Publications by authors named "Alessandra Bettiol"

63 Publications

The first 1000 days of life: traffic-related air pollution and development of wheezing and asthma in childhood. A systematic review of birth cohort studies.

Environ Health 2021 Apr 17;20(1):46. Epub 2021 Apr 17.

Unit of Epidemiology, Meyer Children's University Hospital, Viale Pieraccini 24, 50139, Florence, Italy.

Background: The first 1000 days of life -including pregnancy and the first 2 years after birth- represent a critical window for health interventions. This systematic review aimed to summarize the evidence on the relationship between traffic-related air pollutants exposure in the first 1000 days of life and the development of wheezing and asthma, with a particular focus on windows of exposure.

Methods: Medline and Embase were searched from January 2000 to May 2020 to retrieve population-based birth-cohort studies, including registries, providing quantitative information on the association between exposure to traffic-related air pollutants during pregnancy or early life, and the risk of developing wheezing and asthma in childhood. Screening and selection of the articles were completed independently by three reviewers. The quality of studies was assessed using the Newcastle-Ottawa scale.

Results: Out of 9681 records retrieved, 26 studies from 21 cohorts were included. The most common traffic-related air pollutant markers were particulate matter (PM) and nitric oxides (NOx). The variability in terms of pollutants, exposure assessment methods, and exposure levels chosen to present the results did not allow a meta-analysis. Exposure to PM and NOx in pregnancy (10 cohorts) was consistently associated with an increased risk of asthma development, while the association with wheezing development was unclear. The second trimester of pregnancy seemed to be particularly critical for asthma risk. As for exposure during early life (15 cohorts), most studies found a positive association between PM (7/10 studies) and NOx (11/13 studies) and the risk of asthma development, while the risk of wheezing development was controversial. The period of postnatal exposure, however, was less precisely defined and a partial overlap between the period of exposure measurement and that of outcome development was present in a consistent number of studies (14 out of 15) raising doubts on the associations found.

Conclusions: Traffic-related air pollution during pregnancy is associated with an increased risk of asthma development among children and adolescents. The relationship between exposure in the first two years of life and the development of wheezing and asthma needs to be confirmed in studies with more precise exposure assessment.
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http://dx.doi.org/10.1186/s12940-021-00728-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053261PMC
April 2021

Risk of Hospitalization Associated with Cardiovascular Medications in the Elderly Italian Population: A Nationwide Multicenter Study in Emergency Departments.

Front Pharmacol 2020 29;11:611102. Epub 2021 Jan 29.

Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Florence, Italy.

There is a significant gap in knowledge addressing cardiovascular (CV) medications safety in elderly. In this context, our purposes were to define clinical and pharmacological characteristics of outpatients' adverse drug events (ADEs) related to CV medications leading to emergency department (ED) visits in the elderly Italian patients according to different age groups, and to evaluate the risk of hospitalization associated to ADEs in this population. A multicentre, retrospective study was performed on reports of suspected ADEs collected between 2007-2018 in 94 EDs involved in the MEREAFaPS Study. Elderly patients who experienced one or more CV medications-related ADEs leading to ED visit were selected. Patients' characteristics, suspected (ATC classes B and C) and concomitant drugs, and ADE description were collected. Elderly patients were stratified into three age groups (65-74, 75-84, and ≥85 years) and compared to adults (18-64 years). Logistic regression analyses were used to estimate the reporting odds ratios (RORs) with 95% confidence intervals (CIs) of ADE-related hospitalization adjusting for sex, presence of two or more suspected drugs, concomitant drugs, and one or more comorbidities. Among elderly, 16,926 reports of suspected ADE related to CV medications were collected, and 6,694 (39.5%) resulted in hospitalization. Patients were mostly female, Caucasians, and middle-old (75-84). 78.9% of patients were treated with only one suspected drug, and 71.9% and 47.1% reported concomitant medications and comorbidities, respectively. Compared to adults, risk of hospitalization was significantly higher for middle-old and oldest-old patients exposed to vitamin K antagonists (1.29 [1.09-1.52] and 1.56 [1.30-187]), direct thrombin inhibitors (3.41 [1.44-8.08] and 4.12 [1.67-10.17]), antiplatelets (1.51 [1.26-1.81] and 2.09 [1.71-2.57]), and beta-blockers (1.89 [1.38-2.59 and 2.31 [1.60-3.35]). Overall, a higher risk of hospitalization was observed for renin-angiotensin system inhibitors (1.32 [1.04-1.68], 1.65 [1.32-2.06], and 2.20 [1.70-2.85]), presence of two or more concomitant drugs, and concomitant conditions. Our real-world findings underline relevant safety aspects of CV medications in the elderly Italian population. ED clinicians must always consider the higher risk of hospitalization related to the use of CV drugs in elderly, particularly in oldest-old ones, for antiarrhythmics, beta-blocking agents, renin-angiotensin system inhibitors, antiplatelets, and anticoagulants.
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http://dx.doi.org/10.3389/fphar.2020.611102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941274PMC
January 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

