RNA sequencing unravels novel L cell constituents and mechanisms of GLP-1 secretion in human gastric bypass-operated intestine.

AIMS/HYPOTHESIS: Roux-en-Y gastric bypass surgery (RYGB) frequently results in remission of type 2 diabetes as well as exaggerated secretion of glucagon-like peptide-1 (GLP-1). Here, we assessed RYGB-induced transcriptomic alterations in the small intestine and investigated how they were related to the regulation of GLP-1 production and secretion in vitro and in vivo. METHODS: Human jejunal samples taken perisurgically and 1 year post RYGB (n=13) were analysed by RNA-seq. Guided by bioinformatics analysis we targeted four genes involved in cholesterol biosynthesis, which we confirmed to be expressed in human L cells, for potential involvement in GLP-1 regulation using siRNAs in GLUTag and STC-1 cells. Gene expression analyses, GLP-1 secretion measurements, intracellular calcium imaging and RNA-seq were performed in vitro. OGTTs were performed in C57BL/6j and iScd1-/- mice and immunohistochemistry and gene expression analyses were performed ex vivo. RESULTS: Gene Ontology (GO) analysis identified cholesterol biosynthesis as being most affected by RYGB. Silencing or chemical inhibition of stearoyl-CoA desaturase 1 (SCD1), a key enzyme in the synthesis of monounsaturated fatty acids, was found to reduce Gcg expression and secretion of GLP-1 by GLUTag and STC-1 cells. Scd1 knockdown also reduced intracellular Ca2+ signalling and membrane depolarisation. Furthermore, Scd1 mRNA expression was found to be regulated by NEFAs but not glucose. RNA-seq of SCD1 inhibitor-treated GLUTag cells identified altered expression of genes implicated in ATP generation and glycolysis. Finally, gene expression and immunohistochemical analysis of the jejunum of the intestine-specific Scd1 knockout mouse model, iScd1-/-, revealed a twofold higher L cell density and a twofold increase in Gcg mRNA expression. CONCLUSIONS/INTERPRETATION: RYGB caused robust alterations in the jejunal transcriptome, with genes involved in cholesterol biosynthesis being most affected. Our data highlight SCD as an RYGB-regulated L cell constituent that regulates the production and secretion of GLP-1.

Metabolic outcomes in obese mice undergoing one-anastomosis gastric bypass (OAGB) with a long or a short biliopancreatic limb.

One-anastomosis gastric bypass (OAGB) has gained importance as a simple, safe, and effective operation to treat morbid obesity. We previously found that Roux-en-Y gastric bypass surgery with a long compared with a short biliopancreatic limb (BPL) leads to improved weight loss and glucose tolerance in obese mice. However, it is not known whether a long BPL in OAGB surgery also results in beneficial metabolic outcomes. Five-week-old male C57BL/6J mice fed a high-fat diet (HFD) for 8 weeks underwent OAGB surgery with defined BPL lengths (5.5 cm distally of the duodenojejunal junction for short and 9.5 cm for long BPL), or sham surgery combined with caloric restriction. Weight loss, glucose tolerance, obesity-related comorbidities, endocrine effects, gut microbiota, and bile acids were assessed. Total weight loss was independent of the length of the BPL after OAGB surgery. However, a long BPL was associated with lower glucose-stimulated insulin on day 14, and an improved glucose tolerance on day 35 after surgery. Moreover, a long BPL resulted in reduced total cholesterol, while there were no differences in the resolution of metabolic dysfunction-associated steatotic liver disease (MASLD) and adipose tissue inflammation. Tendencies of an attenuated hypothalamic-pituitary-adrenal (HPA) axis and aldosterone were present in the long BPL group. With both the short and long BPL, we found an increase in primary conjugated bile acids (pronounced in long BPL) along with a loss in bacterial Desulfovibrionaceae and Erysipelotrichaceae and simultaneous increase in Akkermansiaceae, Sutterellaceae, and Enterobacteriaceae. In summary, OAGB surgery with a long compared with a short BPL led to similar weight loss, but improved glucose metabolism, lipid, and endocrine outcomes in obese mice, potentially mediated through changes in gut microbiota and related bile acids. Tailoring the BPL length in humans might help to optimize metabolic outcomes after bariatric surgery.NEW & NOTEWORTHY Weight loss following OAGB surgery in obese mice was not influenced by BPL length, but a longer BPL was associated with improved metabolic outcomes, including glucose and lipid homeostasis. These changes could be mediated by bile acids upon altered gut microbiota. Further validation of these findings is required through a randomized human study.

