Comparative Risks of Post-ERCP Adverse Events in Patients with Asymptomatic and Symptomatic Choledocholithiasis: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is the standard of care for the management of choledocholithiasis but carries risk of complications which may result in significant morbidity and mortality. While currently available guidelines endorse the use of ERCP for the management of symptomatic common bile duct stones, the need for ERCP in incidentally found asymptomatic choledocholithiasis is more controversial, and practice varies on a geographic and institutional level. This systematic review and meta-analysis is conducted to compare post-ERCP adverse events between asymptomatic and symptomatic choledocholithiasis patients. METHODS: We searched PubMed/Embase/Web of Science databases to include all studies comparing post-ERCP outcomes between asymptomatic and symptomatic choledocholithiasis patients. The primary outcome was post-ERCP pancreatitis (PEP), while secondary outcomes included post-ERCP cholangitis, bleeding, and perforation. We calculated pooled risk ratios (RR) and 95% confidence intervals (CIs) using the Mantel-Haenszel method within a random-effect model. RESULTS: Our analysis included six observational studies, totaling 2,178 choledocholithiasis patients (392 asymptomatic and 1786 symptomatic); 53% were female. Asymptomatic patients exhibited a higher risk of PEP compared with symptomatic patients (11.7% versus 4.8%; RR 2.59, 95% CI 1.56-4.31, p ≤ 0.001). No significant difference was observed in post-ERCP cholangitis, bleeding, or perforation rates between the two groups. CONCLUSIONS: Asymptomatic patients with choledocholithiasis appear to have a higher risk of PEP than symptomatic patients, while the risk of other post-ERCP adverse events is similar between the two groups. Interventional endoscopists should thoroughly discuss potential adverse events (particularly PEP) with asymptomatic patients before performing ERCP and utilize PEP-prevention measures more liberally in this subgroup of patients.

Effects of chronic inhibition of phosphodiesterase-4D on behavior and regional rates of cerebral protein synthesis in a mouse model of fragile X syndrome.

Fragile X Syndrome (FXS) is caused by silencing the FMR1 gene which results in intellectual disability, hyperactivity, sensory hypersensitivity, autistic-like behavior, and susceptibility to seizures. This X-linked disorder is also associated with reduced cAMP levels in humans as well as animal models. We assessed the therapeutic and neurochemical effects of chronic administration of the phosphodiesterase-4D negative allosteric modulator, BPN14770, in a mouse model of FXS (Fmr1 KO). Groups of male Fmr1 KO mice and control littermates were treated with dietary BPN14770 commencing postnatal day 21. A dose-response effect was investigated. At 90 days of age, mice underwent behavior tests including open field, novel object recognition, three chambered sociability and social novelty tests, passive avoidance, and sleep duration analysis. These tests were followed by in vivo measurement of regional rates of cerebral protein synthesis (rCPS) with the autoradiographic L-[1-14C]leucine method. BPN14770 treatment had positive effects on the behavioral phenotype in Fmr1 KO mice. Some effects such as increased sleep duration and increased social behavior occurred in both genotypes. In the open field, the hyperactivity response in Fmr1 KO mice was ameliorated by BPN14770 treatment at low and intermediate doses. BPN14770 treatment tended to increase rCPS in a dose-dependent manner in WT mice, whereas in Fmr1 KO mice effects on rCPS were less apparent. Results indicate BPN14770 treatment improves some behavior in Fmr1 KO mice. Results also suggest a genotype difference in the regulation of translation via a cAMP-dependent pathway.

Risk factors for biliary strictures and leaks after living-donor liver transplantation: a systematic review and meta-analysis.

