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1. Post-translational modifications of fibrinogen: implications for clotting, fibrin structure and degradation

Author

Francesca Nencini, Alessandra Bettiol, Flavia Rita Argento, Serena Borghi, Elvira Giurranna, Giacomo Emmi, Domenico Prisco, Niccolò Taddei, Claudia Fiorillo, and Matteo Becatti

Subjects
Fibrin, Fibrinogen, Post-translational modifications, Thrombosis, Medicine
Abstract

Abstract Fibrinogen, a blood plasma protein with a key role in hemostasis and thrombosis, is highly susceptible to post-translational modifications (PTMs), that significantly influence clot formation, structure, and stability. These PTMs, which include acetylation, amidation, carbamylation, citrullination, dichlorination, glycation, glycosylation, guanidinylation, hydroxylation, homocysteinylation, malonylation, methylation, nitration, oxidation, phosphorylation and sulphation, can alter fibrinogen biochemical properties and affect its functional behavior in coagulation and fibrinolysis. Oxidation and nitration are notably associated with oxidative stress, impacting fibrin fiber formation and promoting the development of more compact and resistant fibrin networks. Glycosylation and glycation contribute to altered fibrinogen structural properties, often resulting in changes in fibrin clot density and susceptibility to lysis, particularly in metabolic disorders like diabetes. Acetylation and phosphorylation, influenced by medications such as aspirin, modulate clot architecture by affecting fiber thickness and clot permeability. Citrullination and homocysteinylation, although less studied, are linked to autoimmune conditions and cardiovascular diseases, respectively, affecting fibrin formation and stability. Understanding these modifications provides insights into the pathophysiology of thrombotic disorders and highlights potential therapeutic targets. This review comprehensively examines the current literature on fibrinogen PTMs, their specific sites, biochemical pathways, and their consequences on fibrin clot architecture, clot formation and clot lysis.

Published
2024
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2. Prevalence and Predictors of Diabetic Retinopathy, Its Progression and Regression in Indian Children and Youth With Type-1 Diabetes

Author

Chirantap Oza, Anuradha Khadilkar, Shital Bhor, Katie Curran, Chitra Sambare, Dipali Ladkat, Alessandra Bettiol, Michael Quinn, Alan Sproule, Colin Willoughby, and Tunde Peto

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Objective: There are very few reports on the prevalence of diabetic retinopathy (DR) in children and youth with type-1 diabetes (T1D). Studies have also found very low rates of referral for DR screening in children and youth with T1D. We conducted this study to determine the prevalence of DR, to study the reliability of ISPAD screening recommendations and to identify predictors of DR, its progression and regression in Indian children and youth with T1D. Methods: This study included 882 children and youth with T1D. Demographic data, anthropometry, blood pressure, sexual maturity rating, ophthalmological examination (slit lamp for cataract) and biochemical measurements were performed using standard protocols. Fundus images were captured using the Forus Health 3netra classic digital non-mydriatic fundus camera by the same experienced operator. De-identified images were assessed by a senior grader and ophthalmologist (Belfast Ophthalmic Reading Center). Severity of DR was graded as per the UK National Health Service (NHS) DR classification scale. Result: We report 6.4% and 0.2% prevalence of DR and cataract in Indian children and youth with T1D, respectively. All the subjects with DR had early non-proliferative DR. We report that amongst subjects with DR, only 2 subjects were aged less than 11 years and had duration of illness less than 2 years. Presence of hypertension and older age were significant predictors of DR ( P

Published
2024
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3. Epidemiology of SLE in Italy: an observational study using a primary care database

Author

Pietro Ferrara, Giacomo Emmi, Lorenzo G Mantovani, Alessandra Bettiol, Giampiero Mazzaglia, Carla Fornari, Cristiana Borrelli, Irene Mattioli, Manuel Zamparini, Ippazio C Antonazzo, Silvia Boarino, Pasquale Palladino, and Elena Zanzottera Ferrari

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Objectives To estimate the incidence and prevalence of SLE in Italy, and to describe the demographic and clinical characteristics of patients with newly diagnosed SLE.Methods A retrospective cohort study was conducted using The Health Improvement Network general practice database in Italy, encompassing data from 634 753 people. SLE cases were identified over the period 2017–2022, employing three alternative definitions to provide a more detailed understanding of SLE characteristics. Incidence rates were expressed as cases per 100 000 person-years and prevalence as cases per 100 000 people. Demographic and clinical characteristics of incident SLE cases were also studied.Results From 2017 to 2022, a total of 191 incident and 1385 prevalent cases were identified under our first definition. In 2022, the incidence rate was 6.51 cases (95% CI 6.29 to 6.74) per 100 000 person-years, and the prevalence 60.57 (95% CI 59.89 to 61.25) per 100 000 people, being the prevalence five times higher in women compared with men. Both estimates have trended upwards since 2017. A geographical variation across the country was also seen. The demographic and clinical characteristics of incident SLE cases were described, while the potential associations of SLE incidence with some pre-existing conditions were observed, such as chronic kidney disease, chronic hepatic disease, rheumatoid arthritis and Sjogren’s syndrome.Conclusions The results of this nationwide study, the first conducted in Italy, showed that the incidence of SLE has increased in Italy in recent years. Age, sex, and area of residence strongly correlate with the epidemiology of this condition.

Published
2024
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5. SIRT1 and thrombosis

Author

Alessandra Bettiol, Maria Letizia Urban, Giacomo Emmi, Silvia Galora, Flavia Rita Argento, Eleonora Fini, Serena Borghi, Giacomo Bagni, Irene Mattioli, Domenico Prisco, Claudia Fiorillo, and Matteo Becatti

Subjects
SIRT1, thrombosis, oxidative stress, atherosclerosis, sirtuins, Biology (General), QH301-705.5
Abstract

Thrombosis is a major cause of morbidity and mortality worldwide, with a complex and multifactorial pathogenesis. Recent studies have shown that SIRT1, a member of the sirtuin family of NAD + -dependent deacetylases, plays a crucial role in regulating thrombosis, modulating key pathways including endothelial activation, platelet aggregation, and coagulation. Furthermore, SIRT1 displays anti-inflammatory activity both in vitro, in vivo and in clinical studies, particularly via the reduction of oxidative stress. On these bases, several studies have investigated the therapeutic potential of targeting SIRT1 for the prevention of thrombosis. This review provides a comprehensive and critical overview of the main preclinical and clinical studies and of the current understanding of the role of SIRT1 in thrombosis.

Published
2024
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6. The new era of anticoagulation: factor XI and XII inhibitors

Author

Domenico Prisco, Irene Mattioli, Raffaele De Caterina, and Alessandra Bettiol

Subjects
Anticoagulation, bleeding, factor XI, factor XII, thrombosis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

The two last decades have witnessed a revolution in the field of anticoagulation, mainly due to the advent of direct anticoagulant with targeted action against single coagulation proteins. However, the residual risk of cardio- and cerebrovascular events, particularly in some critical settings, and the risk of major bleeding still represent unmet medical needs. Preclinical studies and experience from families with genetic deficiencies of factor XI or XII (FXI and FXII) allowed to identify these factors involved in the contact pathway of coagulation as potential targets for new anticoagulant approaches. To date, several pharmacological classes of FXI and FXII inhibitors have been developed, including antisense oligonucleotides, monoclonal antibodies, small molecules, natural inhibitors, and aptamers, and various molecules are currently under phase 2 or 3 clinical investigation. Particularly, promising results have been obtained in patients undergoing major orthopedic surgery, in those with end-stage kidney disease, atrial fibrillation and acute coronary syndrome. This review summarizes current knowledge on FXI and FXII inhibitors, with a particular focus on their pharmacological properties and potential clinical indications.

Published
2023
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8. 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

Author

Alessandra Bettiol, Elena Gelain, Erika Milanesio, Federica Asta, and Franca Rusconi

Subjects
Air pollution, Asthma, Children, Cohort studies, Early life, Pregnancy, Industrial medicine. Industrial hygiene, RC963-969, Public aspects of medicine, RA1-1270
Abstract

Abstract 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.

Published
2021
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9. Evaluation of RAS Mutational Status in Liquid Biopsy to Monitor Disease Progression in Metastatic Colorectal Cancer Patients

Author

Elena Lastraioli, Alessandra Bettiol, Jessica Iorio, Elvira Limatola, Daniele Checcacci, Erica Parisi, Cristina Bianchi, Annarosa Arcangeli, Mauro Iannopollo, Francesco Di Costanzo, and Marco Di Lieto

Subjects
KRAS, NRAS, liquid biopsy, metastatic colorectal cancer, Cytology, QH573-671
Abstract

In this study we evaluated both~ K- and N-RAS mutations in plasma samples from patients with metastatic colorectal cancer by means of the BEAMing technology, and we assessed their diagnostic performance compared to RAS analyses performed on tissue. The sensitivity of BEAMing in identifying KRAS mutations was of 89.5%, with a fair specificity. The agreement with tissue analysis was moderate. The sensitivity for NRAS was high with a good specificity, and the agreement between tissue analysis and BEAMing was fair. Interestingly, significantly higher mutant allele fraction (MAF) levels were detected in patients with G2 tumors, liver metastases, and in those who did not receive surgery. NRAS MAF level was significantly higher in patients with mucinous adenocarcinoma and for those with lung metastases. A sharp increase in the MAF values was observed in patients who moved towards disease progression. More strikingly, molecular progression always anticipated the radiological one in these patients. These observations pave the way to the possibility of using liquid biopsy to monitor patients during treatment, and to enable oncologists to anticipate interventions compared to radiological analyses. This will allow time to be saved and ensure a better management of metastatic patients in the near future.

Published
2023
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10. Blood Leukocyte ROS Production Reflects Seminal Fluid Oxidative Stress and Spermatozoa Dysfunction in Idiopathic Infertile Men

Author

Matteo Becatti, Gianmartin Cito, Flavia Rita Argento, Eleonora Fini, Alessandra Bettiol, Serena Borghi, Amanda Mannucci, Rossella Fucci, Claudia Giachini, Rita Picone, Giacomo Emmi, Niccolò Taddei, Maria Elisabetta Coccia, and Claudia Fiorillo

Subjects
men infertility, leukocyte ROS production, oxidative stress, sperm dysfunction, Therapeutics. Pharmacology, RM1-950
Abstract

A large proportion of infertile men do not receive a clear diagnosis, being considered as idiopathic or unexplained cases due to infertility diagnosis based on standard semen parameters. Particularly in unexplained cases, the search for new indicators seems mandatory to provide specific information. In the etiopathogenesis of male infertility oxidative stress displays important roles by negatively affecting sperm quality and function. In this study, performed in a population of 34 idiopathic infertile men and in 52 age-matched controls, redox parameters were assessed in blood, leukocytes, spermatozoa, and seminal fluid and related to semen parameters. The main findings indicate that blood oxidative stress markers reflect seminal oxidative stress. Interestingly, blood leukocyte ROS production was significantly correlated to sperm ROS production and to semen parameters. Overall, these results suggest the potential employ of blood redox markers as a relevant and adjunctive tool for sperm quality evaluation aimed to preconception care.

Published
2023
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11. Pathogenesis of Behçet's Syndrome: Genetic, Environmental and Immunological Factors

Author

Irene Mattioli, Alessandra Bettiol, Güher Saruhan-Direskeneli, Haner Direskeneli, and Giacomo Emmi

Subjects
Behçet's syndrome, pathogenesis, HLA-B*51, neutrophils, epigenetic, microbiome, Medicine (General), R5-920
Abstract

Behçet's syndrome (BS) is a rare systemic vasculitis, characterized by a wide range of different clinical involvements and unpredictable phases of recurrence and remission. BS can be described as a multifactorial disease with an incompletely known etiopathogenesis; in fact, though presenting some peculiar features, such as its typical geographic distribution and the strong association with the well-known genetic predisposing factor HLA-B*51, the cause behind the onset and progression of the disease remains currently not fully understood. Besides genetic HLA and non-HLA predisposing associations and epigenetic influence, environmental factors also play an important role in the pathogenesis of the disease, and among these, infectious agents (both bacterial and viral) and specific microbiome alterations are considered of particular relevance in BS pathogenesis. BS has been included for decades among autoimmune diseases, in light of evidence showing T- and B-cell aberrant responses. However, because of recurrent mucocutaneous lesions and episodes of inflammation without antigen-specific T-cell or autoantibody responses, BS has also been classified among autoinflammatory disorders. Nevertheless, differently from autoinflammatory diseases, BS mildly responds to therapies targeting IL-1, its onset is not usually in childhood, and has high neutrophilic vasculitic involvement. Finally, given the association with HLA class I alleles, similar to spondyloarthropathies, the concept of BS as a major histocompatibility complex (MHC) I -opathy has been introduced. Understanding the complex etiopathogenesis of BS is essential to identify modifiable risk factors of BS occurrence or exacerbation and to develop targeted therapies. This review summarizes current evidence on the main genetic, environmental and immunological factors contributing to BS development.

Published
2021
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12. Association between anthraquinone laxatives and colorectal cancer: protocol for a systematic review and meta-analysis

Author

Niccolò Lombardi, Alessandra Bettiol, Giada Crescioli, Valentina Maggini, Eugenia Gallo, Francesco Sivelli, Francesco Sofi, Gian Franco Gensini, Alfredo Vannacci, and Fabio Firenzuoli

Subjects
Medicine
Abstract

Abstract 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

Published
2020
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13. Risk of Hospitalization Associated with Cardiovascular Medications in the Elderly Italian Population: A Nationwide Multicenter Study in Emergency Departments

Author

Giada Crescioli, Alessandra Bettiol, Roberto Bonaiuti, Marco Tuccori, Marco Rossi, Annalisa Capuano, Silvia Pagani, Giulia Spada, Mauro Venegoni, Giuseppe Danilo Vighi, Guido Mannaioni, Alfredo Vannacci, Niccolò Lombardi, and MEREAFaPS Study group

Subjects
emergency department, hospitalization, adverse drug event, cardiovascular drug, elderly, Therapeutics. Pharmacology, RM1-950
Abstract

Background: 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.Methods: 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.Results: 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.Conclusion: 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.

Published
2021
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14. Italian Emergency Department Visits and Hospitalizations for Outpatients’ Adverse Drug Events: 12-Year Active Pharmacovigilance Surveillance (The MEREAFaPS Study)

Author

Niccolò Lombardi, Giada Crescioli, Alessandra Bettiol, Marco Tuccori, Annalisa Capuano, Roberto Bonaiuti, Alessandro Mugelli, Mauro Venegoni, Giuseppe Danilo Vighi, Alfredo Vannacci, the MEREAFaPS Study group, Maria Luisa Aiezza, Daria Bettoni, Corrado Blandizzi, Valentina Borsi, Errica Cecchi, Irma Convertino, Martina Del Lungo, Cristina Di Mauro, Gabriella Farina, Sara Ferraro, Annamaria Fucile, Elena Galfrascoli, Elisabetta Geninatti, Linda Giovannetti, Luca Leonardi, Rosa Liccardo, Anna Marra, Eleonora Marrazzo, Giovanna Monina, Silvia Pagani, Maria Parrilli, Concetta Rafaniello, Francesco Rossi, Marco Rossi, Stefania Rostan, Marco Ruocco, Marita Sironi, Giulia Spada, Liberata Sportiello, and Giuditta Violetta Vighi

Subjects
emergency department, hospitalization, adverse drug events, pharmacovigilance, drug safety, preventability, Therapeutics. Pharmacology, RM1-950
Abstract

BackgroundAdverse 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.MethodsWe 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).ResultsWithin 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.ConclusionOur 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.

