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Background: The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants., Objectives: To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines., Methods: Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex., Results: Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease., Conclusion: Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Limited screening and delays in diagnosis and linkage-to-care are barriers for hepatitis C virus (HCV) elimination. The LiverTAI study focused on patients tested for HCV using AI technologies to describe their demographic and clinical characteristics and pre-testing patient journeys, reflecting clinical practice in hospitals., Patients and Methods: LiverTAI is a retrospective, secondary analysis of electronic health records (EHRs) from 6 tertiary Spanish hospitals, extracting unstructured clinical data using natural language processing (NLP) EHRead® technology. Adult subjects with an HCV testing procedure from January 2014 to December 2018 were grouped according to HCV seropositivity and viremia., Results: From 2,440,358 patients, 16,261 patients were tested for HCV (13,602 [83.6%] HCV seronegative; 2659 [16.4%] seropositive). Active HCV viremia appeared in 37.7% (n=1003) of patients, 18.6% (n=494) had negative viremia, and 43.7% (n=1162) unknown viremia. Patient journeys showed core departments (Gastroenterology, Internal Medicine, and Infectious Disease) and others including Emergency perform ample HCV testing in Spanish hospitals, whereas Medical Oncology lags. Patients were PCR-tested and genotyped significantly faster in core departments (p<.001)., Conclusions: Our results highlight hospital departments responsible for HCV testing. However, further testing was sub-optimal during the study period. Therefore, we underscore the need for HCV screening and reflex testing to accelerate diagnosis and linkage-to-care., (Copyright © 2022 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Insulclock ® is an electronic device designed to improve treatment adherence and insulin injection tracking. This randomized, single-center, pilot study assessed the clinical impact of Insulclock on glycemic control and variability, treatment adherence, and satisfaction in patients with uncontrolled type 1 diabetes mellitus (T1DM). We also compared these outcomes between the Active and Masked groups (with or without receiving reminders and app alerts). Sixteen patients completed the study: 10 in the Active group and 6 in the Masked group. Insulclock use was associated with a decrease in mean glucose (-27.0 mg/dL [1.5 mmol/L]; P  = 0.013), glucose standard deviation (-14.4 mg/dL [0.8 mmol/L]; P  = 0.003), and time above range (-12.5%; P  = 0.0026), and an increase in time in range (TIR) (+7%; P  = 0.038) in the overall population. The use of app information and alerts in the Active group was associated with an increase in TIR (+8%; P  = 0.026). We observed a -3.9 ( P  = 0.1352) and -5.4 ( P  = 0.032) reduction per month in the number of missed and mistimed insulin doses in the overall population, respectively. Most of the items of the Insulin Treatment Satisfaction Questionnaire (ITSQ) improved after 4 weeks of Insulclock use. This pilot study points out an improvement in glycemic levels, adherence, and satisfaction in T1DM patients, supporting the development of clinical trials powered to confirm these effects.

Background and Aim: Elderly patients are frequently affected by gallstone-related disease. Current guidelines support cholecystectomy after a first acute biliary complication. In the aging, these recommendations are irregularly followed., Methods: We analyzed data from patients 65 or older admitted between June 30, 2004 and June 30, 2013 with a diagnosis of acute pancreatitis, cholangitis, or cholecystitis. Diagnosis and severity assessment were defined according to current guidelines. Harms, mortality, and cholecystectomy rates were evaluated. Baseline factors independently predicting cholecystectomy were identified., Results: A total of 491 patients were included. The median age was 78.8 years, and 51.7 % were women. Acute cholecystitis was present in 51.7 %, acute pancreatitis in 36.5 %, and acute cholangitis in 11.8 %. Cholecystectomy was performed in 47.1 %. Age, myocardial infarct, dementia, diabetes, nonmetastatic tumor, and severe liver disease were risk factors for not undergoing surgery. Complications related to hospital stay appeared in 33 % of patients. Surgery, cholecystostomy, and ERCP presented harms in 21-25 %. Overall mortality rate was 5.4 %: 10.4 % in acute cholangitis, 6.8 % in acute cholecystitis, and 2.2 % in acute pancreatitis. Mild cases presented a 1.3 % mortality, while 28.6 % of severe cases died. After discharge, 24.7 % of patients presented a new biliary complication, 9.7 % of them severe. Relapse was more frequent in patients managed without invasive procedures, 42.3 % than in cholecystectomy patients, 9.9 % (p < 0.001) and than in ERCP patients, 19.4 % (p = 0.01)., Conclusions: Cholecystectomy should be recommended to elderly patients after a first acute biliary complication. If not previously performed, ERCP should be offered as an alternative when surgery is contraindicated or refused.

