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Daniela Iacono,1 Elvira Favoino,2 Alessia Borgia,1 Serena Fasano,1 Ilenia Pantano,1 Virginia D’Abrosca,1 Giuseppe Picillo,1 Rosa Daniela Grembiale,3 Federico Perosa,2 Gabriele Valentini1 1Department of Clinical and Experimental Medicine, Rheumatology Section, University of Campania “Luigi Vanvitelli”, Naples, Italy; 2Department of Biomedical Sciences and Human Oncology (DIMO), Rheumatologic and Systemic Autoimmune Diseases Unit, University of Bari Medical School, Bari, Italy; 3Department of Medical and Surgical Sciences, University of Magna Graecia, Catanzaro, Italy Background and objective: Anti-carbamylated protein antibodies (anti-CarP Ab) represent a novel kind of autoantibodies specificity detectable in the sera of patients with rheumatoid arthritis (RA). They have been recently reported to be associated with increased mortality in Spanish patients with RA. The aim of our study was to compare the incidence mortality rates (IMRs) detected in RA patients from a tertiary Italian center with those reported in other European tertiary centers and to evaluate the putative role of anti-CarP Ab in modulating the low IMR detected in our patients.Methods: Clinical charts of patients consecutively admitted to our center, from January 1, 2008, to December 31, 2014, were retrospectively reviewed. The mortality rate (expressed as the number of deaths in the cohort divided by the number of years of IMR follow-up) and causes of death were assessed at December 31, 2015. Sera of 61 patients, representative of the whole cohort, collected at the time of admission to our center were investigated for the presence and the level of anti-CarP Ab. Demographic and clinical features, mortality rates and prevalence of anti-CarP Ab in our series were compared with those reported in other European cohorts.Results: We observed 608 patients for a median of 3.51 years. All-cause and cause-specific IMRs in our cohort were significantly lower than the Better Anti-rheumatic Farmaco-therapy and the Spanish cohort, while only all-cause and cardiovascular IMRs were significantly lower in our series with respect to the Leiden Early Arthritis Clinic cohort. Anti-CarP Ab prevalence was significantly lower in our series than in any other European cohorts.Conclusion: We confirm that the mortality rate is lower in our Italian RA cohort with respect to other European cohorts. Whether the low prevalence of anti-CarP Ab might be responsible for this result awaits to be furtherly investigated. Keywords: rheumatoid arthritis, mortality, anti-carbamylated protein antibodies, death causes

Daniela Iacono, Serena Fasano, Virginia D’Abrosca, Ilenia Pantano, Gabriele Valentini Department of Clinical and Experimental Medicine, Rheumatology Section, University of Campania “Luigi Vanvitelli,” Naples, Italy Objectives: Mortality in patients with rheumatoid arthritis (RA) has never been investigated in Italy. This study is devoted to investigating all the distinct causes of mortality in Italian RA patients.Methods: Clinical charts of patients consecutively admitted to an Italian tertiary center, from January 1, 2008 to December 31, 2014, were reviewed. Mortality rates (incidence mortality rate [IMR] and standardized mortality rate [SMR]) and causes of death as assessed at December 31, 2015, were registered. Mortality rates detected in our series were compared to those reported in other European cohorts and in the general Italian population.Results: Six hundred and eight patients were observed for a median of 3.51 years. Overall IMR was 0.79 deaths/100 person-years. No significant difference between our IMR and that reported in Italian population by the National Institute of Statistics was observed. All-cause and neoplasm IMRs in our series were found to be significantly lower than that reported in the Norfolk Arthritis Registry, while no difference was detected in cardiovascular (CV) mortality. On the other hand, all causes and CV SMRs in our series were found to be higher than that reported in the general Italian population, while cancer and infectious SMRs were found to be lower.Conclusion: In our series, RA patients had an increased all-cause mortality, and in particular an increased death rate due to CV. However, a lower death rate due to cancer and infections was observed. This figure might be due to the careful follow-up of RA patients in tertiary centers, and the results underlines the need to improve the management of CV risk. Keywords: rheumatoid arthritis, mortality, cancer, infections, cardiovascular deaths