Published
2020
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15. Gut Microbiota and Associated Mucosal Immune Response in Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Author

Elena Niccolai, Alessandra Bettiol, Simone Baldi, Elena Silvestri, Leandro Di Gloria, Federica Bello, Giulia Nannini, Federica Ricci, Maria Nicastro, Matteo Ramazzotti, Augusto Vaglio, Gianluca Bartolucci, Giacomo Emmi, Amedeo Amedei, and Domenico Prisco

Subjects
eosinophilic granulomatosis with polyangiitis, ANCA-associated vasculitis, microbiota, T lymphocytes, short-chain fatty acids, Biology (General), QH301-705.5
Abstract

Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A genome-wide association study showed a correlation between ANCA-negative EGPA and variants of genes encoding proteins with intestinal barrier functions, suggesting that modifications of the mucosal layer and consequent gut dysbiosis might be involved in EGPA pathogenesis. Here, we characterized the gut microbiota (GM) composition and the intestinal immune response in a cohort of EGPA patients. Faeces from 29 patients and 9 unrelated healthy cohabitants were collected, and GM and derived metabolites’ composition were compared. Seven intestinal biopsies from EGPA patients with gastrointestinal manifestations were analysed to assess the T-cell distribution and its correlation with GM and EGPA clinical and laboratory features. No significant differences in GM composition, nor in the total amount of faecal metabolites, emerged between patients and controls. Nevertheless, differences in bacterial taxa abundances and compositional GM-derived metabolites profile were observed. Notably, an enrichment of potential pathobionts (Enterobacteriacee and Streptococcaceae) was found in EGPA, particularly in patients with active disease, while lower levels were found in patients on immunosuppression, compared with non-immunosuppressed ones. Significantly lower amounts of hexanoic acid were found in patients, compared to controls. The analysis of the immune response in the gut mucosa revealed a high frequency of IFN-γ/IL-17-producing T lymphocytes, and a positive correlation between EGPA disease activity and intestinal T-cell levels. Our data suggest that an enrichment in potential intestinal pathobionts might drive an imbalanced inflammatory response in EGPA.

Published
2022
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16. STOP Pain Project—Opioid Response in Pediatric Cancer Patients and Gene Polymorphisms of Cytokine Pathways

Author

Giada Crescioli, Niccolò Lombardi, Laura Vagnoli, Alessandra Bettiol, Laura Giunti, Valentina Cetica, Maria Luisa Coniglio, Aldesia Provenzano, Sabrina Giglio, Roberto Bonaiuti, Alessandro Mugelli, Maurizio Aricò, Andrea Messeri, Alfredo Vannacci, and Valentina Maggini

Subjects
opioid, pharmacogenetics, genetic polymorphisms, cancer, cytokines, pain, Pharmacy and materia medica, RS1-441
Abstract

Moderate to severe cancer pain treatment in children is based on the use of weak and strong opioids. Pharmacogenetics play a central role in developing personalized pain therapies, as well as avoiding treatment failure and/or intolerable adverse drug reactions. This observational study aimed to investigate the association between IL-6, IL-8, and TNFα genetic single nucleotide polymorphisms (SNPs) and response to opioid therapy in a cohort of pediatric cancer patients. Pain intensity before treatment (PIt0) significantly differed according to IL-6 rs1800797 SNP, with a higher PI for A/G and G/G individuals (p = 0.017), who required a higher dose of opioids (p = 0.047). Moreover, compared to G/G subjects, heterozygous or homozygous individuals for the A allele of IL-6 rs1800797 SNP had a lower risk of having a PIt0 > 4. Dose24h and Dosetot were both higher in G/G individuals for TNFα rs1800629 (p = 0.010 and p = 0.031, respectively), while risk of having a PIt0 > 4 and a ∆VAS > 2 was higher for G/G subjects for IL-6 rs1800795 SNP compared to carriers of the C allele. No statistically significant association between genotypes and safety outcomes was found. Thus, IL-6 and TNFα SNPs could be potential markers of baseline pain intensity and opioid dose requirements in pediatric cancer patients.

Published
2022
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17. Impact of cardiovascular and immunologic variables on subclinical carotid atherosclerosis in subjects with anti-phospholipid antibodies

Author

Matteo Nicola Dario Di Minno, Giacomo Emmi, Pasquale Ambrosino, Antonella Scalera, Antonella Tufano, Giovanni Cafaro, Rosario Peluso, Alessandra Bettiol, Gerardo Di Scala, Elena Silvestri, and Domenico Prisco

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390
Abstract

Whereas some previous data on carriers with isolated antiphospholipid antibodies positivity (APP) suggested an increased risk of arterial events in this clinical setting, no data are available on subclinical atherosclerosis in this clinical setting. This article reports data on intima-media thickness of the common carotid artery (CCA-IMT) and of the Bulb (Bulb-IMT) and on the prevalence of carotid plaques in APP carriers and in subjects with antiphospholipid syndrome (APS) specifically stratifying for the presence of thrombotic manifestations, cardiovascular risk factors, antibody isotype and concomitant Systemic Lupus Erythematosus (SLE) or other autoimmune diseases.

Published
2018
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18. Characterization of serious adverse drug reactions as cause of emergency department visit in children: a 5-years active pharmacovigilance study

Author

Niccolò Lombardi, Giada Crescioli, Alessandra Bettiol, Ettore Marconi, Antonio Vitiello, Roberto Bonaiuti, Anna Maria Calvani, Stefano Masi, Ersilia Lucenteforte, Alessandro Mugelli, Lisa Giovannelli, and Alfredo Vannacci

Subjects
Pediatrics, Adverse events, Safety, Observational study, Preventability, Drug interactions, Therapeutics. Pharmacology, RM1-950, Toxicology. Poisons, RA1190-1270
Abstract

Abstract Background To describe frequency, preventability and seriousness of adverse drug reactions (ADRs) in children as cause of emergency department (ED) admission and to evaluate the association between specific factors and the reporting of ADRs. Methods A retrospective analysis based on reports of suspected ADRs collected between January 1st, 2012 and December 31st, 2016 in the ED of Meyer Children’s Hospital (Italy). Demographics, clinical status, suspected drugs, ADR description, and its degree of seriousness were collected. Logistic regression was used to estimate the reporting odds ratios (RORs) with 95% confidence intervals (CIs) of potential predictors of ADR seriousness. Results Within 5 years, we observed 834 ADRs (1100 drug-ADR pairs), of whom 239 were serious; of them, 224 led to hospitalization. Patients were mostly treated with one drug. Among patients treated with more than one drug, 78 ADRs presented a potential interaction. The most frequently reported ADRs involved gastrointestinal system. The most frequently reported medication class was antinfectives. Risk of serious ADR was significantly lower in children and infants compared to adolescents (ROR 0.41 [95% CI: 0.27–0.61] and 0.47 [0.32–0.71], respectively), and it was significantly increased in subjects exposed to more than one drug (ROR 1.87 [1.33–2.62] and 3.01 [2.07–4.37] for subjects exposed to 2 and 3 or more drugs, respectively). Gender, interactions and off-label drug use did not influence the risk of serious ADRs. Conclusion Active surveillance in pharmacovigilance might represent the best strategy to estimate and characterize the clinical burden of ADRs in children.

Published
2018
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19. Stem-Cell-Derived Circulating Progenitors Dysfunction in Behçet's Syndrome Patients Correlates With Oxidative Stress

Author

Giacomo Emmi, Amanda Mannucci, Flavia Rita Argento, Elena Silvestri, Augusto Vaglio, Alessandra Bettiol, Alessandra Fanelli, Laura Stefani, Niccolò Taddei, Domenico Prisco, Claudia Fiorillo, and Matteo Becatti

Subjects
Behçet's syndrome, thrombosis, circulating progenitor cells, oxidation, apoptosis, Immunologic diseases. Allergy, RC581-607
Abstract

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−/dim and CD34+/CD45−/dim/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.

Published
2019
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20. Treating the Different Phenotypes of Behçet's Syndrome

Author

Alessandra Bettiol, Gulen Hatemi, Lorenzo Vannozzi, Alessandro Barilaro, Domenico Prisco, and Giacomo Emmi

Subjects
Behçet's syndrome, phenotypes, cluster analysis, anti-TNF-α, DMARDs, Immunologic diseases. Allergy, RC581-607
Abstract

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.

Published
2019
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21. Vaccines Safety in Children and in General Population: A Pharmacovigilance Study on Adverse Events Following Anti-Infective Vaccination in Italy

Author

Niccolò Lombardi, Giada Crescioli, Alessandra Bettiol, Marco Tuccori, Marco Rossi, Roberto Bonaiuti, Claudia Ravaldi, Miriam Levi, Alessandro Mugelli, Silvia Ricci, Francesca Lippi, Chiara Azzari, Paolo Bonanni, and Alfredo Vannacci

Subjects
vaccines, adverse events following immunization, pharmacovigilance, safety, observational study, preventability, Therapeutics. Pharmacology, RM1-950
Abstract

Background: The concern for adverse events following immunization (AEFI) and anti-vaccination movements that lacked scientific evidence-based supports may reduce vaccine uptake in the general population. Thus, the aims of the present study were to characterize AEFI in general population (all age groups), in terms of frequency, preventability, and seriousness and to define predictors of their seriousness in children.Methods: A retrospective study was performed on suspected AEFI reports for children and adults who received any form of vaccinations, collected in Tuscany, Italy, between 1 January and 31 December 2017. Patients’ characteristics, suspected vaccines, and AEFI description were collected. Causality and preventability were assessed using WHO and Schumock and Thornton algorithms, respectively. Logistic regression was used to estimate the reporting odds ratios of potential predictors of AEFI seriousness in children.Results: A total of 223 suspected AEFI reports were collected, and the majority of them were defined as non-serious (76.7%). Reports were mostly related to one vaccine, and to a median of two to five strains/toxoids. The total number of simultaneously administered strains/toxoids and the presence of allergens did not correlate with AEFI seriousness. Considering vaccines with a high number of administered doses (≥60,000 doses), the rates estimated for serious AEFI reports were always very low, ranging between 0.01 and 0.2/1,000 doses. Twenty-four vaccines (8,993 doses) were not related to any AEFI.Conclusion: Results of present study showed that AEFI were very rare; the vast majority of them was non-serious and, despite the claims of anti-vaccination movements, the simultaneous administration of vaccines was safe and did not influence the risk of reporting a serious AEFI, particularly in children.

Published
2019
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22. Pharmacological interventions for the prevention of fetal growth restriction: protocol for a systematic review and network meta-analysis

Author

Alessandra Bettiol, Niccolò Lombardi, Giada Crescioli, Laura Avagliano, Alessandro Mugelli, Claudia Ravaldi, and Alfredo Vannacci

Subjects
Medicine
Abstract

Introduction Fetal growth restriction (FGR) includes different conditions in which a fetus fails to reach the own full growth, and accounts for 28%–45% of non-anomalous stillbirths. The management of FGR is based on the prolongation of pregnancy long enough for fetal organs to mature while preventing starvation. As for pharmacological management, most guidelines recommend treatment with low-dose aspirin and/or with heparin, although this approach is still controversial and innovative promising therapies are under investigation. As no firm evidence exists to guide clinicians towards the most effective therapeutic intervention, this protocol describes methods for a systematic review and network meta-analysis (NetMA) of pharmacological treatments for FGR prevention.Methods and analysis We will search MEDLINE and Embase for clinical trials and observational studies performed on gestating women with clinically diagnosed risk of FGR. Experimental interventions will include heparin and low-molecular-weight heparin, acetylsalicylic acid, antiplatelet agents, phosphodiesterase type 3 and 5 inhibitors, maternal vascular endothelial growth factor gene therapy, nanoparticles, microRNA, statins, nitric oxide donors, hydrogen sulphide, proton pump inhibitors, melatonin, creatine and N-acetylcysteine, and insulin-like growth factors, compared between each other or to placebo or no treatment. Primary efficacy outcome is FGR. Secondary efficacy outcomes will be preterm birth, fetal or neonatal death and neonatal complications. For the safety outcome, all adverse events reported in included studies and experienced by either mothers, fetuses or newborns will be considered. Two review authors will independently screen title, abstract and full paper text, and will independently extract data from included studies. Where possible and appropriate, for primary and secondary efficacy outcomes, a NetMA will be performed using a random-effects model within a frequentist framework. Adverse events will be narratively described.Ethics and dissemination Results will be disseminated through a peer-reviewed scientific journal, and by scientific congresses and meetings.PROSPERO registration number CRD42019122831.

Published
2019
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23. Behçet's Syndrome as a Model of Thrombo-Inflammation: The Role of Neutrophils

Author

Giacomo Emmi, Matteo Becatti, Alessandra Bettiol, Gülen Hatemi, Domenico Prisco, and Claudia Fiorillo

Subjects
Behçet's syndrome, thrombosis, neutrophils, oxidative stress, fibrinogen, Immunologic diseases. Allergy, RC581-607
Abstract

Behçet's syndrome (BS) is a systemic vasculitis, clinically characterized by different organ involvement and often complicated by thrombosis which occurs in vessels of all sizes. Thrombosis is more frequent in male patients with active disease and represents an important cause of morbidity and mortality. Neutrophil involvement in BS has been repeatedly suggested in the last few years. Indeed, neutrophils have been shown to be hyperactivated in BS patients, probably with a HLAB51 related contribution, and represent the main cells infiltrating not only oral and genital ulcers or erythema nodosum, but also other sites. Besides being deputed to host defense against micro-organisms, neutrophils display fundamental roles both in inflammation and tissue damage becoming inappropriately activated by cytokines, chemokines and autoantibodies and subsequently producing large amounts of superoxide anion (O2.) via NADPH oxidase (NOX2). The strict relationship between inflammation and hemostasis has been already demonstrated. Indeed, inflammation and immune-mediated disorders increase the risk of thrombosis, but the pathways that link these processes have not been completely elucidated. In this regard, we recently demonstrated, in a large population of BS patients, a new neutrophil-dependent pathogenetic mechanism of thrombosis. In particular, it was shown that neutrophils, mainly through NADPH oxidase, produce excessive amounts of reactive oxygen species (ROS), which are able to markedly modify the secondary structure of fibrinogen and hence the overall architecture of the fibrin clot that becomes less susceptible to plasmin-induced lysis. These data point out that BS represents “per se” a model of inflammation-induced thrombosis and suggest that neutrophils specifically contribute to thrombo-inflammation in this rare disease. In particular, it is suggested that an alteration in fibrinogen structure and function are associated with enhanced ROS production via neutrophil NADPH oxidase. Altogether, these findings improve our understanding of the intricate pathogenetic mechanisms of thrombo-inflammation and may indicate potential new therapeutic targets.

