Colombo Dott.ssa Giulia
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Laboratory investigation of peritoneal fluids: an updated practical approach based on the available evidence.
J Clin Pathol2024 Apr;():. doi: jcp-2023-209282.
Colombo Giulia, Aloisio Elena, Panteghini Mauro
Abstract
Even though analysis of peritoneal fluids (PF) is often requested to medical laboratories for biochemical and morphological tests, there is still no mutual agreement on what the most appropriate way is to manage PF samples and which tests should be appropriately executed. In this update, we tried to identify the most useful tests for PF analysis to establish best practice indications. We performed a literature review and examined available guidelines to select the most appropriate tests by an evidence-based approach. Accordingly, the basic PF profile should include (1) serum to effusion albumin gradient and (2) automated cell counts with differential analysis. This profile allows to determine the PF nature, differentiating between 'high-albumin gradient' and 'low-albumin gradient' effusions, which helps to identify the pathophysiological process causing the ascites formation. Restricted to specific clinical situations, additional tests can be requested as follows: PF lactate dehydrogenase (LDH) and glucose, to exclude (LDH) or confirm (glucose) secondary bacterial peritonitis; PF total protein, to differentiate ascites of cardiac origin from other causes; PF (pancreatic) amylase, for the identification of pancreatic ascites; PF bilirubin, when a choleperitoneum is suspected; PF triglycerides, in differentiating chylous from pseudochylous ascites and PF creatinine, to detect intraperitoneal urinary leakage.
© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.
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Arrhythmogenic Cardiomyopathy: Definition, Classification and Arrhythmic Risk Stratification.
J Clin Med2024 Jan;13(2):. doi: 456.
Varrenti Marisa, Preda Alberto, Frontera Antonio, Baroni Matteo, Gigli Lorenzo, Vargiu Sara, Colombo Giulia, Carbonaro Marco, Paolucci Marco, Giordano Federica, Guarracini Fabrizio, Mazzone Patrizio
Abstract
Arrhythmogenic cardiomyopathy (ACM) is a heart disease characterized by a fibrotic replacement of myocardial tissue and a consequent predisposition to ventricular arrhythmic events, especially in the young. Post-mortem studies and the subsequent diffusion of cardiac MRI have shown that left ventricular involvement in arrhythmogenic cardiomyopathy is common and often develops early. Regarding the arrhythmic risk stratification, the current scores underestimate the arrhythmic risk of patients with arrhythmogenic cardiomyopathy with left involvement. Indeed, the data on arrhythmic risk stratification in this group of patients are contradictory and not exhaustive, with the consequence of not correctly identifying patients at a high arrhythmic risk who deserve protection from arrhythmic death. We propose a literature review on arrhythmic risk stratification in patients with ACM and left involvement to identify the main features associated with an increased arrhythmic risk in this group of patients.
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The Fluoroless Future in Electrophysiology: A State-of-the-Art Review.
Diagnostics (Basel)2024 Jan;14(2):. doi: 182.
Preda Alberto, Bonvicini Eleonora, Coradello Elena, Testoni Alessio, Gigli Lorenzo, Baroni Matteo, Carbonaro Marco, Vargiu Sara, Varrenti Marisa, Colombo Giulia, Paolucci Marco, Mazzone Patrizio, Guarracini Fabrizio
Abstract
Fluoroscopy has always been the cornerstone imaging method of interventional cardiology procedures. However, radiation exposure is linked to an increased risk of malignancies and multiorgan diseases. The medical team is even more exposed to X-rays, and a higher incidence of malignancies was reported in this professional group. In the last years, X-ray exposure has increased rapidly, involving, above all, the medical team and young patients and forcing alternative fluoroless imaging methods. In cardiac electrophysiology (EP) and pacing, the advent of 3D electroanatomic mapping systems with dedicated catheters has allowed real-time, high-density reconstruction of both heart anatomy and electrical activity, significantly reducing the use of fluoroscopy. In addition, the diffusion of intracardiac echocardiography has provided high anatomical resolution of moving cardiac structures, providing intraprocedural guidance for more complex catheter ablation procedures. These methods have largely demonstrated safety and effectiveness, allowing for a dramatic reduction in X-ray delivery in most arrhythmias' ablations. However, some technical concerns, as well as higher costs, currently do not allow their spread out in EP labs and limit their use to only procedures that are considered highly complex and time-consuming and in young patients. In this review, we aim to update the current employment of fluoroless imaging in different EP procedures, focusing on its strengths and weaknesses.
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Inactivation of hypocretin receptor-2 signaling in dopaminergic neurons induces hyperarousal and enhanced cognition but impaired inhibitory control.
Mol Psychiatry2023 Dec;():. doi: 10.1038/s41380-023-02329-z.
Bandarabadi Mojtaba, Li Sha, Aeschlimann Lea, Colombo Giulia, Tzanoulinou Stamatina, Tafti Mehdi, Becchetti Andrea, Boutrel Benjamin, Vassalli Anne
Abstract
Hypocretin/Orexin (HCRT/OX) and dopamine (DA) are both key effectors of salience processing, reward and stress-related behaviors and motivational states, yet their respective roles and interactions are poorly delineated. We inactivated HCRT-to-DA connectivity by genetic disruption of Hypocretin receptor-1 (Hcrtr1), Hypocretin receptor-2 (Hcrtr2), or both receptors (Hcrtr1&2) in DA neurons and analyzed the consequences on vigilance states, brain oscillations and cognitive performance in freely behaving mice. Unexpectedly, loss of Hcrtr2, but not Hcrtr1 or Hcrtr1&2, induced a dramatic increase in theta (7-11?Hz) electroencephalographic (EEG) activity in both wakefulness and rapid-eye-movement sleep (REMS). DA-deficient mice spent more time in an active (or theta activity-enriched) substate of wakefulness, and exhibited prolonged REMS. Additionally, both wake and REMS displayed enhanced theta-gamma phase-amplitude coupling. The baseline waking EEG of DA-deficient mice exhibited diminished infra-theta, but increased theta power, two hallmarks of EEG hyperarousal, that were however uncoupled from locomotor activity. Upon exposure to novel, either rewarding or stress-inducing environments, DA-deficient mice featured more pronounced waking theta and fast-gamma (52-80?Hz) EEG activity surges compared to littermate controls, further suggesting increased alertness. Cognitive performance was evaluated in an operant conditioning paradigm, which revealed that DA-ablated mice manifest faster task acquisition and higher choice accuracy under increasingly demanding task contingencies. However, the mice concurrently displayed maladaptive patterns of reward-seeking, with behavioral indices of enhanced impulsivity and compulsivity. None of the EEG changes observed in DA-deficient mice were seen in DA-ablated mice, which tended to show opposite EEG phenotypes. Our findings establish a clear genetically-defined link between monosynaptic HCRT-to-DA neurotransmission and theta oscillations, with a differential and novel role of HCRTR2 in theta-gamma cross-frequency coupling, attentional processes, and executive functions, relevant to disorders including narcolepsy, attention-deficit/hyperactivity disorder, and Parkinson's disease.
© 2023. The Author(s).
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Global genetic diversity, introgression, and evolutionary adaptation of indicine cattle revealed by whole genome sequencing.
Nat Commun2023 Nov;14(1):7803. doi: 7803.
