Publications by authors named "Domenico Prisco"

219 Publications

Management of ongoing direct anticoagulant treatment in patients with hip fracture.

Sci Rep 2021 May 4;11(1):9467. Epub 2021 May 4.

Dipartimento Medicina Sperimentale e Clinica, Università di Firenze, Florence, Italy.

Aim of the present study was to investigate the effects of ongoing treatment with DOACs on time from trauma to surgery and on in-hospital clinical outcomes (blood losses, need for transfusion, mortality) in patients with hip fracture. Moreover we evaluated the adherence to current guidelines regarding the time from last drug intake and surgery. In this observational retrospective study clinical records of patients admitted for hip fracture from January 2016 to January 2019 were reviewed. 74 patients were in treatment with DOACs at hospital admission. Demographic data, comorbidities and functional status before trauma were retrieved. As control group we evaluated 206 patients not on anticoagulants matched for age, gender, type of fracture and ASA score. Time to surgery was significantly longer in patients treated with DOACs (3.6 + 2.7 vs. 2.15 ± 1.07 days, p < 0.0001) and treatment within 48 h was 47% vs. 80% in control group (p < 0.0001). The adherence to guidelines' suggested time from last drug intake to surgery was 46%. Neither anticipation nor delay in surgery did result in increased mortality, length of stay or complication rates with the exception of larger perioperative blood loss (Hb levels < 8 g/dl) in DOACs patients (34% vs 9% p < 0.0001). Present results suggest that time to surgery is significantly longer in DOAC patients in comparison to controls and adherence to guidelines still limited.
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http://dx.doi.org/10.1038/s41598-021-89077-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096972PMC
May 2021

Direct oral anticoagulant for venous thrombosis in Behçet's syndrome.

Autoimmun Rev 2021 Apr 17;20(4):102783. Epub 2021 Feb 17.

Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMR S 959, Immunology-Immunopathology- Immunotherapy (I3), F-75005, Paris, France; Immunology-Immunopathology-Immunotherapy (i3) Laboratory, INSERM UMR-S 959, Sorbonne Université, 75005 Paris, France; Biotherapy Unit (CIC-BTi), Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP), 75013 Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2021.102783DOI Listing
April 2021

Comment on: Obstetric Antiphospholipid Syndrome is not Associated with an Increased Risk of Subclinical Atherosclerosis. Reply.

Rheumatology (Oxford) 2021 Feb 9. Epub 2021 Feb 9.

Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.

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http://dx.doi.org/10.1093/rheumatology/keab136DOI Listing
February 2021

Significant and Conflicting Correlation of IL-9 With and in Human Colorectal Cancer.

Front Immunol 2020 8;11:573158. Epub 2021 Jan 8.

Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy.

Background And Aim: Gut microbiota (GM) can support colorectal cancer (CRC) progression by modulating immune responses through the production of both immunostimulatory and/or immunosuppressive cytokines. The role of IL-9 is paradigmatic because it can either promote tumor progression in hematological malignancies or inhibit tumorigenesis in solid cancers. Therefore, we investigate the microbiota-immunity axis in healthy and tumor mucosa, focusing on the correlation between cytokine profile and GM signature.

Methods: In this observational study, we collected tumor (CRC) and healthy (CRC-S) mucosa samples from 45 CRC patients, who were undergoing surgery in 2018 at the Careggi University Hospital (Florence, Italy). First, we characterized the tissue infiltrating lymphocyte subset profile and the GM composition. Subsequently, we evaluated the CRC and CRC-S molecular inflammatory response and correlated this profile with GM composition, using Dirichlet multinomial regression.

Results: CRC samples displayed higher percentages of Th17, Th2, and Tregs. Moreover, CRC tissues showed significantly higher levels of MIP-1α, IL-1α, IL-1β, IL-2, IP-10, IL-6, IL-8, IL-17A, IFN-γ, TNF-α, MCP-1, P-selectin, and IL-9. Compared to CRC-S, CRC samples also showed significantly higher levels of the following genera: , , , , and . Finally, the abundance of spp. in CRC samples negatively correlated with IL-17A and positively with IL-9. On the contrary, spp. presence negatively correlated with IL-9.

Conclusions: Our data consolidate antitumor immunity impairment and the presence of a distinct microbiota profile in the tumor microenvironment compared with the healthy mucosa counterpart. Relating the CRC cytokine profile with GM composition, we confirm the presence of bidirectional crosstalk between the immune response and the host's commensal microorganisms. Indeed, we document, for the first time, that spp. and spp. are, respectively, positively and negatively correlated with IL-9, whose role in CRC development is still under debate.
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http://dx.doi.org/10.3389/fimmu.2020.573158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820867PMC
January 2021

Comparison of treatments for the prevention of fetal growth restriction in obstetric antiphospholipid syndrome: a systematic review and network meta-analysis.

