Characteristics and Graft Outcomes of Kidney Transplant Candidates with Enteric Risk Factors and Elevated Plasma Oxalate Levels.

INTRODUCTION: This study describes patient characteristics and examines graft function of kidney transplant recipients (without primary hyperoxaluria) with elevated plasma oxalate (POx) and enteric risk factors prior to transplant at our institution. METHODS: Kidney transplant recipients between 2012 and 2020 with elevated POx at the time of kidney transplant evaluation were included. A matched control cohort was gathered using patient/donor age, living/deceased donor type, panel reactive antibody, kidney donor profile index, and human leukocyte antigen mismatch as matching variables. Graft function at 1 year and at last follow-up was reported. RESULTS: A total of 106 patients with elevated POx were identified. A third of the patients had Roux-en-Y gastric bypass, a third had other enteric risks, and a third did not have an identifiable enteric risk. Median eGFR (estimated glomerular filtration rate) at 1 year and at last follow-up was similar between cases and controls except for subgroup of patients with pre-transplant POx >30 µmol/L where 1-year eGFR was lower compared to controls. Across eGFR categories, more cases were in eGFR category <30 mL/min/1.73 m2 compared to controls. CONCLUSION: Roux-en-Y gastric bypass is the most common identifiable risk for elevated POx in kidney transplant candidates. 1-year graft function was not inferior in cases compared to matched controls except for subgroup with POx >30 µmol/L pre-transplant.

Internal hernia trends following gastric bypass surgery.

BACKGROUND: Internal hernia is a well-known complication of laparoscopic Roux-en-Y gastric bypass (LRYGB), with reported rates ~ 5% within three months to three years after surgery. Internal hernia through a mesenteric defect can lead to small bowel obstruction. Mesenteric defects began to be more routinely closed, often considered standard practice by 2010. To our knowledge, there are no large population-based studies looking at rates of internal hernia post-LRYGB. This study utilizes a statewide database to characterize the trends of internal hernia post-LRYGB over the last two decades in multiple centers. METHODS: LRYGB procedure records between January 2005 and September 2015 were extracted from the New York SPARCS database. Exclusion criteria included age < 18, in-hospital deaths, bariatric revision procedures, and internal hernia repair during the same hospitalization as LRYGB. Time to internal hernia was calculated from initial LRYGB hospital stay to admission date of the first internal hernia repair record. A multivariable proportional sub-distribution hazards model was utilized to analyze the trend of internal hernia incidence within three-year post-LRYGB. RESULTS: 46,918 patients were identified between 2005 and 2015, with 2950 (6.29) undergoing internal hernia repair post-LRYGB by the end of 2018. The cumulative incidence of internal hernia repair at the 3rd-year post-LRYGB was 4.80% (95% CI: 4.59%-5.02%). By the end of the 13th year, the longest follow-up period, the cumulative incidence was 12.00% (95% CI: 11.30%-12.70%). Overall, there was a decreasing trend over time of undergoing internal hernia repair within three-year post-LRYGB (HR = 0.94, 95% CI: 0.93-0.96), after adjusting for confounding factors. CONCLUSION: This multicenter study maintains the rate of internal hernia following LRYGB reported in smaller studies and provides a longer follow-up period demonstrating decreasing occurrences of internal hernia after bypass as a function of year of index operation. This data is important as internal hernia continues to be a complication post-LRYGB.

Post-laparoscopic sleeve gastrectomy, intrathoracic sleeve migration and its management: A case series and review of literature.

De novo or persistent gastro-oesophageal reflux disease which may or may not be associated with injury of the oesophageal mucosa is now a known complication in post-sleeve gastrectomy patients. Repair of hiatal hernias to avoid such circumstances has been commonly performed, although recurrences may occur resulting in migration of gastric sleeve into the thorax, which is now a well-known complication. We report four cases of post-sleeve gastrectomy patients who presented with reflux symptoms, with their contrast-enhanced computed tomography abdomen showing intrathoracic sleeve migration and had hypotensive lower oesophageal sphincter with normal body motility on their oesophageal manometry. A laparoscopic revision Roux-en-Y gastric bypass surgery with hiatal hernia repair was performed for all four of them. No post-operative complications were seen at 1-year follow-up. Laparoscopic reduction of migrated sleeve with posterior cruroplasty and conversion to Roux-en-Y gastric bypass surgery can be safely performed for patients presenting with reflux symptoms in cases of intra-thoracic sleeve migration with good short-term outcomes.

