SOSTIENICI
Spanò Dott.ssa Francesca
Pubblicazioni su PubMed
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Primary mediastinal large B-cell lymphoma and pregnancy: a challenging clinical scenario.
Monaldi Arch Chest Dis2022 Feb;92(4):. doi: 10.4081/monaldi.2022.2198.
Intravaia Rita, De Chiara Benedetta, Musca Francesco, Casadei Francesca, Santambrogio Gloria, Spanò Francesca, Belli Oriana, Quattrocchi Giuseppina, Giannattasio Cristina, Moreo Antonella
Abstract
A 26-weeks pregnant woman presented with progressively worsening dyspnoea and poor general conditions. Using low-dose radiation multi-imaging techniques and thoracic biopsy a primary mediastinal large B cell was diagnosed. A multidisciplinary approach identified the correct hemodynamic management, the best therapeutic strategy and the timing for delivery.
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Prevalence of hypertension mediated organ damage in subjects with high-normal blood pressure without known hypertension as well as cardiovascular and kidney disease.
J Hum Hypertens2022 Jul;36(7):610-616. doi: 10.1038/s41371-021-00604-6.
Maloberti Alessandro, Rebora Paola, Occhino Giuseppe, Alloni Marta, Musca Francesco, Belli Oriana, Spano Francesca, Santambrogio Gloria Maria, Occhi Lucia, De Chiara Benedetta, Casadei Francesca, Moreo Antonella, Valsecchi Maria Grazia, Giannattasio Cristina
Abstract
Purpose of our study was to assess the prevalence of hypertension mediated organ damage (HMOD) in healthy subjects with high-normal Blood Pressure (BP) comparing them with subjects with BP values that are considered normal (
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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Could two-dimensional radial strain be considered as a novel tool to identify pre-clinical hypertrophic cardiomyopathy mutation carriers?
Int J Cardiovasc Imaging2019 Dec;35(12):2167-2175. doi: 10.1007/s10554-019-01668-9.
Santambrogio Gloria Maria, Maloberti Alessandro, Vallerio Paola, Peritore Angelica, Spanò Francesca, Occhi Lucia, Musca Francesco, Belli Oriana, De Chiara Benedetta, Casadei Francesca, Facchetti Rita, Turazza Fabio, Manfredini Emanuela, Giannattasio Cristina, Moreo Antonella
Abstract
Treatment of overt form of hypertrophic cardiomyopathy (HCM) is often unsuccessful. Efforts are focused on a possible early identification in order to prevent or delaying the development of hypertrophy. Our aim was to find an echocardiographic marker able to distinguish mutation carriers without left ventricular hypertrophy (LVH) from healthy subjects. We evaluated 28 patients, members of eight families. Three types of mutation were recognized: MYBPC3 (five families), MYH7 (two families) and TNNT2 (one family). According to genetic (G) and phenotypic (Ph) features, patients were divided in three groups: Group A (10 patients), mutation carriers with LVH (G+/Ph+); Group B (9 patients), mutation carriers without LVH (G+/Ph-); Group C (9 patients), healthy subjects (G-/Ph-). Echocardiography examination was performed acquiring standard 2D, DTI and 2D-strain imaging. Global longitudinal strain (GLS) and global radial strain (GRS) at basal and mid-level were measured. GRS was significantly different between group B and C at basal level (32.18%?±?9.6 vs. 44.59%?±?12.67 respectively; p-value?0.0001). In basal posterior and basal inferior segments this difference was particularly evident. ROC curves showed for both the involved segments good AUCs (0.931 and 0.861 for basal posterior and inferior GRS respectively) with the best predictive cut-off for basal posterior GRS at 43.65%, while it was 38.4% for basal inferior GRS. Conversely, GLS values were similar in the three group. 2D longitudinal strain is a valid technique to study HCM. Radial strain and particularly basal posterior and inferior segmental reduction could be able to identify mutation carriers in a pre-clinical phase of disease.
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Vaccine-preventable infections in Systemic Lupus Erythematosus.
Hum Vaccin Immunother2016 Mar;12(3):632-43. doi: 10.1080/21645515.2015.1107685.