Short-term effects of gastric bypass versus sleeve gastrectomy on high LDL cholesterol: The BASALTO randomized clinical trial.

BACKGROUND: There has been a substantial increase in the use of laparoscopic sleeve gastrectomy (SG) to treat morbid obesity despite observational evidence demonstrating the superiority of Roux-en-Y gastric bypass (RYGB) for reducing low-density lipoprotein (LDL) cholesterol. The main aim was to ascertain whether high LDL cholesterol levels should be considered when selecting the most appropriate surgical procedure for each patient (RYGB or SG). METHODS: In this single-center, randomized clinical trial using intention-to-treat analysis, 38 patients with severe obesity and elevated levels of LDL cholesterol were randomly assigned to undergo RYGB or SG. The primary outcome was LDL cholesterol remission at 12 months, defined as LDL cholesterol < 3.36 nmol/l without lipid-lowering medications. Secondary outcomes included changes in weight, other comorbidities, qualitative lipoprotein traits, cholesterol esters, glycoproteins, cholesterol absorption and synthesis metabolites and complications. RESULTS: Intention-to-treat analysis revealed that LDL cholesterol remission occurred in 66.6% of RYGB patients compared to 27.8% of SG patients (p = 0.019). Among patients completing follow-up, RYGB demonstrated superior remission (80.0% vs. 29.4%, p = 0.005). Exclusive benefits of RYGB included a reduction in large, medium, and small LDL particles. Cholesterol absorption markers showed differential behavior after both techniques: campesterol (Δ -15.2 µg/mg, 95% CI -30.2 to -0.1) decreased after RYGB, and sitosterol (Δ 21.1 µg/mg, 95% CI 0.9 to 41.2), cholestanol (Δ 30.6 µg/mg, 95% CI 14.8 to 57.9) and campesterol (Δ 18.4 µg/mg, 95% CI 4.4 to 32.3) increased after SG. No differences in weight loss, cholesterol esters, glycoproteins, cholesterol synthesis metabolites or postoperative complications were observed between techniques. CONCLUSION: In conclusion, RYGB is superior to SG in terms of short-term of high LDL cholesterol remission. Furthermore, RYGB also led to a greater improvement in lipoprotein parameters that confer an atherogenic profile. Therefore, the presence of elevated levels of LDL cholesterol should be considered when determining the optimal bariatric surgery procedure for each patient. TRIAL REGISTRATION: Clinicaltrials.gov number, NCT03975478).

Canagliflozin or acarbose versus placebo to ameliorate post-bariatric hypoglycaemia - The HypoBar I randomized clinical trial protocol.

INTRODUCTION: Post-bariatric hypoglycaemia (PBH) is a rare yet disabling clinical condition, mostly reported after Roux-en-Y gastric bypass (RYGB) surgery. RYGB is one of the most widely used and effective bariatric procedures. The pathophysiology of PBH remains unclear, and treatment options are limited in effectiveness and/or carry significant side effects. Acarbose slows carbohydrates digestion and absorption and is generally considered first-line pharmacological treatment for PBH but its gastrointestinal side effects limit patient compliance. Canagliflozin inhibits intestinal and renal sodium-dependent glucose absorption and reduces postprandial excursions of glucose, insulin and incretins after RYGB - effects that could be beneficial in ameliorating PBH. AIMS: The trial aims to investigate how blood glucose levels are affected during daily living in subjects with PBH during treatment with canagliflozin or acarbose compared with placebo, and to study the meal-induced entero-endocrine mechanisms implied in the treatment responses. METHODS: In a double-blinded, randomized, crossover clinical trial, HypoBar I will investigate the effectiveness in reducing the risk of PBH, safety, ambulatory glucose profile and entero-endocrine responses when PBH is treated with canagliflozin 300 mg twice daily during a 4-week intervention period, compared with acarbose 50 mg thrice daily or placebo. ETHICS AND DISSEMINATION: HypoBar I is approved by the Local regulatory entities. Results will be published in peer-reviewed journals. CONCLUSION: If effective, well-tolerated and safe, canagliflozin could be a novel treatment for people with PBH. HypoBar I might also unravel new mechanisms underlying PBH, potentially identifying new treatment targets. TRIAL REGISTRATION: EudraCT number 2022-000157-87.