Intern Emerg Med 2021 Jan 21. Epub 2021 Jan 21.

Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

Women with criteria and non-criteria obstetric antiphospholipid syndrome (APS) carry an increased risk of pregnancy complications, including fetal growth restriction (FGR). The management of obstetric APS traditionally involves clinicians, obstetricians and gynaecologists; however, the most appropriate prophylactic treatment strategy for FGR prevention in APS is still debated. We performed a systematic review and network meta-analysis (NetMA) to summarize current evidence on pharmacological treatments for the prevention of FGR in APS. We searched PubMed and Embase from inception until July 2020, for randomized controlled trials and prospective studies on pregnant women with criteria or non-criteria obstetric APS. NetMA using a frequentist framework were conducted for the primary outcome (FGR) and for secondary outcomes (fetal or neonatal death and preterm birth). Adverse events were narratively summarised. Out of 1124 citations, we included eight studies on 395 pregnant patients with obstetric APS treated with low-dose aspirin (LDA) + unfractionated heparin (UFH) (n = 132 patients), LDA (n = 115), LDA + low molecular weight heparin (n = 100), LDA + corticosteroids (n = 29), LDA + UFH + intravenous immunoglobulin (n = 7), or untreated (n = 12). No difference among treatments emerged in terms of FGR prevention, but estimates were largely imprecise, and most studies were at high/unclear risk of bias. An increased risk of fetal or neonatal death was found for LDA monotherapy as compared to LDA + heparin, and for no treatment as compared to LDA + corticosteroids. The risk of preterm birth was higher for LDA + UFH + IVIg as compared to LDA or LDA + heparin, and for LDA + corticosteroids as compared to LDA or LDA + LMWH. No treatment was associated with an increased risk of bleeding, thrombocytopenia or osteopenia.
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http://dx.doi.org/10.1007/s11739-020-02609-4DOI Listing
January 2021

Cardiac involvement in eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome): Prospective evaluation at a tertiary referral centre.

Eur J Intern Med 2021 Mar 23;85:68-79. Epub 2020 Dec 23.

Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis. Cardiac specific involvement (CSI) is caused by coronary artery vasculitis, but also by myocardial eosinophilic infiltration. To date, the prevalence of CSI associated with EGPA is unresolved. Aim of this study was to systematically assess the prevalence and clinical impact of CSI in a consecutive outpatient EGPA population.

Methods: Between October 2018 and July 2019, we prospectively enrolled 52 consecutive EGPA patients. All underwent comprehensive evaluation including a standardized questionnaire, physical examination, 12-lead-ECG, echocardiography. Cardiac magnetic resonance and 24 h-Holter were performed as deemed clinically appropriate. Cardiac abnormalities were defined as CSI based on the likelihood of their relation to EGPA vasculitis, after exclusion of alternative diagnoses.

Results: 52 enrolled patients, mean age 59±1 years. Thirteen of the 52 patients (25%) were classified as CSI+. CSI was characterized by myocarditis in four patients, non-scar-related regional wall motions abnormalities (RWMA) in three, apical thrombosis in two (one also had RWMA), pericarditis in three and non-atherosclerotic coronary disease (Prinzmetal angina and coronaritis) in 2. Five (38%) of the 13 CSI+ patients, presented an apical aneurysm. Peak eosinophil count at diagnosis was higher in CSI+: 8000 /μl vs CSI-: 3000 /μl, p = 0.017. Overall, 2 patients had severe LV dysfunction, 5 required urgent hospitalization and 8 required long-term cardioactive therapy.

Conclusions: CSI was present in one-quarter of patients, often associated with high peak eosinophils. Myocarditis, RWMA and apical aneurysms were the most common manifestations. Although rarely severe and life-threatening, CSI often required long-term cardioactive treatment.
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http://dx.doi.org/10.1016/j.ejim.2020.12.008DOI Listing
March 2021

Butyrate-Rich Diets Improve Redox Status and Fibrin Lysis in Behçet's Syndrome.

Circ Res 2021 Jan 17;128(2):278-280. Epub 2020 Nov 17.

Department of Experimental and Clinical Biomedical Sciences "Mario Serio", (M.R., N.T., C.F., M.B.), University of Firenze, Italy.