Murdaca Giuseppe, Orsi Andrea, Spanò Francesca, Faccio Valeria, Puppo Francesco, Durando Paolo, Icardi Giancarlo, Ansaldi Filippo
Abstract
Systemic Lupus Erythematosus (SLE) is characterized by abnormal autoantibody production and clearance. Infections are among the most important causes of morbidity and mortality in SLE patients; they have an increased frequency of severe bacterial and viral infections possibly due to inherited genetic and immunologic defects and to immunosuppressive therapies. In addition, infectious agents can switch on lupus disease expression and activity. Among the strategies to reduce the risk of infection, vaccination can be considered the most reliable option. Most vaccines are effective and safe in SLE patients, although in certain cases immunogenicity may be sub-optimal and vaccination can trigger a flare. Although these issues are currently unresolved, the risk benefit balance is in favor for vaccination to reduce the risk of infection in SLE patients. In the present review we discuss the preventive strategies currently recommended to reduce bacterial and viral infections in SLE.
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Immunogenicity of infliximab and adalimumab: what is its role in hypersensitivity and modulation of therapeutic efficacy and safety?
Expert Opin Drug Saf2016 Jan;15(1):43-52. doi: 10.1517/14740338.2016.1112375.
Murdaca Giuseppe, Spanò Francesca, Contatore Miriam, Guastalla Andrea, Penza Elena, Magnani Ottavia, Puppo Francesco
Abstract
INTRODUCTION:
TNF-? inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying antirheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases such as rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriasis and/or psoriatic arthritis, and may be administered off-label to treat disseminated granuloma annulare systemic lupus erythematosus and systemic sclerosis. There are several TNF-? inhibitors available for clinical use including infliximab, adalimumab, golimumab, certolizumab pegol and etanercept.
AREAS COVERED:
infliximab and adalimumab can induce the development of anti-infliximab (anti-IFX) and anti-adalimumab (anti-ADA) monoclonal antibodies (mAbs). In this review, we discuss the impact of anti-IFX and anti-ADA mAbs upon efficacy and safety of these biological agents.
EXPERT OPINION:
IgG/IgE neutralizing antibodies against infliximab and adalimumab decrease the possibility of achieving a minimal disease activity state or clinical remission, decrease drug survival, increase the need for doctors to prescribe a higher drug dosage and, finally, favor the occurrence of adverse events. Concomitant administration of DMARDs such as methotrexate or leflunomide prevents the development of neutralizing Abs against infliximab and adalimumab.
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[Syncope: an untreated symptom with a lifesaving intervention].
G Ital Cardiol (Rome)2015 Sep;16(9):517-8. doi: 10.1714/1988.21532.
Giupponi Luca, De Chiara Benedetta, Spanò Francesca, Giannattasio Cristina, Taglieri Corrado, Moreo Antonella
Abstract
We report the case of a 61-year-old woman referred to our center for cardiac evaluation after a syncope, with echocardiographic findings of a papillary fibroelastoma on the edge of the non-coronary aortic cusp. The three-dimensional transesophageal approach provided a unique understanding of the size and shape of the mass and it favorably directed the surgeon towards treatment with conservative surgery.
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Autoimmune central diabetes insipidus in a patient with ureaplasma urealyticum infection and review on new triggers of immune response.
Arch Endocrinol Metab2015 Dec;59(6):554-8. doi: 10.1590/2359-3997000000072.
Murdaca Giuseppe, Russo Rodolfo, Spanò Francesca, Ferone Diego, Albertelli Manuela, Schenone Angelo, Contatore Miriam, Guastalla Andrea, De Bellis Annamaria, Garibotto Giacomo, Puppo Francesco
Abstract
Diabetes insipidus is a disease in which large volumes of dilute urine (polyuria) are excreted due to vasopressin (AVP) deficiency [central diabetes insipidus (CDI)] or to AVP resistance (nephrogenic diabetes insipidus). In the majority of patients, the occurrence of CDI is related to the destruction or degeneration of neurons of the hypothalamic supraoptic and paraventricular nuclei. The most common and well recognized causes include local inflammatory or autoimmune diseases, vascular disorders, Langerhans cell histiocytosis (LCH), sarcoidosis, tumors such as germinoma/craniopharyngioma or metastases, traumatic brain injuries, intracranial surgery, and midline cerebral and cranial malformations. Here we have the opportunity to describe an unusual case of female patient who developed autoimmune CDI following ureaplasma urealyticum infection and to review the literature on this uncommon feature. Moreover, we also discussed the potential mechanisms by which ureaplasma urealyticum might favor the development of autoimmune CDI.
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Eosinophilic myocarditis: a paraneoplastic event.
Lancet2015 Jun;385(9986):2546. doi: 10.1016/S0140-6736(15)60903-5.
