Intestinal Obstruction

BackgroundSmall bowel obstruction (SBO) is a common surgical emergency associated with substantial morbidity, hospital length of stay (LOS), and healthcare cost. The World Society of Emergency Surgery (WSES) Bologna guidelines provide evidence-informed recommendations for managing adhesive SBO, promoting timely surgical intervention (or non-operative management (NOM) when ischaemia, strangulation, or peritonitis are absent). However, guideline adoption and its impact on outcomes remain under studied. Compliance with the Bologna guidelines was evaluated to determine the impact of compliance on outcomes.MethodsSnapSBO, a prospective, multicentre, time-bound, observational cohort study, captured data on patients with adhesive SBO across diverse healthcare settings and patient populations. Patient care was categorized into: successful NOM, surgery after an unsuccessful appropriate trial of NOM (NOM-T), and direct to surgery (DTS). Compliance with diagnostic, therapeutic, and postoperative Bologna guideline recommendations was assessed as either complete or partial. Primary outcomes included adherence to the Bologna guidelines, LOS, complications, and the incidence of the composite metric 'optimal outcomes' (LOS ≤5 days, discharge without complications, and no readmission within 30 days).ResultsAmong 982 patients with adhesive SBO, successful NOM occurred in 561 (57.1%), 224 (22.8%) underwent NOM-T, and 197 (20.1%) proceeded DTS. The mean(s.d.) LOS was 5.3(9.0), 12.9(11.4), and 7.7(8.0) days respectively (P ConclusionPatients with adhesive SBO whose care was aligned with the Bologna guidelines had a shorter LOS and a greater incidence of optimal outcomes. Addressing evidence-to-practice gaps through implementation strategies that consider contextual factors will enhance guideline adoption and patient outcomes.

Ex situ normothermic machine perfusion (NMP) is rapidly emerging as a novel platform for testing therapeutics in human donor livers. Recently, perfusion of explanted patient livers was achieved, raising the possibility of using these diseased organs to increase the fidelity and resolution of drug testing and development. Here, we provide proof-of-principle for the feasibility of this approach in the context of gene therapy. We report the first successful administration of adeno-associated virus serotype 8 (AAV8) vector treatment in the explanted liver of a 34-year-old patient with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), using machine perfusion. MNGIE is caused by mutations in the thymidine phosphorylase (TYMP) gene, leading to nucleoside accumulation. The patient's liver was split into anatomical left and right lobes and perfused using separate machine perfusion devices. Prior to treatment, nucleoside accumulation was observed in the perfusate of both lobes, recapitulating the cardinal feature of MNGIE. An AAV8 vector carrying the human TYMP gene was administered in the left lobe with the right serving as a control. AAV8 gene therapy resulted in successful vector uptake, with complete nucleoside clearance within 6 days of administration. Our results constitute the first demonstration of the efficacy of gene therapy for MNGIE in a human organ and provide proof-of-principle for using machine perfusion as a new strategy for disease modelling and testing novel therapeutics, e.g. gene therapy, in explanted livers.

Postoperative ileus is a prolonged impairment of gastrointestinal motility following surgical procedures. This often leads to increased morbidity, extended hospital stays, and high healthcare expenditures. In this review, we discuss the pathophysiology underlying postoperative ileus, its epidemiology, and perioperative management strategies. Patient characteristics, as well as expected perioperative course, could be used to stratify the risks of postoperative ileus. Preventive measures hinge upon a multimodal approach, minimally invasive surgical techniques, fluid management, early postoperative ambulation, and opioid-sparing analgesia strategies. Adjuvant interventions such as alvimopan, caffeine, and chewing gum have demonstrated efficacy in modulating the neurogenic and inflammatory components of postoperative ileus. Minimally invasive approaches, comprehensive perioperative management, and adjuvant therapies hold promise for prevention. Current management relies heavily on supportive care, underscoring the need for research into the underlying neurogenic and inflammatory mechanisms to guide the development of targeted treatments.

Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors have reshaped pharmacological management of type 2 diabetes, but emerging safety signals suggest a possible association with intestinal obstruction. Because many candidates for these agents already harbor risk factors for ileus and bowel obstruction, clarifying agent- and dose-specific gastrointestinal safety is clinically important. We aimed to re-evaluate the risk of intestinal obstruction across individual GLP-1 receptor agonists and SGLT2 inhibitors, with particular attention to dose stratification. We systematically searched eight databases through 21 January 2025 to identify randomized controlled trials (RCTs) comparing GLP-1 receptor agonists or SGLT2 inhibitors with placebo or active comparators in adults. The primary outcome was incident intestinal obstruction (small or large bowel). A frequentist random-effects network meta-analysis estimated odds ratios (ORs) with 95% confidence intervals (CIs) across drugs and dose tiers; Bayesian models and surface under the cumulative ranking (SUCRA) metrics were used for sensitivity analyses and treatment ranking. Risk of bias and certainty of evidence were assessed with standard Cochrane and GRADE-adapted tools. Fifty RCTs (47 publications; 192,359 participants) met inclusion criteria. Overall, canagliflozin use was associated with a higher incidence of intestinal obstruction than control therapies (OR 2.56, 95% CI 1.01-6.49), corresponding to an absolute risk difference of 0.15% and a number needed to harm of 658. High-dose canagliflozin (300 mg/day) showed the clearest signal (OR 3.42, 95% CI 1.08-10.76). In contrast, liraglutide was associated with a lower risk of intestinal obstruction (OR 0.44, 95% CI 0.24-0.81), with an absolute risk reduction of 0.34% and a number needed to treat of 295. No other GLP-1 receptor agonist or SGLT2 inhibitor demonstrated a statistically significant increase in obstruction risk. Frequentist and Bayesian analyses yielded concordant estimates and rankings. From a randomized-trial perspective, intestinal obstruction risk is not elevated for most GLP-1 receptor agonists and SGLT2 inhibitors. A dose-dependent safety signal was observed only for high-dose canagliflozin, whereas liraglutide may confer a protective effect. These findings refine gastrointestinal safety profiles for modern antidiabetic agents and may inform perioperative bowel management, drug selection, and dose optimization in patients at risk for ileus or adhesive obstruction.