Chen Ningbo, Xia Xiaoting, Hanif Quratulain, Zhang Fengwei, Dang Ruihua, Huang Bizhi, Lyu Yang, Luo Xiaoyu, Zhang Hucai, Yan Huixuan, Wang Shikang, Wang Fuwen, Chen Jialei, Guan Xiwen, Liu Yangkai, Li Shuang, Jin Liangliang, Wang Pengfei, Sun Luyang, Zhang Jicai, Liu Jianyong, Qu Kaixing, Cao Yanhong, Sun Junli, Liao Yuying, Xiao Zhengzhong, Cai Ming, Mu Lan, Siddiki Amam Zonaed, Asif Muhammad, Mansoor Shahid, Babar Masroor Ellahi, Hussain Tanveer, Silva Gamamada Liyanage Lalanie Pradeepa, Gorkhali Neena Amatya, Terefe Endashaw, Belay Gurja, Tijjani Abdulfatai, Zegeye Tsadkan, Gebre Mebrate Genet, Ma Yun, Wang Yu, Huang Yongzhen, Lan Xianyong, Chen Hong, Migliore Nicola Rambaldi, Colombo Giulia, Semino Ornella, Achilli Alessandro, Sinding Mikkel-Holger S, Lenstra Johannes A, Cheng Haijian, Lu Wenfa, Hanotte Olivier, Han Jianlin, Jiang Yu, Lei Chuzhao
Abstract
Indicine cattle, also referred to as zebu (Bos taurus indicus), play a central role in pastoral communities across a wide range of agro-ecosystems, from extremely hot semiarid regions to hot humid tropical regions. However, their adaptive genetic changes following their dispersal into East Asia from the Indian subcontinent have remained poorly documented. Here, we characterize their global genetic diversity using high-quality whole-genome sequencing data from 354 indicine cattle of 57 breeds/populations, including major indicine phylogeographic groups worldwide. We reveal their probable migration into East Asia was along a coastal route rather than inland routes and we detected introgression from other bovine species. Genomic regions carrying morphology-, immune-, and heat-tolerance-related genes underwent divergent selection according to Asian agro-ecologies. We identify distinct sets of loci that contain promising candidate variants for adaptation to hot semi-arid and hot humid tropical ecosystems. Our results indicate that the rapid and successful adaptation of East Asian indicine cattle to hot humid environments was promoted by localized introgression from banteng and/or gaur. Our findings provide insights into the history and environmental adaptation of indicine cattle.
© 2023. The Author(s).
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The genomic echoes of the last Green Sahara on the Fulani and Sahelian people.
Curr Biol2023 Dec;33(24):5495-5504.e4. doi: 10.1016/j.cub.2023.10.075.
D'Atanasio Eugenia, Risi Flavia, Ravasini Francesco, Montinaro Francesco, Hajiesmaeil Mogge, Bonucci Biancamaria, Pistacchia Letizia, Amoako-Sakyi Daniel, Bonito Maria, Onidi Sara, Colombo Giulia, Semino Ornella, Destro Bisol Giovanni, Anagnostou Paolo, Metspalu Mait, Tambets Kristiina, Trombetta Beniamino, Cruciani Fulvio
Abstract
The population history of the Sahara/Sahelian belt is understudied, despite previous work highlighting complex dynamics. The Sahelian Fulani, i.e., the largest nomadic pastoral population in the world, represent an interesting case because they show a non-negligible proportion of an Eurasian genetic component, usually explained by recent admixture with northern Africans. Nevertheless, their origins are largely unknown, although several hypotheses have been proposed, including a possible link to ancient peoples settled in the Sahara during its last humid phase (Green Sahara, 12,000-5,000 years before present [BP]). To shed light about the Fulani ancient genetic roots, we produced 23 high-coverage (30×) whole genomes from Fulani individuals from 8 Sahelian countries, plus 17 samples from other African groups and 3 from Europeans as controls, for a total of 43 new whole genomes. These data have been compared with 814 published modern whole genomes and with relevant published ancient sequences (> 1,800 samples). These analyses showed some evidence that the non-sub-Saharan genetic ancestry component of the Fulani might have also been shaped by older events, possibly tracing the Fulani origins to unsampled ancient Green Saharan population(s). The joint analysis of modern and ancient samples allowed us to shed light on the genetic ancestry composition of such ancient Saharans, suggesting a similarity with Late Neolithic Moroccans and possibly pointing to a link with the spread of cattle herding. We also identified two different Fulani clusters whose admixture pattern may be informative about the historical Fulani movements and their later involvement in the western African empires.
Copyright © 2023 Elsevier Inc. All rights reserved.
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How to recognize pulmonary embolism in syncope patients: A simple rule.
Eur J Intern Med2024 Mar;121():121-126. doi: 10.1016/j.ejim.2023.10.036.
Gianni Francesca, Bonzi Mattia, Jachetti Alessandro, Solbiati Monica, Dreon Giulia, Colombo Giorgio, Colombo Giulia, Russo Antonio, Furlan Ludovico, Casazza Giovanni, Costantino Giorgio
Abstract
BACKGROUND:
Syncope can be the presenting symptom of Pulmonary Embolism (PE). It is not known wether using a standardized algorithm to rule-out PE in all patients with syncope admitted to the Emergency Departments (ED) is of value or can lead to overdiagnosis and overtreatment.
METHODS:
We tested if simple anamnestic and clinical parameters could be used as a rule to identify patients with syncope and PE in a multicenter observational study. The rule's sensitivity was tested on a cohort of patients that presented to the ED for syncopal episodes caused by PE. The clinical impact of the rule was assessed on a population of consecutive patients admitted for syncope in the ED.
RESULTS:
Patients were considered rule-positive in the presence of any of the following: hypotension, tachycardia, peripheral oxygen saturation ? 93 % (SpO2), chest pain, dyspnea, recent history of prolonged bed rest, clinical signs of deep vein thrombosis, history of previous venous thrombo-embolism and active neoplastic disease. The sensitivity of the rule was 90.3 % (95 % CI: 74.3 % to 98.0 %). The application of the rule to a population of 217 patients with syncope would have led to a 70 % reduction in the number of subjects needing additional diagnostic tests to exclude PE.
CONCLUSIONS:
Most patients with syncope due to PE present with anamnestic and clinical features indicative of PE diagnosis. A clinical decision rule can be used to identify patients who would benefit from further diagnostic tests to exclude PE, while reducing unnecessary exams that could lead to over-testing and over-diagnosis.
Copyright © 2023. Published by Elsevier B.V.
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Fighting Cardiac Thromboembolism during Transcatheter Procedures: An Update on the Use of Cerebral Protection Devices in Cath Labs and EP Labs.
Life (Basel)2023 Aug;13(9):. doi: 1819.
Preda Alberto, Montalto Claudio, Galasso Michele, Munafò Andrea, Garofani Ilaria, Baroni Matteo, Gigli Lorenzo, Vargiu Sara, Varrenti Marisa, Colombo Giulia, Carbonaro Marco, Della Rocca Domenico Giovanni, Oreglia Jacopo, Mazzone Patrizio, Guarracini Fabrizio
Abstract
Intraprocedural stroke is a well-documented and feared potential risk of cardiovascular transcatheter procedures (TPs). Moreover, subclinical neurological events or covert central nervous system infarctions are concerns related to the development of dementia, future stroke, cognitive decline, and increased risk of mortality. Cerebral protection devices (CPDs) were developed to mitigate the risk of cardioembolic embolism during TPs. They are mechanical barriers designed to cover the ostium of the supra-aortic branches in the aortic arch, but newer devices are able to protect the descending aorta. CPDs have been mainly designed and tested to provide cerebral protection during transcatheter aortic valve replacement (TAVR), but their use in both Catheterization and Electrophysiology laboratories is rapidly increasing. CPDs have allowed us to perform procedures that were previously contraindicated due to high thromboembolic risk, such as in cases of intracardiac thrombosis identified at preprocedural assessment. However, several concerns related to their employment have to be defined. The selection of patients at high risk of thromboembolism is still a subjective choice of each center. The aim of this review is to update the evidence on the use of CPDs in either Cath labs or EP labs, providing an overview of their structural characteristics. Future perspectives focusing on their possible future employment are also discussed.