Ammirati Enrico, Stucchi Miriam, Brambatti Michela, Spanò Francesca, Bonacina Edgardo, Recalcati Fabio, Cerea Giulio, Vanzulli Angelo, Frigerio Maria, Oliva Fabrizio
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Efficacy of cilostazol for the treatment of Raynaud's phenomenon in systemic sclerosis patients.
Clin Exp Med2016 Aug;16(3):407-12. doi: 10.1007/s10238-015-0370-5.
Negrini Simone, Spanò Francesca, Penza Elena, Rollando Daniela, Indiveri Francesco, Filaci Gilberto, Puppo Francesco
Abstract
Cilostazol is a selective inhibitor of phosphodiesterase-III with antiplatelet, antithrombotic and vasodilating properties. The aim of our study was to evaluate the effect of the drug on vasculopathy and Raynaud's phenomenon (RP), in a series of patients with systemic sclerosis (SSc), before and after cilostazol treatment. Twenty-one consecutive SSc patients with moderate or severe RP were enrolled in an open-label study. Cilostazol was administered at the dose of 100 mg twice a day, for 12 months. Evaluations included: daily RP attack diary documenting the frequency and duration of RP episodes, Health Assessment Questionnaire-Disability Index, scleroderma visual analogue scales (VAS), flow-mediated dilation and immunological status, including endothelin 1 and interleukin 6 plasma levels. Thirteen patients completed the study. RP duration and daily number episodes recorded over a 3-week period significantly decreased after cilostazol treatment (p = 0.0049 and p = 0.0067, respectively). VAS score indicated a significant amelioration of the patients' perception of RP (p = 0.0117), and both baseline and post-ischemic brachial artery diameters were significantly increased after cilostazol treatment, as compared with basal values (p = 0.0119 and p = 0.0076, respectively). None of the patients developed digital ulcers during the study. A significant clinical improvement of RP was recorded in SSc patients undergoing cilostazol treatment. Study results indicate a potential role of cilostazol as oral maintenance therapy in SSc patients with RP.
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Paroxysmal supraventricular tachycardia as first manifestation of right atrial hemangioma during endovascular treatment of intracranial arteriovenous fistulas.
Oncotarget2015 Jun;6(16):14060-4.
Spanò Francesca, Cereda Alberto, Moreo Antonella, Bonacina Edgardo, Peritore Angelica, Roghi Alberto, Giannattasio Cristina, Pedrotti Patrizia
Abstract
We report the description of a cardiac mass occupying almost the entire right atrium in a young man who developed paroxysmal supraventricular tachycardia during endovascular treatment of intracranial arteriovenous fistulas. The mass was detected at echocardiographic examination, its tissue characteristics were defined with cardiac magnetic resonance and it was successfully surgically removed. The histopathological findings were consistent with a mixed type cavernous-capillary hemangioma of the heart. The intriguing co-existence of cardiac hemangioma and cerebral arteriovenous fistulas, to the best of our knowledge, has not been previously reported in English Literature.
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Infection risk associated with anti-TNF-? agents: a review.
Expert Opin Drug Saf2015 Apr;14(4):571-82. doi: 10.1517/14740338.2015.1009036.
Murdaca Giuseppe, Spanò Francesca, Contatore Miriam, Guastalla Andrea, Penza Elena, Magnani Ottavia, Puppo Francesco
Abstract
INTRODUCTION:
TNF-? is a pro-inflammatory cytokine known to a have a key role in the pathogenesis of chronic immune-mediated diseases. TNF-? inhibitors can be administered either as monotherapy or in combination with other anti-inflammatory or disease-modifying anti-rheumatic drugs (DMARDs) to treat chronic immune-mediated diseases.
AREAS COVERED:
Patients receiving TNF-? inhibitors are at high risk of infections. Based on our experience, in this paper, we discuss the risk of infections associated with the administration of TNF-? inhibitors and the strategies for mitigating against the development of these serious adverse events.
EXPERT OPINION:
Infliximab more so than etanercept appears to be responsible for the increased risk of infections. Re-activation of latent tuberculosis (LTB) infection and the overall risk of opportunistic infections should be considered before beginning TNF-? inhibitor therapy. A careful medical history, Mantoux test and chest-x-ray should always be performed before prescribing TNF-? inhibitors. Particular attention should be paid to risk factors for Pneumocystis jirovecii infection. Hepatitis B and C virological follow-up should be considered during TNF-? inhibitor treatment. Finally, patients who are at high risk of herpes zoster (HZ) reactivation would benefit from a second vaccination in adulthood when receiving TNF-? inhibitors.
