ABSTRACT Introduction The goal of this project was to develop a joint European clinical practice guideline for the diagnosis and treatment of obstructed defecation syndrome (ODS), based on the best available evidence. These guidelines are intended to support all healthcare professionals involved in the care of patients with ODS, such as general practitioners, colorectal surgeons, gastroenterologists, gynecologists, radiologists, physiotherapists, and psychologists, as well as to provide accessible information for patients themselves. Methods A multidisciplinary Guideline Development Group representing seven European scientific societies and including patient representatives formulated PICO‐based clinical questions. Evidence was identified through a systematic literature review and assessed using the GRADE approach. Recommendations were formulated according to the available evidence and, where evidence was insufficient, as expert opinions. Results The final guideline includes 28 statements (1 moderate grade evidence, 2 low grade evidence, 3 very low grade evidence, 22 expert opinion) covering the diagnosis, conservative and surgical management of ODS, including indications for various imaging modalities, functional tests, and both transanal and transabdominal surgical approaches. Multidisciplinary assessment is recommended throughout the diagnostic and therapeutic pathway. Conservative treatment represents the initial management strategy, with biofeedback recommended before surgery in patients with ODS and dyssynergic defecation who fail dietary and laxative treatment. Surgery should be reserved for selected patients with persistent symptoms after conservative treatment and considered following multidisciplinary pelvic floor evaluation. Conclusion These multidisciplinary European guidelines offer a comprehensive and evidence‐based framework for the diagnosis and management of ODS. They are intended to promote standardized, high‐quality care across Europe and to improve outcomes and quality of life for individuals affected by this complex condition. Given the limited quality of evidence supporting many interventions, individualized decision‐making within a multidisciplinary setting remains central to ODS management.
ABSTRACT Background We previously proposed that three or more episodes of acute pancreatitis (AP) without radiological evidence of CP constitute early chronic pancreatitis (ECP), but it remains unclear whether ECP represents advanced recurrent acute pancreatitis (RAP) or a distinct clinical stage. Methods We performed a post hoc analysis of prospectively collected data from the AP Registry of the Hungarian Pancreatic Study Group, including 1717 patients enrolled between 2017 and 2025. Patients were categorized as AP (single episode; n = 1143), RAP (two episodes without CP morphology; n = 215), ECP (≥ 3 episodes without CP morphology; n = 152), or acute‐on‐chronic pancreatitis (ACP; radiological CP with at least one AP episode; n = 207). Demographic characteristics, risk factors, outcomes, and endoscopic interventions were compared across the groups. Results Male predominance increased progressively from RAP (58%) to ECP (72%) and ACP (79%). Similarly, alcohol‐related etiology rose from 23% in RAP to 36% in ECP and 45% in ACP. Smoking prevalence increased markedly from 36% in RAP to 49% in ECP and 68% in ACP. A change in therapeutic indications became apparent in ECP. While endoscopic interventions in AP and RAP were predominantly prophylactic (71% and 67%, respectively), pancreatic duct–directed procedures emerged as a leading indication in ECP (42%) and became dominant in ACP (77%), consistent with increasing pancreatic duct involvement across disease stages. Conclusions ECP represents a distinct transitional phenotype between RAP and established CP and already exhibits characteristic epidemiological, etiological, and therapeutic features. Recognition of ECP may therefore identify a critical window for targeted intervention before irreversible morphological damage to the pancreas occurs.
ABSTRACT Background Creeping fat (CrF) in Crohn's disease (CD) is a metabolically active perilesional adipose tissue involved in intestinal inflammation. Whether biological therapies modify its browning‐associated phenotype remains largely unexplored. We investigated whether anti‐TNF treatment is associated with changes in browning‐, mitochondrial biogenesis‐ and immune‐related pathways in CrF and whether similar molecular changes occur following ex vivo infliximab exposure. Methods Two independent human cohorts were analysed. (1) Observational cohort: CrF biopsies from anti‐TNF‐treated and anti‐TNF–naïve CD patients ( n = 14 and n = 19, respectively) were analysed for metabolic and inflammatory gene and protein expression. AdMSCs and mature CrF‐derived adipocytes were isolated, and UCP1 protein abundance was assessed by immunohistochemistry and western blotting. (2) Ex vivo cohort: Paired CrF explants from anti‐TNF‐naïve patients with CD undergoing surgery were cultured with or without infliximab (5 mg/kg‐equivalent, 24 h) and analysed by RT‐qPCR and immunohistochemistry. Results Anti‐TNF‐treated patients showed higher UCP1 expression in CrF at mRNA and protein levels. CrF‐derived mature adipocytes from treated patients exhibited increased expression of browning‐/thermogenesis‐ and mitochondrial biogenesis‐associated genes, together with reduced selected pro‐inflammatory markers. AdMSCs also showed exploratory differences in their conditioned‐medium protein profile, although no protein remained significant after FDR correction. Ex vivo infliximab exposure was associated with changes in selected browning‐, mitochondrial biogenesis‐ and immune‐related markers. Discussion Together, the observational and ex vivo findings identify CrF as an anti‐TNF‐responsive immunometabolic compartment in CD, characterised by coordinated browning‐, mitochondrial biogenesis‐ and immune‐related molecular changes. Functional studies are needed to establish the metabolic significance of these changes.
ABSTRACT Bacterial infections are a major cause of mortality in cirrhosis, with antibiotic prophylaxis and empirical treatment embedded in international guidelines. However, the prevalence of multidrug‐resistant organisms and the epidemiology of infections have shifted considerably in recent decades. This review critically appraises the evidence underlying guideline recommendations on antibiotic prophylaxis for spontaneous bacterial peritonitis and acute variceal bleeding in cirrhosis, and antimicrobial management in acute liver failure. The evidence‐underlying current recommendations is limited and predates the current era of widespread antimicrobial resistance, challenging their applicability in current practice. Emerging evidence suggests that primary prophylaxis should be reconsidered, alternatives such as rifaximin warrant further evaluation against established fluoroquinolone regimens, and shorter antibiotic courses may be non‐inferior to standard durations. New double‐blind placebo‐controlled, non‐inferiority and Bayesian trials are needed to evaluate antibiotic regimens and microbiome‐ and barrier‐directed interventions, supported by improved diagnostics, while minimising treatment duration, toxicity and selection for antimicrobial resistance.
