Roux-en-Y gastric bypass (RYGB) is highly effective in reversing obesity and associated diabetes. Recent observations in humans suggest a contributing role of increased circulating bile acids in mediating such effects. Here we use a diet-induced obesity (DIO) mouse model and compare metabolic remission when bile flow is diverted through a gallbladder anastomosis to jejunum, ileum or duodenum (sham control). We find that only bile diversion to the ileum results in physiologic changes similar to RYGB, including sustained improvements in weight, glucose tolerance and hepatic steatosis despite differential effects on hepatic gene expression. Circulating free fatty acids and triglycerides decrease while bile acids increase, particularly conjugated tauro-β-muricholic acid, an FXR antagonist. Activity of the hepatic FXR/FGF15 signalling axis is reduced and associated with altered gut microbiota. Thus bile diversion, independent of surgical rearrangement of the gastrointestinal tract, imparts significant weight loss accompanied by improved glucose and lipid homeostasis that are hallmarks of RYGB.

Overall findings suggest that bacterially derived bile acids may mediate the early improvements at 1 month after RYGB. Future studies should examine the changes in specific bile acid chemical species after bariatric procedures and bile acid-specific signaling changes.

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The incidence of extremity amputation is estimated at about 200,000 cases annually. Over 25% of patients suffer from terminal neuroma or phantom limb pain (TNPLP), resulting in pain, inability to wear a prosthetic device, and lost work. Once TNPLP develops, there is no definitive cure. Therefore, there has been an emerging focus on TNPLP prevention. We examined the current literature on TNPLP prevention in patients undergoing extremity amputation. A literature review was performed using Ovid Medline, Cochrane Collaboration Library, and Google Scholar to identify all original studies that addressed surgical prophylaxis against TNPLP. The search was conducted using both Medical Subject Headings and free-text using the terms “phantom limb pain,” “amputation neuroma,” and “surgical prevention of amputation neuroma.” Fifteen studies met the inclusion criteria, including six prospective trials, two comprehensive literature reviews, four retrospective chart reviews, and three case series/technique reviews. Five techniques were identified, and each was incorporated into a target-based classification system. A small but growing body of literature exists regarding the surgical prevention of TNPLP. Targeted muscle reinnervation (TMR), a form of physiologic target reassignment, has the greatest momentum in the academic surgical community, with multiple recent prospective studies demonstrating superior prevention of TNPLP. Neurorrhaphy and transposition with implantation are supported by less robust evidence, but merit future study as alternatives to TMR.

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Background: Racial/ethnic disparities have been well-documented in access to cancer screening and treatment, as well as treatment outcomes. Less is known regarding the yield of genetic pathogenic variants (PVs) in non-white populations. Methods: Patient data was obtained from the Informed Genetics Annotated Patient Registry (iGAP), an IRB-approved multi-center longitudinal, observational study, in which 2148 patients self-declared race/ethnicity and underwent germline genetic testing at any lab. Analyses were limited to 24 cancer susceptibility genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, NBN, PALB2, PTEN, STK11, TP53, APC, BMPR1A, CDK4, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, RAD51C, RAD51D, SMAD4), 21 of which have clinical management guidelines from the NCCN (excluding NBN, BARD1, CDK4).1 Descriptive statistics were used to assess and compare data from these populations and germline genetic testing results. Results: The Registry included 2148 patients, 1662 (77.37%) with a personal history and 1536 (71.51%) with a family history of cancer. The patients were 74.39% White, 6.33% Hispanic, 5.59% African/Black, 5.03% Asian, 1.63% Other, 1.35% Ashkenazi, and 5.68% Unknown. The overall germline PV rate in the cohort was 0.1089 PVs/patient tested, with 234 PVs detected in 227 patients. The PV rate among racial/ethnic groups were as follows: White 170/1598 (0.1064), Asian 8/108 (0.0741), Hispanic 27/136 (0.1985), African/Black 11/120 (0.0917), Ashkenazi 6/29 (0.2069). In patients self-reporting as Hispanic, the PV rate was similar to PV rate in those self-reporting as Ashkenazi, and significantly higher (p=0.00027) than PV rate in those of other self-reported race/ethnicity. Gene level PV rates are shown in Table 1. Conclusions: Those who reported being Hispanic had an increased overall PV rate. This could be due to the greater representation of Hispanics from New Mexico who may have Ashkenazi ethnicity. Further studies are needed to understand whether these differences are a result of disparate access to testing, true population differences, lack of data in non-White populations skewing variant classification or other factors. Table 1. Gene PV Rates by Racial/Ethnic Category. Citation Format: Peter Beitsch, Chloe Wernecke, Rakesh Patel, Barry Rosen, Gia Compagnoni, Ian Grady, Eric Brown, Lindsay Gold, Pat Whitworth, Linda Ann Smith, Mariusz Wirga, Richard Reitherman, Steven Cai, Toan Nguyen, Valerie Traina, Dennis Holmes, Paul Baron, Brittany Krautheim, Anne Peled, Walt Taylor, Kelly Bontempo, Brenna Bentley, Krista Ortega, Pouyan Ahmadi. Racial/Ethnic Groups Have Different Rates of Pathogenic Variants in Common Cancer Genes [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-02-09.

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