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Pharmacogenetics and future therapeutic scenarios: what affects the prediction of response to treatment with etanercept?
Drug Dev Res2014 Nov;75 Suppl 1():S7-S10. doi: 10.1002/ddr.21185.
Murdaca Giuseppe, Gulli Rossella, Spanò Francesca, Mandich Paola, Puppo Francesco
Abstract
There are five tumor necrosis factor alpha (TNF-?) inhibitors available for clinical use that have demonstrated efficacy as monotherapy or in combination with other anti-inflammatory or disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of immune-mediated diseases. These include the anti-TNF-? monoclonal antibodies infliximab, adalimumab, golimumab, and certolizumab pegol, and the fusion protein, etanercept. The use of pharmacogenetic testing has the potential to increase drug efficiency by identifying genetic factors responsible for a lack of response to, or toxicities from, TNF-? inhibitors, and could be used to individualize therapy. Several studies have reported associations between genetic polymorphisms and the response to etanercept, but most are small and insufficiently powered to detect effect, and markers tend to be more prognostic than predictive of therapeutic response. Limitations of pharmacogenetic studies include the use of single nucleotide polymorphisms (SNPs), genes in linkage with other loci, interaction of environmental factors, and cohort heterogeneity, all of which can complicate the relationship between genetic polymorphisms and treatment response. Further studies are needed for pharmacogenetics to become a routine part of daily clinical therapeutic practice.
© 2014 Wiley Periodicals, Inc.
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Pharmacogenetics of etanercept: role of TNF-? gene polymorphisms in improving its efficacy.
Expert Opin Drug Metab Toxicol2014 Dec;10(12):1703-10. doi: 10.1517/17425255.2014.970165.
Murdaca Giuseppe, Spanò Francesca, Contatore Miriam, Guastalla Andrea, Magnani Ottavia, Puppo Francesco
Abstract
INTRODUCTION:
During the last decade, many new biological immune modulators have entered the market as new therapeutic principles. Biologics, including TNF-? inhibitors, are the new frontier in the treatment of immune-mediated or inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, ankylosing spondylitis, systemic sclerosis, disseminated granuloma annulare, psoriasis and/or psoriatic arthritis. TNF-? inhibitors have demonstrated efficacy and are well tolerated in large, randomized, controlled clinical trials. However, a substantial proportion of patients do not respond to these agents and potential adverse drug reactions may be associated with its use.
AREAS COVERED:
Pharmacogenetics has the potential of increasing drug efficiency by identifying genetic factors responsible for lack of response or toxicities to TNF-? inhibitors. In this review, we analyze the influence of several polymorphisms upon the efficacy and safety of TNF-? inhibitors.
EXPERT OPINION:
Several polymorphisms have been proven to influence the response to etanercept. Among them, single nucleotide polymorphisms (SNPs) -308 G/G, -857 C/T, +489 GG and GA, HLA-DRB1-encoding SE (allele *0404 and allele *0101) favor the response to etanercept, whereas SNP -308 A/A and TNFR1A AA decrease the response. Large clinical studies are needed to confirm the relevance of these associations in order to tailor treatment and to decrease unnecessary toxicity.
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Potential use of TNF-? inhibitors in systemic sclerosis.
Immunotherapy2014 ;6(3):283-9. doi: 10.2217/imt.13.173.
Murdaca Giuseppe, Spanò Francesca, Contatore Miriam, Guastalla Andrea, Puppo Francesco
Abstract
Systemic sclerosis (SSc) is a rare connective tissue disease characterized by chronic inflammation and fibrosis of the skin, vascular abnormalities and variable involvement of organs. TNF-? has a central role in initial host response to infections and in the pathogenesis of various systemic immune-mediated diseases. Serum levels of TNF-? are elevated in patients with SSc and favor the development of pulmonary fibrosis and pulmonary arterial hypertension. Inflammatory arthritis can occur in patients with SSc. Infliximab and etanercept may improve the inflammatory arthritis and disability in SSc. TNF-? inhibitors reduce the systemic inflammation, improve the endothelial function decreasing the risk of pulmonary arterial hypertension progression and of acute cardiovascular and/or cerebrovascular events. Physicians need to be aware of the potential risks of tuberculosis reactivation and opportunistic infections. Randomized controlled trials with TNF-? inhibitors in patients with SSc are needed to confirm the potential role of these agents in the treatment of SSc.