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http://dx.doi.org/10.1161/CIRCRESAHA.120.317789DOI Listing
January 2021

Trial of Rivaroxaban in AntiPhospholipid Syndrome (TRAPS): Two-year outcomes after the study closure.

J Thromb Haemost 2021 02 29;19(2):531-535. Epub 2020 Nov 29.

Thrombosis Research Laboratory, Department of Cardiac Thoracic and Vascular Sciences, and Public Health, University of Padova, Padova, Italy.

Background: Trial of Rivaroxaban in AntiPhospholipid Syndrome was a prospective randomized, open-label, noninferiority study conducted in 14 centers in Italy. Rivaroxaban was compared with warfarin for the prevention of thromboembolic events, major bleeding, and vascular death in high-risk, triple-positive patients with antiphospholipid syndrome.

Objective: The aim of this paper is to report the events during the 2-year follow-up after the study closure.

Methods: On January 28, 2018, the trial was prematurely stopped by adjudication and safety committee for an excess of events in the rivaroxaban group. Randomized patients were advised on trial results and those randomized to rivaroxaban were solicited to switch to warfarin. All 14 participating centers were asked and accepted to follow their patients for clinical events. This report describes the rate of events that occurred between January 28, 2018, and January 28, 2020.

Results: Of 120 randomized patients, 115 were available for follow-up. Outcome events were two in six (33.3%) patients who remained on direct oral anticoagulants (DOACs) and six in 109 (5.7%) patients on warfarin (hazard ratio [HR] 6.9; 95% confidence interval [CI] 1.4-34.5, P = .018). The two patients on DOACs (one taking dabigatran and one taking rivaroxaban) suffered from thromboembolic events, whereas of the six patients with composite outcomes on warfarin, three had thromboembolic events (HR for thrombosis 13.3; 95% CI 2.2-79.9, P = .005).

Conclusion: These data further support the use of warfarin in high-risk patients with antiphospholipid syndrome.
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http://dx.doi.org/10.1111/jth.15158DOI Listing
February 2021

"COVID-19: diagnosis, management and prognosis": a new topical collection of Internal and Emergency Medicine.

Intern Emerg Med 2020 08 30;15(5):747-750. Epub 2020 Jul 30.

Dipartimento Di Medicina Sperimentale E Clinica (DMSC), Università Di Firenze, Florence, Italy.

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http://dx.doi.org/10.1007/s11739-020-02461-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391015PMC
August 2020

Intravenous immunoglobulin for the secondary prevention of stillbirth in obstetric antiphospholipid syndrome: A case series and systematic review of literature.

Autoimmun Rev 2020 Sep 16;19(9):102620. Epub 2020 Jul 16.

Department of Biomedical, Experimental and Clinical Sciences-Division of Obstetrics and Gynaecology, University of Florence, Florence, Italy.

Objective: To evaluate the efficacy and safety of intravenous immunoglobulin (IVIg) in secondary prevention of pregnancy complications for patients with obstetric antiphospholipid syndrome (APS) and history of stillbirth.

Methods: We described three cases of obstetric APS patients with history of stillbirth treated with IVIg in four pregnancies. In addition, we conducted a systematic literature review on the use of IVIg in obstetric APS with history of stillbirth.

Results: Three patients with obstetric APS and history of stillbirth were treated with prophylactic IVIg, in addition to standard treatment (hydroxychloroquine, low-dose aspirin, low molecular weight heparin, and prednisone), in four pregnancies (three singleton and one twin). All pregnancies resulted in live healthy newborns. Long-term follow-up re-evaluations (24-53 months) did not shown any sign or symptom of active systemic disease, and the children were healthy. The systematic literature review retrieved only three cases of use of IVIg in obstetric APS patients with history of stillbirth. All three cases resulted in live healthy newborns. Only in one case, mild thrombocytopenia occurred during treatment, although this event was unlikely to be related to IVIg.

Conclusion: Our experience suggests that IVIg as secondary prevention of APS-related stillbirth is associated with good pregnancy and long-term outcomes, with no relevant safety concerns. However, the literature evidence on this topic is limited to few isolated cases, and further studies are needed to clarify which obstetric APS patients may benefit the most from IVIg.
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http://dx.doi.org/10.1016/j.autrev.2020.102620DOI Listing
September 2020

Antiarrhythmic efficacy of anakinra in a young patient with autoimmune lymphocytic myocarditis.

Rheumatology (Oxford) 2020 11;59(11):e88-e90

Department of Clinical and Experimental Medicine, University of Florence.