Aim: To determine the incidence and characteristics of intestinal and extra-intestinal cancers among patients with inflammatory bowel disease in a Spanish hospital and to compare them with those of the local population., Methods: This was a prospective, observational, 7-year follow-up, cohort study. Cumulative incidence, incidence rates based on person-years of follow-up and relative risk were calculated for patients with inflammatory bowel disease and compared with the background population. The incidence of cancer was determined using a hospital-based data registry from Hospital Universitario de Fuenlabrada. Demographic data and details about time from diagnosis of inflammatory bowel disease to occurrence of cancer, disease extent, inflammatory bowel disease treatment, cancer therapy and cancer evolution were also collected in the inflammatory bowel disease cohort., Results: Eighteen of 590 patients with inflammatory bowel disease developed cancer [cumulative incidence = 3% (95%CI: 1.58-4.52) vs 2% (95%CI: 1.99-2.11) in the background population; RR = 1.5; 95%CI: 0.97-2.29]. The cancer incidence among inflammatory bowel disease patients was 0.53% (95%CI: 0.32-0.84) per patient-year of follow-up. Patients with inflammatory bowel disease had a significantly increased relative risk of urothelial carcinoma (RR = 5.23, 95%CI: 1.95-13.87), appendiceal mucinous cystadenoma (RR = 36.6, 95%CI: 7.92-138.4), neuroendocrine carcinoma (RR = 13.1, 95%CI: 1.82-29.7) and rectal carcinoid (RR = 8.94, 95%CI: 1.18-59.7). Colorectal cancer cases were not found., Conclusion: The overall risk of cancer did not significantly increase in our inflammatory bowel disease patients. However, there was an increased risk of urinary bladder cancer and, with less statistical power, an increased risk of appendiceal mucinous cystadenoma and of neuroendocrine tumors. Colorectal cancer risk was low in our series.

Background: Angiogenic and lymphangiogenic factors (ALFs) may play an important role in inflammatory bowel disease (IBD). Our aims were to evaluate levels of ALFs in serum and the colonic mucosa culture supernatant (MCS) of patients with active and quiescent IBD and healthy subjects and to correlate them with the endoscopic, clinical and histological activity and with acute-phase reactants., Methods: This is a prospective study of 28 controls and 72 IBD patients. Serum and MCS concentration of VEGFA, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, PlGF, Ang1, Ang2 and Tie2 were measured by ELISA. Activity was established by specific indexes (CDAI, Mayo score, SES-CD, D'Haens scale and Riley index). Acute-phase reactants were routinely measured., Results: MCS levels of all ALFs except VEGFR3 were higher in patients with endoscopic (p<0.05), clinical (p<0.05) and histological (p<0.01) activity than in those without it. In serum, VEGFA, VEGFC and Ang1 and VEGFA and Ang1 levels were lower in patients in remission than in patients with clinical and histological activity, respectively (p<0.05). There was a correlation between serum and MCS concentrations for VEGFD, VEGFR3, PlGF and Tie2 (r=0.25, r=0.48, r=-0.45 and r=0.36; p<0.05). Ang2 in MCS was the best predictor for the diagnosis of endoscopic, histological and clinical activity (area under ROC curve>0.8)., Conclusions: MCS determination suggests a local increase in ALFs that correlates with IBD activity. Although the correlation between ALFs in serum and MCS was not good, the study of some of these factors as possible targets of new drugs for IBD constitutes a key new line of research., (Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Objective: Crohn's disease commonly involves the small intestine, which is the site of vitamin B12 and folate absorption. Our aim was to define the prevalence of vitamin B12 and folate deficiency in patients with Crohn's disease and to identify predictive factors associated with such abnormalities., Methods: Two years prospective study of 180 consecutive Crohn's disease patients. Vitamin B12 and folate deficiency was defined as serum levels below 200 pg/ml and 3 ng/ml, respectively. We analysed prevalence of these deficiencies