Long-term changes in adipose tissue gene expression following bariatric surgery.

OBJECTIVE: Patients undergoing bariatric surgery present long-term metabolic improvements and reduced type 2 diabetes risk, despite long-term weight regain. We hypothesized that part of these protective effects could be linked to altered gene expression in white adipose tissue (WAT). METHODS: Transcriptomic profiling by gene microarray was performed in abdominal subcutaneous WAT from women before (n = 50) and two (n = 49) and five (n = 38) years after Roux-en-Y gastric bypass (RYGB) surgery as well as in 28 age-matched nonoperated women. RESULTS: In the obese women, the average body weight decrease was 38 kg 2 years postsurgery followed by an 8 kg weight regain between 2 and 5 years. Most of the long-term changes in WAT gene expression occurred during the first 2 years. However, a subset of genes encoding proteins involved in inflammation displayed a continued decrease between baseline, 2 and 5 years, respectively; that is an expression pattern independent of body weight regain. Expression of 71 of these genes correlated with measurements of adipocyte morphology or serum adipokine levels. CONCLUSION: The continuous improvement in WAT inflammatory gene expression, despite body weight relapse, may contribute to the sustained effects on adipose morphology after bariatric surgery.

PBPK modeling of CYP3A and P-gp substrates to predict drug-drug interactions in patients undergoing Roux-en-Y gastric bypass surgery.

Roux-en-Y gastric bypass surgery (RYGBS) is an effective surgical intervention to reduce mortality in morbidly obese patients. Following RYGBS, the disposition of drugs may be affected by anatomical alterations and changes in intestinal and hepatic drug metabolizing enzyme activity. The aim of this study was to better understand the drug-drug interaction (DDI) potential of CYP3A and P-gp inhibitors. The impacts of RYGBS on the absorption and metabolism of midazolam, acetaminophen, digoxin, and their major metabolites were simulated using physiologically-based pharmacokinetic (PBPK) modeling. PBPK models for verapamil and posaconazole were built to evaluate CYP3A- and P-gp-mediated DDIs pre- and post-RYGBS. The simulations suggest that for highly soluble drugs, such as verapamil, the predicted bioavailability was comparable pre- and post-RYGBS. For verapamil inhibition, RYGBS did not affect the fold-change of the predicted inhibited-to-control plasma AUC ratio or predicted inhibited-to-control peak plasma concentration ratio for either midazolam or digoxin. In contrast, the predicted bioavailability of posaconazole, a poorly soluble drug, decreased from 12% pre-RYGBS to 5% post-RYGBS. Compared to control, the predicted posaconazole-inhibited midazolam plasma AUC increased by 2.0-fold pre-RYGBS, but only increased by 1.6-fold post-RYGBS. A similar trend was predicted for pre- and post-RYGBS inhibited-to-control midazolam peak plasma concentration ratios (2.0- and 1.6-fold, respectively) following posaconazole inhibition. Absorption of highly soluble drugs was more rapid post-RYGBS, resulting in higher predicted midazolam peak plasma concentrations, which was further increased following inhibition by verapamil or posaconazole. To reduce the risk of a drug-drug interaction in patients post-RYGBS, the dose or frequency of object drugs may need to be decreased when administered with highly soluble inhibitor drugs, especially if toxicities are associated with plasma peak concentrations.

Bariatric Surgery for Adolescents with Type 2 Diabetes: an Emerging Therapeutic Strategy.

PURPOSE OF REVIEW: Type 2 diabetes (T2D) is a growing public health problem in youth, but conventional treatments are often insufficient to treat this disease and its comorbidities. We review evidence supporting an emerging role for bariatric surgery as a treatment for adolescent T2D. RECENT FINDINGS: Paralleling what has been seen in adult patients, bariatric surgery dramatically improves glycemic control in patients with T2D. In fact, remission of T2D has been observed in as many as 95-100% of adolescents with diabetes after bariatric surgery, particularly vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) surgery. This striking outcome may be due to both weight-dependent- and weight-independent factors, and recent studies suggest that T2D-related comorbidities may also improve after surgery. Bariatric surgery including RYGB and VSG is a powerful therapeutic option for obese adolescents with T2D. Benefits must be weighed against risk for postoperative complications such as nutritional deficiencies, but earlier surgical intervention might lead to more complete metabolic remission in obese patients with T2D.