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http://dx.doi.org/10.1093/rheumatology/keaa207DOI Listing
November 2020

Design and rationale of a randomized, placebo-controlled trial on the efficacy and safety of sulodexide for extended treatment in elderly patients after a first venous thromboembolism.

Intern Emerg Med 2021 Mar 25;16(2):359-368. Epub 2020 May 25.

Centro Trombosi, Azienda Ospedaliera Careggi, Florence, Italy.

How to prevent recurrences after a first venous thromboembolic (VTE) event in elderly patients is still an open issue, especially because of the high bleeding risk of anticoagulation in these patients. The placebo-controlled "Jason" study aims at assessing the efficacy and safety for secondary VTE prevention in elderly patients of oral Sulodexide (Vessel) administration, a mixture of glycosaminoglycans (Alfasigma, Bologna, Italy) which proved effective against recurrences in a general population (SURVET study) without major bleeding (MB) complications. 1450 patients, aged ≥ 75 years, after at least 3 months of anticoagulation treatment for a first VTE episode, are double-blind randomized to receive for 12 months either sulodexide 500 lipasemic units (LSUs) twice daily, or sulodexide 250 LSU twice daily + indistinguishable placebo, or indistinguishable placebo. Primary outcomes for efficacy are the composite of death for VTE and recurrent VTE, and occurrence of MB for safety. Secondary outcomes include stroke, cardiovascular death and other thromboembolic events, and MB + clinically relevant non-MB. The first patient is scheduled to be randomized in May 2020. The study protocol has been approved by AIFA (Agenzia Italiana del Farmaco) and the Ethics Committee of the coordinating center. Written informed consent will be obtained from all patients prior to study participation. Jason study is an investigator-initiated trial, promoted by "Arianna Anticoagulazione" Foundation, Bologna, Italy, and supported by Alfasigma, Bologna, Italy. Study findings will be disseminated to participant centers, at research conferences and in peer-reviewed journals. Trial registration numbers NCT04257487; EudraCT (2019-000570-33).
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http://dx.doi.org/10.1007/s11739-020-02381-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952285PMC
March 2021

Postoperative atrial fibrillation is related to a worse outcome in patients undergoing surgery for hip fracture.

Intern Emerg Med 2021 Mar 21;16(2):333-338. Epub 2020 May 21.

Dipartimento Medicina Sperimentale e Clinica, Università Di Firenze, Viale Morgagni 85, 50134, Florence, Italy.

Few information exist about incidence and prognostic significance of postoperative atrial fibrillation (POAF) in patients undergoing hip fracture surgery. In the period comprised between January 2012 and December 2016, we evaluated 3129 patients referred for hip fracture. At hospital admission 277 were in permanent atrial fibrillation and were excluded from the study. POAF was defined as symptomatic or asymptomatic AF of duration > 10 min occurring during hospitalization after hip surgery. In-hospital and 1-year outcomes of POAF patients were compared to that of an age- and sex-matched hip fracture control group. Survival rates were estimated by Kaplan-Meier curves and differences between groups compared by log-rank test. One hundred and four patients (mean age 83.7 years, men 27%) developed POAF (3.6%). Time of onset after surgery was on average 2 days after surgery. Eight POAF patients died during hospitalization. 81.7% were discharged in sinus rhythm. Patients with POAF had a longer time to surgery (3.8 ± 3.3 vs. 2.4 ± 1.6 days, p = 0.0007) and length of hospital stay (19.7 ± 10.4 vs. 14.4 ± 5.1 days p < 0.0001) in comparison to control group. Eight patients had AF recurrence during follow-up. 1-year mortality was significantly higher in POAF group in comparison to control group (39.3. vs 20.9%, p < 0.001). Postoperative atrial fibrillation in patients undergoing hip fracture surgery is associated with a longer length of hospital stay in comparison to patients who maintain stable sinus rhythm. Moreover, these patients had a significant higher mortality at 1-year follow-up.
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http://dx.doi.org/10.1007/s11739-020-02372-6DOI Listing
March 2021

Obstetric antiphospholipid syndrome is not associated with an increased risk of subclinical atherosclerosis.

Rheumatology (Oxford) 2020 Dec;59(12):3709-3716

Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA).

Objectives: The persistent positivity of aPLs, either isolated or associated with thrombotic and/or obstetric events (APS), has been associated with the increase of intima-media thickness (IMT) and carotid plaques. Despite the fact that aPLs can promote both thrombotic and obstetric complications, some pathogenic differences have been documented between the two entities. This study aimed to evaluate whether the atherosclerotic risk differs between subjects with obstetric and thrombotic APS.