Introduction: ERAS (Enhanced Recovery After Surgery) protocol is now proposed as the standard of care in elective major abdominal surgery. Implementation of the ERAS protocol in emergency setting has been proposed but his economic impact has not been investigated. Aim of this study was to evaluate the cost saving of implementing ERAS in abdominal emergency surgery in a single institution., Methods: A group of 80 consecutive patients treated by ERAS protocol for gastrointestinal emergency surgery in 2021 was compared with an analogue group of 75 consecutive patients treated by the same surgery the year before implementation of ERAS protocol. Adhesion to postoperative items, length of stay, morbidity and mortality were recorded. Cost saving analysis was performed., Results: 50% Adhesion to postoperative items was reached on day 2 in the ERAS group in mean. Laparoscopic approach was 40 vs 12% in ERAS and control group respectively (p ,002). Length of stay was shorter in ERAS group by 3 days (9 vs 12 days p ,002). Morbidity and mortality rate were similar in both groups. The ERAS group had a mean cost saving of 1022,78 € per patient., Conclusions: ERAS protocol implementation in the abdominal emergency setting is cost effective resulting in a significant shorter length of stay and cost saving per patient., (© 2024. The Author(s).)

Objective: To assess the effectiveness of home videogame-based exercise (exergaming) as an additional rehabilitative tool in young patients with rheumatoid arthritis (RA). Materials and Methods: After a baseline (T0) evaluation, 40 RA inpatients (18-35 years of age) underwent both a 4-week-lasting traditional rehabilitation program and a training by Nintendo ® Wii-Fit™ videogame system. At discharge (T1), subjects were randomly assigned (1:1) to two groups: Group A (experimental group), including subjects who continued Wii-Fit training at home for additional 8 weeks, and Group B (control group), including subjects maintaining their habitual activity during the 8-week follow-up (T2). Measures of disease activity, quality of life, and fatigue were evaluated at each time point. Results: From T0 to T1, a significant improvement in most evaluated outcomes was reported in both study groups. At T2 assessment, only Group A patients experienced a significant improvement of quality of life and fatigue, with a 13.4% reduction in Global Health (GH) values, only a slight increase (4.2%) in Health Assessment Questionnaire (HAQ) score, and a 19.1% Functional Assessment of Chronic Illness Therapy (FACIT) improvement as compared with T1. In contrast, Group B patients reported a 65.8% increase in GH values, a 33% increase in HAQ score, and a 53.4% reduction in FACIT values from T1 to T2. The extended videogame-based home training was an independent predictor of Δ%GH ( β  = 0.851; P  < 0.001), Δ%HAQ ( β  = 0.542; P  < 0.001), and Δ%FACIT ( β  = -0.505; P  < 0.001). Conclusions: Home exergaming may be an effective additional rehabilitative tool in RA, since it allows to maintain the benefits of traditional multidisciplinary rehabilitation.

Background: The inflammatory contribution to type 2 diabetes (T2D) has suggested new therapeutic targets using biologic drugs designed for rheumatoid arthritis (RA). On this basis, we aimed at investigating whether interleukin-1 (IL-1) inhibition with anakinra, a recombinant human IL-1 receptor antagonist, could improve both glycaemic and inflammatory parameters in participants with RA and T2D compared with tumour necrosis factor (TNF) inhibitors (TNFis)., Methods and Findings: This study, designed as a multicentre, open-label, randomised controlled trial, enrolled participants, followed up for 6 months, with RA and T2D in 12 Italian rheumatologic units between 2013 and 2016. Participants were randomised to anakinra or to a TNFi (i.e., adalimumab, certolizumab pegol, etanercept, infliximab, or golimumab), and the primary end point was the change in percentage of glycated haemoglobin (HbA1c%) (EudraCT: 2012-005370-62 ClinicalTrial.gov: NCT02236481). In total, 41 participants with RA and T2D were randomised, and 39 eligible participants were treated (age 62.72 ± 9.97 years, 74.4% female sex). The majority of participants had seropositive RA disease (rheumatoid factor and/or anticyclic citrullinated peptide antibody [ACPA] 70.2%) with active disease (Disease Activity Score-28 [DAS28]: 5.54 ± 1.03; C-reactive protein 11.84 ± 9.67 mg/L, respectively). All participants had T2D (HbA1c%: 7.77 ± 0.70, fasting plasma glucose: 139.13 ± 42.17 mg). When all the enrolled participants reached 6 months of follow-up, the important crude difference in the main end point, confirmed by an unplanned ad interim analysis showing the significant effects of anakinra, which were not observed in the other group, led to the study being stopped for early benefit. Participants in the anakinra group had a significant reduction of HbA1c%, in an unadjusted linear mixed model, after 3 months (β: -0.85, p < 0.001, 95% CI -1.28 to -0.42) and 6 months (β: -1.05, p < 0.001, 95% CI -1.50 to -0.59). Similar results were observed adjusting the model for relevant RA and T2D clinical confounders (male sex, age, ACPA positivity, use of corticosteroids, RA duration, T2D duration, use of oral antidiabetic drug, body mass index [BMI]) after 3 months (β: -1.04, p < 0.001, 95% CI -1.52 to -0.55) and 6 months (β: -1.24, p < 0.001, 95% CI -1.75 to -0.72). Participants in the TNFi group had a nonsignificant slight decrease of HbA1c%. Assuming the success threshold to be HbA1c% ≤ 7, we considered an absolute risk reduction (ARR) = 0.42 (experimental event rate = 0.54, control event rate = 0.12); thus, we estimated, rounding up, a number needed to treat (NNT) = 3. Concerning RA, a progressive reduction of disease activity was observed in both groups. No severe adverse events, hypoglycaemic episodes, or deaths were observed. Urticarial lesions at the injection site led to discontinuation in 4 (18%) anakinra-treated participants. Additionally, we observed nonsevere infections, including influenza, nasopharyngitis, upper respiratory tract infection, urinary tract infection, and diarrhoea in both groups. Our study has some limitations, including open-label design and previously unplanned ad interim analysis, small size, lack of some laboratory evaluations, and ongoing use of other drugs., Conclusions: In this study, we observed an apparent benefit of IL-1 inhibition in participants with RA and T2D, reaching the therapeutic targets of both diseases. Our results suggest the concept that IL-1 inhibition may be considered a targeted treatment for RA and T2D., Trial Registration: The trial is registered with EU Clinical Trials Register, EudraCT Number: 2012-005370-62 and with ClinicalTrial.gov, number NCT02236481., Competing Interests: The authors have declared that no competing interests exist for this work.