Published
2019
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24. [Untitled]

Author

Annachiara Bellin, Giulia Franchin, Jenny Bolcato, Alessandra Bettiol, Roberta Pirolo, Alberto Schiavon, Pietro Giusti, Michele Tessarin, and Alessandro Chinellato

Subjects
Medical technology, R855-855.5
Published
2019
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25. Twenty Years of Hepatitis C in the Treviso District (Local Health Unit 2): Treatments, Clinical Management and Cost Analysis

Author

Annachiara Bellin, Giulia Franchin, Jenny Bolcato, Alessandra Bettiol, Roberta Pirolo, Alberto Schiavon, Pietro Giusti, Michele Tessarin, and Alessandro Chinellato

Subjects
Medical technology, R855-855.5
Abstract

Chronic hepatitis C virus (HCV) infection is a global health problem, and about 10-30% of patients develop cirrhosis or hepatocellular carcinoma several years after being infected. In past decades, treatment of HCV infection was based on peginterferon and ribavirin, which lead to a sustained virologic response (SVR) in only 50-60% of patients. Since 2014, direct acting antiviral (DAA) agents have been available. Patients administered DAA agents usually reach SVR in 12 weeks. The aim of this study was to estimate the cost analysis of these innovative drugs while also taking into account the total health expenditure for managing HCV infection. The pharmaceutical and hospitalisation databases of the Local Health Unit (ULSS2) of Treviso were retrospectively analysed between 1997 and 2016 for each HCV patient. During this twenty-year period, people affected by HCV totalled 2,949; 277 of these patients were treated with DAA and, of these, only 2% did not reach SVR. The HCV genotype 1b was the most common, accounting for 58% of the total patients. The treatment for HCV genotype 3 was associated with higher costs. The expenses for the new treatments were found to be significantly higher compared to those for the old ones (i.e., peginterferon and ribavirin). The average costs for a cycle of therapy were €8,000 and €24,000 for interferon and DAA therapy, respectively. Total health care costs associated with HCV (excluding DAA treatments) for an individual HCV infection patient were estimated to be €32,000. Our results confirm the high efficacy of DAA therapy. Furthermore, these agents improve the clinical conditions and reduce both the treatment cost and health care in patients with HCV infection.

Published
2019
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26. Risk of Hospitalization for Adverse Drug Events in Women and Men: A Post Hoc Analysis of an Active Pharmacovigilance Study in Italian Emergency Departments

Author

Giada Crescioli, Ennio Boscia, Alessandra Bettiol, Silvia Pagani, Giulia Spada, Giuditta Violetta Vighi, Roberto Bonaiuti, Mauro Venegoni, Giuseppe Danilo Vighi, Alfredo Vannacci, Niccolò Lombardi, and on behalf of the MEREAFaPS Study Group

Subjects
pharmacovigilance, clinical pharmacology, male, female, emergency department, Medicine, Pharmacy and materia medica, RS1-441
Abstract

This post hoc analysis of an Italian active pharmacovigilance study describes pharmacological differences of ADEs leading to emergency department (ED) visits and hospitalization in women and men. During the study period (January 2007–December 2018), 61,855 reports of ADEs leading to ED visits were collected. Overall, 30.6% of ADEs resulted in hospitalization (30% in women and 31% in men). Multivariate logistic regression showed that, among women, drug classes significantly associated with an increased risk of hospitalization were heparins (ROR 1.41, CI 1.13–176), antidepressants (ROR 1.12, CI 1.03–1.23) and antidiabetics (ROR 1.13, CI 1.02–1.24). Among men, only vitamin K antagonists (ROR 1.28, CI 1.09–1.50), opioids (ROR 1.30, CI 1.06–1.60) and digitalis glycosides (ROR 1.32, CI 1.09–1.59) were associated with a higher risk of hospitalization. Overall, older age, multiple suspected drugs and the presence of comorbidities were significantly associated with a higher risk of hospitalization. A significantly reduced risk of hospitalization was observed in both women and men experiencing an adverse event following immunization (ROR 0.36, CI 0.27–0.48 and 0.83, 0.42–0.74, respectively) compared to drugs. Results obtained from this real-world analysis highlight important aspects of drug safety between sexes.

Published
2021
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27. An Insight into Giant Cell Arteritis Pathogenesis: Evidence for Oxidative Stress and SIRT1 Downregulation

Author

Alessandro Ianni, Poonam Kumari, Shahriar Tarighi, Flavia Rita Argento, Eleonora Fini, Giacomo Emmi, Alessandra Bettiol, Thomas Braun, Domenico Prisco, Claudia Fiorillo, and Matteo Becatti

Subjects
giant cell arteritis (GCA), oxidative stress, SIRT1, Therapeutics. Pharmacology, RM1-950
Abstract

Giant cell arteritis (GCA), medium and large vessel granulomatous vasculitis affecting the elderly, is characterized by a multitude of vascular complications, including venous thrombosis, myocardial infraction and stroke. The formation of granulomatous infiltrates and the enhanced accumulation of proinflammatory cytokines are typical features of this condition. The GCA pathogenesis remains largely unknown, but recent studies have suggested the involvement of oxidative stress, mainly sustained by an enhanced reactive oxygen species (ROS) production by immature neutrophils. On this basis, in the present study, we intended to evaluate, in GCA patients, the presence of systemic oxidative stress and possible alterations in the expression level of nuclear sirtuins, enzymes involved in the inhibition of inflammation and oxidative stress. Thirty GCA patients were included in the study and compared to 30 healthy controls in terms of leukocyte ROS production, oxidative stress and SIRT1 expression. Our results clearly indicated a significant increase (p < 0.05) both in the ROS levels in the leukocyte fractions and plasma oxidative stress markers (lipid peroxidation and total antioxidant capacity) in the GCA patients compared to the healthy controls. In PBMCs from the GCA patients, a significant decrease in SIRT1 expression (p < 0.05) but not in SIRT6 and SIRT7 expression was found. Taken together, our preliminary findings indicate that, in GCA patients, plasma oxidative stress is paralleled by a reduced SIRT1 expression in PBMC. Further studies are needed to highlight if and how these alterations contribute to GCA pathogenesis.

Published
2021
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28. Galenic Preparations of Therapeutic Cannabis sativa Differ in Cannabinoids Concentration: A Quantitative Analysis of Variability and Possible Clinical Implications

Author

Alessandra Bettiol, Niccolò Lombardi, Giada Crescioli, Valentina Maggini, Eugenia Gallo, Alessandro Mugelli, Fabio Firenzuoli, Roberto Baronti, and Alfredo Vannacci

Subjects
cannabis, galenic preparations, Bediol®, Bedrocan®, Bedrolite®, FM-2®, Therapeutics. Pharmacology, RM1-950
Abstract

Introduction: Magistral preparations of therapeutic cannabis are extracted from standardized products imported from Holland or from the Florence Military Pharmaceutical Chemical Works, but extraction protocols differ among galenic laboratories. This study assessed the inter-laboratory variability in concentrations of cannabidiol (CBD), cannabinol (CBN), tetrahydrocannabinol (THC), and tetrahydrocannabinolic acid (THCA) among different magistral oil preparations.Methods: 219 samples of Bediol, Bedrobinol, Bedrolite or FM-2 70 or 100 mg/ml in oil were collected from 3 laboratories. Concentrations of CBD, CBN, THC, and THCA were quantified by high-pressure liquid chromatography; inter-laboratories variability was assessed using the Kruskal–Wallis test.Results: A significant variability in CBD and THC concentrations was found for Bediol 70 mg/ml samples from 2 laboratories [for CBD: median 5.4 (range 4.8–6.6) vs. 6.1 (4.9–7.2) mg/ml, p = 0.033; for THC: 3.6 (3.1–3.9) vs. 4.0 (2.6–5.1) mg/ml, p = 0.020]. As for Bediol 100 mg/ml, a significant variability emerged in THC concentrations among the three considered laboratories [5.7 (-) vs. 4.2 (1.5–4.8) vs. 5.2 (4.2–6.9), p = 0.030]. No significant inter-laboratory variability emerged for Bedrocan and Bedrolite. Concentrations of CBD, CBN, and THC were

Published
2019
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29. Adalimumab Accounts for Long-Term Control of Noninfectious Uveitis Also in the Absence of Concomitant DMARD Treatment: A Multicenter Retrospective Study

Author

Alice Bitossi, Alessandra Bettiol, Elena Silvestri, Gerardo Di Scala, Daniela Bacherini, Giuseppe Lopalco, Vincenzo Venerito, Florenzo Iannone, Antonio Vitale, Gian Marco Tosi, Domenico Prisco, Stanislao Rizzo, Claudia Fabiani, Luca Cantarini, Gianni Virgili, Lorenzo Vannozzi, and Giacomo Emmi

Subjects
Pathology, RB1-214
Abstract

Objective. This study was aimed at assessing the long-term ocular control of adalimumab (ADA) in a large real-world population with noninfectious primary or secondary uveitis, focusing on the steroid-sparing effect and on disease-modifying antirheumatic drug (DMARD) cotreatment. Methods. In this retrospective, multicenter study, the efficacy of ADA was evaluated in terms of ocular control, changes in best-corrected visual acuity (BCVA), corticosteroid-sparing effect, and drug retention rate, overall and stratified according to DMARD cotreatment. Results. 106 patients were included. 88.7% had an associated systemic disease. After 6 and 12 months, proportions of patients with effective ocular control were 83.7% and 83.3%, respectively. At last the follow-up, 94.6% of patients had satisfactory ocular control. No difference in terms of ocular control at all time points emerged among patients starting ADA for ocular vs. systemic involvements. Patients with poor baseline BCVA remained stable or improved, while those with good BCVA hardly worsened. At 6 and 12 months, the median dose of prednisone significantly reduced to 5 mg/day (0-5) and 2.5 mg/day (0-5) (p

Published
2019
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30. [Untitled]

Author

Paola Deambrosis, Alessandra Bettiol, Jenny Bolcato, Roberta Pirolo, Giulia Franchin, Sakis Themistoclakis, Pietro Giusti, and Alessandro Chinellato

Subjects
Medical technology, R855-855.5
Published
2018
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31. [Untitled]

Author

Roberta Pirolo, Alessandra Bettiol, Jenny Bolcato, Giulia Franchin, Paola Deambrosis, Agostino Paccagnella, Pietro Giusti, and Alessandro Chinellato

Subjects
Medical technology, R855-855.5
Published
2016
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32. [Untitled]

Author

Alessandra Bettiol, Jenny Bolcato, Roberta Pirolo, Giulia Franchin, Paola Deambrosis, Pietro Giusti, and Alessandro Chinellato

Subjects
Medical technology, R855-855.5
Published
2016
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33. Evidence-Based Guideline for the diagnosis and management of eosinophilic granulomatosis with polyangiitis

Author

Giacomo Emmi, Alessandra Bettiol, Elena Gelain, Ingeborg M. Bajema, Alvise Berti, Stella Burns, Maria C. Cid, Jan W. Cohen Tervaert, Vincent Cottin, Eugenia Durante, Julia U. Holle, Alfred D. Mahr, Marcos Martinez Del Pero, Chiara Marvisi, John Mills, Sergey Moiseev, Frank Moosig, Chetan Mukhtyar, Thomas Neumann, Iacopo Olivotto, Carlo Salvarani, Benjamin Seeliger, Renato A. Sinico, Camille Taillé, Benjamin Terrier, Nils Venhoff, George Bertsias, Loïc Guillevin, David R. W. Jayne, Augusto Vaglio, Emmi, G, Bettiol, A, Gelain, E, Bajema, I, Berti, A, Burns, S, Cid, M, Cohen Tervaert, J, Cottin, V, Durante, E, Holle, J, Mahr, A, Del Pero, M, Marvisi, C, Mills, J, Moiseev, S, Moosig, F, Mukhtyar, C, Neumann, T, Olivotto, I, Salvarani, C, Seeliger, B, Sinico, R, Taillé, C, Terrier, B, Venhoff, N, Bertsias, G, Guillevin, L, Jayne, D, and Vaglio, A

Subjects
Rheumatology, EGPA, Churg-Strauss syndrome, guidelines, evidence based
Abstract

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis, characterized by asthma, eosinophilia and granulomatous or vasculitic involvement of several organs. The diagnosis and management of EGPA are often challenging and require an integrated, multidisciplinary approach. Current practice relies on recommendations and guidelines addressing the management of ANCA-associated vasculitis and not specifically developed for EGPA. Here, we present evidence-based, cross-discipline guidelines for the diagnosis and management of EGPA that reflect the substantial advances that have been made in the past few years in understanding the pathogenesis, clinical subphenotypes and differential diagnosis of the disease, as well as the availability of new treatment options. Developed by a panel of European experts on the basis of literature reviews and, where appropriate, expert opinion, the 16 statements and five overarching principles cover the diagnosis and staging, treatment, outcome and follow-up of EGPA. These recommendations are primarily intended to be used by healthcare professionals, pharmaceutical industries and drug regulatory authorities, to guide clinical practice and decision-making in EGPA. These guidelines are not intended to limit access to medications by healthcare agencies, nor to impose a fixed order on medication use.

Published
2023
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34. Clinical phenotypes and long-term outcome of kidney involvement in Erdheim-Chester histiocytosis

Author

Thibaud, Chazal, Francesco, Pegoraro, Gaia, Manari, Alessandra, Bettiol, Valerio, Maniscalco, Elena, Gelain, Frédéric, Charlotte, Roei D, Mazor, Raphaele, Renard-Penna, Zahir, Amoura, Fleur, Cohen-Aubart, Julien, Haroche, Hassan, Izzedine, and Augusto, Vaglio

Subjects
Erdheim-Chester Disease, Phenotype, Nephrology, Humans, Renal Insufficiency, Renal Insufficiency, Chronic, Kidney
Abstract

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that frequently infiltrates the peri-kidney space ("hairy kidney" appearance), kidney pelvis and proximal ureters, leading to obstructive uropathy. Here, we analyzed the clinical characteristics, imaging findings and long-term kidney outcome of a large multicenter cohort comprising 195 consecutive patients with ECD. Retroperitoneal peri-kidney or peri-ureteral involvement was detected at diagnosis in 147 patients. Of them, 70 had hydronephrosis (bilateral in 47), and 16 with kidney atrophy (unilateral in 14). Kidney vascular peduncle infiltration was found in 60 patients, and kidney artery stenosis in 31. The estimated glomerular filtration rate (eGFR) at diagnosis was significantly lower in patients with than in those without peri-kidney involvement (median 74 vs. 98 mL/min/1.73 m

Published
2023
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35. The Sound of Interconnectivity; The European Vasculitis Society 2022 Report

Author

Allyson C. Egan, Andreas Kronbichler, Irmgard Neumann, Alessandra Bettiol, Nicholas Carlson, Maria C. Cid, Giacomo Emmi, Seerapani Gopaluni, Lorraine Harper, Thomas Hauser, Mark A. Little, Raashid A. Luqmani, Alfred Mahr, Mark McClure, Aladdin J. Mohammad, Karl Emil Nelveg-Kristensen, Sophie Ohlsson, Chen Au Peh, Matthew Rutherford, Beatriz Sanchez Alamo, Jennifer Scott, Mårten Segelmark, Rona M. Smith, Wladimir M. Szpirt, Gunnar Tomasson, Giorgio Trivioli, Augusto Vaglio, Michael Walsh, Maria Wester Trejo, Kerstin Westman, Ingeborg M. Bajema, and David R.W. Jayne

Subjects
Nephrology
Abstract

The first European Vasculitis Society (EUVAS) meeting report was published in 2017. Herein, we report on developments in the past 5 years which were greatly influenced by the pandemic. The adaptability to engage virtually, at this critical time in society, embodies the importance of networks and underscores the role of global collaborations. We outline state-of-the-art webinar topics, updates on developments in the last 5 years, and proposals for agendas going forward. A host of newly reported clinical trials is shaping practice on steroid minimization, maintenance strategies, and the role of newer therapies. To guide longer-term strategies, a longitudinal 10-year study investigating relapse, comorbidity, malignancy, and survival rates is at an advanced stage. Disease assessment studies are refining classification criteria to differentiate forms of vasculitis more fully. A large international validation study on the histologic classification of anti-neutrophil cytoplasmic antibody (ANCA) glomerulonephritis, recruiting new multicenter sites and comparing results with the Kidney Risk Score, has been conducted. Eosinophilic granulomatosis with polyangiitis (EGPA) genomics offers potential pathogenic subset and therapeutic insights. Among biomarkers, ANCA testing is favoring immunoassay as the preferred method for diagnostic evaluation. Consolidated development of European registries is progressing with an integrated framework to analyze large clinical data sets on an unprecedented scale.