Methods: A total of 167 APS women (36 obstetric and 131 thrombotic) were compared with 250 aPLs negative controls. IMT of the common carotid artery (CCA) and of the bulb and the prevalence of carotid plaques were assessed.

Results: CCA- and bulb-IMT were significantly higher in women with thrombotic APS, while being similar between the obstetric APS and the controls [CCA-IMT: mean (s.d.) 0.97 (0.49), 0.78 (0.22) and 0.81 (0.12) mm for the thrombotic, obstetric and control groups, respectively, P < 0.001 between thrombotic and controls, P = 0.002 between thrombotic and obstetric; bulb-IMT: mean (s.d.) 1.38 (0.79), 0.96 (0.27) and 0.96 (0.51) mm for the thrombotic, obstetric and control groups, P < 0.001]. Women with thrombotic APS had significantly increased risk of presenting carotid plaques. This risk was significantly lower in obstetric APS.

Conclusion: Unlike thrombotic APS, obstetric APS is not associated with an increase of markers of subclinical atherosclerosis. If confirmed on wider populations, these results could suggest different pathogenetic role of aPLs in promoting atherosclerosis in vascular and obstetric APS, and raise questions on the risk-benefit profile of thromboprophylaxis in obstetric APS outside pregnancy periods.
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http://dx.doi.org/10.1093/rheumatology/keaa116DOI Listing
December 2020

Long-term effectiveness and safety of secukinumab for treatment of refractory mucosal and articular Behçet's phenotype: a multicentre study.

Ann Rheum Dis 2020 08 7;79(8):1098-1104. Epub 2020 May 7.

Department of Experimental and Clinical Medicine, University of Florence, Firenze, Italy.

Objective: To evaluate the effectiveness and safety of secukinumab in patients with a mucosal and articular Behçet's phenotype resistant to conventional and biologic treatment.

Methods: A multicentre retrospective study was performed on 15 patients with a mucosal and articular phenotype of Behçet's syndrome fulfilling the International Criteria for Behçet's Disease and refractory to treatment with colchicine, disease-modifying antirheumatic drugs and at least one antitumour necrosis factor-α agent. Minimum follow-up was set at 6 months. Six patients with a polyarticular involvement were treated with secukinumab 300 mg/month, while all other cases received secukinumab 150 mg/month. Dose increase from 150 to 300 mg per month and shortening of administration frequency were allowed for poor disease control. Response evaluation was based on the number of oral ulcers in the previous 28 days and Disease Activity Score-28 for articular manifestations.

Results: At 3 months of follow-up, nine (66.7%) patients achieved a response (complete or partial), and this proportion further increased to 86.7% at 6 months, 76.9% at 12 months, 90.0% at 18 months and 100.0% after 24 months. Notably, all patients who started with secukinumab 300 mg/month achieved complete response by month 6. Seven (46.7%) patients could achieve a response only after switching to a higher dosage.

Conclusions: Our study suggests that secukinumab at a dose of 150 and 300 mg per month is safe and effective for the long-term treatment of patients with Behçet's syndrome with a mucosal and articular phenotype refractory to previous treatments. Notably, secukinumab 300 mg/month resulted in superior complete mucosal and articular responses with no serious or dose-related adverse effects.
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http://dx.doi.org/10.1136/annrheumdis-2020-217108DOI Listing
August 2020

SARS-CoV-2 infection among patients with systemic autoimmune diseases.

Autoimmun Rev 2020 Jul 5;19(7):102575. Epub 2020 May 5.

Department of Experimental and Clinical Medicine, University of Firenze, Italy.

Objectives: This study aimed to evaluate the prevalence of clinically overt SARS-CoV-2 infection (COVID-19) among patients with systemic autoimmune diseases residing in Tuscany, and to compare it with that observed in the general Tuscan population.

Methods: In this cross-sectional study, Tuscan outpatients with systemic autoimmune diseases followed at a tertiary referral centre were telephonically interviewed between April 1st-14th 2020 to collect demographic and clinical data, information on ongoing immunomodulating/immunosuppressive treatments, and on the presence of symptoms suspected of SARS-CoV-2 or of a confirmed infection.

Results: 458 patients were interviewed [74% female, median age 56 years (IQR 43-68)]; 56% of them were receiving corticosteroids, 44% traditional disease-modifying anti-rheumatic drugs (DMARDs), of whom 23% hydroxychloroquine, 5% colchicine, while 41% were on biologic DMARDs (of whom 9% on tocilizumab). Thirteen patients reported symptoms suggesting SARS-CoV-2 infection. Of them, 7 had undergone nasopharyngeal swab and only one was positive and developed severe SARS-CoV-2 complications. Within our cohort, the prevalence of SARS-CoV-2 infection was therefore 0.22% (0.01-1.21%), comparable to that observed in the general population of Tuscany [0.20% (0.20-0.21%), p = .597].