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Efficacy and safety of etanercept in chronic immune-mediated disease.
Expert Opin Drug Saf2014 May;13(5):649-61. doi: 10.1517/14740338.2014.899579.
Murdaca Giuseppe, Spanò Francesca, Contatore Miriam, Guastalla Andrea, Magnani Ottavia, Puppo Francesco
Abstract
INTRODUCTION:
TNF-? inhibitors have demonstrated efficacy in large, randomized controlled clinical trials either as monotherapy or in combination with other anti-inflammatory or disease-modifying antirheumatic drugs in the treatment of chronic inflammatory immune-mediated diseases. Etanercept is a fusion protein that acts as a 'decoy receptor' for TNF-?.
AREAS COVERED:
This paper evaluates the efficacy and safety of etanercept in patients with chronic inflammatory immune-mediated diseases.
EXPERT OPINION:
Etanercept was first approved for the treatment of rheumatoid arthritis (RA) and subsequently of chronic plaque psoriasis, psoriatic arthritis, ankylosing spondylitis and juvenile RA. Etanercept as other TNF-? inhibitors, particularly infliximab, may be administered off-label to treat other chronic inflammatory immune-mediated diseases such as systemic sclerosis, Behcet disease, systemic lupus erythematosus, polymyositis, dermatomyositis and mixed connective tissue disease. Early etanercept treatment prevents joint damage and helps to avoid long-term disability in arthritis. Etanercept administered at a dose of 50 mg once weekly is effective in inducing an earlier remission of RA, and etanercept 50 mg twice weekly may favor a more rapid improvement of psoriasis and psoriatic arthritis. Etanercept and adalimumab may exert beneficial effects on lipid profile and improve endothelial dysfunction. Appropriate screening tests for latent tuberculosis, hepatitis B virus and hepatitis C virus should be performed before starting etanercept. TNF-? inhibitors including etanercept are contraindicated in patients with demyelinating diseases.
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TNF-? gene polymorphisms: association with disease susceptibility and response to anti-TNF-? treatment in psoriatic arthritis.
J Invest Dermatol2014 Oct;134(10):2503-2509. doi: 10.1038/jid.2014.123.
Murdaca Giuseppe, Gulli Rossella, Spanò Francesca, Lantieri Francesca, Burlando Martina, Parodi Aurora, Mandich Paola, Puppo Francesco
Abstract
The tumor necrosis factor-? (TNF-?) gene has been proposed as a major candidate gene in psoriatic arthritis (PsA). TNF-? is a therapeutic target for patients responding poorly to conventional treatments. We investigated the role of single-nucleotide polymorphisms (SNPs) at positions -238, -308, and +489 of the TNF-? gene in the genetic susceptibility to PsA, in the severity of the disease, and, finally, in the response to TNF-? inhibitors (adalimumab, etanercept, or infliximab). Fifty-seven Caucasian PsA patients and 155 healthy matched controls were studied. The SNP +489 variant allele A was significantly associated with PsA susceptibility (P=0.0136) and severity of clinical (Psoriasis Area and Severity Index score, American College of Rheumatology criteria, Disease Activity Score 28, and Disability Index Health Assessment Questionnaire) and laboratory (C-reactive protein and erythrocyte sedimentation rate) parameters (P-values ranging from 0.016 to 2.908 × 10(-12)). The difference in severity was accounted for by the differences between the AA and GA genotypes with respect to the GG genotype. The SNP +489A allele shows a trend of association with the response to PsA treatment with etanercept. These findings suggest a role of the SNP +489A allele in the susceptibility and severity of PsA.
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Current therapies for the treatment of systemic sclerosis-related pulmonary arterial hypertension: efficacy and safety.
Expert Opin Drug Saf2014 Mar;13(3):295-305. doi: 10.1517/14740338.2014.872238.
Murdaca Giuseppe, Spanò Francesca, Puppo Francesco
Abstract
INTRODUCTION:
Systemic sclerosis (SSc) is a rare connective tissue disease characterized by chronic inflammation and fibrosis of the skin, vascular abnormalities and variable involvement of organs. Patients with limited SSc typically develop pulmonary arterial hypertension (PAH). TNF-?, VEGF, platelet-derived growth factor and endothelin-1 play a key role in the development of PAH.
AREAS COVERED:
This paper addresses the efficacy and safety of current drugs used for the treatment of PAH.