Comparative Effects of GLP-1 Agonists, Sleeve Gastrectomy and Roux-en-Y Gastric Bypass on Diabetes Mellitus Outcomes.

PURPOSE OF REVIEW: The purpose of this review is to assess the effects of glucagon-like peptide-1 (GLP-1) agonists, sleeve gastrectomy (SG), and Roux-en-Y gastric bypass (RYGB) on type 2 diabetes mellitus (T2DM) remission. This review explores the efficacy, safety, and durability of these surgical and medical modalities of diabetes management. RECENT FINDINGS: Studies have shown that GLP-1 agonists achieve higher rates of T2DM remission compared to standard glucose-lowering medications and lifestyle changes. In addition to weight loss, bariatric surgery has been found to be highly effective in treating and inducing remission of T2DM. Studies suggest that post-surgical patients see enhanced glycemic control. Both surgical interventions and GLP1 agonists are effective in achieving T2DM remission. Long-term follow-up and randomized controlled trials comparing bariatric surgery and GLP-1 agonists are necessary to evaluate their relative effectiveness in T2DM control. Further research is also needed to assess the combined effects of these treatment modalities.

Varying concentrations of tyrosine kinase inhibitors in chronic myeloid leukemia patients following bariatric surgery: a case series.

Bariatric surgery is increasingly performed to treat severe obesity. As a result of anatomical and physiological changes in the gastrointestinal tract, the pharmacokinetics (PK) of oral drugs can be altered, affecting their efficacy and safety. This includes the class of tyrosine kinase inhibitors (TKIs) which are used to treat chronic myeloid leukemia (CML). This case series describes the clinical course of four CML cases with a history of bariatric surgery. The patients used various TKIs (nilotinib, dasatinib, bosutinib, ponatinib, and imatinib) for which 15 drug levels were measured. The measured TKI concentrations were in part subtherapeutic, and highly variable when compared to mean levels measured in the general population. Multiple drug levels were measured in these patients, as the clinicians were aware of the possible impact of bariatric surgery. The drug levels were used as additional input for clinical decision-making. All four patients required TKI switches and/or dose modifications to achieve an effective and tolerable treatment. Eventually, adequate clinical and molecular remissions were achieved in all cases. In summary, TKI concentrations of patients undergoing bariatric surgery may be subtherapeutic. Moreover, there is substantial interindividual and intraindividual variation, which may be explained by the complex interference of bariatric surgery and associated weight loss. For clinical practice, therapeutic drug monitoring is advised in patients with a history of bariatric surgery in case of suboptimal response or loss of response.

How best to combine liver transplantation and bariatric surgery?-Results from a global, web-based survey.

BACKGROUND AND AIMS: Obesity is a growing healthcare challenge worldwide and a significant risk factor for liver failure as seen with non-alcoholic steatohepatitis (NASH). Combining metabolic-bariatric surgery (MBS) with liver transplantation (LT) appears as attractive strategy to treat both, the underlying liver disease and obesity. However, there is an ongoing debate on best timing and patient selection. This survey was designed to explore the current treatment practice for patients with NASH and obesity worldwide. METHODS: A web-based survey was conducted in 2022 among bariatric and LT surgeons, and hepatologists from Europe, North and South America and Asia. RESULTS: The survey completion rate was 74% (145/196). The average respondents were 41-50 years (38%), male (82.1%) and had >20 years of clinical experience (42.1%). Centres with a high LT-caseload for NASH were mainly located in the USA and United Kingdom. Almost 30% have already performed a combination of LT with MBS and 49% plan to do it. A majority of bariatric surgeons prefer MBS before LT (77.2%), whereas most of LT surgeons (52%) would perform MBS during LT. Most respondents (n = 114; 80%) favour sleeve gastrectomy over other bariatric techniques. One third (n = 42; 29.4%) has an established protocol regarding MBS for LT candidates. CONCLUSION: The most experienced centres doing LT for NASH are in the USA and United Kingdom with growing awareness worldwide. Overall, a combination of MBS and LT has already been performed by a third of respondents. Sleeve gastrectomy is the bariatric technique of choice-preferably performed either before or during LT.