Published
2022
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36. Evidence of subclinical atherosclerosis in eosinophilic granulomatosis with polyangiitis

Author

Federica Bello, Alessandra Bettiol, Elena Silvestri, Irene Mattioli, Maria Letizia Urban, Adalgisa Palermo, Matteo Mazzetti, Danilo Malandrino, Ilenia Calcaterra, Augusto Vaglio, Matteo Nicola Dario Di Minno, Giacomo Emmi, and Domenico Prisco

Subjects
Rheumatology, Pharmacology (medical)
Abstract

Objectives Patients affected by eosinophilic granulomatosis with polyangiitis (EGPA) display an increased risk of atherothrombotic events compared with the general population. An increased frequency of subclinical markers of atherosclerosis has been observed in other ANCA-associated vasculitis, but no specific study focused on EGPA. We therefore evaluated subclinical atherosclerosis in EGPA patients and in a control population. Methods Forty EGPA patients and 80 controls matched by age, sex and traditional cardiovascular risk factors underwent sonographic assessment of common carotid artery (CCA) intima–media thickness (IMT). The presence of plaques of the CCA was also investigated. The correlation between CCA-IMT and clinical and laboratory features was also assessed. Results Median CCA-IMT was significantly higher in EGPA patients compared with controls (P = 0.002). Also, the proportion of subjects with increased CCA-IMT and with presence of plaques was significantly higher among EGPA patients (P Conclusion Ultrasound markers of subclinical atherosclerosis are increased in EGPA patients as compared with controls, independently of traditional cardiovascular risk factors.

Published
2022
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37. Behçet syndrome in children and adults: discovering similarities and differences by a comparative study

Author

Maria Vincenza Mastrolia, Alessandra Bettiol, Edoardo Marrani, Ilaria Maccora, Emilia Taddei, Ilaria Pagnini, Maria Canfora, Giacomo Emmi, Elena Silvestri, Domenico Prisco, and Gabriele Simonini

Subjects
Rheumatology, Pharmacology (medical)
Abstract

Objective Behçet’s syndrome (BS) is a rare disorder with a relapsing-remitting course. Clinical variance across geographical regions and different age groups has been observed. This study matched the demographic, clinical and treatment features of adult- and juvenile-onset BS in the Italian population. Methods Two clinical databases of BS patients were compared. The paediatric BS database was collected at the Meyer Children’s Hospital, Florence, while the adult BS database was collected at the Careggi University Hospital, Florence. Results A familiar predisposition for BS was significantly more frequent in the paediatric cohort (3/33 vs 1/165, P = 0.015). No difference emerged in terms of prevalence of HLA-B51 positivity. The proportion of patients meeting the revised ICBD and/or the ISG criteria at BS diagnosis was comparable in the two cohorts. No significant difference emerged between the two cohorts in terms of muco-cutaneous, ocular and neurological involvement, and gastrointestinal symptoms. Articular manifestations resulted as more common in the paediatric cohort, whereas venous vascular events were more frequent in the adult cohort. Regarding treatment strategy, paediatric patients more frequently received no treatment or corticosteroid monotherapy. Conversely, the use of DMARDs, both traditional and biologic, was significantly higher in the adult cohort. Conclusion Remarkable differences between juvenile-onset and adult-onset BS, both in terms of gender, familiar predisposition and clinical manifestations have been observed and a different therapeutic approach in the real clinical practice of the two settings emerged. Prospective, comparison studies with a longer follow-up are encouraged to provide further data about the disease course for juvenile- and adult-onset BS.

Published
2022
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38. Serum Interleukin-36 α as a Candidate Biomarker to Distinguish Behçet’s Syndrome and Psoriatic Arthritis

Author

D’Elios, Alessandra Bettiol, Filippo Fagni, Irene Mattioli, Giacomo Bagni, Gianfranco Vitiello, Alessia Grassi, Chiara Della Bella, Marisa Benagiano, Arianna Troilo, Katarzyna Stella Holownia, David Simon, Flavia Rita Argento, Jurgen Sota, Claudia Fabiani, Matteo Becatti, Claudia Fiorillo, Georg Schett, Giuseppe Lopalco, Luca Cantarini, Domenico Prisco, Elena Silvestri, Giacomo Emmi, and Mario Milco

Subjects
Behçet disease, biomarkers, cytokines, interleukin 36, vasculitis
Abstract

Behçet’s syndrome (BS) is a rare systemic vasculitis characterized by different clinical manifestations. As no specific laboratory tests exist, the diagnosis relies on clinical criteria, and the differential diagnosis with other inflammatory diseases can be challenging. Indeed, in a relatively small proportion of patients, BS symptoms include only mucocutaneous, articular, gastrointestinal, and non-typical ocular manifestations, which are frequently found also in psoriatic arthritis (PsA). We investigate the ability of serum interleukin (IL)-36α—a pro-inflammatory cytokine involved in cutaneous and articular inflammatory diseases—to differentiate BS from PsA. A cross-sectional study was performed on 90 patients with BS, 80 with PsA and 80 healthy controls. Significantly lower IL-36α concentrations were found in patients with BS as compared to PsA, although in both groups IL-36α was significantly increased compared to healthy controls. An empirical cut-off of 420.6 pg/mL displayed a specificity of 0.93, with a sensitivity of 0.70 (AUC 0.82) in discriminating PsA from BS. This cut-off displayed a good diagnostic performance also in BS patients lacking highly specific BS manifestations. Our results indicate that IL-36α might be involved in the pathogenesis of both BS and PsA, and might be a candidate biomarker to support the differential diagnosis of BS.

Published
2023
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39. Prevalence and clinical associations of ultrasound-confirmed enthesitis in systemic lupus erythematosus

Author

Filippo Fagni, Alessandra Bettiol, Elena Silvestri, Roberto Fedi, Adalgisa Palermo, Maria Letizia Urban, Ruggero Mazzotta, Danilo Malandrino, Federica Bello, Irene Mattioli, David Simon, Gerardo Di Scala, Georg Schett, Domenico Prisco, and Giacomo Emmi

Subjects
Rheumatology, Pharmacology (medical)
Abstract

Objectives To assess the prevalence of US-confirmed enthesitis in a cohort of patients with SLE and to analyse the clinical associations to enthesitis during the course of SLE. Methods In a retrospective analysis of the SLE cohort of the Lupus Unit of the Careggi University Hospital, US examinations of SLE patients presenting with tender and/or swollen joints were retrieved to assess the presence of enthesitis. Patients with US-proven enthesitis were compared with SLE controls with tender and/or swollen joints who showed no US evidence of enthesitis. Clinical and laboratory features were compared at disease onset and during follow-up. Results A total of 400 patients fulfilling EULAR/ACR classification criteria for SLE were assessed. Of these, 106 underwent articular US examination. Evidence of enthesitis was found in 31/106 (29.2%) patients. Seventy-one patients without US-enthesitis were included as controls; four were excluded due to lack of follow-up data. Laboratory and clinical features were comparable between cases and controls at disease onset. Throughout a median follow-up of 10.0 (interquartile range [IQR] 8.3–23.3) years for cases and 12.4 (IQR 7.2–13.3) years for controls, patients with enthesitis were less likely to develop renal involvement (22.6% vs 46.5%, P = 0.028) and failed B cell depletion more frequently (75.0% vs 0%). Conclusion In SLE patients with clinically active joints, US-proven enthesitis is a fairly common finding. Enthesitis in SLE could be the hallmark of a distinct disease phenotype with less renal involvement, more arthritis and low response to anti-CD 20 therapy, potentially requiring a tailored treatment.

Published
2023
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40. The BLOSSoM study: Burnout after perinatal LOSS in Midwifery. Results of a nation-wide investigation in Italy

Author

Eleonora Cossu, Alfredo Vannacci, Aurora Frontini, Sara Tagliavini, Laura Mosconi, Giada Crescioli, Elisa Carelli, Claudia Ravaldi, Alessandra Bettiol, Roberto Bonaiuti, Fabio Facchinetti, and Niccolò Lombardi

Subjects
Adult, medicine.medical_specialty, education, Flowers, Guidelines, Burnout, Psychological, Burnout, Midwifery, Midwives, 03 medical and health sciences, Perinatal loss, 0302 clinical medicine, Pregnancy, Surveys and Questionnaires, Maternity and Midwifery, Humans, Medicine, Bereavement Care, Emotional exhaustion, Burnout, Professional, 030219 obstetrics & reproductive medicine, 030504 nursing, business.industry, Obstetrics, Obstetrics and Gynecology, Professional burnout, PTSD, Mean age, Stillbirth, Cross-Sectional Studies, 0305 other medical science, business, Psychometric tests, Event scale
Abstract

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).

Published
2022
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41. Anthraquinone laxatives use and colorectal cancer: A systematic review and meta‐analysis of observational studies

Author

Niccolò Lombardi, Giada Crescioli, Valentina Maggini, Raffaele Bellezza, Iacopo Landi, Alessandra Bettiol, Francesca Menniti‐Ippolito, Ilaria Ippoliti, Gabriela Mazzanti, Annabella Vitalone, Eugenia Gallo, Francesco Sivelli, Francesco Sofi, Gian Franco Gensini, Alfredo Vannacci, and Fabio Firenzuoli

Subjects
Pharmacology, laxatives, colorectal cancer, anthraquinone, laxatives, Humans, Anthraquinones, colorectal cancer, anthraquinone, Colorectal Neoplasms, Constipation
Abstract

This systematic review and meta-analysis were conducted to determine the effects of anthraquinone (AQ) laxatives on colorectal cancer (CRC). We searched PubMed, Embase, Google Scholar, and CENTRAL from inception until March 2021, for randomized controlled trials (RCTs) and observational studies. Through the systematic review, we identified 8 observational studies evaluating AQ laxatives use as a risk factor for CRC development, and 5 studies on CRC risk were included in the meta-analysis using a random-effects model. Through the meta-analysis, we found that a history of AQ laxatives use compared with "other" and "no laxatives" use was associated with CRC development (OR: 1.41; 95% CI: 0.94-2.11), although not at a statistically significant level. The possible association persists even after removal of the outlier studies (OR: 1.51; 95% CI: 0.97-2.34). Selection of cases and controls was judged at low or unclear risk of bias across almost all studies, and the quality of evidence was from moderate to low. In conclusion, it is not possible to associate the use of AQ laxatives with the development of CRC. However, the trend toward an increased risk of CRC provides a strong indication for investigating this issue by performing further high-quality studies.

Published
2022
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43. Antihypertensive treatment changes and related clinical outcomes in older hospitalized patients