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The Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) randomized clinical trial.
Intern Emerg Med2023 Nov;18(8):2419-2421. doi: 10.1007/s11739-023-03419-0.
Bartoli Arianna, D'Angelo Andrea, Ippolito Domenico, Delgado Francesca, Colombo Giulia
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Validation of metrological traceability of the new generation of Abbott Alinity alkaline phosphatase assay.
Clin Chem Lab Med2024 Jan;62(2):280-287. doi: 10.1515/cclm-2023-0553.
Bianchi Giorgia, Frusciante Erika, Colombo Giulia, Infusino Ilenia, Aloisio Elena, Panteghini Mauro
Abstract
OBJECTIVES:
Recently, Abbott Diagnostics marketed a new generation of Alinity enzyme assays, introducing a multiparametric calibrator [Consolidated Chemistry Calibrator (ConCC)] in place of or in addition to factor-based calibrations. For alkaline phosphatase (ALP), both calibration options are offered, i.e., with ConCC (ALP2) and with an experimental calibration factor (ALP2F). Both options are declared traceable to the 2011 IFCC reference measurement procedure (RMP). Before to replace the old generation (ALP1) with the new one, we decided to validate the trueness of ALP2/ALP2F.
METHODS:
Three approaches were employed: (a) preliminary comparison on 48 native frozen serum samples with ALP1, of which traceability to RMP was previously successfully verified; (b) examination of three banked serum pools (BSP) with values assigned by RMP; (c) direct comparison with RMP on a set of 24 fresh serum samples. Bias estimation and regression studies were performed, and the standard measurement uncertainty associated with ALP measurements on clinical samples (u) was estimated and compared with established analytical performance specifications (APS). ConCC commutability was also assessed.
RESULTS:
A positive proportional bias was found with both ALP2 and ALP2F when compared to ALP1 and RMP. This positive bias was confirmed on BSP: in average, +13.1?% for ALP2 and +10.0?% for ALP2F, respectively. u were 13.28?% for ALP2 and 10.04?% for ALP2F, both not fulfilling the minimum APS of 4.0?%. Furthermore, ConCC was not commutable with clinical samples.
CONCLUSIONS:
Our results unearth problems in the correct implementation of traceability of Alinity ALP2/ALP2F, with the risk for the new assay to be unfit for clinical purposes.
© 2023 Walter de Gruyter GmbH, Berlin/Boston.
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C-reactive protein and clinical outcome in COVID-19 patients: the importance of harmonized measurements.
Clin Chem Lab Med2023 Aug;61(9):1546-1551. doi: 10.1515/cclm-2023-0276.
Aloisio Elena, Colombo Giulia, Dolci Alberto, Panteghini Mauro
Abstract
C-reactive protein (CRP) is a cytokine-mediated acute phase reactant with a recognized role in inflammatory conditions and infectious disease. In coronavirus disease 2019 (COVID-19), elevated CRP concentrations in serum were frequently detected and significantly associated with poor outcome in terms of disease severity, need for intensive care, and in-hospital death. For these reasons, the marker was proposed as a powerful test for prognostic classification of COVID-19 patients. In most of available publications, there was however confounding information about how interpretative criteria for CRP in COVID-19 should be derived, including quality of employed assays and optimal cut-off definition. Assuring result harmonization and controlling measurement uncertainty in terms of performance specifications are fundamental to allow worldwide application of clinical information according to specific CRP thresholds and to avoid risk of patient misclassification.
© 2023 Walter de Gruyter GmbH, Berlin/Boston.
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The BaSICS randomized clinical trial.
Intern Emerg Med2023 Jan;18(1):273-274. doi: 10.1007/s11739-022-03095-6.
Rocchi Barbara, Massafra Agnese Costanza, Moscardi Marco, Colombo Giulia
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The worldwide spread of : New insights from mitogenomes.
Front Genet2022 ;13():931163. doi: 931163.
Battaglia Vincenza, Agostini Vincenzo, Moroni Elisabetta, Colombo Giulia, Lombardo Gianluca, Rambaldi Migliore Nicola, Gabrieli Paolo, Garofalo Maria, Gagliardi Stella, Gomulski Ludvik M, Ferretti Luca, Semino Ornella, Malacrida Anna R, Gasperi Giuliano, Achilli Alessandro, Torroni Antonio, Olivieri Anna
Abstract
The tiger mosquito ( is one of the most invasive species in the world and a competent vector for numerous arboviruses, thus the study and monitoring of its fast worldwide spread is crucial for global public health. The small extra-nuclear and maternally-inherited mitochondrial DNA represents a key tool for reconstructing phylogenetic and phylogeographic relationships within a species, especially when analyzed at the mitogenome level. Here the mitogenome variation of 76 tiger mosquitoes, 37 of which new and collected from both wild adventive populations and laboratory strains, was investigated. This analysis significantly improved the global mtDNA phylogeny of , uncovering new branches and sub-branches within haplogroup A1, the one involved in its recent worldwide spread. Our phylogeographic approach shows that the current distribution of tiger mosquito mitogenome variation has been strongly affected by clonal and sub-clonal founder events, sometimes involving wide geographic areas, even across continents, thus shedding light on the Asian sources of worldwide adventive populations. In particular, different starting points for the two major clades within A1 are suggested, with A1a spreading mainly along temperate areas from Japanese and Chinese sources, and A1b arising and mainly diffusing in tropical areas from a South Asian source.
Copyright © 2022 Battaglia, Agostini, Moroni, Colombo, Lombardo, Rambaldi Migliore, Gabrieli, Garofalo, Gagliardi, Gomulski, Ferretti, Semino, Malacrida, Gasperi, Achilli, Torroni and Olivieri.
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Alignment of the new generation of Abbott Alinity ?-glutamyltransferase assay to the IFCC reference measurement system should be improved.
Clin Chem Lab Med2022 Sep;60(10):e228-e231. doi: 10.1515/cclm-2022-0684.
Bianchi Giorgia, Colombo Giulia, Pasqualetti Sara, Panteghini Mauro
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Clinicians at Crossroads for a Dangerous Interference in Neonatal Bilirubin Determination at the Point-of-Care.
Clin Chem2022 Jul;68(7):887-891. doi: 10.1093/clinchem/hvac077.
Colombo Giulia, Szoke Dominika, Aloisio Elena, Cavigioli Francesco, Dolci Alberto, Panteghini Mauro
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The Mitogenome Relationships and Phylogeography of Barn Swallows (Hirundo rustica).
Mol Biol Evol2022 Jun;39(6):. doi: msac113.