Objective: To investigate the role of acetylsalicylic acid (ASA) in reducing the incidence of cardiovascular (CV) events in an Italian multicentre rheumatoid arthritis (RA) inception cohort., Methods: The clinical charts of RA patients consecutively admitted to 4 Italian centres for their 1 st visit from November 1, 2000, to December 31, 2015, and followed up till December 2016 were retrospectively investigated for the incidence of CV events. Patients were subdivided into two groups, namely, ASA- and non-ASA-treated groups. The Kaplan-Meier curve and log-rank test were used to investigate differences in event-free survival. Cox regression analysis was carried out to identify factors associated with CV event occurrence., Results: Seven hundred forty-six consecutive RA patients were enrolled and followed up for a median of 5.6 years (range 2.9-8.9 years). The incidence rate (IR) of CV events was 8/1000 person-years (p-ys) in the overall cohort. The IR of CV events was significantly lower in the ASA-treated group with respect to the non-ASA-treated group (IR 1.7 vs. 11.8/1000 p-ys; p =0.0002). The CV event-free rate was longer in ASA-treated patients than in non-ASA-treated patients (log-rank test 12.8; p =0.0003). At multivariable analysis, arterial hypertension (HR 9.3) and hypercholesterolemia (HR 2.8) resulted to be positive predictors and ASA (HR 0.09) and hydroxychloroquine (HCQ) (HR 0.22) to be negative predictors., Conclusion: The IR of CV events in our Italian multicentre cohort was lower than that reported in other European and non-European cohorts. Low-dose ASA may have a role in the primary prophylaxis of CV events in RA patients.

Background: Despite the improvement of medical therapies, nearly half of patients with Crohn's disease require surgery within 10 years after diagnosis. However, intestinal resection is not curative and recurrence may occur., Aims: To evaluate post-surgical outcomes for patients with Crohn's disease in a large monocentric cohort, and to identify variables associated with clinical and surgical relapse., Methods: Patients with Crohn's disease who had surgery for ileal and colonic Crohn's disease between 2004 and 2016 and on at least one-year follow-up following surgery were included., Results: One hundred ninety-three patients were included in the study. Crohn's disease recurrence concerned 53% of patients after a median 56-month (6-158) follow-up and 29% of patients required a second surgical intervention. At logistic regression analysis, active smoking and young age at diagnosis were identified as independent risk factor for post-surgical relapse (p = 0.01), while colonic or ileocolonic resection was recognized as a risk factor for surgical Crohn's disease relapse (p = 0.003)., Conclusions: Post-surgery recurrence is frequent for patients with Crohn's disease. Active smoking and young age at diagnosis are risk factors for Crohn's disease recurrence. As compared with patients undergoing small-bowel surgery, patients with colonic resection are proner to relapse requiring a second surgical intervention., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Screening for active tuberculosis (TB) and latent TB infection (LTBI) is mandatory to the initiation of biological therapy in patients with rheumatic diseases. To determine the prevalence of LTBI in patients with rheumatoid arthritis before treatment with biological therapy (anti-TNF, abatacept, and tocilizumab) and the rate of TB conversion during treatment in rheumatoid arthritis (RA) patients, we evaluated the file of 275 patients with RA treated with biological agents. We considered patients with negative baseline TB screening (tuberculin skin test (TST); quantiferon TB gold in tube (QFT-GIT); chest x-ray) and with rescreening for a TB assay every year. Twenty-six patients (10.6%) resulted positive to TB screening at baseline. Two hundred and forty-nine patients (mean age 55.3 ± 11.9; median 55.8 years, range 16-81.9; 210 female) with TB screening negative at baseline were enrolled. One hundred and sixty-eight (67.5%) patients were treated with anti-TNF, 37 (14.9%) patients with abatacept, and 44 (17.7%) patients with tocilizumab. After a period of 12-120 months (median 24), 34 (13.6%) patients displayed conversion of at least one screening assay. Out of the 34 patients with conversion, 6 (16.2%) were treated with abatacept, 7 (15.9%) with tocilizumab, and 21 (12.5%) with anti-TNF. During the follow-up period, no patients developed active TB. Our study shows that a proportion of patients (13.6%) converts at least one TB screening assay during biological therapy. This study underscores the American College of Rheumatology advice for annual screening in some or all biologically treated patients.