Blockade of glucagon-like peptide 1 receptor corrects postprandial hypoglycemia after gastric bypass.

BACKGROUND & AIMS: Postprandial glycemia excursions increase after gastric bypass surgery; this effect is even greater among patients with recurrent hypoglycemia. These patients also have increased postprandial levels of insulin and glucagon-like peptide 1 (GLP-1). We performed a clinical trial to determine the role of GLP-1 in postprandial glycemia in patients with hyperinsulinemic hypoglycemia syndrome after gastric bypass. METHODS: Nine patients with recurrent hypoglycemia after gastric bypass (H-GB), 7 patients who were asymptomatic after gastric bypass (A-GB), and 8 healthy control subjects underwent a mixed-meal tolerance test (350 kcal) using a dual glucose tracer method on 2 separate days. On 1 day they received continuous infusion of the GLP-1 receptor antagonist exendin (9-39) (Ex-9), and on the other day they received a saline control. Glucose kinetics and islet and gut hormone responses were measured before and after the meal. RESULTS: Infusion of Ex-9 corrected hypoglycemia in all patients with H-GB. The reduction in postprandial insulin secretion by Ex-9 was greater in the H-GB group than in the other groups (H-GB, 50% ± 8%; A-GB, 13% ± 10%; controls, 14% ± 10%) (P < .05). The meal-derived glucose appearance was significantly greater in subjects who had undergone gastric bypass compared to the controls and in the H-GB group compared to the A-GB group. Ex-9 shortened the time to reach peak meal-derived glucose appearance in all groups without a significant effect on overall glucose flux. Postprandial glucagon levels were higher among patients who had undergone gastric bypass than controls and increased with administration of Ex-9. CONCLUSIONS: Hypoglycemia after gastric bypass can be corrected by administration of a GLP-1 receptor antagonist, which might be used to treat this disorder. These findings are consistent with reports that increased GLP-1 activity contributes to hypoglycemia after gastric bypass. ClinicalTrials.gov, Number: NCT01803451.

Roux-en-Y gastric bypass for intractable biliary reflux in an individual with incomplete tetraplegia.

CONTEXT: Gastroesophageal reflux disease (GERD) is a common complication in the spinal cord injury (SCI) population. Surgical treatment of GERD has a unique risk/benefit profile in this population. FINDINGS: This 68-year-old male with chronic incomplete tetraplegia, dyslipidemia, and well-controlled diabetes mellitus underwent Roux-en-Y gastric bypass surgery (RYGBP) for intractable biliary reflux. Postoperatively, the patient had resolution of his symptoms but he also presented with significant weight loss and dumping syndrome. While he did have improvement in his dyslipidemia there was no change in his functional status. CONCLUSIONS: RYGBP is an option for refractory GERD treatment in the SCI population but preoperative risk assessment and close monitoring postoperatively is essential.

Impact of RYGB surgery on plasma immunoglobulins: association between blood pressure and glucose levels six months after surgery.

We aimed to study levels of natural antibodies in plasma, and their associations to clinical and fecal biomarkers, before and 6 months after Roux-en-Y gastric bypass (RYGB) surgery. Thirty individuals with obesity [16 type 2 diabetic, 14 non-diabetic (ND)] had RYGB surgery. Total plasma IgA, IgG and IgM antibody levels and specific antibodies to oxidized low-density lipoprotein (oxLDL), malondialdehyde-acetaldehyde adducts, Porphyromonas gingivalis gingipain A hemagglutinin domain (Rgp44), and phosphocholine were measured using chemiluminescence immunoassay. Associations between plasma and fecal antibodies as well as clinical markers were analyzed. RYGB surgery reduced blood pressure, and the glycemic state was improved. A higher level of diastolic blood pressure was associated with lower plasma antibodies to oxLDL after surgery. Also, lower level of glucose markers associated with lower level of plasma antibodies to bacterial virulence factors. Antibodies to oxLDL decreased after surgery, and positive association between active serum lipopolysaccharide and specific oxLDL antibodies was detected. Total IgG levels decreased after surgery, but only in ND individuals. Reduced level of total plasma IgG, improved state of hypertension and hyperglycemia and their associations with decreased levels of specific antibodies in plasma, suggest an improved state of systemic inflammation after RYGB surgery.