EXPERT OPINION:
Bosentan, ambrisentan, sildenafil, tadalafil, iloprost, epoprostenol and treprostinil were associated with hemodynamic improvements in PAH patients. Ambrisentan has a better safety profile compared with bosentan, regarding the risk of increase in hepatic transaminases. Flushing, dyspepsia and diarrhea were the most frequent adverse events in patients treated with sildenafil, while headache, myalgia and flushing were the adverse events in those receiving tadalafil. Inhaled iloprost is also effective, but it requires multiple daily nebulizations up to 15 min each and may induce cough, flushing, jaw pain and headache. Epoprostenol is considered the most effective approved therapy for severe PAH in WHO functional class III and class IV. TNF-? inhibitors reduce the systemic inflammation in patients with chronic immune-mediated diseases and improve the endothelial function, decreasing the risk of PAH progression.
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Influenza and pneumococcal vaccinations of patients with systemic lupus erythematosus: current views upon safety and immunogenicity.
Autoimmun Rev2014 Feb;13(2):75-84. doi: 10.1016/j.autrev.2013.07.007.
Murdaca Giuseppe, Orsi Andrea, Spanò Francesca, Puppo Francesco, Durando Paolo, Icardi Giancarlo, Ansaldi Filippo
Abstract
Systemic lupus erythematosus (SLE) is a chronic immune-mediated inflammatory multisystem disease. The onset of viral and bacterial infections may favor the exacerbation of the disease, amplify autoimmune processes and contribute to mortality and morbidity. The prevention of influenza and Streptococcus pneumoniae infections with vaccination should receive particular attention in SLE patients considering their elevated incidence, their high attack rate in epidemic periods, their potentially severe complications as well as the immunocompromised state of the host. The use of non-adjuvanted vaccine preparations should be preferred in order to avoid the onset of the "Autoimmune (auto-inflammatory) Syndrome Induced by Adjuvants" or "ASIA". In this review, we report that influenza and pneumococcal vaccinations in SLE patients are: 1) recommended to reduce the risk of development of these infections; 2) strongly suggested in elderly subjects and in those receiving high dose immunosuppressive treatments; 3) efficacious, even if specific immune responses may be lower than in the general population, as generally the humoral response fulfills the criteria for vaccine immunogenicity; and 4) safe in inactive disease although may favor a transient increase in autoantibody levels and rarely disease flares.
© 2013.
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Use of leflunomide plus TNF-? inhibitors in rheumatoid arthritis.
Expert Opin Drug Saf2013 Nov;12(6):801-4. doi: 10.1517/14740338.2013.823947.
Murdaca Giuseppe, Spanò Francesca, Puppo Francesco
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory immune-mediated systemic disease which primarily affects the joints. Leflunomide (LFN) is a disease modifying anti-rheumatic drugs (DMARDs) which acts by inhibiting the synthesis of pyrimidines. Several trials have demonstrated the efficacy and safety of LFN alone or in combination with biological agents such as tumor necrosis factor-? (TNF-?) inhibitors in the treatment of RA patients. TNF-? is a pro-inflammatory cytokine known to a have a key role in the pathogenesis of RA. TNF-? inhibitors have demonstrated efficacy as monotherapy or in combination with other anti-inflammatory or DMARDs in the treatment of RA. Five TNF-? inhibitors are available for clinical use and include infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. In this editorial, we briefly discuss the efficacy and safety of LFN and TNF-? inhibitors in the treatment of RA, and the potential beneficial effect of both LFN and TNF-? inhibitors in improving the endothelial dysfunction and in reducing the risk of acute cardiovascular and/or cerebrovascular events.
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Free radicals and endothelial dysfunction: potential positive effects of TNF-? inhibitors.
Redox Rep2013 ;18(3):95-9. doi: 10.1179/1351000213Y.0000000046.
Murdaca Giuseppe, Spanò Francesca, Cagnati Paola, Puppo Francesco
Abstract
OBJECTIVES:
During the last decade many new biological immune modulators have entered the market as new therapeutic principles. Tumor necrosis factor (TNF)-? is a pro-inflammatory cytokine known to a have a key role in the pathogenic mechanisms of various immune-mediated or inflammatory diseases. However, TNF-? also plays a key role in endothelial dysfunction and, thus, in the development and progression of atherosclerosis. What, then, is the potential therapeutic role of TNF-? inhibitors?
METHODS:
We analysed the current literature concerning the administration of TNF-? inhibitors and their potential benefits upon endothelial function.
