Ursodeoxycholic acid for prevention of gallstone disease after laparoscopic sleeve gastrectomy: an Atlantic Canada perspective.

BACKGROUND: Prophylactic ursodeoxycholic acid (UDCA) may be beneficial in reducing gallstone disease after bariatric surgery. The American Society for Metabolic and Bariatric Surgery (ASMBS) 2019 guidelines recommend a 6-month course of UDCA for patients undergoing laparoscopic sleeve gastrectomy (LSG). This has not been adopted broadly. This study intends to assess the effect of routine UDCA administration following LSG on symptomatic gallstone disease. METHODS: We performed a retrospective chart review of patients who underwent LSG, between 2009 and 2019, at two tertiary care centers in Atlantic Canada. At one center, UDCA 250 mg oral twice daily was routinely prescribed following LSG for 6 months to patients with an intact gallbladder. At the other center, UDCA was not prescribed. Primary and secondary outcomes were cholecystectomy and endoscopic retrograde cholangiopancreatography (ERCP) rates. Compliance with and side effects of UDCA therapy were analyzed. RESULTS: A total of 751 patients were included in the study. Patients who had prior cholecystectomy or were lost to follow up were excluded. After exclusion criteria were applied, 461 patients were included for analysis: 303 in the UDCA group and 158 in the group who did not receive UDCA. Cholecystectomy rate was not significantly associated with UDCA administration, however there was a trend towards less cholecystectomy in patients who received UDCA (8.3% vs. 13.9%, p = 0.056). ERCP rate was significantly lower in patients who received UDCA (0.3% vs 2.5%, p = 0.031). Rate of gallstone disease requiring intervention, either cholecystectomy or ERCP, was significantly decreased in patients who received UDCA (8.9% vs 15.8%, p = 0.022). The most common barriers to compliance with UDCA were cost (45.4%) and nausea (18.1%). CONCLUSION: This is the first study to demonstrate lower rates of ERCP in patients receiving routine UDCA following LSG. Our findings support the ASMBS 2019 guidelines for administering UDCA after LSG for preventing gallstone disease.

The effect of deleterious mutations and age on recombination in Drosophila melanogaster.

At the population level, recombination mediates the efficiency with which selection can eliminate deleterious mutations. At the individual level, deleterious alleles may influence recombination, which would change the rate at which linkage disequilibrium is eroded and thereby alter the efficiency with which deleterious alleles are purged. Here, we test whether the presence of a deleterious allele on one autosome affects recombination on another autosome. We find that deleterious alleles not only alter the rate but also the pattern of recombination. However, there is little support that different deleterious alleles affect recombination in a consistent manner. Because we have detailed information on individual females across their lifetimes, we are able to examine how recombination patterns change with age and find that these patterns are also affected by the presence of deleterious alleles. The differences among genotypes or among age classes are large enough to add substantial noise to genetic mapping experiments that do not consider these sources of variation.

Selection, epistasis, and parent-of-origin effects on deleterious mutations across environments in Drosophila melanogaster.

Understanding the nature of selection against deleterious alleles is central to determining how populations are affected by the constant influx of new mutations. Important progress has been made in estimating basic attributes of the distribution of selection coefficients and gene interaction effects (epistasis). Although most aspects of selection are likely to be context dependent, little is known about the effect of stress on selection and epistasis at the level of individual genes, especially in multicellular organisms. Using Drosophila melanogaster, we measure how selection on 20 mutant alleles is affected by direct and indirect genetic factors across two environments. We find that environmental stress increases selection against individual mutations but reduces selection against combinations of mutations (i.e., epistasis becomes more positive). In addition, we find a high incidence of indirect genetic effects whereby the strength of selection against the alleles carried by offspring is dependent on the genotypes of their parents.