Slowly progressive anti-neutrophil cytoplasmic antibody-associated renal vasculitis: clinico-pathological characterization and outcome.

Clin Kidney J 2021 Jan 6;14(1):332-340. Epub 2020 Sep 6.

Department of Biomedical Experimental and Clinical Sciences "Mario Serio", University of Firenze, and Nephrology Unit, Meyer Children's Hospital, Firenze, Italy.

Background: Although rapidly progressive glomerulonephritis is the main renal phenotype of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), slow renal disease progression is sometimes observed. These forms have been rarely discussed; we analysed their prevalence, clinico-pathological characteristics and outcome.

Methods: We screened patients with microscopic  polyangiitis (MPA) and granulomatosis with polyangiitis followed at seven referral centres and selected those with estimated glomerular filtration rate (eGFR) reduction <50% over a 6-month period preceding diagnosis. Data regarding patient features and response to treatment were retrieved.

Results: Of 856 patients, 41 (5%) had slowly progressive renal AAV. All had MPA and all but one was P-ANCA/myeloperoxidase (MPO) ANCA-positive. At diagnosis, the median age was 70 years [interquartile range (IQR) 64-78] and extra-renal manifestations were absent or subclinical (interstitial lung lesions in 10, 24%). The median (IQR) eGFR was 23 mL/min/1.73 m (15-35); six patients (15%) had started renal replacement therapy (RRT). All had proteinuria (median 1180 mg/24 h, IQR 670-2600) and micro-haematuria. Main histologic findings were extracapillary proliferation at chronic stages and glomerulosclerosis; following Berden's classification, 6/28 biopsies (21%) were 'focal', 1/28 (4%) 'crescentic', 9/28 (32%) 'mixed' and 12/28 (43%) 'sclerotic'. At last follow-up (median 32 months, IQR 12-52), 20/34 patients (59%) treated with immunosuppression had eGFR improvement >25% as compared with diagnosis, while 4/34 (12%) had started RRT.

Conclusions: AAV may present with slow renal disease progression; this subset is hallmarked by advanced age at diagnosis, positive MPO-ANCA, subclinical interstitial lung lesions and chronic damage at kidney biopsy. Partial renal recovery may occur following immunosuppression.
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http://dx.doi.org/10.1093/ckj/sfaa139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857823PMC
January 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

The BLOSSoM study: Burnout after perinatal LOSS in Midwifery. Results of a nation-wide investigation in Italy.

Women Birth 2021 Jan 25. Epub 2021 Jan 25.

Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy; CiaoLapo, Charity for Healthy Pregnancy, Stillbirth and Perinatal Loss Support, Prato, Italy; PEARL Perinatal Research Laboratory, CiaoLapo Foundation & University of Florence, Florence, Italy. Electronic address:

Background: Respectful care of bereaved parents after stillbirth plays a pivotal role in enabling the grieving process and reducing the traumatic impact of this life-changing event. Unfortunately, professionals and midwives, in particular, are often emotionally unprepared and frequently left alone when dealing with these stressful events.

Aim: The BLOSSoM (Burnout after perinatal LOSS in Midwifery) study aims to address the levels of professional burnout in Italian midwives and evaluate the psychological impact of bereavement care on professionals.

Methods: Web-based cross-sectional study, including socio-demographic questionnaire, survey on the knowledge of guidelines for stillbirth management and two psychometric tests: Maslach Burnout Inventory (MBI) and Impact of Event Scale - Revised (IES-R).