RESULTS:
TNF-? inhibitors decrease the serum levels of inflammatory markers such as TNF-? itself, CRP, IL-6, and increased the tissue expression of endothelial NO synthase and the vasodilatory response to bradykinin.
DISCUSSION:
TNF-? inhibitors may change the progression of endothelial dysfunction and, thus, slow down the atherosclerotic process.
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Long-term treatment of rheumatoid arthritis with adalimumab.
Open Access Rheumatol2013 ;5():43-49.
Murdaca Giuseppe, Spanò Francesca, Puppo Francesco
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory disease that is associated with joint damage and progressive disability, an increased risk of morbidity related to comorbid conditions and substantial socioeconomic costs. Tumor necrosis factor-alpha (TNF-?) is a proinflammatory cytokine known to have a central role in the initial host response to infection and in the pathogenesis of various immune-mediated diseases, such as RA, ankylosing spondylitis, psoriasis and/or psoriatic arthritis, Crohn's disease, and systemic lupus erythematosus. Five TNF-? inhibitors are available for the clinical use: infliximab; adalimumab; etanercept; golimumab; and certolizumab pegol. Infliximab is a chimeric human/murine IgG1 monoclonal antibody (mAb); adalimumab, and golimumab are human mAbs; certolizumab pegol is composed of the fragment antigen-binding anti-binding domain of a humanized anti-TNF-? mAb, combined with polyethylene glycol to increase its half-life in the body; etanercept is a fusion protein that acts as a "decoy receptor" for TNF-?. In this paper, we will briefly review the current data on efficacy and safety of adalimumab in patients with RA, its potential beneficial effects upon comorbid conditions, such as endothelial dysfunction and accelerated atherosclerosis in RA, and the immunogenicity.
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Effects of TNF-? inhibitors upon the mechanisms of action of VEGF.
Immunotherapy2013 Feb;5(2):113-5. doi: 10.2217/imt.12.151.
Murdaca Giuseppe, Spanò Francesca, Miglino Maurizio, Puppo Francesco
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Selective TNF-? inhibitor-induced injection site reactions.
Expert Opin Drug Saf2013 Mar;12(2):187-93. doi: 10.1517/14740338.2013.755957.
Murdaca Giuseppe, Spanò Francesca, Puppo Francesco
Abstract
INTRODUCTION:
During the last decade, many new biological immune modulators entered the market as new therapeutic principles. TNF-? is a pro-inflammatory cytokine known to a have a key role in the pathogenic mechanisms of various immune-mediated or inflammatory diseases. TNF-? blockers have demonstrated efficacy in large, randomized controlled clinical trials either as monotherapy or in combination with other anti-inflammatory or disease-modifying anti-rheumatic drugs.
AREAS COVERED:
Although generally well tolerated and safe, potential adverse events may be associated with TNF-? inhibitor treatment. The authors will briefly review the potential adverse drug reactions and the immunological mechanisms of injection site reactions (ISRs) in patients treated with etanercept and adalimumab.
EXPERT OPINION:
Patients treated with TNF-? inhibitors can develop ISR around the sites of injections. 'Type IV delayed type reaction' or 'recall ISRs'. Eosinophilic cellulitis or 'Wells syndrome', 'type III' and 'type I' reactions are reported. Long-term studies are necessary to determine the durability of response and the real risk of ISRs with golimumab and certolizumab pegol. Further studies are also necessary to evaluate the immunogenicity of these drugs.
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Endothelial dysfunction in rheumatic autoimmune diseases.
Atherosclerosis2012 Oct;224(2):309-17. doi: 10.1016/j.atherosclerosis.2012.05.013.