and possible predictive factors including small intestine resection, disease location, activity and duration of disease. Controls were ulcerative colitis patients (n = 70)., Results: The prevalence of B12 deficiency in Crohn's disease was 15.6% (95%CI 9.7-20%) compared with 2.8% (95%CI 0.8-9.8%) in ulcerative colitis (p = 0.007). With regard to folate deficiency, the prevalence in patients with Crohn's disease was 22.2% (95%CI 16-28%) compared with 4.3% (95%CI 1.4-12%) in ulcerative colitis (p = 0.001); 7.8% of Crohn's disease patients had macrocytic anemia. Ileal resection was found to be a risk factor for B12 deficiency (OR 2.7; 1.2-6.7; p = 0.02), and disease activity a risk factor for folate deficiency (OR 2.4; 1.2-5.1; p = 0.01)., Conclusion: A significant proportion of patients with Crohn's disease suffer from vitamin B12 and/or folate deficiency, suggesting that regular screening should be performed, with closer monitoring in patients with ileal resection or active disease.

Background: Tuberculosis reactivation can lead to severe complications in patients treated with anti-tumour necrosis factor-alpha., Aim: To assess the usefulness of repeat tuberculosis screening tests in inflammatory bowel disease patients on stable anti-TNF therapy., Methods: Cross-sectional study, in patients on prolonged anti-TNF treatment (≥ 12 months) and basal negative screening for latent tuberculosis. Quantiferon(®)-TB Gold In-tube test was performed and then, tuberculin skin test was administered., Results: 74 patients were included, median duration of anti-TNF treatment was 30 months (IQR 19-54); 47 patients on infliximab and 27 on adalimumab; no patient was on glucocorticoids. Previous BCG vaccination was present in 5 cases. After anti-TNF was started, 4 patients suffered from potential tuberculosis exposure and two cases travelled to endemic areas. The cumulative incidence of tuberculin skin test conversion was 2.7% (95% CI 0.3-9.4%, 2/74), and the incidence rate of tuberculin skin test conversion was 0.83% (95% CI 0.1-2.9%) per patient-year of treatment with anti-TNF drugs. All Quantiferon tests but one (a patient with an indeterminate result and a negative tuberculin skin test) were negative., Conclusions: The incidence rate of conversion of tuberculosis screening tests among patients on anti-TNF treatment seems to be low and these conversions were diagnosed based on a positive tuberculin skin test and were discordant with Quantiferon testing., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Genital fistulas (GF) can arise in the course of Crohn's disease (CD), are difficult to manage and determine a significant alteration of the quality of life., Aims: To review the joint experience of the Inflammatory Bowel Disease Units in six University Hospitals in the management of GF in Crohn's disease on female patients., Results: A total of 47 patients with GF were identified, affecting 3.8% of women with CD treated in our centers. A 47.5% of patients were smokers. The median of time from the diagnosis of CD reached 102 months. According to anatomical type, GF were classified as rectovaginal (74.5%), anovaginal/anovulvar (21.3%) and enterovaginal (4.3%). Main symptoms were vaginal discharge of fecal material (55.3%), vaginal passage of gas (40.4%), or both. Fistulas were treated with antibiotics in 59.6% of patients, without any lasting success. Thiopurines were used in 80.9% of cases, with 13.2% of complete and 23.7% of partial responses. Anti TNF-alpha therapy was applied in 63.8%, with a 16.7% of complete and a 30% of partial responses (all responding patients received infliximab). Surgery was indicated in 38.3% of patients, with a 22% of complete responses after a first operation and 38.8% after reintervention. In all, definitive closure after one or more of these therapies was achieved in only 31.9% of cases., Conclusion: Genital fistulas are a significant problem in female Crohn's disease patients. Therapy is not well defined and only partially effective (one in three cases). Surgical therapy stands out as the most effective treatment., (Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)