Findings: Of 445 female midwives, mean age 35.1 (SD 9.9), working years 11.2 (SD 10.2), 149 (33.4%) reported specific training on stillbirth and 420 (94.6%) highlighted the need for further training and support. Medium to high levels of burnout (Emotional Exhaustion) were present in 65 midwives (15.9%) with a high prevalence of Reduced Personal Accomplishment (292, 64.2%). 'Communicating the diagnosis of death' was considered the hardest task, followed by 'assisting the meeting with the baby'; 109 midwives (24.5%) reported high IES-R scores (>30), suggesting symptoms of PTSD related to stillbirth events; a good level of knowledge of guidelines favoured Personal Accomplishment (OR 0.3 [0.1 - 0.6]). The number of stillbirths assisted by midwives was not associated with burnout levels.

Conclusion: Midwives are particularly at risk of developing professional burnout, as early as after five years of work, with a significant association with the psychological impact exerted by stressful events (stillbirth).
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http://dx.doi.org/10.1016/j.wombi.2021.01.003DOI Listing
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

The management of pediatric severe traumatic brain injury: Italian Guidelines.

Minerva Anestesiol 2021 May 12;87(5):567-579. Epub 2021 Jan 12.

Società Italiana di Pediatria (SIP), Rome, Italy.

Introduction: The aim of the work was to update the "Guidelines for the Management of Severe Traumatic Brain Injury" published in 2012, to reflect the new available evidence, and develop the Italian national guideline for the management of severe pediatric head injuries to reduce variation in practice and ensure optimal care to patients.

Evidence Acquisition: MEDLINE and EMBASE were searched from January 2009 to October 2017. Inclusion criteria were English language, pediatric populations (0-18 years) or mixed populations (pediatric/adult) with available age subgroup analyses. The guideline development process was started by the Promoting Group that composed a multidisciplinary panel of experts, with the representatives of the Scientific Societies, the independent expert specialists and a representative of the Patient Associations. The panel selected the clinical questions, discussed the evidence and formulated the text of the recommendations. The documentarists of the University of Florence oversaw the bibliographic research strategy. A group of literature reviewers evaluated the selected literature and compiled the table of evidence for each clinical question.

Evidence Synthesis: The search strategies identified 4254 articles. We selected 3227 abstract (first screening) and, finally included 67 articles (second screening) to update the guideline. This Italian update includes 25 evidence-based recommendations and 5 research recommendations.

Conclusions: In recent years, progress has been made on the understanding of severe pediatric brain injury, as well as on that concerning all major traumatic pathology. This has led to a progressive improvement in the clinical outcome, although the quantity and quality of evidence remains particularly low.
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http://dx.doi.org/10.23736/S0375-9393.20.14122-1DOI Listing
May 2021

Pharmacological Interventions for the Prevention of Fetal Growth Restriction: A Systematic Review and Network Meta-Analysis.

Clin Pharmacol Ther 2021 Jan 10. Epub 2021 Jan 10.

Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.

The prevention of fetal growth restriction (FGR) is challenging in clinical practice. To date, no meta-analysis summarized evidence on the relative benefits and harms of pharmacological interventions for FGR prevention. We performed a systematic review and network meta-analysis (NetMA), searching PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception until November 2019. We included clinical trials and observational studies on singleton gestating women evaluating antiplatelet, anticoagulant, or other treatments, compared between each other or with controls (placebo or no treatment), and considering the pregnancy outcome FGR (primary outcome of the NetMA). Secondary efficacy outcomes included preterm birth, placental abruption, and fetal or neonatal death. Safety outcomes included bleeding and thrombocytopenia. Network meta-analyses using a frequentist framework were conducted to derive odds ratios (ORs) and 95% confidence intervals (CIs). Of 18,780 citations, we included 30 studies on 4,326 patients. Low molecular weight heparin (LMWH), alone or associated with low-dose aspirin (LDA), appeared more efficacious than controls in preventing FGR (OR 2.00, 95% CI 1.27-3.16 and OR 2.67, 95% CI 1.21-5.89 for controls vs. LMWH and LDA + LMWH, respectively). No difference between active treatments emerged in terms of FGR prevention, but estimates for treatments other than LMWH +/- LDA were imprecise. Only the confidence in the evidence regarding LMWH vs. controls was judged as moderate, according to the Confidence in Network Meta-Analysis framework. No treatment was associated with an increased risk of bleeding, although estimates were precise enough only for LMWH. These results should inform clinicians on the benefits of active pharmacological prophylaxis for FGR prevention.
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http://dx.doi.org/10.1002/cpt.2164DOI Listing
January 2021

Effectiveness of ibuprofen plus paracetamol combination on persistence of acute musculoskeletal disorders in primary care patients.