Murdaca Giuseppe, Colombo Barbara Maria, Cagnati Paola, Gulli Rossella, Spanò Francesca, Puppo Francesco
Abstract
Rheumatic autoimmune diseases have been associated with accelerated atherosclerosis and various types of vasculopathies. Atherosclerosis is an inflammatory condition which starts as a "response to injury" favoring endothelial dysfunction which is associated with increased expression of adhesion molecules, pro-inflammatory cytokines, pro-thrombotic factors, oxidative stress upregulation and abnormal vascular tone modulation. Endothelial dysfunction in rheumatic autoimmune diseases involves innate immune responses, including macrophages and dendritic cells expression of scavenger and toll-like receptors for modified or native LDL as well as neutrophil and complement activation, and dysregulation of adaptive immune responses, including proliferation of autoreactive T-helper-1 lymphocytes and defective function of dendritic and regulatory T cells. Specific differences for endothelial function among different disorders include: a) increased amounts of pro-atherogenic hormones, decreased amounts of anti-atherogenic hormones and increased insulin resistance in rheumatoid arthritis; b) autoantibodies production in systemic lupus erythematosus and antiphospholipid syndrome; c) smooth muscle cells proliferation, destruction of internal elastic lamina, fibrosis and coagulation and fibrinolytic system dysfunction in systemic sclerosis. Several self-antigens (i.e. high density lipoproteins, heat shock proteins, ?2-glycoprotein1) and self-molecules modified by oxidative events (i.e. low density lipoproteins and oxidized hemoglobin) have been identified as targets of autoimmune responses. Endothelial dysfunction leads to accelerated atherosclerosis in rheumatoid arthritis, systemic lupus erythematosus and spondyloarthropaties whereas obliterative vasculopathy is associated with systemic sclerosis. In this paper, we will briefly review the most relevant information upon endothelial dysfunction and inflammatory mechanisms in atherosclerosis and we will summarize the similarities and differences in vascular disease patterns underlying different rheumatic autoimmune diseases.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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Current views on diagnostic approach and treatment of lymphedema.
Am J Med2012 Feb;125(2):134-40. doi: 10.1016/j.amjmed.2011.06.032.
Murdaca Giuseppe, Cagnati Paola, Gulli Rossella, Spanò Francesca, Puppo Francesco, Campisi Corradino, Boccardo Francesco
Abstract
Lymphedema is a chronic, progressive, and often debilitating condition. Primary lymphedema is a lymphatic malformation developing during the later stage of lymphangiogenesis. Secondary lymphedema is the result of obstruction or disruption of the lymphatic system, which can occur as a consequence of tumors, surgery, trauma, infection, inflammation, and radiation therapy. In this review, we report an update upon the diagnostic approach and the medical and surgical therapy for both primary and secondary lymphedema.
Copyright © 2012 Elsevier Inc. All rights reserved.
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Update upon efficacy and safety of TNF-? inhibitors.
Expert Opin Drug Saf2012 Jan;11(1):1-5. doi: 10.1517/14740338.2012.630388.
Murdaca Giuseppe, Colombo Barbara Maria, Cagnati Paola, Gulli Rossella, Spanò Francesca, Puppo Francesco
Abstract
The ongoing progresses in the knowledge of the pathogenic mechanisms of various immune-mediated and inflammatory diseases as well as the availability of innovative biotechnological approaches have led to the development of new drugs that add to conventional treatments. Among these, tumor necrosis factor (TNF)-? inhibitors, that is, infliximab, adalimumab, etanercept, golimumab and certolizumab pegol, are now available for clinical use. This editorial discusses the recent indications of TNF-? inhibitors, the pretreatment considerations, the reported adverse events and, finally, the recommendations for its use in pregnancy.
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Soluble human leukocyte antigen-G serum levels in patients with acquired immune deficiency syndrome affected by different disease-defining conditions before and after antiretroviral treatment.
Hum Immunol2011 Sep;72(9):712-6. doi: 10.1016/j.humimm.2011.05.008.
Murdaca Giuseppe, Contini Paola, Setti Maurizio, Cagnati Paola, Spanò Francesca, Lantieri Francesca, Puppo Francesco
Abstract
We have previously reported that the serum levels of soluble human leukocyte antigen (HLA)-A, -B, -C, and -G antigens are elevated in human immunodeficiency virus (HIV)-infected subjects and decrease after antiretroviral therapy. In this study, we measured soluble HLA-G serum levels in patients with acquired immune deficiency syndrome (AIDS) affected by different AIDS-defining conditions before and during antiretroviral therapy and correlated them with virologic and immunologic parameters of response to treatment. Soluble HLA-G levels were significantly higher in AIDS patients before treatment as compared with healthy controls and significantly decreased after 36 months of therapy. The decrease of soluble HLA-G correlated with the decrease of plasma HIV-RNA level and CD8(+) T-lymphocytes number and with the increase of CD4(+) T-lymphocytes number. Soluble HLA-G levels were significantly higher in patients with opportunistic infections and Kaposi's sarcoma compared with patients with the wasting syndrome. These data suggest that infections and neoplasms may trigger the shedding of soluble HLA-G molecules, and confirm that the level of soluble HLA-G in serum might represent a surrogate marker to monitor virologic response and immune reconstitution in HIV-positive individuals.
Copyright © 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
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