Differential effect of endogenous glucagon-like peptide-1 on prandial glucose counterregulatory response to hypoglycaemia in humans with and without bariatric surgery.

AIM: To determine the effect of endogenous glucagon-like peptide 1 (GLP-1) on prandial counterregulatory response to hypoglycaemia after gastric bypass (GB). MATERIALS AND METHODS: Glucose fluxes, and islet-cell and gut hormone responses before and after mixed-meal ingestion, were compared during a hyperinsulinaemic-hypoglycaemic (~3.2 mmol/L) clamp with and without a GLP-1 receptor (GLP-1R) antagonist exendin-(9-39) infusion in non-diabetic patients who had previously undergone GB compared to matched participants who had previously undergone sleeve gastrectomy (SG) and non-surgical controls. RESULTS: Exendin-(9-39) infusion raised prandial endogenous glucose production (EGP) response to insulin-induced hypoglycaemia in the GB group but had no consistent effect on EGP response among the SG group or non-surgical controls (p < 0.05 for interaction). The rates of systemic appearance of ingested glucose or prandial glucose utilization did not differ among the three groups or between studies with and without exendin-(9-39) infusion. Blockade of GLP-1R had no effect on insulin secretion or insulin action but enhanced prandial glucagon in all three groups. CONCLUSIONS: These results indicate that impaired post-meal glucose counterregulatory response to hypoglycaemia after GB is partly mediated by endogenous GLP-1, highlighting a novel pathogenic mechanism of GLP-1 in developing hypoglycaemia in this population.

Remission and relapse of diabetes after sleeve gastrectomy and one-anastomosis gastric bypass: The Tehran Obesity Treatment Study.

AIMS: To evaluate the rates and predictors of remission and relapse of type 2 diabetes mellitus (T2DM) in individuals with T2DM undergoing sleeve gastrectomy (SG) or one-anastomosis gastric bypass (OAGB). METHODS: An observational prospective study with 5 years of follow-up was conducted in a total of 891 patients (82.5% female) with concomitant T2DM and obesity (body mass index ≥ 30.0 kg/m2) undergoing SG or OAGB between March 2013 and March 2021. T2DM remission was defined as achieving a glycated haemoglobin (HbA1c) level < 48 mmol/mol and a fasting plasma glucose (FPG) level <7 mmol/L, and being off glucose-lowering agents/insulin. T2DM relapse was defined as when FPG or HbA1c reverted to the diabetic range (≥7 mmol/L and ≥48 mmol/mol, respectively), or there was a need for pharmacotherapy. RESULTS: After bariatric surgery, the overall T2DM remission and relapse rates were 61.4 per 1000 person-months (95% confidence interval [CI] 56.8-66.4) and 5.7 per 1000 person-months (95% CI 4.1-7.9), respectively. These rates were similar in the SG and OAGB groups. Multivariate hazard ratio analysis identified history of insulin therapy and T2DM duration prior to surgery as predictors of remission, while treatment with ≥2 glucose-lowering agents was the only relapse predictor. Additionally, patients undergoing SG experienced either remission or relapse within a significantly shorter time frame compared to those undergoing OAGB. CONCLUSION: After 5 years of follow-up, there were no significant differences between the SG and OAGB groups with regard to T2DM remission and relapse. Bariatric surgery was less likely to result in remission in patients with a history of insulin therapy and longer durations of T2DM prior to surgery. Furthermore, patients who received ≥2 glucose-lowering agents, despite possible remission, were at a higher risk of experiencing late relapse.

Rerouting cardiovascular management following gastric bypass surgery: Dose optimization of carvedilol using population-based analysis.