Author

Sebastiano, Cicco, D'Abbondanza, Marco, Proietti, Marco, Vincenzo, Zaccone, Chiara, Pes, Federica, Caradio, Mattioli, Massimo, Salvatore, Piano, Alberto Maria Marra, Alessandro, Nobili, Pier Mannuccio Mannucci, Antonello, Pietrangelo, Giorgio, Sesti, Elena, Buzzetti, Andrea, Salzano, Antonio, Cimellaro, Francesco, Perticone, Francesco, Violi, Gino Roberto Corazza, Salvatore, Corrao, Alessandra, Marengoni, Francesco, Salerno, Matteo, Cesari, Mauro, Tettamanti, Luca, Pasina, Carlotta, Franchi, Alessio, Novella, Gabriella, Miglio, Alessia Antonella Galbussera, Ilaria, Ardoino, Prisco, Domenico, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Michele, Zaccari, Massimiliano, Chiuch, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Pirro, Matteo, Lupattelli, Graziana, Bianconi, Vanessa, Alcidi, Riccardo, Giotta, Alessia, Massimo, R Mannarino, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Giuseppe, Natoli, Salvatore, Mularo, Massimo, Raspanti, Christiano, Argano, Federica, Cavallaro, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Serafini, Giovanni, Angelo, Simili, Mattia, Brunori, Ilaria, Lazzari, Cappellini, MARIA DOMENICA, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Valeria Di Stefano, Simona, Leoni, Sonia, Seghezzi, Alessandra Danuto Di Mauro, Diletta, Maira, Marta, Mancarella, Tiziano, Lucchi, Paolo Dionigi Rossi, Marta, Clerici, Alessandra Danuta Di Mauro, Giulia, Bonini, Conti, Federica, Silvia, Prolo, Maddalena, Fabrizi, Miriana, Martelengo, Giulia, Vigani, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Lavinia, Pitotti, Donatella, Padula, Valentina, Antoci, Ginevra, Cambiè, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Jacopo, Alberto, Federico, Cattaneo, Luigi, Anastasio, Lucia, Sofia, Carbone, LUIGI MARIA, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Emanuele, Valeriani, Damiani, D'Ardes, Lucia, Esposito, Simona, Sestili, Ermanno, Angelucci, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Giovanni, Imbimbo, Giuseppe, Zuccalà, Gabriella, D'Aurizio, Giuseppe, Romanelli, Andrea, Volpini, Daniela, Lucente, Francesca, Manzoni, Annalisa, Pirozzi, Alberto, Zucchelli, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Chiara, Dell'Unto, Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Alessandra, Bonfanti, Hajnalka, Szabo, Mazzola, Paolo, Piazzoli, Andrea, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Grazia Serra, Maria Antonietta Bleve, Antonio, Brucato, Teresa De Falco, Enrica, Negro, Martino, Brenna, Lucia, Trotta, Giovanni Lorenzo Squintani, Maria Luisa Randi, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Francesco, Ratti, Chiara, Zurlo, Lorenzo, Cerruti, Elisabetta, Cosi, Roberto, Manfredini, Fabio, Fabbian, Benedetta, Boari, Alfredo De Giorgi, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Irene Di Meo, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Francesca Giulia Leoni, Valeria De Sando, Sara, Scarduelli, Michela, Cammarosano, Ilenia, Pareo, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Giuseppe, Re, Andrea, Schilardi, Francesca, Loparco, Luigi, Fenoglio, Andrea, Falcetta, Alessia Valentina Giraudo, Salvatore, D'Aniano, Anna, L Fracanzani, Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Felice, Cinque, Flora, Peyvandi, Raffaella, Rossio, Giulia, Colombo, Pasquale, Agosti, Erica, Pagliaro, Eleonora, Semproni, Canetta, Ciro, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Christian, Folli, Giada, Pallini, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Salam, Kassem, Luca, Liberale, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Camillo, Ferrandina, Francesca, Mazzeo, Elena, Spazzini, Giulia, Cono, Giulia, Cesaroni, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Ludovica, Perri, Luigina, Guasti, Francesca, Rotunno, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Francesco, Dentali, Bertolotti, Marco, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Elena, Bigi, Pellegrini, Elisa, Laura, Orlandi, Giulia, Dondi, Lucia, Carulli, Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Aleandra, Scozzafava, Valentino, Condoleo, Tania, Falbo, Lidia, Colangelo, Marco, Filice, Elvira, Clausi, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara Del Vecchio, Ilaria, Benzoni, Andrea, Salvi, Leonardi, Roberto, Giampaolo, Damiani, Gianluca, Moroncini, William, Capeci, Giuseppe Pio Martino, Biondi, Lorenzo, Pietro, Pettinari, Monica, Ormas, Emanuele, Filippini, Devis, Benfaremo, Roberto, Romiti, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Samuele, Pignataro, Francesca, Mete, Miriam, Gino, Guido, Moreo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Paolo, Setti, Chiara, Traversa, Camilla, Scarsi, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Marcello Giuseppe Maggio Gian Paolo Ceda, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giovanni, Paoletti, Francesca, Losa, Montalto, GIUSEPPE ALBERT, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Mecocci, Patrizia, Ruggiero, Carmelinda, Boccardi, Virginia, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Sarah, Morellini, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Tarquini, Roberto, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Volpi, Riccardo, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, Federica, Gandolfo, Franco Laghi Pasini, Pier Leopoldo Capecchi, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Vittorio, Durante, Daniela, Tirotta, Giovanna, Eusebi, Cattaneo, Marco Natale, Amoruso, MARIA VALENTINA, Paola, Fracasso, Cristina, Fasolino, Moreno, Tresoldi, Enrica, Bozzolo, Sarah, Damanti, Massimo, Porta, Giuseppe, Armentaro, Maria Immacolata Arnone, Milena, Barone, Lorenzo, Bertolino, Sara, Bianco, Nicolò, Binello, Simona, Brancati, Agostino, Buonauro, William, Cordeddu, Curcio, Rosa, Andrea, Dalbeni, Salvatore, D'Agnano, Damiano, D'Ardes, Martina De Feo, Emilia, Donnarumma, Marco, Fei, Carmine Gabriele Gambino, Paolo, Giorgini, Lombardi, Rosa, Giuseppe, Miceli, Paola, Naccarato, Silvia, Noviello, Gaia, Olivieri, Roberta, Parente, Francesca Serena Pignataro, Sonia, Poma, Enrica, Porceddu, Pucci, Giacomo, Marco, Ricchio, Anna, Sabena, Marco, Salice, Claudia, Santarossa, Ambra, Savona, Caterina, Savrié, Roberto, Scicali, Mario, Stabile, Giovanni, Talerico, Michela, Talia, Eliezer Joseph Tassone, Thomas, Teatini, Elisabetta, Tombolini, Matteo, Traversa, Elia, Vettore, Alessandro, Vignal, Luca, Vilardi, Rosanna, Villani, Francesco, Vitale, Cicco, Sebastiano, D Abbondanza, Marco, Proietti, Marco, Zaccone, Vincenzo, Pes, Chiara, Caradio, Federica, Mattioli, Massimo, Piano, Salvatore, Marra, Alberto Maria, Nobili, Alessandro, Mannucci, Pier Mannuccio, Pietrangelo, Antonello, Sesti, Giorgio, Buzzetti, Elena, Salzano, Andrea, Cimellaro, Antonio, Antonio Cimellaro, Salvatore, Corrao, Mario, Barbagallo, Anna, Licata, Giuseppe, Montalto, Paolisso, Giuseppe, Rizzo, Maria Rosaria, and Cimellaro, Antonio - Giovani Internisti Società Italiana di Medicina Interna (GIS-SIMI) and of the REPOSI Investigators

Subjects
cardiovascular events, older patient, hypertension, antihypertensive drugs, older patients, survival, Clinical Biochemistry, antihypertensive drug, General Medicine, Biochemistry, cardiovascular event
Abstract

Background: Hypertension management in older patients represents a challenge, particularly when hospitalized. Objective: The objective of this study is to investigate the determinants and related outcomes of antihypertensive drug prescription in a cohort of older hospitalized patients. Methods: A total of 5671 patients from REPOSI (a prospective multicentre observational register of older Italian in-patients from internal medicine or geriatric wards) were considered; 4377 (77.2%) were hypertensive. Minimum treatment (MT) for hypertension was defined according to the 2018 ESC guidelines [an angiotensin-converting-enzyme-inhibitor (ACE-I) or an angiotensin-receptor-blocker (ARB) with a calcium-channel-blocker (CCB) and/or a thiazide diuretic; if >80 years old, an ACE-I or ARB or CCB or thiazide diuretic]. Determinants of MT discontinuation at discharge were assessed. Study outcomes were any cause rehospitalization/all cause death, all-cause death, cardiovascular (CV) hospitalization/death, CV death, non-CV death, evaluated according to the presence of MT at discharge. Results: Hypertensive patients were older than normotensives, with a more impaired functional status, higher burden of comorbidity and polypharmacy. A total of 2233 patients were on MT at admission, 1766 were on MT at discharge. Discontinuation of MT was associated with the presence of comorbidities (lower odds for diabetes, higher odds for chronic kidney disease and dementia). An adjusted multivariable logistic regression analysis showed that MT for hypertension at discharge was associated with lower risk of all-cause death, all-cause death/hospitalization, CV death, CV death/hospitalization and non-CV death. Conclusions: Guidelines-suggested MT for hypertension at discharge is associated with a lower risk of adverse clinical outcomes. Nevertheless, changes in antihypertensive treatment still occur in a significant proportion of older hospitalized patients.

Published
2023

44. Non-anti TNFα biologic agents for noninfectious uveitis associated with systemic inflammatory diseases: a systematic review

Author

Alice Bitossi, Irene Mattioli, Alessandra Bettiol, Adalgisa Palermo, Danilo Malandrino, Daniela Bacherini, Gianni Virgili, Fabrizio Giansanti, Lorenzo Vannozzi, and Elena Silvestri

Subjects
Immunology, Immunology and Allergy
Abstract

Noninfectious uveitis related to systemic inflammatory diseases represents a leading cause of blindness. Anti-TNFα agents are the first-line biologic therapy after traditional immunosuppressants, for ocular and systemic involvement. However, some patients fails anti-TNFα agents, due to primary inefficacy, loss of efficacy or adverse events. This systematic review summarizes evidence on the efficacy and safety of non-anti-TNFα biologics in adult patients with noninfectious uveitis associated with systemic inflammatory diseases. The systematic review of PubMed and Embase yielded 3663 records, from which 16 studies were included (13 non-controlled, 3 controlled trials). Most studies focused on Behçet’s syndrome (BS) and juvenile idiopathic arthritis (JIA) and assessed the efficacy of tocilizumab (n = 11), rituximab (n = 3), secukinumab (n = 1), or anakinra/canakinumab (n = 1). A body of evidence supports the use of tocilizumab BS and JIA-associated uveitis, for improving visual acuity, reducing central macular thickness, inducing ocular remission, and sparing corticosteroids. Preliminary data suggest that rituximab may represent a valid alternative, particularly in JIA, while anakinra/canakinumab might play a role in BS-associated uveitis. The role of secukinumab appears limited. Current evidence encourages investigations on the efficacy and safety of non-anti-TNFα agents in noninfectious non-idiopathic uveitis.

Published
2023
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45. Contributors

Author

Mostafa A. Abdel-Maksoud, Maryam Akhtari, Ayda AlHammadi, Amer Ali Almohssen, Amedeo Amedei, Kosar Asnaashari, Raul Aviles, Samar Freschi de Barros, İlke Coşkun Benlidayı, Alessandra Bettiol, Nicola Bizzaro, Carlos Eduardo Branco, Femke Broere, Luigi Cinquanta, Maria do Carmo Pereira Nunes, Ana Caroline Melo dos Santos, Bárbara Rayssa Correia dos Santos, Jean Carlos Vencioneck Dutra, Willem van Eden, Giacomo Emmi, Mickael Essouma, Elham Farhadi, Jean Moisés Ferreira, Michael Frech, Vadim Gorodetskiy, Luiza Guilherme, Agnès Hamzaoui, Kamel Hamzaoui, Gunnar Houen, Janaki Iyer, Hongxing Jia, Jorge Kalil, Parisa Khayambashi, Dominika Kwiatkowska, Jacob M. van Laar, José Luiz de Lima Filho, Mahdi Mahmoudi, Anselm Mak, Irene Mattioli, Edilson Leite de Moura, Elena Niccolai, Sean O’Neill, Yasunori Omata, Win Min Oo, Martin E. Perry, Domenico Prisco, Silvia Bellando Randone, Adam Reich, Nima Rezaei, Lazaros I. Sakkas, Blake Savage, Georg Schett, Syahrul Sazliyana Shaharir, Theodora Simopoulou, Nicole Marie Smith, Elaine Virgínia Martins de Souza Figueiredo, Arie J. Stoppelenburg, Rossella Talotta, Ithallo Sathio Bessoni Tanabe, Sakae Tanaka, Antonio Lucio Teixeira, Renato Tozzoli, Simon D. Tran, Nicole Hartwig Trier, Katie S. Turnbull, Luiz Paulo Bastos Vasconcelos, Marcelle Cristina Vasconcelos, H. John Visser, Asrul Abdul Wahab, Joshua Wolfe, Niloufar Yazdanpanah, Mario M. Zaiss, and Peipei Zhang

Published
2023
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46. Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Author

