Healthy First-Degree Relatives From Multiplex Families vs Simplex Families Have a Higher Subclinical Intestinal Inflammation, a Distinct Fecal Microbial Signature, and Harbor a Higher Risk of Developing Crohn's Disease.

BACKGROUND & AIMS: Unaffected first-degree relatives (FDRs) from families with ≥2 affected FDRs with Crohn's disease (CD, multiplex families) have a high risk of developing CD, although the underlying mechanisms driving this risk are poorly understood. We aimed to identify differences in biomarkers between FDRs from multiplex vs simplex families and investigate the risk of future CD onset accounting for potential confounders. METHODS: We assessed the Crohn's and Colitis Canada Genetic Environmental Microbial cohort of healthy FDRs of patients with CD. Genome-wide CD-polygenic risk scores, urinary fractional excretion of lactulose-to-mannitol ratio, fecal calprotectin (FCP), and fecal 16S ribosomal RNA microbiome were measured at recruitment. Associations between CD multiplex status and baseline biomarkers were determined using generalized estimating equations models. Cox models were used to assess the risk of future CD onset. RESULTS: There were 4051 participants from simplex families and 334 from CD multiplex families. CD multiplex status was significantly associated with higher baseline FCP (P = .026) but not with baseline CD-polygenic risk scores or the lactulose-to-mannitol ratio. Three bacterial genera were found to be differentially abundant between both groups. CD multiplex status at recruitment was independently associated with an increased risk of developing CD (adjusted hazard ratio, 3.65; 95% confidence interval, 2.18-6.11, P < .001). CONCLUSION: Within FDRs of patients with CD, participants from multiplex families had a 3-fold increased risk of CD onset, a higher FCP, and an altered bacterial composition, but not genetic burden or altered gut permeability. These results suggest that putative environmental factors might be enriched in FDRs from multiplex families.

Effectiveness and safety of a GLP-1 agonist in obese patients with inflammatory bowel disease.

BACKGROUND: obesity affects many patients with inflammatory bowel disease (IBD). Glucagon-like peptide (GLP)-1 agonists are a promising therapy for obese patients. However, there is a lack of evidence of the use of these drugs in IBD patients. This study investigated the effectiveness and safety of GLP-1 agonists in a cohort of obese patients with IBD. METHODS: a retrospective series of cases of consecutive IBD patients who received GLP-1 agonists indicated to treat obesity between 2019 and 2021 was analyzed. The GLP-1 agonists included were semaglutide 1.0 mg or liraglutide 3.0 mg. The coprimary endpoints were the percentage of change in body weight from baseline to six months and a weight reduction of 5 % or more at six months. In addition, the safety profile of GLP-1 agonist therapy and its impact on the IBD course were reviewed. RESULTS: sixteen obese patients with IBD (nine with Crohn's disease [CD] and seven with ulcerative colitis [UC]) were included in the study. The median body mass index at baseline was 35 (32-37). The percentage of change in body weight was -6.2 % (-3.4-[-8.5]) at six months, and a 5 % or more weight reduction was achieved in 58.3 % (7/12) of patients at six months. The most common side effect was nausea (13.3 %), and one patient withdrew due to diarrhea. IBD activity score did not change significantly during follow-up. CONCLUSION: our results showed that GLP-1 agonists were effective and had a good safety profile in IBD patients. Most adverse effects were mild, and the IBD activity had no significant changes.

Gastrointestinal symptoms and complications in patients hospitalized due to COVID-19, an international multicentre prospective cohort study (TIVURON project).

BACKGROUND: Retrospective studies suggest that coronavirus disease (COVID-19) commonly involves gastrointestinal (GI) symptoms and complications. Our aim was to prospectively evaluate GI manifestations in patients hospitalized for COVID-19. METHODS: This international multicentre prospective cohort study recruited COVID-19 patients hospitalized at 31 centres in Spain, Mexico, Chile, and Poland, between May and September 2020. Patients were followed-up until 15 days post-discharge and completed comprehensive questionnaires assessing GI symptoms and complications. A descriptive analysis as well as a bivariate and multivariate analysis were performer using binary logistic regression. p<0.05 was considered significant. RESULTS: Eight hundred twenty-nine patients were enrolled; 129 (15.6%) had severe COVID-19, 113 (13.7%) required ICU admission, and 43 (5.2%) died. Upon admission, the most prevalent GI symptoms were anorexia (n=413; 49.8%), diarrhoea (n=327; 39.4%), nausea/vomiting (n=227; 27.4%), and abdominal pain (n=172; 20.7%), which were mild/moderate throughout the disease and resolved during follow-up. One-third of patients exhibited liver injury. Non-severe COVID-19 was associated with ≥2 GI symptoms upon admission (OR 0.679; 95% CI 0.464-0.995; p=0.046) or diarrhoea during hospitalization (OR 0.531; 95% CI 0.328-0.860; p=0.009). Multivariate analysis revealed that worse hospital outcomes were not independently associated with liver injury or GI symptoms. CONCLUSION: GI symptoms were more common than previously documented, and were mild, rapidly resolved, and not independently associated with COVID-19 severity. Liver injury was a frequent complication in hospitalized patients not independently associated with COVID-19 severity.