BACKGROUND: Liver transplantation is the only curative treatment of end-stage liver disease. Unfortunately, a significant number of patients on the organ waitlist die waiting for an organ. Living-donor liver transplantation (LDLT) is an approach that has been used to expand organ availability. Although LDLT has excellent outcomes, biliary complications remain a significant drawback. This meta-analysis aimed to precisely assess the predictors of biliary stricture and leak after LDLT. METHODS: PubMed, Embase, and Web of Science databases were searched from inception to January 2024. Only studies that used a multivariate model to assess risk factors for post-LDLT biliary stricture or leak in adult participants were included. Studies reporting unadjusted risk factors were excluded. Pooled adjusted odds ratios (ORs) and pooled hazard ratios (HRs) with 95% CIs for risk factors reported in ≥2 studies were obtained within a random-effects model. RESULTS: Overall, 22 studies with 9442 patients who underwent LDLT were included. The post-LDLT biliary stricture rate was 22%, whereas the post-LDLT biliary leak rate was 14%. In addition, 13 unique risk factors were analyzed. Postoperative bile leak (OR, 4.10 [95% CI, 2.88-5.83]; HR, 3.88 [95% CI, 2.15-6.99]) was the most significant predictor of biliary stricture after LDLT. Other significant predictors of biliary stricture after LDLT were right lobe graft (OR, 2.56; 95% CI, 1.23-5.32), multiple ducts for anastomosis (OR, 1.62; 95% CI, 1.08-2.43), ductoplasty (OR, 2.07; 95% CI, 1.36-3.13), ABO incompatibility (OR, 1.45; 95% CI, 1.16-1.81), and acute cellular rejection (OR, 4.10; 95% CI, 2.88-5.83). Donor bile duct size (HR, 0.82; 95% CI, 0.74-0.91; P = .001, I2 = 0%) was found to be significantly associated with reduced risk of post-LDLT biliary stricture. Donor age, recipient age, recipient male sex, and duct-to-duct anastomosis were not associated with an increased risk of post-LDLT biliary strictures. Multiple ducts for anastomosis (OR, 1.86; 95% CI, 1.43-2.43) was a significant predictor of post-LDLT biliary leak. Recipient age, warm ischemia time, and duct-to-duct anastomosis were not associated with an increased risk of post-LDLT biliary leak. CONCLUSION: In this meta-analysis, 7 unique risk factors were shown to be predictive of post-LDLT biliary stricture, one of which was associated with both post-LDLT biliary stricture and leak. Donor bile duct size was found to be protective against post-LDLT biliary strictures. Identifying reliable predictors is crucial for recognizing high-risk patients. This approach can facilitate the implementation of preventive measures, surveillance protocols, and targeted interventions to reduce the incidence of biliary strictures after LDLT.

New-onset Bell's palsy after neuroinvasive West Nile virus.

In this case report, a patient was diagnosed with new-onset Bell's palsy 3 weeks after the onset of neuroinvasive West Nile virus. This was the second case report of West Nile virus-associated Bell's palsy, highlighting the need to monitor these patients for peripheral neuropathies. This case report is also intended to raise awareness about the prevalence of West Nile virus in the USA.

Quantitative Autoradiographic Method for Determination of Regional Rates of Cerebral Protein Synthesis In Vivo.

Protein synthesis is required for development and maintenance of neuronal function and is involved in adaptive changes in the nervous system. Moreover, it is thought that dysregulation of protein synthesis in the nervous system may be a core phenotype in some developmental disorders. Accurate measurement of rates of cerebral protein synthesis in animal models is important for understanding these disorders. The method that we have developed was designed to be applied to the study of awake, behaving animals. It is a quantitative autoradiographic method, so it can yield rates in all regions of the brain simultaneously. The method is based on the use of a tracer amino acid, L-[1-14C]-leucine, and a kinetic model of the behavior of L-leucine in the brain. We chose L-[1-14C]-leucine as the tracer because it does not lead to extraneous labeled metabolic products. It is either incorporated into protein or rapidly metabolized to yield 14CO2 which is diluted in a large pool of unlabeled CO2 in the brain. The method and the model also allow for the contribution of unlabeled leucine derived from tissue proteolysis to the tissue precursor pool for protein synthesis. The method has the spatial resolution to determine protein synthesis rates in cell and neuropil layers, as well as hypothalamic and cranial nerve nuclei. To obtain reliable and reproducible quantitative data, it is important to adhere to procedural details. Here we present the detailed procedures of the quantitative autoradiographic L-[1-14C]-leucine method for the determination of regional rates of protein synthesis in vivo.