Crisafulli, Ernesto, Sartori, Giulia, Vianello, Alice, Busti, Fabiana, Nobili, Alessandro, Mannucci, Pier Mannuccio, Girelli, Domenico Investigators—Domenico Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene Mattioli (Azienda Ospedaliero Universitaria Careggi Firenze, SOD Medicina Interna Interdisciplinare), Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Michele, Zaccari, Massi- miliano Chiuch (Azienda Sanitaria Universitaria Integrata di Trieste, Clinica Medica Generale, e Terapia Medica), Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi (Azienda Ospedaliera della Pro- vincia di Lecco, Ospedale di Merate, Lecco, Medicina, Interna), Matteo, Pirro, Graziana, Lupattelli, Vanessa, Bianconi, Riccardo, Alcidi, Alessia, Giotta, Mannarino (Azienda Ospedaliera Santa Maria della Misericordia, Massimo R., Perugia, Medicina, Interna, Angiologia Malattie da Arteriosclerosi), Domenico, Girelli, Fabiana, Busti, Giacomo Marchi (Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Medicina Generale e Malattie Aterotrombotiche, e Degenerative), Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica Cacioppo (Azienda Ospedaliera Universitaria Policlinico Giaccone Policlinico di Palermo, Palermo, Unità Operativa di Geriatria, e Lun- godegenza), Salvatore, Corrao, Giuseppe, Natoli, Salvatore, Mularo, Massimo, Raspanti, Christiano, Argano, Civico, Federica Cavallaro (A. R. N. A. S., Cristina, Di, Benfratelli, Palermo, UOC Medicina Interna ad Indirizzo Geriatrico- Riabilitativo), Marco, Zoli, Maria Laura Mata- cena, Giuseppe, Orio, Eleonora, Magnolfi, Giovanni, Serafini, Angelo, Simili, Mattia, Brunori, Ilaria, Lazzari, Orsola-Malpighi, Angelo Simili (Azienda Ospe- daliera Universitaria Policlinico S., Bologna, Unità Operativa di Medicina Interna Zoli), Maria Domenica Cappellini, Gio- vanna Fabio, Margherita Migone De Amicis, Giacomo De Luca, Nata- lia Scaramellini, Valeria Di Stefano, Simona, Leoni, Sonia, Seghezzi, Alessandra Danuto Di Mauro, Diletta, Maira, Marta Mancarella (Fon- dazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Unità Operativa Medicina Interna IA), Tiziano, Lucchi, Paolo Dionigi Rossi, Marta, Clerici, Alessandra Danuta Di Mauro, Giulia, Bonini, Federica, Conti, Silvia, Prolo, Maddalena, Fabrizi, Miriana, Martelengo, Giulia, Vigani, Paola Nicolini (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Geriatria), Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Lavinia, Pitotti, Donatella, Padula, Valentina, Antoci, Ginevra Cambiè (IRCCS Policlinico San Matteo di Pavia, Pavia, Clinica Medica, I, Reparto, 11), Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Jacopo, Alberto, Federico Cattaneo (IRCCS Azienda Ospedaliera Universitaria San Martino-IST di Genova, Gen-, Ova, Clinica di Medicina Interna 2), Luigi, Anastasio, Lucia, Sofia, Maria Carbone (Ospedale Civile Jazzolino di Vibo Valentia, Vibo Val- entia, Medicina, Generale), Francesco, Cipollone, Maria Teresa Guag- nano, Ilaria, Rossi, Emanuele, Valeriani, Damiani, D’Ardes, Lucia, Esposito, Simona, Sestili, Annunziata, Ermanno Angelucci (Ospedale Clinicizzato SS., Chieti, Clinica, Medica), Gerardo, Mancuso, Daniela, Calipari, Mosè Bartone (Ospedale Giovanni Paolo II Lamezia Terme, Catanzaro, Unità Operativa Complessa Medicina Interna), Giuseppe, Delitala, Maria, Berria, Alessandro Delitala (Azienda ospedaliera- universitaria di Sassari, Maurizio, Muscaritoli, Ales- sio Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Gio- vanni Imbimbo (Policlinico Umberto, I, Sapienza Università di Roma, Medicina Interna, e Nutrizione Clinica Policlinico Umberto I), Giuseppe, Zuccalà, Gemelli, Gabriella D’Aurizio (Policlinico Universitario A., Roma, Roma, Unità Operativa Complessa Medicina d'Urgenza, e Pronto Soccorso)Giuseppe Romanelli, Alessandra, Marengoni, Andrea, Volpini, Daniela, Lucente, Francesca, Manzoni, Annalisa, Pirozzi, Alberto Zucchelli (Unità Operativa Complessa di Medicina I, a indirizzo geriatrico, Spedali, Civili, Montichiari, Brescia), Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Chiara Dell’Unto (Università Campus Bio- Medico, Roma, Medicina Clinica-Epatolo- gia), Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Alessandra, Bonfanti, Hajnalka, Szabo, Paolo, Mazzola, Andrea, Piazzoli, Gerardo, Maurizio Corsi (Università degli studi di Milano-Bicocca Ospedale S., Monza, Unità Operativa di Geri- atria), Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica Giofrè (Università degli Studi Magna Grecia, Policlinico Mater Domini, Cat-, Anzaro, Unità Operativa Complessa di Medicina Interna), Maria Grazia Serra, Maria Antonietta Bleve (Azienda Ospedaliera, Lecce, Unità Operativa Complessa Medicina), Antonio, Brucato, Teresa De Falco, Enrica, Negro, Martino, Brenna, Lucia, Trotta, Giovanni Lorenzo Squintani (ASST FatebenefratelliSacco, Maria Luisa Randi, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Francesco, Ratti, Chiara, Zurlo, Lorenzo, Cerruti, Elisabetta Cosi (Azienda Ospe- daliera Università di Padova, Padova, Clinica Medica I), Roberto Man- fredini, Benedetta, Boari, Alfredo De Giorgi, Ruana, Tiseo, Giulia Marta Viglione, Caterina Savriè (Azienda OspedalieraUniversitaria Sant'Anna, Ferrara, Unità Operativa Clinica Medica), Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Irene Di Meo (Azienda Ospedaliera Universitaria della Seconda Università degli Studi di Napoli, Napoli, VI Divisione di Medicina Interna, e Malattie Nutrizionali dell'Invecchiamento), Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, 13 Francesca Giulia Leoni, Valeria De Sando, Sara, Scarduelli, Michela, Cammarosano, Orsola-Malpighi, Ilenia Pareo (Azienda Ospedaliera Universitaria Poli- clinico S., Unità Operativa di Medicina Interna Borghi), Carlo, Sabbà, Francesco Saverio Vella, Patrizia Sup- pressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Ema- nuele Amoruso, Carlo, Custodero, Giuseppe, Re, Andrea, Schilardi, Francesca Loparco (Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Bari, Frugoni), Medicina Interna Universitaria C., Luigi, Fenoglio, Andrea, Falcetta, Alessia Valentina Giraudo, Salvatore D’Aniano (Azienda Sanitaria Ospedaliera Santa Croce, e Carle di Cuneo, Cuneo, Ademe, Medicina Interna), S. C., Fracanzani, Anna L., Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Felice Cinque (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, UOC Medicina Generale ad Indirizzo Metabolico), Flora, Peyvandi, Raffaella, Rossio, Colombo, Giulia, Pasquale, Agosti, Erica, Pagliaro, Eleonora Semproni (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Medicina Interna, 2, Emato- logia non tumorale, e Coagulopatie), Canetta, Ciro, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Christian Folli (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Medicina Interna Alta Intensità di Cure), Francesco, Salerno, Giada Pallini (IRCCS Policlinico San Donato, e Università di Milano, San Donato Milanese, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Salam, Kassem, Luca Liberale (IRCCS Ospedale Policlinico San Martino, e Università di Genova, Genova, Clinica Medica, 1, Medicina Interna, e Specialità Mediche), Nicola Lucio Liberato, Tiziana Tognin (ASST di Pavia, UOSD Medicina Interna, Ospedale di Casorate Primo, Pavia), Francesco, Purrello, Antonino Di Pino, Salvatore Piro (Ospedale Garibaldi Nesima, Catania, Giorgia, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano Buf- felli, Camillo, Ferrandina, Francesca, Mazzeo, Elena, Spazzini, Giulia, Cono, Giulia Cesaroni (Ospedale Poliambulanza, Brescia, Medicina Interna, e Geriatria), Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura Sanino (Dipartimento di Scienze Mediche, Università di Torino, Città della Scienza, e della Salute, Torino, Medicina Interna, 2 Unità Indirizzo d'Urgenza), Franc- esco Violi, Ludovica Perri (Policlinico Umberto, I, Prima Clinica Medica), Guasti, Luigina, Rotunno, Francesca, Castiglioni, Luana, Maresca, ANDREA MARIA, Squizzato, Alessandro, Campiotti, Leonardo, Ales- sandra Grossi, Diprizio, ROBERTO DAVIDE, Francesco Dentali (Università degli Studi dell'Insubria, Ospedale di Circolo, e Fondazione Macchi, Varese, Elena, Medicina, e Geriatria), Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Elena, Bigi, Elisa, Pellegrini, Laura, Orlandi, Giulia, Dondi, Lucia Carulli (Università di Modena, e Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Unità Operativa di Geriatria), Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Aleandra, Scozzafava, Valentino, Condoleo, Tania, Falbo, Lidia, Colangelo, Marco Filice, Elvira Clausi (Università Geriatriche), Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara del Vec- chio, Ilaria Benzoni (Dipartimento di Scienze Mediche, e Chirurgiche, Unità Operativa di Medicina Interna, Orsola-Malpighi, Università degli Studi di Bologna/ Azienda Ospedaliero- Universitaria S., Bologna), Andrea, Salvi, Roberto, Leonardi, Giampaolo Damiani (Spedali Civili di Brescia, Medicina Generale), U. O. 3a., Gianluca, Moroncini, William, Capeci, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Monica, Ormas, Emanuele, Filippini, Devis, Benfaremo, Roberto Romiti (Clinica Medica, Azienda Ospedaliera Universitaria- Ospedali Riuniti di Ancona), Riccardo, Ghio, Anna Dal Col (Azienda Ospedaliera Università San Martino, Medicina, III), Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo Labbadia (Poli- clinico Umberto, I, SMSC03Medicina Interna F, e Malattie Meta- boliche dell'osso), Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita (Policlinico Campus Biomedico Roma, Medicina, Clinica), Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Emanuele, Samuele Pignataro (Azienda Ospedaliera Universitaria Poli- clinico – V., Catania, Dipartimento di Medicina), Francesca, Mete, Miriam Gino (Ospedale degli Infermi di Rivoli, Medicina Interna)Guido Moreo, Gloria Pina (Clinica San Carlo Casa di Cura Polispecialistica, Paderno, Dugnano, Unità Operativa di Medicina Generale Emilio Bernardelli), Alberto Balle- strero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Paolo, Setti, Chiara, Traversa, Camilla Scarsi (Clinica Di Medicina Interna ad Indirizzo Oncologico, Azienda Ospedaliera Università San Martino di Genova), Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella Gruden (Medicina Interna III, Giovanni Battista Molinette, Ospedale S., Torino), Franco, Berti, Giuseppe, Famularo, Patrizia Tarsitani (Azienda Ospedaliera San Camillo Forlanini, Medicina Interna II), Roberto, Castello, Michela Pasino (Ospedale Civile Maggiore Borgo Trento, Medicina Generale, e Sezione di Decisione Cli- nica), Marcello Giuseppe Maggio Gian Paolo Ceda, Simonetta Mor- ganti, Andrea, Artoni, Margherita Grossi (Azienda Ospedaliero Uni- versitaria di Parma, Clinica Geriatrica), U. O. C., Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giovanni, Paoletti, Francesca Losa (Policlinico Universitario Duilio Casula, Azienda Ospedaliero-Universitaria di Cagliari, Cagliari, Allergologia ed Immunologia Clinica), Giuseppe, Montalto, Anna, Licata, Filippo Alessandro Montalto, Angelo Rizzo (Azienda Ospe- daliera Universitaria Policlinico Paolo Giaccone, UOC di Medicina Interna), Francesco, Corica, Giorgio, Basile, Antonino Cata- lano, Federica, Bellone, Martino, Concetto Principato (Azienda Ospedaliera Universitaria Policlinico G., Messina, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella Caruso (Azienda Ospedaliera per l'Emergenza Cannizzaro, Clinica Medica Università di Catania), Patrizia, Mecocci, Carmelinda, Ruggiero, della Misericordia, Virginia Boccardi (Università degli Studi di Perugia-Azienda Ospedaliera S. M., Struttura Complessa di Geriatria), Tiziana, Meschi, Andrea, Ticinesi, Antonio Nouvenne (Azienda Ospedaliera Universitaria di Parma, Medicina Interna e Lungodegenza Critica), U. O., Pietro, Minuz, Luigi, Fondrieschi, Giandomen- ico Nigro Imperiale, Sarah Morellini (Azienda Ospedaliera Universi- taria Verona, Policlinico GB Rossi, Medicina Generale per lo Studio ed il Trattamento dell’Ipertensione Arteriosa), Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia Bellan (Azienda Ospedaliera Universitaria Maggiore della Carità, Medicina Interna 1), Roberto, Quadri, Erica, Larovere, Marco Novelli (Ospedale di Ciriè, Asl, To4, Emilio, Simeone, Rosa, Scurti, Fabio Tolloso (Ospedale Spirito Santo di Pescara, Geriatria), Roberto Tar- quini, Alice, Valoriani, Silvia, Dolenti, Giulia Vannini (Ospedale San Giuseppe, Empoli, USL Toscana Centro, Firenze, Medicina Interna I), Riccardo, Volpi, Pietro, Bocchi, Alessandro Vignali (Azienda Ospe- daliera Universitaria di Parma, Clinica, e Terapia Medica), Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia Aiello (Divisione di Medicina Interna, Multimedica, Ircss, Milano), Antonino Di Pino (Ospedale GaribaldiNesima, – Catania, Medicina Interna), U. O. C., Teresa, Salvatore, Lucio, Monaco, Vanvitelli, Carmen Ricozzi (Policlinico Università della Campania L., UOC Medicina Interna), Alberto, Pilotto, Ilaria, Indiano, Federica Gandolfo (Ente Ospe- daliero Ospedali Galliera Genova, SC Geriatria Dipartimento Cure Geriatriche, Ortogeriatria, e Riabilitazione)Franco Laghi Pasini, Pier Leopoldo Capecchi (Azienda Ospedaliera Universitaria Senese, Siena, Unità Operativa Complessa Medicina 2), Ranuccio, Nuti, Roberto Val- enti, Martina, Ruvio, Silvia, Cappelli, Alberto Palazzuoli (Azienda Ospedaliera Università Senese, Mauro Ber- nardi, Silvia Li Bassi, Luca, Santi, Giacomo Zaccherini (Azienda Ospe- daliera Policlinico Sant’Orsola-Malpighi, Semeiotica Medica Bernardi), Vittorio, Durante, Daniela, Tirotta, Giovanna Eusebi (Ospedale di Cattolica, Rimini, Marco, Cattaneo, Maria Valentina Amoruso, Paola, Fracasso, Cristina Fasolino (Azienda ospedaliera San Paolo, Moreno, Tresoldi, Enrica 13 Internal and Emergency Medicine Internal and Emergency Medicine Bozzolo, Sarah Damanti (IRCCS Ospedale San Raffaele, – Milano, Medicina Generale, e delle Cure Avanzate), Massimo, Porta, Miriam Gino (AOU Città della Salute e della Scienza di Torino, – Torino, and Medicina Interna, 1U).

Subjects
Hospital cure, Chronic obstructive pulmonary disease, Heart failure, Mortality, Multimorbidity, Prognosis
Published
2023

47. Neutrophil-mediated mechanisms of damage and in-vitro protective effect of colchicine in non-vascular Behçet's syndrome

Author

Adalgisa Palermo, Giacomo Emmi, Matteo Becatti, Niccolò Taddei, Alessandra Bettiol, Silvia Galora, Irene Mattioli, Maria Letizia Urban, Amanda Mannucci, Domenico Prisco, Flavia Rita Argento, Eleonora Fini, Claudia Fiorillo, Elena Silvestri, and Danilo Malandrino

Subjects
Adult, Male, Neutrophils, Immunology, Anti-Inflammatory Agents, Inflammation/Inflammatory Disease, Pharmacology, medicine.disease_cause, Extracellular Traps, vasculitis, Antioxidants, Autoimmunity, Pathogenesis, chemistry.chemical_compound, medicine, Humans, Immunology and Allergy, Colchicine, human, Retrospective Studies, reactive oxygen species, chemistry.chemical_classification, Reactive oxygen species, business.industry, Behcet Syndrome, autoimmunity, Neutrophil extracellular traps, Middle Aged, medicine.disease, Oxidative Stress, chemistry, Apoptosis, Case-Control Studies, Original Article, Female, ORIGINAL ARTICLES, business, Intracellular, Systemic vasculitis
Abstract

Behçet’s syndrome (BS) is a systemic vasculitis with several clinical manifestations. Neutrophil hyperactivation mediates vascular BS pathogenesis, via both a massive reactive oxygen species (ROS) production and neutrophil extracellular traps (NETs) release. Here, we investigated neutrophil‐mediated mechanisms of damage in non‐vascular BS manifestations and explored the in‐vitro effects of colchicine in counteracting these mechanisms. NETs and intracellular ROS production was assessed in blood samples from 80 BS patients (46 with active non‐vascular BS, 34 with inactive disease) and 80 healthy controls. Moreover, isolated neutrophils were incubated for 1 h with an oxidating agent [2,2′‐azobis (2‐amidinopropane) dihydrochloride; 250 nM] and the ability of pure colchicine pretreatment (100 ng/ml) to counteract oxidation‐induced damage was assessed. Patients with active non‐vascular BS showed remarkably increased NET levels [21.2, interquartile range (IQR) = 18.3–25.9 mU/ml] compared to patients with inactive disease (16.8, IQR = 13.3–20.2 mU/ml) and to controls (7.1, IQR = 5.1–8.7 mU/ml, p, Neutrophil‐mediated mechanisms of damage might be directly involved in non‐vascular Behçet's syndrome. Neutrophil extracellular traps (NETs), more than an impaired redox status, might play a central role in the pathogenesis of mucosal, articular and intestinal BS manifestations. Colchicine might be effective to counteract neutrophils‐mediated damage in Behçet's syndrome, via the inhibition of NETs release.

Published
2021
Full Text
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48. Vascular Behçet syndrome: from pathogenesis to treatment

Author

Alessandra Bettiol, Fatma Alibaz-Oner, Haner Direskeneli, Gulen Hatemi, David Saadoun, Emire Seyahi, Domenico Prisco, Giacomo Emmi, and Bettiol A., ALİBAZ ÖNER F., DİRESKENELİ R. H., HATEMİ G., Saadoun D., SEYAHİ E., Prisco D., Emmi G.