Time to Revisit Disease Classification in Inflammatory Bowel Disease: Is the Current Classification of Inflammatory Bowel Disease Good Enough for Optimal Clinical Management?

Inflammatory bowel disease (IBD), historically subdivided into Crohn's disease and ulcerative colitis, is a very heterogeneous condition. While the tendency in medicine is to try to reduce complexity, IBD is a disease that cannot justify a one-size-fits-all principle. Our current clinical classification tools are suboptimal and need further refinement to capture, at least in part, the variety of phenotypes encountered in daily clinical practice. Although these revised classification tools alone will not be sufficient and should be complemented by more detailed molecular subclassifications, optimized clinical phenotypes can contribute to improved trial designs, future translational research approaches, and better treatment outcomes. In the current review, we discuss key clinical features important in IBD disease heterogeneity, tackle limitations of the current classification systems, propose some potential improvements, and raise priorities for future research in this domain.

Histological inflammatory activity can predict endoscopic relapse in patients with ulcerative colitis who have achieved mucosal healing.

BACKGROUND AIMS: Current therapeutic goals in ulcerative colitis (UC) include clinical and endoscopic remission, named mucosal healing (MH). Despite MH, a proportion of patients suffer a clinical relapse, which has been related to histological inflammation. We aimed to identify which histopathological features or histopathological index cut-off was associated with endoscopic relapse (ER) in UC patients with MH. METHODS: Retrospective analysis of UC patients who underwent surveillance colonoscopy showing complete MH (endoscopic Mayo subscore=0) with random biopsies, and at least one more endoscopy along the follow-up. After a consensus meeting, expert pathologist performed histological assessment according to Simplified Geboes Score (SGS), Nancy Index (NI) and Robarts Histopathological Index (RHI). Other histopathological features were also evaluated. Patients were followed until ER or last endoscopy performed showing persistence of MH. RESULTS: A total of 95 patients (150 colonoscopies) were included. After mean follow-up of 31.2 months (SD 21.7), 33 patients (34.7%) suffered ER. Neutrophils in lamina propria (OR 2.6; P = 0.037), within the epithelium (OR 2.6; P = 0.03), SGS ≥3.1 (OR 2.6; P = 0.037), NI ≥2 (OR 2.6; P = 0.03) and RHI ≥5 (OR 2.6; P = 0.037) were associated with ER in univariate analysis. In multivariate analysis, eosinophils in the lamina propria (HR 2.5; P = 0.01) and clinical remission<12 months (HR 3.2; P = 0.002) were associated with ER. CONCLUSIONS: Histopathological findings in UC patients who have achieved endoscopic MH may predict ER. Standardized histopathology reports according to the presence of neutrophils, eosinophils or to defined cut-off of validated histopathologic indexes may represent a useful tool to predict ER and should be considered at therapeutic and surveillance decision process.

Overlapping of Independent SARS-CoV-2 Nosocomial Transmissions in a Complex Outbreak.