Int J Clin Pharm 2021 Jan 7. Epub 2021 Jan 7.

Health Search, Italian College of General Practitioners and Primary Care, Florence, Italy.

Background General practitioners often deal with patients suffering acute musculoskeletal disorders. Paracetamol, non-steroidal anti-inflammatory drugs, and opioids are the most prescribed medications, according to pain intensity and patient's features. Combinations of different analgesics can be adopted to enhance pain relief, but only one fixed-dose combination has been recently launched to treat acute musculoskeletal pain. Objective This study aimed to investigate the effectiveness of ibuprofen plus paracetamol (fixed-dose) combination compared to other analgesics in preventing musculoskeletal pain persistence. Setting Italian outpatients' data extracted from a national general practice database. Method A retrospective cohort study was conducted on the Health Search Database. Patients prescribed with analgesics for acute musculoskeletal painful conditions were considered (i.e., non-chronic painful conditions, identified using a query validated by two expert General Practitioners (GPs)). For each patient, the first prescription of an analgesic was defined as index date. A new GP's visit related to musculoskeletal disorders in the first 3 months following the index date was defined as "pain persistence". Main outcome measure Risk of pain persistence among users of the ibuprofen plus paracetamol combination compared to other systemic analgesics. Results Overall, 102,216 patients were treated with systemic analgesics for acute musculoskeletal disorders. Most patients were middle-aged or elderly women. 939 (0.92%) patients were prescribed with the fixed-dose ibuprofen plus paracetamol combination for a mean duration of 7.23 ± 2.68 days, mainly for low back pain and cervicalgia. Musculoskeletal pain persistence was found in 22,125 (21.65%) patients. Compared to other systemic analgesics, the ibuprofen plus paracetamol combination resulted significantly more effective in preventing pain persistence (adjusted hazard ratio 0.72, 95% confidence interval 0.61-0.85). Conclusion These findings suggest that the fixed-dose ibuprofen plus paracetamol combination might be effective in controlling musculoskeletal pain persistence.
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http://dx.doi.org/10.1007/s11096-020-01215-wDOI 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

Systematic review with meta-analysis: the efficacy and safety of direct-acting antivirals in children and adolescents with chronic hepatitis C virus infection.

Aliment Pharmacol Ther 2020 10 18;52(7):1125-1133. Epub 2020 Aug 18.

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

Background: The effect of direct-acting anti-virals (DAAs) in children and adolescents with chronic hepatitis C virus (HCV) infection is difficult to determine, since few, aged between 3 and 18 years, have been enrolled in clinical trials, and some data come from observational studies.

Aim: To summarise the evidence on efficacy and safety of DAAs in children and adolescents with chronic HCV infection.

Methods: We performed a systematic review and meta-analysis of prospective studies on the efficacy and safety of DAAs in subjects <18 years of age. We considered the sustained virological response at post-treatment week 12 as efficacy outcome and adverse events as safety outcome. We considered intervention effect for each study arm by calculating the proportion of sustained virologic response at post-treatment week 12 in subjects receiving all doses of treatment and proportion of adverse events in subjects receiving at least one dose of treatment. Pooled proportions were calculated using the Freeman-Tukey double arcsine transformation. Random effects model was used for all analyses.

Results: Among 39 included studies (1796 subjects), the pooled proportion among those receiving all doses of treatment and reaching sustained virologic response at post-treatment week 12 was 100% (95% confidence interval: 100-100). Considering subjects receiving at least one dose of treatment, lowest estimates were reported among children with cirrhosis (83%). Headache and fatigue were the most common adverse events. Serious adverse events were uncommon.

Conclusions: Children and adolescents with chronic HCV infection can be safely treated with DAAs with similar efficacy as reported in adults.
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http://dx.doi.org/10.1111/apt.16037DOI Listing
October 2020

Low-dose methadone for refractory chronic migraine accompanied by medication-overuse headache: a prospective cohort study.

Neurol Sci 2021 Mar 20;42(3):987-994. Epub 2020 Jul 20.

NEUROFARBA Department, Toxicology Unit, Careggi University Hospital, University of Florence, Florence, Italy.

Objectives: A refractory chronic migraine (RCM) accompanied by medication-overuse headache (MOH) is an extremely disabling disease. Evidence suggests that in selected patients, chronic opioids may be a valuable therapeutic option for RCM. The aim of the present study was to evaluate the effectiveness and safety of prophylaxis with low-dose methadone (LDM) in patients affected by RCM with continuous headache and MOH.