Purpose: To assess the serum profile of factors involved in endothelial, T-cell, and fibroblast interplay in patients with Raynaud's phenomenon (RP) associated with nailfold vodeocapillaroscopy (NVC) scleroderma findings and/or systemic sclerosis (SSc) marker autoantibodies, recently labeled as early SSc patients., Methods: Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), CCL2, CXCL8, IL-13, IL-33, and transforming growth factor-β (TGF-β) were measured in 24 early SSc patients, 48 definite SSc patients, and 24 osteoarthritis/fibromyalgia controls by multiplex suspension immunoassay. All SSc patients were investigated for the presence/absence of preclinical and clinical organ involvement, SSc marker autoantibodies, and NVC abnormalities., Results: Serum sICAM-1, CCL2, CXCL8, and IL-13 were increased in all SSc patients as compared to controls, and paralleled the severity of the disease subset (early SSc < limited cutaneous SSc < diffuse cutaneous SSc; p < 0.0001). Surprisingly, IL-33 was significantly higher in early SSc patients as compared to both controls (p < 0.01) and definite SSc patients (p < 0.05). In early SSc there were no differences in the investigated markers according to the functional and serological features assessed., Conclusions: Our study suggests that an endothelial, T-cell and fibroblast activation can be present in patients with early SSc and it is associated with a distinct profile of circulating factors involved in the cross-talk of these cells. The marked increase of IL-33 in early SSc patients suggests new routes of investigation of cell-cell dynamics in target tissues predating overt disease manifestations, thus opening to new therapeutic approaches.

Introduction: We investigated early systemic sclerosis (SSc) (that is, Raynaud's phenomenon with SSc marker autoantibodies and/or typical capillaroscopic findings and no manifestations other than puffy fingers or arthritis) versus undifferentiated connective tissue disease (UCTD) to identify predictors of short-term disease evolution., Methods: Thirty-nine early SSc and 37 UCTD patients were investigated. At baseline, all patients underwent clinical evaluation, B-mode echocardiography, lung function tests and esophageal manometry to detect preclinical alterations of internal organs, and were re-assessed every year. Twenty-one early SSc and 24 UCTD patients, and 25 controls were also investigated for serum endothelial, T-cell and fibroblast activation markers., Results: At baseline, 48.7% of early SSc and 37.8% of UCTD patients had at least one preclinical functional alteration (P > 0.05). Ninety-two percent of early SSc patients developed manifestations consistent with definite SSc (that is, skin sclerosis, digital ulcers/scars, two or more teleangectasias, clinically visible nailfold capillaries, cutaneous calcinosis, X-ray bibasilar lung fibrosis, X-ray esophageal dysmotility, ECG signs of myocardial fibrosis and laboratory signs of renal crisis) within five years versus 17.1% of UCTD patients (X² = 12.26; P = 0.0005). Avascular areas (HR = 4.39 95% CI 1.18 to 16.3; P = 0.02), increased levels of soluble IL-2 receptor alpha (HR = 4.39; 95% CI 1.03 to 18.6; P = 0.03), and of procollagen III aminopropeptide predicted disease evolution (HR = 4.55; 95% CI 1.18 to 17; P = 0.04)., Conclusion: Most early SSc but only a few UCTD patients progress to definite SSc within a short-term follow-up. Measurement of circulating markers of T-cell and fibroblast activation might serve to identify early SSc patients who are more likely to develop features of definite SSc.