Intussusception Within a Jejunostomy With Closed Loop Obstruction: A Case Report.

Jejunojejunal intussusception is a rare yet severe complication of Roux-en-Y gastric bypass (RYGBP) surgery. We are presenting a unique case of retrograde jejunal intussusception with a closed-loop blockage and an associated abdominal herniation that occurred two years after a laparoscopic RYGBP. The patient presented with abdominal pain, nausea, and vomiting, prompting a clinical diagnosis and a biphasic contrast-enhanced computed tomography (CT) scan, which later revealed a complicated jejunal intussusception with signs of ischemia showing decreased wall enhancement and distal collapsed jejunal walls with complete closed-loop bowel obstruction. The case was successfully managed through emergent laparoscopy to repair the hernia and reduce the intussusception, after which the postoperative period was unremarkable. This article aims to raise awareness about this rare but significant postoperative complication and stress the importance of early medical attention in similar cases.

The impact of the affordable care act on access to bariatric surgery in Maryland.

INTRODUCTION: This study aims to investigate the influence of the Affordable Care Act (ACA) on the utilization of Roux-en-Y gastric bypass (RYGB) procedures in Maryland. METHODS: Using the Maryland State Inpatient Database, this retrospective study compared all patients undergoing RYGB during the pre-ACA (2007-2009) and post-ACA (2018-2020) periods, including patient demographic factors, pre-existing conditions, and socioeconomic factors. RESULTS: A total of 16,494 RYGB procedures were performed during the study period, of which 12,089 (73.3 â€‹%) were post-ACA. This was a 179.2 â€‹% increase in patients undergoing RYGB post-ACA; nearly triple that of the pre-ACA period. There was a significant decrease in uninsured patients (5.6 â€‹%-1.5 â€‹%, p â€‹< â€‹0.01) an increase in Black patients (32.1 â€‹%-46.8 â€‹%, p â€‹< â€‹0.01) and Medicaid beneficiaries (6.0 â€‹% pre-ACA to 17.8 â€‹% post-ACA, p â€‹< â€‹0.01). There were significant reductions in adverse outcomes (long hospital stays, hemorrhage, GIT leaks, and mortality) across all insurance types (all p â€‹< â€‹0.01). CONCLUSION: The ACA increased access to RYGB procedures, especially in Black and Medicaid recipients in Maryland, enhancing healthcare across all insurance types.

Alcohol Misuse post Metabolic and Bariatric Surgery: A Systematic Review of Longer-term Studies with Focus on new Onset Alcohol use Disorder and Differences Between Surgery Types.

BACKGROUND: Evidence suggests an increased risk of alcohol problems post-surgery where no problematic alcohol use was present prior to surgery which may be different across types of surgery. OBJECTIVE: To characterise the risk of new onset alcohol misuse post bariatric surgery, differences between surgeries and the impact over time. METHODS: All published studies on new and relapsing alcohol use were reviewed. Data were classed as 'subjective' (clinical interview, self-report questionnaires) and 'objective' (hospital admissions, substance misuse programmes) and further categorised by follow up time - 'shorter-term' (one year), 'medium-term' (one year to two years) and 'long-term' (> two years). RESULTS: Twenty-three of the forty-two studies included in the review reported new onset data. Nine studies reported on differences between surgery types. In those reporting objective measures, all of which were long term, RYGB carried a higher risk than SG, followed by LAGB. All but one study using subjective measures reported a small but significant number of new onset concerning alcohol use, and comparisons between surgery types had more varied results than the objective measures. Studies of substance abuse programmes found high rates of new onset cases (17-60%). CONCLUSION: This systematic review provides support for the consensus guidance suggesting patients should be informed of a small but significant risk of new onset alcohol use following bariatric surgery, with the strongest evidence in the medium- to long-term and in those who have had RYGB followed by SG.

