio, Carbone Giorgio, Conti Giorgio, Gamna Federica, Nava Stefano, Calderini Edoardo, Skrobik Yoanna, Antonelli Massimo
  
  Abstract
  
  OBJECTIVE:
  To evaluate patient comfort, skin breakdown and eye irritation when comparing a prototype face mask (PM) and conventional face masks (CMs) during non-invasive ventilation.
  
  SETTING AND DESIGN:
  Eight centers (intensive or intermediate care units). Multicenter randomized study.
  
  POPULATIONS:
  Patients with acute respiratory failure of different etiologies.
  
  INTERVENTIONS:
  Patients were randomized to CMs or PM when ventilation was expected to last at least 12 consecutive hours a day for two consecutive days. Patient comfort, skin breakdown and eye irritation, assessed by means of standardized scoring systems, were measured after 24 and 48 h and before discontinuing ventilation.
  
  RESULTS:
  Hundred ninety-four patients were randomized. Forty-seven patients were finally enrolled: PM (24) and CMs (23). Ventilator settings were similar in the two groups at the beginning of the treatment and after 24 and 48 h. Skin breakdown was significantly higher in the CMs group over the study period ( p<0.001). Patient comfort was higher in the PM group after 24 and 48 h ( p=0.008 and p<0.001, respectively). Eye irritation was absent in both groups after 24 h and did not differ significantly after 48 h (p=0.539). Before ventilation was discontinued skin breakdown and patient comfort were significantly higher in the CMs group, when compared to the PM group ( p<0.001 and p=0.003, respectively). Eye irritation was slightly higher in the PM versus CMs group ( p=0.21). The time on ventilation was not significantly different between the two groups ( p=0.830).
  
  CONCLUSION:
  The PM significantly reduced skin breakdown while improving patient comfort, compared to the CMs.
  
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