Lombardo Gianluca, Rambaldi Migliore Nicola, Colombo Giulia, Capodiferro Marco Rosario, Formenti Giulio, Caprioli Manuela, Moroni Elisabetta, Caporali Leonardo, Lancioni Hovirag, Secomandi Simona, Gallo Guido Roberto, Costanzo Alessandra, Romano Andrea, Garofalo Maria, Cereda Cristina, Carelli Valerio, Gillespie Lauren, Liu Yang, Kiat Yosef, Marzal Alfonso, López-Calderón Cosme, Balbontín Javier, Mousseau Timothy A, Matyjasiak Piotr, Møller Anders Pape, Semino Ornella, Ambrosini Roberto, Bonisoli-Alquati Andrea, Rubolini Diego, Ferretti Luca, Achilli Alessandro, Gianfranceschi Luca, Olivieri Anna, Torroni Antonio
Abstract
The barn swallow (Hirundo rustica) poses a number of fascinating scientific questions, including the taxonomic status of postulated subspecies. Here, we obtained and assessed the sequence variation of 411 complete mitogenomes, mainly from the European H. r. rustica, but other subspecies as well. In almost every case, we observed subspecies-specific haplogroups, which we employed together with estimated radiation times to postulate a model for the geographical and temporal worldwide spread of the species. The female barn swallow carrying the Hirundo rustica ancestral mitogenome left Africa (or its vicinity) around 280 thousand years ago (kya), and her descendants expanded first into Eurasia and then, at least 51?kya, into the Americas, from where a relatively recent (
© The Author(s) 2022. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.
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The ?2 nicotinic subunit linked to sleep-related epilepsy differently affects fast-spiking and regular spiking somatostatin-expressing neurons in murine prefrontal cortex.
Prog Neurobiol2022 Jul;214():102279. doi: 10.1016/j.pneurobio.2022.102279.
Meneghini Simone, Modena Debora, Colombo Giulia, Coatti Aurora, Milani Niccolò, Madaschi Laura, Amadeo Alida, Becchetti Andrea
Abstract
Mutant subunits of the neuronal nicotinic ACh receptor (nAChR) can cause Autosomal Dominant Sleep-related Hypermotor Epilepsy (ADSHE), characterized by frontal seizures during non-rapid eye movement (NREM) sleep. We studied the cellular bases of the pathogenesis in brain slices from mice conditionally expressing the ADSHE-linked ?2 nAChR subunit. ?2 mice displayed minor structural alterations, except for a ~10% decrease of prefrontal cortex thickness. However, they showed a substantial decrease of the excitatory input to layer V fast-spiking (FS) interneurons, despite a concomitant increase in the number of glutamatergic terminals around the cell soma. Hence, prefrontal hyperexcitability may depend on a permanent impairment of surround inhibition. The effect disappeared when ?2 was silenced until postnatal day 15th, suggesting that the transgene selectively affects the maturation of glutamatergic synapses on FS neurons. The other main population of interneurons in layer V was constituted by somatostatin-expressing regular spiking cells. When tested with 10 µM nicotine, these displayed larger somatic nicotinic currents in transgenic mice. Thus, during wakefulness, activation of ?2-containing nAChRs by the high cholinergic tone may counteract hyperexcitability by promoting local inhibition by somatostatin-expressing cells and decreasing the effect of glutamatergic deficit in FS neurons. This interpretation was tested in networks disinhibited by 2 ?M bicuculline. Slices expressing ?2 were more susceptible to develop synchronized activity in the absence of nicotine. Addition of the drug boosted excitability in the controls, but had little effect in ?2. Our findings suggest why NREM sleep favors ADSHE seizures and nicotine can be palliative in patients.
Copyright © 2022 Elsevier Ltd. All rights reserved.
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Overview of the Americas' First Peopling from a Patrilineal Perspective: New Evidence from the Southern Continent.
Genes (Basel)2022 Jan;13(2):. doi: 220.
Colombo Giulia, Traverso Luca, Mazzocchi Lucia, Grugni Viola, Rambaldi Migliore Nicola, Capodiferro Marco Rosario, Lombardo Gianluca, Flores Rodrigo, Karmin Monika, Rootsi Siiri, Ferretti Luca, Olivieri Anna, Torroni Antonio, Martiniano Rui, Achilli Alessandro, Raveane Alessandro, Semino Ornella
Abstract
Uniparental genetic systems are unique sex indicators and complement the study of autosomal diversity by providing landmarks of human migrations that repeatedly shaped the structure of extant populations. Our knowledge of the variation of the male-specific region of the Y chromosome in Native Americans is still rather scarce and scattered, but by merging sequence information from modern and ancient individuals, we here provide a comprehensive and updated phylogeny of the distinctive Native American branches of haplogroups C and Q. Our analyses confirm C-MPB373, C-P39, Q-Z780, Q-M848, and Q-Y4276 as the main founding haplogroups and identify traces of unsuccessful (pre-Q-F1096) or extinct (C-L1373*, Q-YP4010*) Y-chromosome lineages, indicating that haplogroup diversity of the founder populations that first entered the Americas was greater than that observed in the Indigenous component of modern populations. In addition, through a diachronic and phylogeographic dissection of newly identified Q-M848 branches, we provide the first Y-chromosome insights into the early peopling of the South American hinterland (Q-BY104773 and Q-BY15730) and on overlying inland migrations (Q-BY139813).
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Weaving Mitochondrial DNA and Y-Chromosome Variation in the Panamanian Genetic Canvas.
Genes (Basel)2021 Nov;12(12):. doi: 1921.
Rambaldi Migliore Nicola, Colombo Giulia, Capodiferro Marco Rosario, Mazzocchi Lucia, Chero Osorio Ana Maria, Raveane Alessandro, Tribaldos Maribel, Perego Ugo Alessandro, Mendizábal Tomás, Montón Alejandro García, Lombardo Gianluca, Grugni Viola, Garofalo Maria, Ferretti Luca, Cereda Cristina, Gagliardi Stella, Cooke Richard, Smith-Guzmán Nicole, Olivieri Anna, Aram Bethany, Torroni Antonio, Motta Jorge, Semino Ornella, Achilli Alessandro
Abstract
The Isthmus of Panama was a crossroads between North and South America during the continent's first peopling (and subsequent movements) also playing a pivotal role during European colonization and the African slave trade. Previous analyses of uniparental systems revealed significant sex biases in the genetic history of Panamanians, as testified by the high proportions of Indigenous and sub-Saharan mitochondrial DNAs (mtDNAs) and by the prevalence of Western European/northern African Y chromosomes. Those studies were conducted on the general population without considering any self-reported ethnic affiliations. Here, we compared the mtDNA and Y-chromosome lineages of a new sample collection from 431 individuals (301 males and 130 females) belonging to either the general population, mixed groups, or one of five Indigenous groups currently living in Panama. We found different proportions of paternal and maternal lineages in the Indigenous groups testifying to pre-contact demographic events and genetic inputs (some dated to Pleistocene times) that created genetic structure. Then, while the local mitochondrial gene pool was marginally involved in post-contact admixtures, the Indigenous Y chromosomes were differentially replaced, mostly by lineages of western Eurasian origin. Finally, our new estimates of the sub-Saharan contribution, on a more accurately defined general population, reduce an apparent divergence between genetic and historical data.
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Sources and clinical significance of aspartate aminotransferase increases in COVID-19.
Clin Chim Acta2021 Nov;522():88-95. doi: 10.1016/j.cca.2021.08.012.