Subjects
Internal Diseases, RHEUMATOLOGY, Internal Medicine Sciences, Klinik Tıp, Dahili Tıp Bilimleri, CLINICAL MEDICINE, Sağlık Bilimleri, İmmünoloji ve Romatoloji, İç Hastalıkları, Clinical Medicine (MED), Tıp, Immunology and Rheumatology, Health Sciences, Medicine, Klinik Tıp (MED), Romatoloji, ROMATOLOJİ
Abstract

© 2022, Springer Nature Limited.Behçet syndrome is a rare, chronic inflammatory disease of unknown aetiopathogenesis, most commonly presenting with mucocutaneous and ocular manifestations. Vascular involvement, most frequently superficial vein and deep vein thrombosis, can occur in up to 50% of patients with Behçet syndrome. Venous thrombosis at atypical sites (inferior and superior vena cava, suprahepatic veins with Budd–Chiari syndrome, portal vein, cerebral sinuses and right atrium and/or ventricle) and arterial involvement (mostly in situ thrombosis and aneurysms of the pulmonary arteries, as well as aneurysms of the abdominal aorta, and peripheral and visceral arteries) are also unique features of Behçet syndrome. Behçet syndrome is considered a natural model of inflammation-induced thrombosis in humans, with an impaired immune-inflammatory response rather than traditional cardiovascular risk factors contributing to thrombogenesis. Specifically, neutrophil hyperactivation and neutrophil-mediated mechanisms of damage directly promote endothelial dysfunction, platelet activation and thrombogenesis in Behçet syndrome. This unusual pathogenesis directly determines the treatment approach, which relies mostly on immunosuppressants rather than anticoagulants for treatment of thrombosis and for secondary prevention. This Review discusses the main histopathological, pathogenetic and clinical aspects of vascular Behçet syndrome, addressing their implications for therapeutic management. Future perspectives in terms of pathogenetic studies, disease monitoring and treatment strategies are also discussed.

Published
2022

49. Exposures and suspected intoxications during SARS-CoV-2 pandemic: preliminary results from an Italian poison control centre

Author

Giada Crescioli, Alfredo Vannacci, Cecilia Lanzi, Giulia Borgioli, Anita Ercolini, Alessandra Bettiol, Niccolò Lombardi, Alessandra Ieri, Guido Mannaioni, and Francesco Gambassi

Subjects
Adult, Poison Control Centers, Isolation (health care), Clinical toxicology, Exposure, Intoxication, Pandemic, Poison control centre, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030231 tropical medicine, Population, Poison control, EM - Original, 03 medical and health sciences, 0302 clinical medicine, Age groups, Environmental health, Internal Medicine, Oral route, Humans, Medicine, 030212 general & internal medicine, Child, education, Pandemics, education.field_of_study, business.industry, COVID-19, University hospital, Italy, Emergency Medicine, business
Abstract

Data on cleaner and disinfectant exposure and misuse-related acute intoxications in Italy during SARS-CoV-2 pandemic are still lacking. The aim of the present study was to analyse and describe cleaner and disinfectant-related intoxications during SARS-CoV-2 pandemic in an Italian poison control centre. Data were obtained from the toxicological consultations requested to the Toxicology Unit and Poison Centre, Careggi University Hospital, Florence (Italy). We compared data from January 1st to April 30th of 2019 and 2020. Data concerning probable or acute intoxication from any causative agent in the general population (all age groups), from private individuals or from Regional and National health structures, were included in the analysis. A toxicological evaluation was also performed to calculate the Poisoning Severity Score.In 2019, 451 phone counselling sessions were performed and compared to a total of 410 calls received during the same period of 2020. In both periods, the majority of events occurred in paediatric (0–17 years) and adult (18–65 years) patients, who were mainly exposed to one toxic agent, and intoxications took place principally at home due to domestic accidents. The oral route of intoxication was the most frequently observed one, followed by inhalation of toxic agents, which increased by 4.7% in 2020. In 2020, sanitizers and cleaners were reported in 21.6% of cases compared to 12.5% in 2019. This is the first study describing cleaner and disinfectant-related intoxications in Italy. Our results suggested a possible misuse of these products during the SARS-CoV-2 pandemic, underling the effects of home isolation on mental health and unintentional toxic exposures.

Published
2021

50. Hyperglycemia at admission, comorbidities, and in-hospital mortality in elderly patients hospitalized in internal medicine wards: data from the RePoSI Registry