SARS-CoV-2 nosocomial outbreaks in the first COVID-19 wave were likely associated with a shortage of personal protective equipment and scarce indications on control measures. Having covered these limitations, updates on current SARS-CoV-2 nosocomial outbreaks are required. We carried out an in-depth analysis of a 27-day nosocomial outbreak in a gastroenterology ward in our hospital, potentially involving 15 patients and 3 health care workers. Patients had stayed in one of three neighboring rooms in the ward. The severity of the infections in six of the cases and a high fatality rate made the clinicians suspect the possible involvement of a single virulent strain persisting in those rooms. Whole-genome sequencing (WGS) of the strains from 12 patients and 1 health care worker revealed an unexpected complexity. Five different SARS-CoV-2 strains were identified, two infecting a single patient each, ruling out their relationship with the outbreak; the remaining three strains were involved in three independent, overlapping, limited transmission clusters with three, three, and five cases. Whole-genome sequencing was key to understand the complexity of this outbreak. IMPORTANCE We report a complex epidemiological scenario of a nosocomial COVID-19 outbreak in the second wave, based on WGS analysis. Initially, standard epidemiological findings led to the assumption of a homogeneous outbreak caused by a single SARS-CoV-2 strain. The discriminatory power of WGS offered a strikingly different perspective consisting of five introductions of different strains, with only half of them causing secondary cases in three independent overlapping clusters. Our study exemplifies how complex the SARS-CoV-2 transmission in the nosocomial setting during the second COVID-19 wave occurred and leads to extending the analysis of outbreaks beyond the initial epidemiological assumptions.

Proper Assignation of Reactivation in a COVID-19 Recurrence Initially Interpreted as a Reinfection.

A 77-year-old man (case R) with previous diagnosis of a mild COVID-19 episode was hospitalized 35 days later. On day 23 postadmission, he developed a second COVID-19 episode, now severe, and finally died. Initially, case R's COVID-19 recurrence was interpreted as a reinfection due to the exposure to a SARS-CoV-2 RT-PCR-positive roommate. However, whole-genome sequencing indicated that case R's recurrence corresponded to a reactivation of the strain involved in his first episode. Case R's reactivation had major consequences, leading to a more severe episode, and causing subsequent transmission to another 2 hospitalized patients, 1 of them with fatal outcome.

Prevalence of biliary acid malabsorption in patients with chronic diarrhoea of functional characteristics: a prospective study.

BACKGROUND: Bile acid malabsorption occurs in up to one third of patients with chronic diarrhoea of functional characteristics. The gold standard test for its diagnosis is the 75Selenium homocholic acid taurine (75SeHCAT) test. The aim of this work is to confirm previous data suggesting that bile acid malabsorption, diagnosed by 75Se-HCAT test, is the underlying cause of diarrhoea in a significant proportion of patients previously diagnosed with a functional disorder. In addition, we have analysed the clinical response of bile acid sequestrants in those patients with a bile acid diarrhoea diagnosis. METHODS: This is a prospective, single-centre study including consecutive adult patients diagnosed with chronic diarrhoea of unknown origin and with functional characteristics; systematic rule out of common causes of chronic diarrhoea was performed before bile acid malabsorption evaluation by 75SeHCAT scanning. A retention percentage less than 10% was considered positive. Clinical response to cholestyramine was further evaluated in those patients with a positive diagnosis of bile acid diarrhoea RESULTS: 38 patients (20 male, mean age 37.5 years) were finally included. Twenty (52.6%) patients included had a positive 75SeHCAT test. Median body mass index was significantly higher in those patients. We did not find significant differences in other clinical or biochemical variables 75SeHCAT-positive and 75SeHCAT-negative groups. Only 6 of 17 (35.3%) patients responded to cholestyramine treatment; 10 patients did not have response or withdraw the drug due to adverse events. Logistic regression analysis showed that none of the included variables was a predictor of clinical response to cholestyramine. CONCLUSIONS: Bile acid malabsorption occurs in a high proportion of patients suffering from chronic diarrhoea with functional characteristics. Systematic investigation of bile acid malabsorption should be included in the diagnostic algorithms of patients with chronic watery diarrhoea in the routine clinical practice. Absence of response to cholestyramine does not rule out bile acid diarrhoea.

A simple nomogram identifies patients with refractory ascites with worse outcome after transjugular intrahepatic portosystemic shunt.

OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) is increasingly used in the management of refractory ascites. Controversy exists regarding the predictive factors of unfavorable outcomes, useful for patient selection. The primary aim was to identify predictive factors of 1-year survival or recurrent severe hepatic encephalopathy in patients with cirrhosis undergoing covered TIPS for refractory ascites. The secondary aim was overall survival. METHODS: Observational, retrospective, multicentric study, that included all cirrhotic patients treated with covered-TIPS for refractory ascites since 2001. Demographic, clinical, laboratory and hemodynamic data were collected at baseline and consecutively until dead, liver transplant or end of follow-up. The Cox model was used to identify predictive factors of overall survival. A Fine-Gray competing risk regression model was used to identify predictive factors of 1-year mortality or recurrent hepatic encephalopathy. A predictive nomogram was created based on those factors. RESULTS: In total 159 patients were included. Predictive factors of survival or recurrent severe encephalopathy were renal dysfunction [hazard ratio, 2.12 (95% CI, 1.11-4.04); P = 0.022], albumin [hazard ratio, 0.58 (95% CI, 0.34-0.97); P = 0.036], serum sodium [hazard ratio, 0.94 (95% CI, 0.89-0.98); P = 0.008] and international normalized ratio [hazard ratio 4.27 (95% CI, 1.41-12.88); P = 0.010]. In the competing risk analysis, predictive factors of 1-year mortality/recurrent severe encephalopathy in multivariate analysis were age [sub-distribution hazard ratio (sHR) 1.05 (95% CI, 1.02-1.09); P = 0.001], creatinine [sHR 1.55 (95% CI, 1.23-1.96); P = 0.001] and serum sodium [sHR 0.94 (95% CI, 0.90-0.99); P = 0.011] at baseline. CONCLUSIONS: Age, creatinine and sodium baseline levels strongly influence 1-year survival/recurrent severe hepatic encephalopathy in patients with cirrhosis undergoing covered TIPS for refractory ascites. A simple nomogram accurately and easily identifies those patients with worse prognosis.

Comparison of original and biosimilar infliximab (CTP-13) in biologic-naïve patients with Crohn's disease and ulcerative colitis: a retrospective, multicenter real-life study in Spain.

PURPOSE: biosimilar infliximab (CTP-13) has been recently approved for the treatment of several immune-mediated inflammatory disorders, including inflammatory bowel disease (IBD). Comparative studies between this biosimilar and original infliximab in the real clinical practice are scarce. The objective of this study was to compare short and long-term safety and efficacy of original (O) and biosimilar infliximab (B-IFX) in biologic-naïve, IBD patients in the real life clinical practice. METHODS: a retrospective, multicentric study was performed in five Spanish hospitals. Consecutive IBD, biologic-naïve patients from an historic cohort who initiated O-IFX from January 2013 were compared with biologic-naïve patients, who started treatment with B-IFX since its approval in January 2015. The evaluation of efficacy was assessed after the induction phase, at week 14 and week 54 of treatment. Time to dose escalation or treatment persistence of both O-IFX and B-IFX was also considered. The appearance of serious adverse events was recorded. RESULTS: two hundred and thirty-nine IBD biologic-naïve patients who started with O-IFX or B-IFX were included: 153 patients were diagnosed with Crohn's disease (95 treated with O- and 58 treated with B-IFX) and 86 with ulcerative colitis (40 received O- and 46 received B-IFX). At weeks 14 and 54, both O-IFX and B-IFX groups reached a similar clinical response and remission rates. Time to dose escalation, treatment persistence and safety profile were comparable between both groups. CONCLUSIONS: this long-term real-life experience provides additional evidence of the similarity of O- and B-IFX CTP-13 in terms of efficacy and safety in IBD patients.

A new pattern in hepatitis A virus infection in an urban population.

INTRODUCTION: hepatitis A virus (HAV) infection is a common cause of acute hepatitis worldwide. Since the generalization of vaccination, its incidence had markedly declined. Nevertheless, several HAV-outbreaks have been described in the last decade, mainly related to contaminated alimentary products. In recent years, a new pattern of acute HAV infection has been described with changes in the demographic profile of the infected population, which is more common in healthy young men. PATIENTS AND METHODS: a retrospective case series study was performed to evaluate this possible change in the pattern of HAV infection. The case series included all patients with a diagnosis of HAV acute infection in our hospital between January 2005 and May 2017. RESULTS: a total of 196 cases were diagnosed which were comprised of two probable outbreaks: one starting in November 2008 of 26 cases and one starting in 2016 with 69 cases at the time of data collection. The two outbreak populations were comparable. While the sporadic cases group was predominantly formed by pediatric and third-age patients with a slight male tendency, the outbreak related cases showed a clear predominance for young males (proportion of males: 63.2% vs 85.3%, p < 0.001). A possible chronological relationship with the national gay festivity celebrated in Madrid was observed. Outbreak related cases had higher bilirubin, alanine aminotransferase and longer APPT at diagnosis as well as a lower albumin concentration. The clinical relevance was minimal with a similar hospitalization rate and clinical outcome in both groups. There were no related deaths, acute liver failure or need for liver transplantation in our cohort. CONCLUSION: these epidemiological findings emphasize the importance of implementing preventive measures as well as social awareness campaigns.