Aloisio Elena, Colombo Giulia, Arrigo Claudia, Dolci Alberto, Panteghini Mauro
Abstract
BACKGROUND:
Aspartate aminotransferase (AST) is often increased in COVID-19 and, in some studies, AST abnormalities were associated with mortality risk.
METHODS:
2054 hospitalized COVID-19 patients were studied. To identify sources of AST release, correlations between AST peak values and other biomarkers of tissue damage, i.e., alanine aminotransferase (ALT) for hepatocellular damage, creatine kinase (CK) for muscle damage, lactate dehydrogenase for multiorgan involvement, alkaline phosphatase and ?-glutamyltransferase for cholestatic injury, and C-reactive protein (CRP) for systemic inflammation, were performed and coefficients of determination estimated. The role of AST to predict death and intensive care unit admission during hospitalization was also evaluated. All measurements were performed using standardized assays.
RESULTS:
AST was increased in 69% of patients. Increases could be fully explained by summing the effects of hepatocellular injury [AST dependence from ALT, 66.8% [95% confidence interval (CI): 64.5-69.1)] and muscle damage [AST dependence from CK, 42.6% (CI: 39.3-45.8)]. We were unable to demonstrate an independent association of AST increases with worse outcomes.
CONCLUSION:
The mechanisms for abnormal AST in COVID-19 are likely multifactorial and a status related to tissue suffering could play a significant role. The clinical significance of AST elevations remains unclear.
Copyright © 2021 Elsevier B.V. All rights reserved.
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Early evidence of SARS-CoV-2 in Milan, Jan-Feb 2020.
Ital J Pediatr2021 Jun;47(1):145. doi: 145.
Milani Gregorio P, Casazza Giovanni, Corsello Antonio, Marchisio Paola, Rocchi Alessia, Colombo Giulia, Agostoni Carlo, Costantino Giorgio
Abstract
BACKGROUND:
A few studies have suggested that the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) was present in Northern Italy several weeks before its official detection on February 21, 2020. On the other hand, no clinical data have been provided so far to support such hypothesis. We investigated clinical-epidemiological evidence of SARS-CoV-2 infection among children and adults referring to emergency department (ED) in the main hospital of the center of Milan (Italy) before February 21, 2020.
METHODS:
A retrospective analysis of medical records of ED visits at the Fondazione Ca' Granda Policlinico, Milan between January 11 and February 15 in 2017, 2018, 2019 and in 2020 was performed. The number of subjects referring with fever, cough or dyspnea was compared between the studied period of 2020 and the previous 3 years, by calculating a standardized referral ratio (SRR, number of observed cases in 2020 divided by the number of expected cases according to 2017-2019) and the corresponding 95% confidence interval (CI).
RESULTS:
In the pediatric ED, 7709 (average 2570/year) and 2736 patients were visited during the period 2017-2019 and in the 2020, respectively. Among adults, 13,465 (average 4488/year) and 4787 were visited during the period 2017-2019 and in the 2020, respectively. The SRR was 1.16 (95% CI 1.10-1.23) in children and 1.25 (95% CI 1.16-1.35) in adults. The ratio for the two (children and adults) SRRs was 0.93 (0.84-1.02), suggesting a trend towards a higher frequency in adults compared to children.
CONCLUSIONS:
This study suggests that SARS-CoV-2 might have spread in Milan before February 21, 2020 with a minor trend among children.
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Archaeogenomic distinctiveness of the Isthmo-Colombian area.
Cell2021 Apr;184(7):1706-1723.e24. doi: 10.1016/j.cell.2021.02.040.
Capodiferro Marco Rosario, Aram Bethany, Raveane Alessandro, Rambaldi Migliore Nicola, Colombo Giulia, Ongaro Linda, Rivera Javier, Mendizábal Tomás, Hernández-Mora Iosvany, Tribaldos Maribel, Perego Ugo Alessandro, Li Hongjie, Scheib Christiana Lyn, Modi Alessandra, Gòmez-Carballa Alberto, Grugni Viola, Lombardo Gianluca, Hellenthal Garrett, Pascale Juan Miguel, Bertolini Francesco, Grieco Gaetano Salvatore, Cereda Cristina, Lari Martina, Caramelli David, Pagani Luca, Metspalu Mait, Friedrich Ronny, Knipper Corina, Olivieri Anna, Salas Antonio, Cooke Richard, Montinaro Francesco, Motta Jorge, Torroni Antonio, Martín Juan Guillermo, Semino Ornella, Malhi Ripan Singh, Achilli Alessandro
Abstract
The recently enriched genomic history of Indigenous groups in the Americas is still meager concerning continental Central America. Here, we report ten pre-Hispanic (plus two early colonial) genomes and 84 genome-wide profiles from seven groups presently living in Panama. Our analyses reveal that pre-Hispanic demographic events contributed to the extensive genetic structure currently seen in the area, which is also characterized by a distinctive Isthmo-Colombian Indigenous component. This component drives these populations on a specific variability axis and derives from the local admixture of different ancestries of northern North American origin(s). Two of these ancestries were differentially associated to Pleistocene Indigenous groups that also moved into South America, leaving heterogenous genetic footprints. An additional Pleistocene ancestry was brought by a still unsampled population of the Isthmus (UPopI) that remained restricted to the Isthmian area, expanded locally during the early Holocene, and left genomic traces up to the present day.
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
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Nicotinic Receptors in Sleep-Related Hypermotor Epilepsy: Pathophysiology and Pharmacology.
Brain Sci2020 Nov;10(12):. doi: 907.
Becchetti Andrea, Grandi Laura Clara, Colombo Giulia, Meneghini Simone, Amadeo Alida
Abstract
Sleep-related hypermotor epilepsy (SHE) is characterized by hyperkinetic focal seizures, mainly arising in the neocortex during non-rapid eye movements (NREM) sleep. The familial form is autosomal dominant SHE (ADSHE), which can be caused by mutations in genes encoding subunits of the neuronal nicotinic acetylcholine receptor (nAChR), Na-gated K channels, as well as non-channel signaling proteins, such as components of the gap activity toward rags 1 (GATOR1) macromolecular complex. The causative genes may have different roles in developing and mature brains. Under this respect, nicotinic receptors are paradigmatic, as different pathophysiological roles are exerted by distinct nAChR subunits in adult and developing brains. The widest evidence concerns ?4 and ?2 subunits. These participate in heteromeric nAChRs that are major modulators of excitability in mature neocortical circuits as well as regulate postnatal synaptogenesis. However, growing evidence implicates mutant ?2 subunits in ADSHE, which poses interpretive difficulties as very little is known about the function of ?2-containing (?2*) nAChRs in the human brain. Planning rational therapy must consider that pharmacological treatment could have different effects on synaptic maturation and adult excitability. We discuss recent attempts towards precision medicine in the mature brain and possible approaches to target developmental stages. These issues have general relevance in epilepsy treatment, as the pathogenesis of genetic epilepsies is increasingly recognized to involve developmental alterations.
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Clinical and pharmacological characteristics of elderly patients admitted for bleeding: impact on in-hospital mortality.
Ann Med2020 Nov;52(7):413-422. doi: 10.1080/07853890.2020.1808238.
Pani Arianna, Pastori Daniele, Senatore Michele, Romandini Alessandra, Colombo Giulia, Agnelli Francesca, Scaglione Francesco, Colombo Fabrizio
Abstract
INTRODUCTION:
Clinical and pharmacological characteristics of elderly patients hospitalized for bleeding and in-hospital mortality according to bleeding type are barely described.