Conclusions: Patients with systemic autoimmune diseases do not seem to carry an increased risk of SARS- CoV-2 infection as compared to the general population.
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http://dx.doi.org/10.1016/j.autrev.2020.102575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200134PMC
July 2020

Behçet: the syndrome.

Rheumatology (Oxford) 2020 05;59(Suppl 3):iii101-iii107

Department of Experimental and Clinical Medicine.

Behçet's syndrome (BS) is a systemic vasculitis characterized by a relapsing and remitting course. It can involve the skin, mucosa, joints, vessels (arteries and/or veins), eyes, and nervous and gastrointestinal systems, and so is referred to as a syndrome rather than as a unique and nosologically distinct condition. These involvements may present alone or co-exist in the same patient. Although all the possible combinations of the above-mentioned manifestations may occur, clusters of commonly co-existing involvements (also referred to as 'disease phenotypes') have been suggested, namely 'mucocutaneous and articular', 'peripheral vascular and extra-parenchymal neurological' and 'parenchymal neurological and ocular' phenotypes have been described. Patient-specific demographic and genetic features have been described as positively or negatively associated with specific disease phenotypes. This review will focus on the different clinical features of Behçet's syndrome, summarizing current evidence on the distinct disease manifestations as well as the major phenotypes.
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http://dx.doi.org/10.1093/rheumatology/kez626DOI Listing
May 2020

Adalimumab effectively controls both anterior and posterior noninfectious uveitis associated with systemic inflammatory diseases: focus on Behçet's syndrome.

Inflammopharmacology 2020 Jun 10;28(3):711-718. Epub 2020 Mar 10.

Department of Experimental and Clinical Medicine, University of Firenze, 50134, Florence, Italy.

Background: To compare the efficacy of Adalimumab (ADA) in noninfectious anterior uveitis (AU) and posterior segment (PS) involvement, associated with different conditions, with a focus on Behçet's syndrome (BS).

Methods: In this retrospective, multicenter post-hoc study, we evaluated the efficacy of ADA in terms of ocular control and relapses in 96 patients with AU and PS uveitis, either idiopathic (IU) or associated with BS or with other systemic disorders (OSD) (Juvenile Idiopathic Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Vogt-Koyanagi-Harada, Inflammatory Bowel Disease), followed in three tertiary referral centers.

Results: Ninety-six patients (45 AU; 51 PS uveitis) were included. Eleven had IU, 58 BS, and 27 OSD. All patients with AU achieved complete long-term ocular control. In PS uveitis, 89%, 67% and 100% of patients with BS, IU and OSD achieved ocular control at the last follow-up (> 12 months), respectively. The lowest ocular relapse rate occurred in patients with AU with BS (1/13) or IU (0/2). ADA accounted for long-term disease control, and no predictors of ocular control and relapse were identified; particularly, ocular relapses seemed not related to systemic ones. Macular edema resolved in 75% and 67% of PS uveitis with BS and IU, respectively.

Conclusions: ADA controls both anterior and posterior uveitis, with an efficacy similar in IU, BS and OSD patients. In BS, the efficacy of ADA seems to be independent of demographic and clinical characteristics, and ocular relapses mostly occurred independently from systemic ones. Based on our results, ADA may represent a valid alternative in anterior refractory uveitis.
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http://dx.doi.org/10.1007/s10787-020-00697-4DOI Listing
June 2020

Stem-Cell-Derived Circulating Progenitors Dysfunction in Behçet's Syndrome Patients Correlates With Oxidative Stress.

Front Immunol 2019 13;10:2877. Epub 2019 Dec 13.

Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Firenze, Firenze, Italy.