Author

Salvatore, Corrao, Alessandro, Nobili, Giuseppe, Natoli, Pier Mannuccio Mannucci, Francesco, Perticone, Antonello, Pietrangelo, Christiano, Argano, Giuseppe, Licata, Francesco, Violi, Gino Roberto Corazza, Alessandra, Marengoni, Francesco, Salerno, Matteo, Cesari, Mauro, Tettamanti, Luca, Pasina, Carlotta, Franchi, Laura, Cortesi, Gabriella, Miglio, Ilaria, Ardoino, Alessio, Novella, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Cenci, Caterina, Gianni, Biolo, Michela, Zanetti, Martina, Guadagni, Michele, Zaccari, Massimiliano, Chiuch, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Graziana, Lupattelli, Elmo, Mannarino, Vanessa, Bianconi, Francesco, Paciullo, Riccardo, Alcidi, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Floriana, Cocita, Vincenza, Beneduce, Lidia, Plances, Salvatore, Mularo, Massimo, Raspanti, Marco, Zoli, Ilaria, Lazzari, Mattia, Brunori, Elisa, Fabbri, Donatella, Magalotti, Raffaella, Arnò, Franco Laghi Pasini, Pier Leopoldo Capecchi, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Diletta, Maira, Valeria Di Stefano, Giovanna, Fabio, Sonia, Seghezzi, Marta, Mancarella, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Federica, Conti, Giulia, Bonini, Barbara Brignolo Ottolini, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Giovanni, Murialdo, Alessio, Marra, Federico, Cattaneo, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Maria Beatrice Secchi, Davide, Ghelfi, Luigi, Anastasio, Lucia, Sofia, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Emanuele, Valeriani, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Chiara, Pes, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Giuseppe, Zuccalà, Gabriella, D'Aurizio, Giuseppe, Romanelli, Alberto, Zucchelli, Francesca, Manzoni, Andrea, Volpini, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Chiara, Dell'Unto, Giorgio, Annoni, Maurizio, Corsi, Giuseppe, Bellelli, Sara, Zazzetta, Paolo, Mazzola, Hajnalka, Szabo, Alessandra, Bonfanti, Franco, Arturi, Elena, Succurro, Mariangela, Rubino, Bruno, Tassone, Giorgio, Sesti, Maria Grazia Serra, Maria Antonietta Bleve, Laura, Gasbarrone, Maria Rosaria Sajeva, Antonio, Brucato, Silvia, Ghidoni, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Elisabetta, Cosi, Paolo, Scarinzi, Annalisa, Amabile, Elisabetta, Omenetto, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Boari, Benedetta, DE GIORGI, Alfredo, Tiseo, Ruana, DE GIORGIO, Roberto, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Andrea, Schilardi, Francesca, Loparco, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Luigi, Fenoglio, Andrea, Falcetta, Christian, Bracco, Anna, L Fracanzani Silvia Fargion, Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Raffaella, Rossio, Barbara, Ferrari, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Christian, Folli, Giuliana, Ceriani, Giada, Pallini, Franco, Dallegri, Luciano, Ottonello, Luca, Liberale, Lara, Caserza, Kassem, Salam, Nicola Lucio Liberato, Tiziana, Tognin, Giovanni Battista Bianchi, Sabrina, Giaquinto, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Elena, Spazzini, Camillo, Ferrandina, Giuseppe, Montrucchio, Paolo, Petitti, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Raffaella, Salmi, Piergiorgio, Gaudenzi, Ludovica, Perri, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Giulia, Dondi, Elisa, Pellegrini, Lucia, Carulli, Matteo, Galassi, Yasmine, Grassi, Maria, Perticone, Rosa, Battaglia, Marco, Filice, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara Del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Armando, Gabrielli, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Samuele, Pignataro, Alfio, Gennaro, Julien, Blanco, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Antonio, Cittadini, Carlo, Vigorito, Michele, Arcopinto, Andrea, Salzano, Emanuele, Bobbio, Alberto Maria Marra, Domenico, Sirico, Guido, Moreo, Francesca, Gasparini, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Giuseppe, Scattolin, Sergio, Martinelli, Mauro, Turrin, Leonardo, Sechi, Cristina, Catena, Gianluca, Colussi, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Stefano Del Giacco, Davide, Firinu, Francesca, Losa, Giovanni, Paoletti, Giulia, Costanzo, Giuseppe, Montalto, Anna, Licata, Valentina, Malerba, Filippo Alessandro Montalto, Antonino, Lasco, Giorgio, Basile, Antonino, Catalano, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Fulvio, Lauretani, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Alberto, Tedeschi, Lucia, Trotta, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Mara, Cattaneo, Federico, Napoli., Corrao S, Nobili A, Natoli G, Mannucci PM, Perticone F, Pietrangelo A, Argano C, REPOSI Investigator, Borghi C, Corrao S., Nobili A., Natoli G., Mannucci P.M., Perticone F., Pietrangelo A., Argano C., Licata G., Violi F., Corazza G.R., Marengoni A., Salerno F., Cesari M., Tettamanti M., Pasina L., Franchi C., Cortesi L., Miglio G., Ardoino I., Novella A., Prisco D., Silvestri E., Emmi G., Bettiol A., Caterina C., Biolo G., Zanetti M., Guadagni M., Zaccari M., Chiuch M., Vanoli M., Grignani G., Pulixi E.A., Bernardi M., Bassi S.L., Santi L., Zaccherini G., Lupattelli G., Mannarino E., Bianconi V., Paciullo F., Alcidi R., Nuti R., Valenti R., Ruvio M., Cappelli S., Palazzuoli A., Girelli D., Busti F., Marchi G., Barbagallo M., Dominguez L., Cocita F., Beneduce V., Plances L., Mularo S., Raspanti M., Zoli M., Lazzari I., Brunori M., Fabbri E., Magalotti D., Arno R., Pasini F.L., Capecchi P.L., Palasciano G., Modeo M.E., Di Gennaro C., Cappellini M.D., Maira D., Di Stefano V., Fabio G., Seghezzi S., Mancarella M., De Amicis M.M., De Luca G., Scaramellini N., Rossi P.D., Damanti S., Clerici M., Conti F., Bonini G., Ottolini B.B., Di Sabatino A., Miceli E., Lenti M.V., Pisati M., Dominioni C.C., Murialdo G., Marra A., Cattaneo F., Pontremoli R., Beccati V., Nobili G., Secchi M.B., Ghelfi D., Anastasio L., Sofia L., Carbone M., Cipollone F., Guagnano M.T., Valeriani E., Rossi I., Mancuso G., Calipari D., Bartone M., Delitala G., Berria M., Pes C., Delitala A., Muscaritoli M., Molfino A., Petrillo E., Zuccala G., D'Aurizio G., Romanelli G., Zucchelli A., Manzoni F., Volpini A., Picardi A., Gentilucci U.V., Gallo P., Dell'Unto C., Annoni G., Corsi M., Bellelli G., Zazzetta S., Mazzola P., Szabo H., Bonfanti A., Arturi F., Succurro E., Rubino M., Tassone B., Sesti G., Serra M.G., Bleve M.A., Gasbarrone L., Sajeva M.R., Brucato A., Ghidoni S., Fabris F., Bertozzi I., Bogoni G., Rabuini M.V., Cosi E., Scarinzi P., Amabile A., Omenetto E., Prandini T., Manfredini R., Fabbian F., Boari B., De Giorgi A., Tiseo R., De Giorgio R., Paolisso G., Rizzo M.R., Borghi C., Strocchi E., Ianniello E., Soldati M., Sabba C., Vella F.S., Suppressa P., Schilardi A., Loparco F., De Vincenzo G.M., Comitangelo A., Amoruso E., Fenoglio L., Falcetta A., Bracco C., Fargion A.L.F.S., Tiraboschi S., Cespiati A., Oberti G., Sigon G., Peyvandi F., Rossio R., Ferrari B., Colombo G., Agosti P., Monzani V., Savojardo V., Folli C., Ceriani G., Pallini G., Dallegri F., Ottonello L., Liberale L., Caserza L., Salam K., Liberato N.L., Tognin T., Bianchi G.B., Giaquinto S., Purrello F., Di Pino A., Piro S., Rozzini R., Falanga L., Spazzini E., Ferrandina C., Montrucchio G., Petitti P., Peasso P., Favale E., Poletto C., Salmi R., Gaudenzi P., Perri L., Landolfi R., Montalto M., Mirijello A., Guasti L., Castiglioni L., Maresca A., Squizzato A., Campiotti L., Grossi A., Bertolotti M., Mussi C., Lancellotti G., Libbra M.V., Dondi G., Pellegrini E., Carulli L., Galassi M., Grassi Y., Perticone M., Battaglia R., FIlice M., Maio R., Stanghellini V., Ruggeri E., del Vecchio S., Salvi A., Leonardi R., Damiani G., Capeci W., Gabrielli A., Mattioli M., Martino G.P., Biondi L., Pettinari P., Ghio R., Col A.D., Minisola S., Colangelo L., Cilli M., Labbadia G., Afeltra A., Marigliano B., Pipita M.E., Castellino P., Zanoli L., Pignataro S., Gennaro A., Blanco J., Saracco V., Fogliati M., Bussolino C., Mete F., Gino M., Cittadini A., Vigorito C., Arcopinto M., Salzano A., Bobbio E., Marra A.M., Sirico D., Moreo G., Gasparini F., Prolo S., Pina G., Ballestrero A., Ferrando F., Berra S., Dassi S., Nava M.C., Graziella B., Baldassarre S., Fragapani S., Gruden G., Galanti G., Mascherini G., Petri C., Stefani L., Girino M., Piccinelli V., Nasso F., Gioffre V., Pasquale M., Scattolin G., Martinelli S., Turrin M., Sechi L., Catena C., Colussi G., Passariello N., Rinaldi L., Berti F., Famularo G., Tarsitani P., Castello R., Pasino M., Ceda G.P., Maggio M.G., Morganti S., Artoni A., Del Giacco S., Firinu D., Losa F., Paoletti G., Costanzo G., Montalto G., Licata A., Malerba V., Montalto F.A., Lasco A., Basile G., Catalano A., Malatino L., Stancanelli B., Terranova V., Di Marca S., Di Quattro R., La Malfa L., Caruso R., Mecocci P., Ruggiero C., Boccardi V., Meschi T., Lauretani F., Ticinesi A., Nouvenne A., Minuz P., Fondrieschi L., Pirisi M., Fra G.P., Sola D., Porta M., Riva P., Quadri R., Larovere E., Novelli M., Scanzi G., Mengoli C., Provini S., Ricevuti L., Simeone E., Scurti R., Tolloso F., Tarquini R., Valoriani A., Dolenti S., Vannini G., Tedeschi A., Trotta L., Volpi R., Bocchi P., Vignali A., Harari S., Lonati C., Cattaneo M., Napoli F., Corrao, S., Nobili, A., Natoli, G., Mannucci, P. M., Perticone, F., Pietrangelo, A., Argano, C., Licata, G., Violi, F., Corazza, G. R., Marengoni, A., Salerno, F., Cesari, M., Tettamanti, M., Pasina, L., Franchi, C., Cortesi, L., Miglio, G., Ardoino, I., Novella, A., Prisco, D., Silvestri, E., Emmi, G., Bettiol, A., Caterina, C., Biolo, G., Zanetti, M., Guadagni, M., Zaccari, M., Chiuch, M., Vanoli, M., Grignani, G., Pulixi, E. A., Bernardi, M., Bassi, S. L., Santi, L., Zaccherini, G., Lupattelli, G., Mannarino, E., Bianconi, V., Paciullo, F., Alcidi, R., Nuti, R., Valenti, R., Ruvio, M., Cappelli, S., Palazzuoli, A., Girelli, D., Busti, F., Marchi, G., Barbagallo, M., Dominguez, L., Cocita, F., Beneduce, V., Plances, L., Mularo, S., Raspanti, M., Zoli, M., Lazzari, I., Brunori, M., Fabbri, E., Magalotti, D., Arno, R., Pasini, F. L., Capecchi, P. L., Palasciano, G., Modeo, M. E., Di Gennaro, C., Cappellini, M. D., Maira, D., Di Stefano, V., Fabio, G., Seghezzi, S., Mancarella, M., De Amicis, M. M., De Luca, G., Scaramellini, N., Rossi, P. D., Damanti, S., Clerici, M., Conti, F., Bonini, G., Ottolini, B. B., Di Sabatino, A., Miceli, E., Lenti, M. V., Pisati, M., Dominioni, C. C., Murialdo, G., Marra, A., Cattaneo, F., Pontremoli, R., Beccati, V., Nobili, G., Secchi, M. B., Ghelfi, D., Anastasio, L., Sofia, L., Carbone, M., Cipollone, F., Guagnano, M. T., Valeriani, E., Rossi, I., Mancuso, G., Calipari, D., Bartone, M., Delitala, G., Berria, M., Pes, C., Delitala, A., Muscaritoli, M., Molfino, A., Petrillo, E., Zuccala, G., D'Aurizio, G., Romanelli, G., Zucchelli, A., Manzoni, F., Volpini, A., Picardi, A., Gentilucci, U. V., Gallo, P., Dell'Unto, C., Annoni, G., Corsi, M., Bellelli, G., Zazzetta, S., Mazzola, P., Szabo, H., Bonfanti, A., Arturi, F., Succurro, E., Rubino, M., Tassone, B., Sesti, G., Serra, M. G., Bleve, M. A., Gasbarrone, L., Sajeva, M. R., Brucato, A., Ghidoni, S., Fabris, F., Bertozzi, I., Bogoni, G., Rabuini, M. V., Cosi, E., Scarinzi, P., Amabile, A., Omenetto, E., Prandini, T., Manfredini, R., Fabbian, F., Boari, B., De Giorgi, A., Tiseo, R., De Giorgio, R., Paolisso, G., Rizzo, M. R., Borghi, C., Strocchi, E., Ianniello, E., Soldati, M., Sabba, C., Vella, F. S., Suppressa, P., Schilardi, A., Loparco, F., De Vincenzo, G. M., Comitangelo, A., Amoruso, E., Fenoglio, L., Falcetta, A., Bracco, C., Fargion, A. L. F. S., Tiraboschi, S., Cespiati, A., Oberti, G., Sigon, G., Peyvandi, F., Rossio, R., Ferrari, B., Colombo, G., Agosti, P., Monzani, V., Savojardo, V., Folli, C., Ceriani, G., Pallini, G., Dallegri, F., Ottonello, L., Liberale, L., Caserza, L., Salam, K., Liberato, N. L., Tognin, T., Bianchi, G. B., Giaquinto, S., Purrello, F., Di Pino, A., Piro, S., Rozzini, R., Falanga, L., Spazzini, E., Ferrandina, C., Montrucchio, G., Petitti, P., Peasso, P., Favale, E., Poletto, C., Salmi, R., Gaudenzi, P., Perri, L., Landolfi, R., Montalto, M., Mirijello, A., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Campiotti, L., Grossi, A., Bertolotti, M., Mussi, C., Lancellotti, G., Libbra, M. V., Dondi, G., Pellegrini, E., Carulli, L., Galassi, M., Grassi, Y., Perticone, M., Battaglia, R., Filice, M., Maio, R., Stanghellini, V., Ruggeri, E., del Vecchio, S., Salvi, A., Leonardi, R., Damiani, G., Capeci, W., Gabrielli, A., Mattioli, M., Martino, G. P., Biondi, L., Pettinari, P., Ghio, R., Col, A. D., Minisola, S., Colangelo, L., Cilli, M., Labbadia, G., Afeltra, A., Marigliano, B., Pipita, M. E., Castellino, P., Zanoli, L., Pignataro, S., Gennaro, A., Blanco, J., Saracco, V., Fogliati, M., Bussolino, C., Mete, F., Gino, M., Cittadini, A., Vigorito, C., Arcopinto, M., Salzano, A., Bobbio, E., Marra, A. M., Sirico, D., Moreo, G., Gasparini, F., Prolo, S., Pina, G., Ballestrero, A., Ferrando, F., Berra, S., Dassi, S., Nava, M. C., Graziella, B., Baldassarre, S., Fragapani, S., Gruden, G., Galanti, G., Mascherini, G., Petri, C., Stefani, L., Girino, M., Piccinelli, V., Nasso, F., Gioffre, V., Pasquale, M., Scattolin, G., Martinelli, S., Turrin, M., Sechi, L., Catena, C., Colussi, G., Passariello, N., Rinaldi, L., Berti, F., Famularo, G., Tarsitani, P., Castello, R., Pasino, M., Ceda, G. P., Maggio, M. G., Morganti, S., Artoni, A., Del Giacco, S., Firinu, D., Losa, F., Paoletti, G., Costanzo, G., Montalto, G., Licata, A., Malerba, V., Montalto, F. A., Lasco, A., Basile, G., Catalano, A., Malatino, L., Stancanelli, B., Terranova, V., Di Marca, S., Di Quattro, R., La Malfa, L., Caruso, R., Mecocci, P., Ruggiero, C., Boccardi, V., Meschi, T., Lauretani, F., Ticinesi, A., Nouvenne, A., Minuz, P., Fondrieschi, L., Pirisi, M., Fra, G. P., Sola, D., Porta, M., Riva, P., Quadri, R., Larovere, E., Novelli, M., Scanzi, G., Mengoli, C., Provini, S., Ricevuti, L., Simeone, E., Scurti, R., Tolloso, F., Tarquini, R., Valoriani, A., Dolenti, S., Vannini, G., Tedeschi, A., Trotta, L., Volpi, R., Bocchi, P., Vignali, A., Harari, S., Lonati, C., Cattaneo, M., Napoli, F., Corrao, S, Nobili, A, Natoli, G, Mannucci, P, Perticone, F, Pietrangelo, A, Argano, C, Licata, G, Violi, F, Corazza, G, Marengoni, A, Salerno, F, Cesari, M, Tettamanti, M, Pasina, L, Franchi, C, Cortesi, L, Miglio, G, Ardoino, I, Novella, A, Prisco, D, Silvestri, E, Emmi, G, Bettiol, A, Caterina, C, Biolo, G, Zanetti, M, Guadagni, M, Zaccari, M, Chiuch, M, Vanoli, M, Grignani, G, Pulixi, E, Bernardi, M, Bassi, S, Santi, L, Zaccherini, G, Lupattelli, G, Mannarino, E, Bianconi, V, Paciullo, F, Alcidi, R, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Girelli, D, Busti, F, Marchi, G, Barbagallo, M, Dominguez, L, Cocita, F, Beneduce, V, Plances, L, Mularo, S, Raspanti, M, Zoli, M, Lazzari, I, Brunori, M, Fabbri, E, Magalotti, D, Arno, R, Pasini, F, Capecchi, P, Palasciano, G, Modeo, M, Di Gennaro, C, Cappellini, M, Maira, D, Di Stefano, V, Fabio, G, Seghezzi, S, Mancarella, M, De Amicis, M, De Luca, G, Scaramellini, N, Rossi, P, Damanti, S, Clerici, M, Conti, F, Bonini, G, Ottolini, B, Di Sabatino, A, Miceli, E, Lenti, M, Pisati, M, Dominioni, C, Murialdo, G, Marra, A, Cattaneo, F, Pontremoli, R, Beccati, V, Nobili, G, Secchi, M, Ghelfi, D, Anastasio, L, Sofia, L, Carbone, M, Cipollone, F, Guagnano, M, Valeriani, E, Rossi, I, Mancuso, G, Calipari, D, Bartone, M, Delitala, G, Berria, M, Pes, C, Delitala, A, Muscaritoli, M, Molfino, A, Petrillo, E, Zuccala, G, D'Aurizio, G, Romanelli, G, Zucchelli, A, Manzoni, F, Volpini, A, Picardi, A, Gentilucci, U, Gallo, P, Dell'Unto, C, Annoni, G, Corsi, M, Bellelli, G, Zazzetta, S, Mazzola, P, Szabo, H, Bonfanti, A, Arturi, F, Succurro, E, Rubino, M, Tassone, B, Sesti, G, Serra, M, Bleve, M, Gasbarrone, L, Sajeva, M, Brucato, A, Ghidoni, S, Fabris, F, Bertozzi, I, Bogoni, G, Rabuini, M, Cosi, E, Scarinzi, P, Amabile, A, Omenetto, E, Prandini, T, Manfredini, R, Fabbian, F, Boari, B, De Giorgi, A, Tiseo, R, De Giorgio, R, Paolisso, G, Rizzo, M, Borghi, C, Strocchi, E, Ianniello, E, Soldati, M, Sabba, C, Vella, F, Suppressa, P, Schilardi, A, Loparco, F, De Vincenzo, G, Comitangelo, A, Amoruso, E, Fenoglio, L, Falcetta, A, Bracco, C, Fargion, A, Tiraboschi, S, Cespiati, A, Oberti, G, Sigon, G, Peyvandi, F, Rossio, R, Ferrari, B, Colombo, G, Agosti, P, Monzani, V, Savojardo, V, Folli, C, Ceriani, G, Pallini, G, Dallegri, F, Ottonello, L, Liberale, L, Caserza, L, Salam, K, Liberato, N, Tognin, T, Bianchi, G, Giaquinto, S, Purrello, F, Di Pino, A, Piro, S, Rozzini, R, Falanga, L, Spazzini, E, Ferrandina, C, Montrucchio, G, Petitti, P, Peasso, P, Favale, E, Poletto, C, Salmi, R, Gaudenzi, P, Perri, L, Landolfi, R, Montalto, M, Mirijello, A, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Campiotti, L, Grossi, A, Bertolotti, M, Mussi, C, Lancellotti, G, Libbra, M, Dondi, G, Pellegrini, E, Carulli, L, Galassi, M, Grassi, Y, Perticone, M, Battaglia, R, Filice, M, Maio, R, Stanghellini, V, Ruggeri, E, del Vecchio, S, Salvi, A, Leonardi, R, Damiani, G, Capeci, W, Gabrielli, A, Mattioli, M, Martino, G, Biondi, L, Pettinari, P, Ghio, R, Col, A, Minisola, S, Colangelo, L, Cilli, M, Labbadia, G, Afeltra, A, Marigliano, B, Pipita, M, Castellino, P, Zanoli, L, Pignataro, S, Gennaro, A, Blanco, J, Saracco, V, Fogliati, M, Bussolino, C, Mete, F, Gino, M, Cittadini, A, Vigorito, C, Arcopinto, M, Salzano, A, Bobbio, E, Sirico, D, Moreo, G, Gasparini, F, Prolo, S, Pina, G, Ballestrero, A, Ferrando, F, Berra, S, Dassi, S, Nava, M, Graziella, B, Baldassarre, S, Fragapani, S, Gruden, G, Galanti, G, Mascherini, G, Petri, C, Stefani, L, Girino, M, Piccinelli, V, Nasso, F, Gioffre, V, Pasquale, M, Scattolin, G, Martinelli, S, Turrin, M, Sechi, L, Catena, C, Colussi, G, Passariello, N, Rinaldi, L, Berti, F, Famularo, G, Tarsitani, P, Castello, R, Pasino, M, Ceda, G, Maggio, M, Morganti, S, Artoni, A, Del Giacco, S, Firinu, D, Losa, F, Paoletti, G, Costanzo, G, Montalto, G, Licata, A, Malerba, V, Montalto, F, Lasco, A, Basile, G, Catalano, A, Malatino, L, Stancanelli, B, Terranova, V, Di Marca, S, Di Quattro, R, La Malfa, L, Caruso, R, Mecocci, P, Ruggiero, C, Boccardi, V, Meschi, T, Lauretani, F, Ticinesi, A, Nouvenne, A, Minuz, P, Fondrieschi, L, Pirisi, M, Fra, G, Sola, D, Porta, M, Riva, P, Quadri, R, Larovere, E, Novelli, M, Scanzi, G, Mengoli, C, Provini, S, Ricevuti, L, Simeone, E, Scurti, R, Tolloso, F, Tarquini, R, Valoriani, A, Dolenti, S, Vannini, G, Tedeschi, A, Trotta, L, Volpi, R, Bocchi, P, Vignali, A, Harari, S, Lonati, C, Cattaneo, M, and Napoli, F

Subjects
Registrie, Male, Comorbidity, Diabetes, Disability, Elderly, Hyperglycemia, Mortality, Aged, Aged, 80 and over, Female, Hospital Mortality, Hospitals, Humans, Internal Medicine, Registries, Hospitalization, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Socio-culturale, Renal function, 030204 cardiovascular system & hematology, Diabete, Hospital, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Rating scale, Internal medicine, Diabetes mellitus, 80 and over, medicine, LS4_4, 030212 general & internal medicine, Class III obesity, business.industry, Mortality rate, Comorbidity, Diabetes, Disability, Elderly, Hyperglycemia, Mortality, General Medicine, medicine.disease, Mood disorders, Geriatric Depression Scale, Original Article, business, Human
Abstract

Aims The association between hyperglycemia at hospital admission and relevant short- and long-term outcomes in elderly population is known. We assessed the effects on mortality of hyperglycemia, disability, and multimorbidity at admission in internal medicine ward in patients aged ≥ 65 years. Methods Data were collected from an active register of 102 internal medicine and geriatric wards in Italy (RePoSi project). Patients were recruited during four index weeks of a year. Socio-demographic data, reason for hospitalization, diagnoses, treatment, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), renal function, functional (Barthel Index), and cognitive status (Short Blessed Test) and mood disorders (Geriatric Depression Scale) were recorded. Mortality rates were assessed in hospital 3 and 12 months after discharge. Results Of the 4714 elderly patients hospitalized, 361 had a glycemia level ≥ 250 mg/dL at admission. Compared to subjects with lower glycemia level, patients with glycemia ≥ 250 mg/dL showed higher rates of male sex, smoke and class III obesity. These patients had a significantly lower Barthel Index (p = 0.0249), higher CIRS-SI and CIRS-CI scores (p = 0.0025 and p = 0.0013, respectively), and took more drugs. In-hospital mortality rate was 9.2% and 5.1% in subjects with glycemia ≥ 250 and p = 0.0010). Regression analysis showed a strong association between in-hospital death and glycemia ≥ 250 mg/dL (OR 2.07; [95% CI 1.34–3.19]), Barthel Index ≤ 40 (3.28[2.44–4.42]), CIRS-SI (1.87[1.27–2.77]), and male sex (1.54[1.16–2.03]). Conclusions The stronger predictors of in-hospital mortality for older patients admitted in general wards were glycemia level ≥ 250 mg/dL, Barthel Index ≤ 40, CIRS-SI, and male sex.

Published
2021

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