METHODS:
Retrospective cohort study of 13,496 consecutive patients admitted to internal medicine wards. Clinical characteristics, comorbidities and pharmacological treatments were collected for each patient. Predictors of in-hospital mortality were investigated.
RESULTS:
Overall, 531 (3.9%) patients were admitted for bleeding: 189 clinically relevant non-major bleeding, 106 cerebral and 236 major non-cerebral (95.8% gastrointestinal (GI)). Among 106 cerebral bleedings, 28.3% and 24.5% were typical and atypical intracranial, respectively, and 47.2% were subdural haemorrhages. Most of patients with GI bleeding presented with anaemia (90.7%). A similar rate of GI bleeding was found in aspirin-treated patients taking or not proton pump inhibitors (PPI). In-hospital mortality was 9.98%. Age ?80 years (odds ratio (OR) 2.513, =.005), cerebral bleeding (OR 5.373, <.001 egfr and copd were positively associated with mortality while ace inhibitors use was negatively>
CONCLUSIONS:
The most frequent type of major haemorrhage was GI bleeding, which was not modified by the use of PPI in patients taking aspirin. Cerebral bleeding increased all-cause death, which was lower in ACE inhibitors/ARBs users. KEY MESSAGE Gastrointestinal (GI) bleeding was the most common reason for hospital admission. The rate of GI bleeding was similar in patients on aspirin using or not PPI. Cerebral bleeding increased in-hospital mortality, which was lower in patients taking ACE inhibitors/ARBs.
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Adult-Onset Still Disease After Human Herpesvirus 6 Infection in an Elderly Patient: A Case Report.
J Clin Rheumatol2021 Dec;27(8S):S466-S468. doi: 10.1097/RHU.0000000000001225.
Rossio Raffaella, Colombo Giulia, Piconi Stefania, Peyvandi Flora
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Y-chromosome and Surname Analyses for Reconstructing Past Population Structures: The Sardinian Population as a Test Case.
Int J Mol Sci2019 Nov;20(22):. doi: 5763.
Grugni Viola, Raveane Alessandro, Colombo Giulia, Nici Carmen, Crobu Francesca, Ongaro Linda, Battaglia Vincenza, Sanna Daria, Al-Zahery Nadia, Fiorani Ornella, Lisa Antonella, Ferretti Luca, Achilli Alessandro, Olivieri Anna, Francalacci Paolo, Piazza Alberto, Torroni Antonio, Semino Ornella
Abstract
Many anthropological, linguistic, genetic and genomic analyses have been carried out to evaluate the potential impact that evolutionary forces had in shaping the present-day Sardinian gene pool, the main outlier in the genetic landscape of Europe. However, due to the homogenizing effect of internal movements, which have intensified over the past fifty years, only partial information has been obtained about the main demographic events. To overcome this limitation, we analyzed the male-specific region of the Y chromosome in three population samples obtained by reallocating a large number of Sardinian subjects to the place of origin of their monophyletic surnames, which are paternally transmitted through generations in most of the populations, much like the Y chromosome. Three Y-chromosome founding lineages, G2-L91, I2-M26 and R1b-V88, were identified as strongly contributing to the definition of the outlying position of Sardinians in the European genetic context and marking a significant differentiation within the island. The present distribution of these lineages does not always mirror that detected in ancient DNAs. Our results show that the analysis of the Y-chromosome gene pool coupled with a sampling method based on the origin of the family name, is an efficient approach to unravelling past heterogeneity, often hidden by recent movements, in the gene pool of modern populations. Furthermore, the reconstruction and comparison of past genetic isolates represent a starting point to better assess the genetic information deriving from the increasing number of available ancient DNA samples.
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Combined leadless pacemaker and subcutaneous implantable cardioverter-defibrillator to manage recurrent transvenous system failures.
J Electrocardiol2019 ;54():43-46. doi: 10.1016/j.jelectrocard.2019.03.002.
Baroni Matteo, Colombo Giulia, Testoni Alessio, Arupi Michele, Lunati Maurizio, Cattafi Giuseppe
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and Nocturnal Frontal Lobe Epilepsy: Identification and Characterization of a Novel Loss of Function Mutation.
Front Mol Neurosci2019 ;12():17. doi: 17.
Villa Chiara, Colombo Giulia, Meneghini Simone, Gotti Cecilia, Moretti Milena, Ferini-Strambi Luigi, Chisci Elisa, Giovannoni Roberto, Becchetti Andrea, Combi Romina
Abstract
Mutations in genes coding for subunits of the neuronal nicotinic acetylcholine receptor (nAChR) have been involved in familial sleep-related hypermotor epilepsy (also named autosomal dominant nocturnal frontal lobe epilepsy, ADNFLE). Most of these mutations reside in and genes, coding for the ?4 and ?2 nAChR subunits, respectively. Two mutations with contrasting functional effects were also identified in the gene coding for the ?2 subunit. Here, we report the third mutation in the , found in a patient showing ADNFLE. The patient was examined by scalp EEG, contrast-enhanced brain magnetic resonance imaging (MRI), and nocturnal video-polysomnographic recording. All exons and the exon-intron boundaries of , , , , were amplified and Sanger sequenced. In the proband, we found a c.754T>C (p.Tyr252His) missense mutation located in the N-terminal ligand-binding domain and inherited from the mother. Functional studies were performed by transient co-expression of ?2 and ?2 , with either ?2 or ?4, in human embryonic kidney (HEK293) cells. Equimolar amounts of subunits expression were obtained by using F2A-based multi-cistronic constructs encoding for the genes relative to the nAChR subunits of interest and for the enhanced green fluorescent protein. The mutation reduced the maximal currents by approximately 80% in response to saturating concentrations of nicotine in homo- and heterozygous form, in both the ?2?4 and ?2?2 nAChR subtypes. The effect was accompanied by a strong right-shift of the concentration-response to nicotine. Similar effects were observed using ACh. Negligible effects were produced by ?2 on the current reversal potential. Moreover, binding of (±)-[H]Epibatidine revealed an approximately 10-fold decrease of both K and B (bound ligand in saturating conditions), in cells expressing ?2. The reduced B and whole-cell currents were not caused by a decrease in mutant receptor expression, as minor effects were produced by ?2 on the level of transcripts and the membrane expression of ?2?4 nAChR. Overall, these results suggest that ?2 strongly reduced the number of channels bound to the agonist, without significantly altering the overall channel expression. We conclude that mutations in are more commonly linked to ADNFLE than previously thought, and may cause a loss-of-function phenotype.
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Analysis of the human Y-chromosome haplogroup Q characterizes ancient population movements in Eurasia and the Americas.
BMC Biol2019 Jan;17(1):3. doi: 3.
Grugni Viola, Raveane Alessandro, Ongaro Linda, Battaglia Vincenza, Trombetta Beniamino, Colombo Giulia, Capodiferro Marco Rosario, Olivieri Anna, Achilli Alessandro, Perego Ugo A, Motta Jorge, Tribaldos Maribel, Woodward Scott R, Ferretti Luca, Cruciani Fulvio, Torroni Antonio, Semino Ornella
Abstract
BACKGROUND:
Recent genome studies of modern and ancient samples have proposed that Native Americans derive from a subset of the Eurasian gene pool carried to America by an ancestral Beringian population, from which two well-differentiated components originated and subsequently mixed in different proportion during their spread in the Americas. To assess the timing, places of origin and extent of admixture between these components, we performed an analysis of the Y-chromosome haplogroup Q, which is the only Pan-American haplogroup and accounts for virtually all Native American Y chromosomes in Mesoamerica and South America.