Behçet's syndrome (BS) is a systemic vasculitis considered as the prototype of a systemic inflammation-induced thrombotic condition whose pathogenesis cannot be explained just by coagulation abnormalities. Circulating hematopoietic progenitor cells (CPC), a population of rare, pre-differentiated adult stem cells originating in the bone marrow and capable of both self-renewal and multi-lineage differentiation, are mobilized in response to vascular injury and play a key role in tissue repair. In cardiovascular and thrombotic diseases, low circulating CPC number and reduced CPC function have been observed. Oxidative stress may be one of the relevant culprits that account for the dysfunctional and numerically reduced CPC in these conditions. However, the detailed mechanisms underlying CPC number reduction are unknown. On this background, the present study was designed to evaluate for the first time the possible relationship between CPC dysfunction and oxidative stress in BS patients. In BS patients, we found signs of plasma oxidative stress and significantly lower CD34+/CD45 and CD34+/CD45/CD133+ CPC levels. Importantly, in all the considered CPC subsets, significantly higher ROS levels with respect to controls were observed. Higher levels of caspase-3 activity in all the considered CPC population and a strong reduction in GSH content in CPC subpopulation from BS patients with respect to controls were also observed. Interestingly, in BS patients, ROS significantly correlated with CPC number and CPC caspase-3 activity and CPC GSH content significantly correlated with CPC number, in all CPC subsets. Collectively, these data demonstrate for the first time that CPC from BS patients show signs of oxidative stress and apoptosis and that a reduced CPC number is present in BS patients with respect to controls. Interestingly, we observed an inverse correlation between circulating CPC number and CPC ROS production, suggesting a possible toxic ROS effect on CPC in BS patients. The significant correlations between ROS production/GSH content and caspase-3 activity point out that oxidative stress can represent a determinant in the onset of apoptosis in CPC. These data support the hypothesis that oxidative-stress-mediated CPC dysfunctioning may counteract their vascular repair actions, thereby contributing to the pathogenesis and the progression of vascular disease in BS.
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http://dx.doi.org/10.3389/fimmu.2019.02877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923242PMC
November 2020

Treating the Different Phenotypes of Behçet's Syndrome.

Front Immunol 2019 6;10:2830. Epub 2019 Dec 6.

Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

Behçet's syndrome (BS) is a multisystemic vasculitis, characterized by different clinical involvements, including mucocutaneous, ocular, vascular, neurological, and gastrointestinal manifestations. Based on this heterogeneity, BS can be hardly considered as a single clinical entity. Growing evidence supports that, within BS, different phenotypes, characterized by clusters of co-existing involvements, can be distinguished. Namely, three major BS phenotypes have been reported: (a) the mucocutaneous and articular phenotype, (b) the extra-parenchymal neurological and peripheral vascular phenotype, and (c) the parenchymal neurological and ocular phenotype. To date, guidelines for the management of BS have been focused on the pharmacological treatment of each specific BS manifestation. However, tailoring the treatments on patient's specific phenotype, rather than on single disease manifestation, could represent a valid strategy for a personalized therapeutic approach to BS. In the present literature review, we summarize current evidence on the pharmacological treatments for the first-, second-, and third-line treatment of the major BS phenotypes.
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http://dx.doi.org/10.3389/fimmu.2019.02830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915087PMC
November 2020

A double-edged sword: e-cigarettes, and other electronic nicotine delivery systems (ENDS): reply.

Intern Emerg Med 2020 09 14;15(6):1119-1121. Epub 2019 Nov 14.

Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

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http://dx.doi.org/10.1007/s11739-019-02228-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467907PMC
September 2020

Management of oral anticoagulation in very old patients with non valvular atrial fibrillation related acute ischemic stroke.

J Thromb Thrombolysis 2020 Jan;49(1):86-93

Internal Medicine II, San Giuseppe Hospital, Empoli, Italy.

The optimal management of oral anticoagulation (OAC) in the acute phase of non valvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS) remains controversial, especially in very old patients. Therefore, the aim of our study was to evaluate the practical management of OAC in this context. We conducted an observational retrospective study on patients 85-years old and older admitted to two Italian hospitals for NVAF-related AIS. For each patient, clinical and brain computed tomography data were recorded. Type of OAC (vitamin K antagonists, VKAs or Direct Oral Anticoagulants, DOACs), dosage and starting day after AIS were registered. For each patient 90-day all cause mortality, stroke recurrence, any bleeding and modified Rankin scale (mRS) were reported. One-hundred-seventeen patients, with mean age 89.2 ± 3.4 years, were enrolled. In-hospital and 90-day mortality (out of 109 patients) were 6% and 19.7%, respectively. OAC was started in 93 patients (80.5%), on average after 6 ± 3 days from the acute event. Of them, 88 patients (94.6%) received DOACs, while 5 (5.4%) received VKAs. Patients receiving OAC were significantly younger and suffering from less severe stroke compared with patients who did not receive OAC. Patients receiving OAC presented a reduced in-hospital (2.2% vs. 20.8%, p < 0.004) and 90-day all-cause mortality (9.4% vs. 62.5%, p < 0.001). In patients receiving DOACs, low dosages were used in 87.5% of patients. The use of OAC was not associated with an increased rate of hemorrhagic transformation (HT) during hospitalization (13.2% vs. 9.5%, p = 0.54) or any bleeding at 90-day follow-up. Severe dysphagia and mRS ≥ 4 were found to be independent risk factors for not prescribing OAC. The optimal management of OAC in very old patients suffering from NVAF-related AIS remains a dilemma. In our real world study the majority of patients received OAC as secondary prevention treatment without increase in bleeding risk. Dysphagia and severe disability were independent factors for not prescribing OAC. Further investigations aimed at identifying the optimal approach to OAC during the acute phase of NVAF-related ischemic stroke in this subgroup of patients are warranted.
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http://dx.doi.org/10.1007/s11239-019-01972-0DOI Listing
January 2020