Utilization and Outcomes of Roux-en-Y Gastric Bypass Surgery Following the Affordable Care Act in the United States.

BACKGROUND: The passage of the Affordable Care Act (ACA) in 2010 marked a pivotal moment in American health care policy, significantly expanding access to health care services. This study aims to explore the relationship between the ACA and the utilization and outcomes of Roux-en-Y Gastric Bypass (RYGB) surgery. METHODS: Using data from the National Inpatient Sample (NIS) Database, this retrospective study compares the pre-ACA period (2007-2009) with the post-ACA period (2017-2019), encompassing patients who had RYGB. Multivariable logistic analysis was done accounting for patient's characteristics, comorbidities, and hospital type. RESULTS: In the combined periods, there were 158 186 RYGB procedures performed, with 30.0% transpiring in pre-ACA and 70.0% in the post-ACA. Post-ACA, the proportion of uninsured patients decreased from 4.8% to 3.6% (P < .05), while Black patients increased from 12.5% to 18.5% (P < .05). Medicaid-insured patients increased from 6.8% to 18.1% (P < .05), and patients in the poorest income quartile increased from 20% to 26% (P < .05). Patients in the post-ACA period were less likely to have longer hospital stays (OR = .16: 95% CI .16-.17, P < .01), in-hospital mortality (OR = .29: 95% CI .18-.46, P < .01), surgical site infection (OR = .25: 95% CI .21-.29, P < .01), postop hemorrhage (OR = .24: 95% CI .21-.28, P < .01), and anastomotic leak (OR = .14: 95% CI .10-.18, P < .01) than those in the pre-ACA period. DISCUSSION: Following the implementation of the ACA, utilization of bariatric surgery significantly increased, especially among Black patients, Medicaid beneficiaries, and low-income patients. Moreover, despite the inclusion of more high-risk surgical patients in the post-ACA period, there were better outcomes after surgery.

Systematic review on sleeve gastrectomy or Roux-en-Y gastric bypass surgery for refractory gastroparesis.

Management of refractory gastroparesis is challenging after diet, prokinetics, and long-term nutritional support have failed. In this review, the efficacy and safety of surgical interventions (sleeve gastrectomy and Roux-en-Y gastric bypass surgery) are evaluated systematically in patients with refractory gastroparesis. The PubMed, Embase, and Scopus databases were searched to identify relevant studies published up to June 2021. Outcome of interest was symptom improvement and gastric emptying. Nineteen studies with 222 refractory gastroparesis patients (147 Roux-en-Y gastric bypass, 39 sleeve gastrectomy, and 36 subtotal gastrectomy) were included. All studies reported symptom improvement postoperatively, particularly vomiting and nausea. Gastric emptying improved postoperatively in 45% up to 67% for sleeve gastrectomy and 87% for Roux-en-Y gastric bypass. The findings of our systematic review suggest that sleeve gastrectomy and Roux-en-Y gastric bypass surgery improve symptoms and gastric emptying in patients with refractory gastroparesis. Surgery may be effective as treatment for a small group of patients when all other therapies have failed.

The Beauty and the Beast: Bariatric Surgery and a Case of Oxalate Nephropathy.

Oxalate nephropathy is a rare cause of kidney failure. Roux-en-Y gastric bypass surgery is a technique used for surgical treatment of obesity as well as for the treatment of gastric carcinoma. We report the case of a 46-year-old male who was admitted to the nephrology department due to kidney dysfunction eight months after bariatric surgery.

Changes in Fat-Free Mass, Protein Intake and Habitual Physical Activity Following Roux-en-Y Gastric Bypass Surgery: A Prospective Study.