RESULTS:
Our analyses of 1.5?Mb of 152 Y chromosomes, 34 re-sequenced in this work, support a "coastal and inland routes scenario" for the first entrance of modern humans in North America. We show a major phase of male population growth in the Americas after 15 thousand years ago (kya), followed by a period of constant population size from 8 to 3 kya, after which a secondary sign of growth was registered. The estimated dates of the first expansion in Mesoamerica and the Isthmo-Colombian Area, mainly revealed by haplogroup Q-Z780, suggest an entrance in South America prior to 15 kya. During the global constant population size phase, local South American hints of growth were registered by different Q-M848 sub-clades. These expansion events, which started during the Holocene with the improvement of climatic conditions, can be ascribed to multiple cultural changes rather than a steady population growth and a single cohesive culture diffusion as it occurred in Europe.
CONCLUSIONS:
We established and dated a detailed haplogroup Q phylogeny that provides new insights into the geographic distribution of its Eurasian and American branches in modern and ancient samples.
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Use of oral anticoagulant drugs in older patients with atrial fibrillation in internal medicine wards.
Eur J Intern Med2018 Jun;52():e12-e14. doi: 10.1016/j.ejim.2018.04.006.
Proietti Marco, Antoniazzi Stefania, Monzani Valter, Santalucia Paola, Franchi Carlotta, , Fenoglio Luigi M, Melchio Remo, Fabris Fabrizio, Sartori Maria Teresa, Manfredini Roberto, De Giorgi Alfredo, Fabbian Fabio, Biolo Gianni, Zanetti Michela, Altamura Nicola, Sabbà Carlo, Suppressa Patrizia, Bandiera Francesco, Usai Carlo, Murialdo Giovanni, Fezza Francesca, Marra Alessio, Castelli Francesca, Cattaneo Federico, Beccati Valentina, di Minno Giovanni, Tufano Antonella, Contaldi Paola, Lupattelli Graziana, Bianconi Vanessa, Cappellini Domenica, Hu Cinzia, Minonzio Francesca, Fargion Silvia, Burdick Larry, Francione Paolo, Peyvandi Flora, Rossio Raffaella, Colombo Giulia, Monzani Valter, Ceriani Giuliana, Lucchi Tiziano, Brignolo Barbara, Manfellotto Dario, Caridi Irene, Corazza Gino Roberto, Miceli Emanuela, Padula Donatella, Fraternale Giacomo, Guasti Luigina, Squizzato Alessandro, Maresca Andrea, Liberato Nicola Lucio, Tognin Tiziana, Rozzini Renzo, Bellucci Francesco Baffa, Muscaritoli Maurizio, Molfino Alessio, Petrillo Enrico, Dore Maurizio, Mete Francesca, Gino Miriam, Franceschi Francesco, Gabrielli Maurizio, Perticone Francesco, Perticone Maria, Bertolotti Marco, Mussi Chiara, Borghi Claudio, Strocchi Enrico, Durazzo Marilena, Fornengo Paolo, Dallegri Franco, Ottonello Luciano Carlo, Salam Kassem, Caserza Lara, Barbagallo Mario, Di Bella Giovanna, Annoni Giorgio, Bruni Adriana Antonella, Odetti Patrizio, Nencioni Alessio, Monacelli Fiammetta, Napolitano Armando, Brucato Antonio, Valenti Anna, Castellino Pietro, Zanoli Luca, Mazzeo Marco
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Determinants of carotid-femoral pulse wave velocity progression in hypertensive patients over a 3.7 years follow-up.
Blood Press2018 Feb;27(1):32-40. doi: 10.1080/08037051.2017.1378069.
Meani Paolo, Maloberti Alessandro, Sormani Paola, Colombo Giulia, Giupponi Luca, Stucchi Miriam, Varrenti Marisa, Vallerio Paola, Facchetti Rita, Grassi Guido, Mancia Giuseppe, Giannattasio Cristina
Abstract
OBJECTIVE:
The role of risk factors on the progression of arterial stiffness has not yet been extensively evaluated. The aim of the current longitudinal study was to evaluate the determinants of the PWV progression over a 4 years follow-up period in hypertensive subjects.
MATERIALS AND METHODS:
We enrolled 333 consecutive hypertensive outpatients 18-80 aged, followed by the Hypertension Unit of St. Gerardo Hospital (Monza, Italy). At baseline anamnestic, clinical, BP, laboratory data and cfPWV were assessed. We performed a PWV follow-up examination with a median time amounting to 3.75?±?0.53 years.
RESULTS:
At baseline the mean age was 54.5?±?12.6 years, SBP and DBP were 141.3?±?18.6 and 86.4?±?10.4?mmHg and PWV was 8.56?±?1.92 m/s. Despite an improvement in BP control (from 37 to 60%), at follow-up the population showed a PWV increase (?PWV 0.87?±?3.05 m/s). PWV and ?PWV gradually increased in age decades. In patients with uncontrolled BP values at follow-up ?PWV showed a greater increase as compared to patients with controlled BP (1.46?±?3.67 vs 0.62?±?2.61 m/s, p?.05). The independent predictors of ?PWV were age, baseline PWV, baseline SBP/MBP and ?SBP/MBP.
CONCLUSIONS:
the accelerated arterial aging in treated hypertensive subjects is in large measure explained by age and BP values. PWV changes over time would probably give important information that need further future research studies.
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K. pneumoniae liver abscess following deferoxamine subcutaneous self-injection.
Am J Hematol2017 May;92(5):480-481. doi: 10.1002/ajh.24675.
Furlan Ludovico, Graziadei Giovanna, Colombo Giulia, Forzenigo Laura Virginia, Solbiati Monica
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Arterial Stiffness in Aortic Stenosis: Relationship with Severity and Echocardiographic Procedures Response.
High Blood Press Cardiovasc Prev2017 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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Mast cells and acute coronary syndromes: relationship between serum tryptase, clinical outcome and severity of coronary artery disease.
Open Heart2016 ;3(2):e000472. doi: e000472.
Morici Nuccia, Farioli Laura, Losappio Laura Michelina, Colombo Giulia, Nichelatti Michele, Preziosi Donatella, Micarelli Gianluigi, Oliva Fabrizio, Giannattasio Cristina, Klugmann Silvio, Pastorello Elide Anna
Abstract
OBJECTIVE:
To assess the relationship between serum tryptase and the occurrence of major cardiovascular and cerebrovascular events (MACCE) at 2-year follow-up in patients admitted with acute coronary syndrome (ACS). To compare serum tryptase to other validated prognostic markers (maximum high-sensitivity troponin (hs-Tn), C reactive protein (CRP) levels at admission, Synergy between percutaneous coronary intervention with Taxus and Cardiac Surgery (SYNTAX) score).
METHODS:
We measured serum tryptase at admission in 140 consecutive patients with ACS and in 50 healthy controls. The patients' follow-up was maintained for 2?years after discharge. The predictive accuracy of serum tryptase for 2-year MACCE was assessed and compared with hs-Tn, CRP and SYNTAX score.
RESULTS:
Serum tryptase levels at admission were significantly higher in patients with ACS compared with the control group (p=0.0351). 2 years after discharge, 28/140 patients (20%) experienced MACCE. Serum tryptase levels, maximum hs-Tn measurements and SYNTAX score were higher in patients who experienced MACCE compared with those without (p
CONCLUSIONS:
In patients with ACS, serum tryptase measured during index admission is significantly correlated to the development of MACCE up to 2?years, demonstrating a possible long-term prognostic role of this biomarker.