Methods: A prospective cohort study was performed between May 2012 and November 2015 at the Headache Center and Toxicology Unit of the Careggi University Hospital. Eligible patients were treated with prophylactic LDM and followed up for 12 months. Headache exacerbations, pain intensity, use of rescue medications, and occurrence of adverse drug reactions (ADRs) were recorded.

Results: Thirty patients (24 females, median age 48 years) were enrolled. Nineteen (63%) patients dropped out, mainly because of early ADRs (n = 10), including nausea, vomiting, and constipation. At last available follow-up, LDM was associated with a significant decrease in the number of headache attacks/month (from a median of 45 (interquartile range 30-150) to 16 (5-30), p < 0.001), in pain intensity (from 8.5 (8-9) to 5 (3-6), p < 0.001), and in the number of rescue medications consumed per month (from 95 (34-240) to 15 (3-28), p < 0.001). No misuse or diversion cases were observed.

Conclusion: LDM could represent a valuable and effective option in selected patients affected by RCM with continuous headache and MOH, although the frequency of early ADRs poses major safety concerns. Randomized controlled trials are needed to confirm the efficacy and safety of LDM prophylaxis.
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http://dx.doi.org/10.1007/s10072-020-04602-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870632PMC
March 2021

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

T1 Glottic Cancer: Does Anterior Commissure Involvement Worsen Prognosis?

Cancers (Basel) 2020 Jun 6;12(6). Epub 2020 Jun 6.

Department of Otorhinolaryngology, Maxillofacial and Thyroid Surgery, Fondazione IRCCS, National Cancer Institute of Milan, University of Milan, 20122 Milan, Italy.

Radiotherapy (RT) and transoral laser microsurgery (TLM) represent the main treatment modalities for early glottic carcinoma. Local failure is notoriously more frequent in T1b glottic cancer in comparison to T1a and T2 tumors. In this scenario, the role of anterior commissure (AC) involvement is still controversial. The aim of the present study was therefore to determine its potential prognostic power in worsening patients' survival and outcomes. We categorized different tumor glottic fold locations with respect to the involvement of one (T1a) or both vocal cords, with or without AC involvement. We analyzed a retrospective cohort of 74 patients affected by Stage I glottic cancer, treated between 2011 and 2018 by TLM or RT at a single academic institution. There were 22 T1a (30%) and 52 T1b (70%) cases. The median follow-up period was 30 months (mean, 32.09 ± 18.738 months; range, 12-79). Three-year overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and laryngectomy-free survival (LFS) were compared according to tumor location, extension, and cT category. According to both uni- and multivariate analyses, an increased risk for recurrence in T1b with AC involvement and T1a tumors was 7.31 and 9.45 times, respectively (-values of 0.054 and 0.030, respectively). Among the 17 recurrences, T1b with AC involvement experienced 15 tumor relapses (88.2%), thus significantly affecting both the RFS and LFS in comparison to the other two tumor subcategories (T1a, = 0.028 and T1b without AC involvement, = 0.043). The deteriorating prognosis in the presence of AC involvement likely reflects the need to power the hazard consistency and discrimination of the T1b category when associated with such a risk factor, thus deserving an independent T category.
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http://dx.doi.org/10.3390/cancers12061485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352716PMC
June 2020

A model to predict postoperative complications for otorhinolaryngology and maxillofacial surgery procedures in elderly patients.

Eur Arch Otorhinolaryngol 2020 Dec 3;277(12):3459-3467. Epub 2020 Jun 3.

Head and Neck and Robotic Surgery, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

Purpose: All kinds of ear, nose, and throat and maxillofacial surgery (ENT/MFS) procedures are being increasingly performed in the elderly although old age is a major risk factor for increased postoperative complications. With only scarce evidence on the topic, surgeons are asked to critically evaluate their procedures' indications and outcomes to balance the treatment risks and benefits. Our primary aim was to identify predictive factors for surgical outcomes in this setting and to create a predictive model for a tailored risk assessment.

Methods: We analyzed a case series of 435 patients from an institutional clinical database at our academic tertiary care center. Multivariate logistic regression was used to identify all possible covariates and nomograms using stepwise backward method were generated. The performance was assessed by calibration curves and c-index.