PURPOSE: Large inter-individual variations in post-bariatric fat-free mass loss (FFML) are observed, which might relate to differences in protein intake and physical activity across patients. We performed repetitive assessments of protein intake and physical activity before and after banded Roux-en-Y gastric bypass surgery, and examined its relations to FFML during 6 months of follow-up. MATERIALS AND METHODS: FFML (bio-impedance analyses), protein intake (24-h dietary recalls) and moderate-to-vigorous physical activity (MVPA; activPAL) were assessed in 28 patients (4 males, age 42 ± 12 years) before surgery and at 1-, 3- and 6-months post-surgery. Changes in protein intake and MVPA were evaluated with mixed model analysis, whereas associations with FFML were assessed by univariate regression analysis. RESULTS: Six-month FFML was -7.3 ± 3.6 kg. Protein intake decreased from 80 ± 29 g/day (pre-surgery) to 45 ± 26 g/day (1 month post-surgery (P < 0.001)) and did not improve thereafter (51 ± 21 g/day; P > 0.05). Seven participants (25%) consumed ≥ 60 g protein/day at 6 months post-surgery. Participants performed 7394 ± 2420 steps/day in 54 ± 20 min/day of MVPA, which did not change from pre- to post-surgery (P > 0.05). A higher step count (B = -0.002; 95%CI = [-0.004 - 0.000]; P = 0.048) and higher level of MVPA (B = -0.29; 95%CI = [-0.54 - -0.03]; P = 0.018) were related to a lower FFML. CONCLUSION: A lower post-surgery FFML was attributable to higher MVPA levels but not protein intake. This may be due to the low total protein intake and the observation that only a minority of patients achieved a protein intake ≥ 60 g/day. Future studies should focus on interventions to increase post-bariatric protein intake and MVPA levels.

Laparoscopic Banded Gastric Bypass: A Case Report of a Successful Weight Loss Despite Gastro-Gastric Fistula.

Obesity is a global health issue, Roux-en-Y gastric bypass (RYGB), is an effective treatment for weight loss. However, some patients experience insufficient weight loss after RYGB, leading to alternative strategies such as adding an adjustable gastric band to the bypass. This case reports a 43-year-old female with morbid obesity who underwent open RYGB in 2004, achieving significant weight loss. However, she experienced weight regain, indicating RYGB failure. A laparoscopic band was placed around her bypass with no post-operative complications and successful steady weight reduction. During follow-up, an upper gastrointestinal series revealed a gastro-gastric fistula. Despite the fistula, the patient maintained a steady weight, with a significant excess weight loss of 40.2% since the banded gastric bypass surgery. The development of a gastro-gastric fistula, which typically affects weight loss outcomes, was managed conservatively without impacting the patient's steady weight maintenance. This highlights an unexpected weight loss outcome in a patient who underwent laparoscopic banding following RYGB failure and later developed a gastro-gastric fistula. Despite the initial RYGB failure, the patient achieved significant weight loss, surpassing the average reported in previous studies.

The effect of gastric bypass surgery on cognitive function of Alzheimer's disease and the role of GLP1-SGLT1 pathway.

OBJECTIVE: Gastric bypass surgery has been shown to improve metabolic profiles via GLP1, which may also have cognitive benefits for Alzheimer's disease (AD) patients. However, the exact mechanism requires further investigation. METHODS: Roux-en-Y gastric bypass or sham surgery was performed on APP/PS1/Tau triple transgenic mice (an AD mice model) or wild type C57BL/6 mice. Morris Water Maze (MWM) test was used to evaluate the cognitive function of mice and animal tissue samples were obtained for measurements two months after the surgery. Additionally, STC-1 intestine cells were treated with siTAS1R2 and siSGLT1, and HT22 nerve cells were treated with Aß, siGLP1R, GLP1 and siSGLT1 in vitro to explore the role of GLP1-SGLT1 related signaling pathway in cognitive function. RESULTS: The MWM test showed that bypass surgery significantly improved cognitive function in AD mice as measured by navigation and spatial probe tests. Moreover, bypass surgery reversed neurodegeneration, down-regulated hyperphosphorylation of Tau protein and Aß deposition, improved glucose metabolism, and up-regulated the expression of GLP1, SGLT1, and TAS1R2/3 in the hippocampus. Furthermore, GLP1R silencing down-regulated SGLT1 expression, whereas SGLT1 silencing increased Tau protein deposition and exacerbated dysregulated of glucose metabolism in HT22 cells. However, RYGB did not alter the level of GLP1 secretion in the brainstem (where central GLP1 is mainly produced). Additionally, GLP1 expression was upregulated by RYGB via TAS1R2/3-SGLT1 activation sequentially in the small intestine. CONCLUSION: RYGB surgery could improve cognition function in AD mice through facilitating glucose metabolism and reducing Tau phosphorylation and Aß deposition in the hippocampus, mediated by peripheral serum GLP1 activation of SGLT1 in the brain. Furthermore, RYGB increased GLP1 expression through sequential activation of TAS1R2/TAS1R3 and SGLT1 in the small intestine.