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Mid-term survival after continuous-flow left ventricular assist device versus heart transplantation.
Heart Vessels2016 May;31(5):722-33. doi: 10.1007/s00380-015-0654-4.
Ammirati Enrico, Oliva Fabrizio G, Colombo Tiziano, Russo Claudio F, Cipriani Manlio G, Garascia Andrea, Guida Valentina, Colombo Giulia, Verde Alessandro, Perna Enrico, Cannata Aldo, Paino Roberto, Martinelli Luigi, Frigerio Maria
Abstract
There is a paucity of data about mid-term outcome of patients with advanced heart failure (HF) treated with left ventricular assist device (LVAD) in Europe, where donor shortage and their aging limit the availability and the probability of success of heart transplantation (HTx). The aim of this study is to compare Italian single-centre mid-term outcome in prospective patients treated with LVAD vs. HTx. We evaluated 213 consecutive patients with advanced HF who underwent continuous-flow LVAD implant or HTx from 1/2006 to 2/2012, with complete follow-up at 1 year (3/2013). We compared outcome in patients who received a LVAD (n = 49) with those who underwent HTx (n = 164) and in matched groups of 39 LVAD and 39 HTx patients. Patients that were treated with LVAD had a worse risk profile in comparison with HTx patients. Kaplan-Meier survival curves estimated a one-year survival of 75.5 % in LVAD vs. 82.3 % in HTx patients, a difference that was non-statistically significant [hazard ratio (HR) 1.46; 95 % confidence interval (CI) 0.74-2.86; p = 0.27 for LVAD vs. HTx]. After group matching 1-year survival was similar between LVAD (76.9 %) and HTx (79.5 %; HR 1.15; 95 % CI 0.44-2.98; p = 0.78). Concordant data was observed at 2-year follow-up. Patients treated with LVAD as bridge-to-transplant indication (n = 22) showed a non significant better outcome compared with HTx with a 95.5 and 90.9 % survival, at 1- and 2-year follow-up, respectively. Despite worse preoperative conditions, survival is not significantly lower after LVAD than after HTx at 2-year follow-up. Given the scarce number of donors for HTx, LVAD therapy represents a valid option, potentially affecting the current allocation strategy of heart donors also in Europe.
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Ultrasonography versus computed tomography for suspected nephrolithiasis.
Intern Emerg Med2015 Jun;10(4):515-6. doi: 10.1007/s11739-015-1192-x.
Colombo Giulia, Solbiati Monica,
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Age-adjusted D-dimer cutoff levels and pulmonary embolism.
JAMA2014 Aug;312(5):557. doi: 10.1001/jama.2014.7604.
Colombo Giorgio, Furlan Ludovico, Colombo Giulia
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Blood pressure control in Italian essential hypertensives treated by general practitioners.
Am J Hypertens2012 Nov;25(11):1182-7. doi: 10.1038/ajh.2012.108.
Giannattasio Cristina, Cairo Matteo, Cesana Francesca, Alloni Marta, Sormani Paola, Colombo Giulia, Grassi Guido, Mancia Giuseppe
Abstract
BACKGROUND:
Adequate control of blood pressure (BP) is limited worldwide. This has serious consequences for public health because in hypertensive patients, uncontrolled BP is associated with a higher incidence of cardiovascular events, particularly stroke. The aim of this study was to investigate BP control in a cohort of treated patients with diagnosed hypertension, who were under general practitioner care in Italy.
METHODS:
Data were collected by 2,643 physicians on 8,572 individual Italian patients. Office BP was measured 5 min after seating each patient and then 3-5 min later. For each patient, data such as medical history of patients, physical examination data, antihypertensive drug usage, and self-BP measurement frequency were obtained.
RESULTS:
Male prevalence was 48.4%, and mean age was 64.3 ± 10.5 years. Based on the second measurement, BP control (
CONCLUSIONS:
In treated Italian hypertensives effective BP control remains uncommon largely due to the failure to appropriately reduce the systolic BP. The stricter values recommended by the ESH/ESC guidelines for diabetic patients are achieved only by a small fraction of hypertensive diabetic population.
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Simvastatin reduces MMP1 expression in human smooth muscle cells cultured on polymerized collagen by inhibiting Rac1 activation.
Arterioscler Thromb Vasc Biol2007 May;27(5):1043-9.
Ferri Nicola, Colombo Giulia, Ferrandi Corrado, Raines Elaine W, Levkau Bodo, Corsini Alberto
Abstract
OBJECTIVE:
Activation of collagen receptors expressed by smooth muscle cells induces matrix metalloproteinase (MMP) expression. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to interfere with integrin signaling, but their effects on collagen receptor-mediated MMP expression have not been investigated.
METHODS AND RESULTS:
In the present study, we show that simvastatin (3 micromol/L) reduces MMP1 expression and secretion in human smooth muscle cells cultured on polymerized type I collagen by 39.9+/-11.2% and 36.0+/-2.3%, respectively. Reduced MMP1 protein levels correlate with a similar decrease in MMP1 promoter activity (-33.0+/-8.9%), MMP1 mRNA levels (-37.8+/-10.5%), and attenuation of smooth muscle cell collagen degradation (-34.2+/-6.1%). Mevalonate, and the isoprenoid derivative geranylgeraniol, precursors of geranylgeranylated proteins, completely prevent the inhibitory effect of simvastatin on MMP1. Moreover, the protein geranylgeranyltransferase inhibitor GGTI-286 significantly decreases MMP1 expression. Retroviral overexpression of dominant-negative mutants of geranylgeranylated Rac1 lead to a reduction of MMP1 protein (-50.4+/-5.4%) and mRNA levels (-97.9+/-1.0%), and knockdown of Rac1 by small interfering RNA downregulates MMP1 expression. Finally, simvastatin reduces GTP-bound Rac1 expression levels in smooth muscle cells cultured on polymerized collagen.
CONCLUSIONS:
These results demonstrate that simvastatin, by inhibiting Rac1 activity, reduces MMP1 expression and collagen degradation in human smooth muscle cells.
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FSH and LH together in ovarian stimulation.
Eur J Obstet Gynecol Reprod Biol2004 Jul;115 Suppl 1():S34-9.
Levi-Setti Paolo E, Cavagna Mario, Baggiani Annamaria, Zannoni Elena, Colombo Giulia V, Liprandi Valeria
Abstract
The authors review the physiology of the ovulatory cycle and the role of the gonadotrophins in ovulation induction in patients with anovulatory disorders and in multifollicular development for assisted reproductive technologies. The use of gonadotrophins with luteinizing hormone (LH) activity and the use of recombinant LH associated with follicle stimulating hormone (FSH) are discussed. The authors point out that administration of gonadotrophins with LH activity is essential in hypogonadotropic hypogonadal anovulation, and data available in the medical literature allow the conclusion that recombinant LH may be added to all ovarian stimulation protocols because it is difficult to determine which patients will benefit from LH administration and there is no evidence that LH affects adversely the outcome of ovarian stimulation. The use of recombinant LH in addition to recombinant FSH may be particularly useful when a GnRH antagonist is associated with the ovarian stimulation regimen, by preventing the fall in estradiol and diminishing FSH requirements.
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