Results: Overall complication rate was 18.3% within the first 30 days and the need for re-intervention was 5.9%. For those under general anesthesia, we identified specific risk factors and developed three risk-predicting models of overall, early, and late complications. All of the nomograms showed satisfactory accuracy with a c-index of 0.83, 0.75, 0.86, and 0.82, respectively.

Conclusion: Using clinical preoperative variables, we constructed a model for predicting major adverse events in ENT/MFS patients. In our experience, patients over 65 showed a non-negligible risk for postoperative complications depending on several factors. Such tools might help in decision-making, by increasing the risk-awareness of clinicians, to better address peri-operative and post-operative care of these patients.
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http://dx.doi.org/10.1007/s00405-020-06084-7DOI Listing
December 2020

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

Risk of hospitalisation associated with benzodiazepines and z-drugs in Italy: a nationwide multicentre study in emergency departments.

Intern Emerg Med 2020 10 24;15(7):1291-1302. Epub 2020 Apr 24.

Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini, 6, 50139, Florence, Italy.

Benzodiazepines (BZD) and z-drugs (ZD) are a widely prescribed group of medicines. They are often used inappropriately, and this is associated with adverse events (AEs), which may cause emergency department (ED) visits. The present study aimed to describe the characteristics of BZD and ZD related AEs leading to emergency department (ED) visit and hospitalisation in Italy, considering their plasma half-life. Ninety-two Italian EDs were monitored between 2007 and 2018. Rates of ED visit and hospitalisation were calculated. Multivariate logistic regression was used to estimate the reporting odds ratios (RORs) of hospitalisation. Univariate linear regression was performed to evaluate the ROR of hospitalisation according the plasma half-life of the suspected agents. A total of 3203 AE reports were collected. Overall, multivariate logistic regression showed that the risk of hospitalisation was higher for prazepam (3.26 [1.31-8.11]), flurazepam (1.62 [1.15-2.27]), and lorazepam (1.36 [1.15-1.61]). In the elderly, this risk was higher for prazepam (3.98 [1.03-15.3]), and lorazepam (1.58 [1.19-2.11]). Parenteral and rectal formulations were associated with a lower risk of hospitalisation compared to oral formulations. Our findings underlined the dangers in the use of BZD and ZD in Italy, particularly in women and older adults. ED clinicians must always take into account that the higher risk in terms of hospitalisation related to the use of BZD and ZD can be observed in patients treated with oral formulations, in those exposed to more than one sedative-hypnotics, and in patients exposed to compounds with intermediate or long plasma half-life.
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http://dx.doi.org/10.1007/s11739-020-02339-7DOI Listing
October 2020

Italian Emergency Department Visits and Hospitalizations for Outpatients' Adverse Drug Events: 12-Year Active Pharmacovigilance Surveillance (The MEREAFaPS Study).

Front Pharmacol 2020 6;11:412. Epub 2020 Apr 6.

Section of Pharmacology and Toxicology, Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.

Background: Adverse drug event (ADEs) are a significant cause of emergency department (ED) visits and consequent hospitalization. Preventing ADEs and their related ED visits in outpatients remains a public health safety challenge. In this context, the aims of the present study were to describe the frequency, seriousness and preventability of outpatients' ADE-related ED visits and hospitalizations in the Italian general population, and to identify the presence of potential predictors of ADE-related hospitalization.

Methods: We performed a nationwide, multicentre, observational, retrospective study based on reports of suspected ADEs collected between January 1, 2007 and December 31, 2018 in 94 EDs involved in the MEREAFaPS project. Patients' demographic characteristics, their clinical status, suspected and concomitant drugs, ADE description, and its degree of seriousness, were collected. Causality and preventability were assessed using validated algorithms, and logistic regression analyses were used to estimate the reporting odds ratios (RORs) with 95% confidence intervals (CIs) of ADE-related hospitalization, considering the following covariates: age, sex, ethnicity, number of implicated medications, parenteral administration, presence of interaction, therapeutic error, and/or complementary and alternative medicines (CAM).

Results: Within 12 years, 61,855 reports of suspected ADE were collected, of which 18,918 (30.6%) resulted in hospitalization (ADE defined as serious). Patients were mostly female (56.6%) and Caucasians (87.7%), with a mean age of 57.5 ± 25.0 years. 58% of patients were treated with more than two drugs, and 47% of ADEs leading to hospitalization were preventable. Anticoagulants, antibiotics, and nonsteroidal anti-inflammatory drugs (NSAIDs) were the most frequently implicated agents for ED visits and/or hospitalization, which included clinically significant ADEs, such as haemorrhage for anticoagulants, moderate to severe allergic reactions for antibiotics, and dermatologic reactions and gastrointestinal disturbances for NSAIDs. Older age (1.54 [1.48-1.60]), higher number of concomitantly taken drugs (2.22 [2.14-2.31]), the presence of drug-drug interactions (1.52 [1.28-1.81]), and therapeutic error (1.54 [1.34-1.78]), were significantly associated with an increased risk of hospitalization.