Anakinra for corticosteroid-dependent and colchicine-resistant pericarditis: The IRAP (International Registry of Anakinra for Pericarditis) study.

Eur J Prev Cardiol 2020 06 15;27(9):956-964. Epub 2019 Oct 15.

Heart and Vascular Institute, Cleveland Clinic, USA.

Aims: Novel therapies are needed for recurrent pericarditis, particularly when corticosteroid dependent and colchicine resistant. Based on limited data, interleukin-1 blockade with anakinra may be beneficial. The aim of this multicentre registry was to evaluate the broader effectiveness and safety of anakinra in a 'real world' population.

Methods And Results: This registry enrolled consecutive patients with recurrent pericarditis who were corticosteroid dependent and colchicine resistant and treated with anakinra. The primary outcome was the pericarditis recurrence rate after treatment. Secondary outcomes included emergency department visits, hospitalisations, corticosteroid use and adverse events. Among 224 patients (46 ± 14 years old, 63% women, 75% idiopathic), the median duration of disease was 17 months (interquartile range 9-33). Most patients had elevated C-reactive protein (91%) and pericardial effusion (88%). After a median treatment of 6 months (3-12), pericarditis recurrences were reduced six-fold (2.33-0.39 per patient per year), emergency department admissions were reduced 11-fold (1.08-0.10 per patient per year), hospitalisations were reduced seven-fold (0.99-0.13 per patient per year). Corticosteroid use was decreased by anakinra (respectively from 80% to 27%;  < 0.001). No serious adverse events occurred; adverse events consisted mostly of transient skin reactions (38%) at the injection site. Adverse events led to discontinuation in 3%. A full-dose treatment duration of over 3 months followed by a tapering period of over 3 months were the therapeutic schemes associated with a lower risk of recurrence.

Conclusion: In patients with recurrent pericarditis, anakinra appears efficacious and safe in reducing recurrences, emergency department admissions and hospitalisations.
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http://dx.doi.org/10.1177/2047487319879534DOI Listing
June 2020

Health impact of electronic cigarettes and heated tobacco systems.

Intern Emerg Med 2019 09 14;14(6):817-820. Epub 2019 Aug 14.

Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

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http://dx.doi.org/10.1007/s11739-019-02167-4DOI Listing
September 2019

New perspectives in eosinophilic granulomatosis with polyangiitis (EGPA): report of the first meeting of the European EGPA Study Group.

Intern Emerg Med 2019 11 6;14(8):1193-1197. Epub 2019 Aug 6.

SOC Nefrologia E Dialisi, Azienda Ospedaliero-Universitaria Meyer, e Dipartimento Di Scienze Biomediche, Sperimentali e Cliniche "Mario Serio", Università Di Firenze, Viale Pieraccini 6, 50139, Florence, Italy.

The European Eosinophilic Granulomatosis with Polyangiitis (EGPA) study group first gathered in Firenze in December 2018. The discussion was centred around the clinical and therapeutic needs in EGPA which still remain unmet. Indeed, EGPA is a puzzling and rare disease which shares clinical features with other anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAVs) and hypereosinophilic syndromes (HESs). Some of the recommendations published in 2015 are based on data derived from EGPA-related diseases, rather than from EGPA itself, and therefore need to be updated. Thus, the aim of the meeting was to stimulate ongoing research, to promote collaborative European studies and to define the main issues on which future studies should be focused. Current fields of research on EGPA include potential serological biomarkers of disease activity and of specific organ involvement, possible links between different genetic variants and clinical phenotypes, and new therapeutic perspectives. Herein, we give an overview of the meeting with the goal to stimulate an international collaboration and new points of discussion.
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http://dx.doi.org/10.1007/s11739-019-02166-5DOI Listing
November 2019