Effects of Heterozygous Variants in the Leptin-Melanocortin Pathway on Roux-en-Y Gastric Bypass Outcomes: a 15-Year Case-Control Study.

INTRODUCTION: Heterozygous variants in the leptin-melanocortin pathway are associated with obesity. However, their effect on the long-term outcomes after Roux-en-Y gastric bypass (RYGB) is still unknown. METHODS: In this matched case-control study, 701 participants from the Mayo Clinic Biobank with a history of RYGB were genotyped. Sixty-three patients had a heterozygous variant in the leptin-melanocortin pathway. After excluding patients with potential confounders, carriers were randomly matched (on sex, age, body mass index [BMI], and years since surgery) with two non-carrier controls. The electronic medical record of carriers and matched non-carriers was reviewed for up to 15 years after RYGB. RESULTS: A total of 50 carriers and 100 matched non-carriers with a history of RYGB were included in the study. Seven different genes (LEPR, PCSK1, POMC, SH2B1, SRC1, MC4R, and SIM1) in the leptin-melanocortin pathway were identified. At the time of surgery, the mean age was 50.8 ± 10.6 years, BMI 45.6 ± 7.3 kg/m2, and 79% women. There were no differences in postoperative years of follow-up, Roux limb length, or gastric pouch size between groups. Fifteen years after RYGB, the percentage of total body weight loss (%TBWL) in carriers was - 16.6 ± 10.7 compared with - 28.7 ± 12.9 in non-carriers (diff = 12.1%; 95% CI, 4.8 to 19.3) and the percentage of weight regain after maximum weight loss was 52.7 ± 29.7 in carriers compared with 29.8 ± 20.7 in non-carriers (diff = 22.9%; 95% CI, 5.3 to 40.5). The nadir %TBWL was lower - 32.1 ± 8.1 in carriers compared with - 36.8 ± 10.4 in non-carriers (diff = 4.8%; 95% CI 1.8 to 7.8). CONCLUSIONS: Carriers of a heterozygous variant in the leptin-melanocortin pathway have a progressive and significant weight regain in the mid- and long-term after RYGB. Genotyping patients experiencing significant weight regain after RYGB could help implement multidisciplinary and individualized weight loss interventions to improve weight maintenance after surgery.

Total fecal IgA levels increase and natural IgM antibodies decrease after gastric bypass surgery.

Obesity is associated with low-grade inflammation and increased systemic oxidative stress. Roux-en-Y gastric bypass (RYGB) surgery is known to ameliorate the obesity-induced metabolic dysfunctions. We aimed to study the levels of natural antibodies in feces, before and 6 months after RYGB surgery in obese individuals with and without type 2 diabetes (T2D). Sixteen individuals with T2D and 14 non-diabetic (ND) individuals were operated. Total IgA, IgG and IgM antibody levels and specific antibodies to oxidized low-density lipoprotein (oxLDL), malondialdehyde-acetaldehyde adducts (MAA adducts), Porphyromonas gingivalis gingipain A hemagglutinin domain (Rgp44) and phosphocholine (PCho) were measured using chemiluminescence immunoassay. Total fecal IgA was elevated, while total IgM and IgG were not affected by the surgery. Fecal natural IgM specific to oxLDL decreased significantly in both T2D and ND individuals, while fecal IgM to Rgp44 and PCho decreased significantly in T2D individuals. A decrease in IgG to MAA-LDL, Rgp44 and PCho was detected. RYGB surgery increases the levels of total fecal IgA and decreases fecal natural IgG and IgM antibodies specific to oxLDL. Natural antibodies and IgA are important in maintaining the normal gut homeostasis and first-line defense against microbes, and their production is markedly altered with RYGB surgery.