Conclusion: Our long-term active pharmacovigilance study in ED provided a valid estimation of ADE-related hospitalization in a representative sample of the Italian general population and can suggest further focus on medication safety in outpatients, in order to early recognise and prevent ADEs.
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http://dx.doi.org/10.3389/fphar.2020.00412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153477PMC
April 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

Adherence to Triple-Free-Drug Combination Therapies Among Patients With Cardiovascular Disease.

Am J Cardiol 2020 05 7;125(9):1429-1435. Epub 2020 Feb 7.

Health Search, Italian College of General Practitioners and Primary Care, Florence, Italy. Electronic address:

Combination therapies are often needed to modify the concomitant risk factors for cardiovascular disease. Nonadherence to cardiovascular medications is a relevant concern, especially in polytherapy. We conducted a population-based, cohort study with the aim of quantifying the level of adherence and its related determinants in patients exposed to free 3-drug combination therapies, namely concurrent use of angiotensin-converting-enzyme inhibitor (ACEi), calcium channel blocker (CCB), and statin or of ACEi, statin, and low-dose aspirin. Within Health Search Database, we selected a cohort of adult patients concurrently prescribed with ACEi, CCB, and statin, as well as those prescribed with ACEi, statin and low-dose aspirin, from the January 1, 2002 to the December 31, 2014. Adherent patients were concurrent users of triple free pill regimen with a proportion of days covered ≥80% during 1-year follow-up; demographics and clinical determinants of 1-year adherence were identified by multivariate logistic regression. We found that more than half of patients prescribed with triple free drug combination therapy with ACEi plus CCB plus statin or ACEi plus statin plus low-dose aspirin, were found to be nonadherent to these treatments. Males and patients at high/very-high cardiovascular risk were more likely to be adherent, whereas depression and atrial fibrillation were associated with nonadherence. Our findings indicate that sex, cardiovascular risk, presence of atrial fibrillation, and depression can influence adherence to polytherapy. In conclusion, given that patients suffering from multiple cardiovascular risk factors are at higher risk of fatal events, strategies are needed to improve medication adherence to combination therapies.
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http://dx.doi.org/10.1016/j.amjcard.2020.01.036DOI Listing
May 2020

Association between anthraquinone laxatives and colorectal cancer: protocol for a systematic review and meta-analysis.

Syst Rev 2020 01 24;9(1):19. Epub 2020 Jan 24.

Research and Innovation Center in Phytotherapy and Integrated Medicine CERFIT, Referring Center for Phytotherapy, Tuscany Region, Careggi University Hospital, Florence, Italy.

Introduction: Products containing anthraquinones (AQ) are mainly used as laxatives and have several biological effects. Long-term use of AQ laxatives is associated with an increased risk of serious adverse events (AEs), such as colorectal cancer (CRC). We will systematically synthesize the evidence on the potential association between the use of AQ laxatives and the risk of CRC.

Methods And Analysis: We will search MEDLINE, Embase, Scopus, the Cochrane Library, Google Scholar, and Clinicaltrials.gov. To avoid missing any relevant studies, we will search the bibliographies of retrieved papers and recent reviews in the field. Interventions will include products containing oral AQ laxatives, in particular, those derived from rhubarb, senna, cascara, buckhorn, and aloe. Two review authors will independently screen title, abstract, and full texts and will independently extract data from included studies. The primary outcome is the number of participants diagnosed with CRC, while the secondary outcome will be cases of melanosis coli. We will also consider all other AEs reported in the included studies, in particular, intestinal bleeding, alterations of gastrointestinal motility, and potential for dependence. When possible and appropriate, for each outcome, a meta-analysis will be performed.

Discussion: This protocol is prepared in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. The protocol gives an insight into the scope and parameters for the systematic review to be carried out.

Systematic Review Registration: PROSPERO CRD42019125414.
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http://dx.doi.org/10.1186/s13643-020-1280-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979293PMC
January 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