AIMS: A population-based pharmacokinetic (PK) modeling approach (PopPK) was used to investigate the impact of Roux-en-Y gastric bypass (RYGB) on the PK of (R)- and (S)-carvedilol. We aimed to optimize carvedilol dosing for these patients utilizing a pharmacokinetic/pharmacodynamic (PK/PD) link model. METHODS: PopPK models were developed utilizing data from 52 subjects, including nonobese, obese, and post- RYGB patients who received rac- carvedilol orally. Covariate analysis included anthropometric and laboratory data, history of RYGB surgery, CYP2D6 and CYP3A4 in vivo activity, and relative intestinal abundance of major drug- metabolizing enzymes and transporters. A direct effect inhibitory Emax pharmacodynamic model was linked to the PK model of (S)- carvedilol to simulate the changes in exercise- induced heart rate. RESULTS: A 2-compartmental model with linear elimination and parallel first-order absorptions best described (S)-carvedilol PK. RYGB led to a twofold reduction in relative oral bioavailability compared to nonoperated subjects, along with delayed absorption of both enantiomers. The intestinal ABCC2 mRNA expression increases the time to reach the maximum plasma concentration. The reduced exposure (AUC) of (S)-carvedilol post-RYGB corresponded to a 33% decrease in the predicted area under the effect curve (AUEC) for the 24-hour ß-blocker response. Simulation results suggested that a 50-mg daily dose in post-RYGB patients achieved comparable AUC and AUEC to 25-mg dose in nonoperated subjects. CONCLUSION: Integrated PK/PD modeling indicated that standard dosage regimens for nonoperated subjects do not provide equivalent ß-blocking activity in RYGB patients. This study highlights the importance of personalized dosing strategies to attain desired therapeutic outcomes in this patient cohort.

Oxalate Nephropathy After Kidney Transplantation: Risk Factors and Outcomes of Two Phenotypes.

Describing risk factors and outcomes in kidney transplant recipients with oxalate nephropathy (ON) may help elucidate the pathogenesis and guide treatment strategies. We used a large single-center database to identify patients with ON and categorized them into delayed graft function with ON (DGF-ON) and late ON. Incidence density sampling was used to select controls. A total of 37 ON cases were diagnosed between 1/2011 and 1/2021. DGF-ON (n = 13) was diagnosed in 1.05% of the DGF population. Pancreatic atrophy on imaging (36.4% vs. 2.9%, p = 0.002) and gastric bypass history (7.7% vs. 0%; p = 0.06) were more common in DGF-ON than with controls with DGF requiring biopsy but without evidence of ON. DGF-ON was not associated with worse graft survival (p = 0.98) or death-censored graft survival (p = 0.48). Late ON (n = 24) was diagnosed after a mean of 78.2 months. Late ON patients were older (mean age 55.1 vs. 48.4 years; p = 0.02), more likely to be women (61.7% vs. 37.5%; p = 0.03), have gastric bypass history (8.3% vs. 0.8%; p = 0.02) and pancreatic atrophy on imaging (38.9% vs. 13.3%; p = 0.02). Late ON was associated with an increased risk of graft failure (HR 2.0; p = 0.07) and death-censored graft loss (HR 2.5; p = 0.10). We describe two phenotypes of ON after kidney transplantation: DGF-ON and late ON. Our study is the first to our knowledge to evaluate DGF-ON with DGF controls without ON. Although limited by small sample size, DGF-ON was not associated with adverse outcomes when compared with controls. Late ON predicted worse allograft outcomes.

One anastomosis gastric bypass as a primary bariatric surgery: MBSAQIP database analysis of short-term safety and outcomes.

BACKGROUND: One anastomosis gastric bypass (OAGB) is described as a simpler, potentially safe, and effective bariatric-metabolic procedure that has been recently endorsed by the American Society of Metabolic and Bariatric Surgery. OBJECTIVES: First, we aim to compare the 30-day outcomes between OAGB and other bypass procedures: Roux-en-Y gastric bypass (RYGB) and single anastomosis duodenoileal bypass with sleeve gastrectomy (SADI-S). Second, identify the odds between postoperative complications and each surgical procedure. METHODS: Patients who underwent primary OAGB, RYGB, and SADI-S were identified using the MBSAQIP database of 2020 and 2021. An analysis of patient demographics and 30-day outcomes were compared between these three bypass procedures. In addition, a multilogistic regression for overall complications, blood transfusions, unplanned ICU admissions, readmission, reoperation, and anastomotic leak stratified by surgical procedure was performed. RESULTS: 1607 primary OAGBs were reported between 2020 and 2021. In terms of patient demographics, patients who underwent RYGB and SADI-S showed a higher incidence of comorbidities. On the other hand, OAGB had shorter length of stay (1.39 ± 1.10 days vs 1.62 ± 1.42 days and 1.90 ± 2.04 days) and operative times (98.79 ± 52.76 min vs 125.91 ± 57.76 min and 139.85 ± 59.20 min) than RYGB and SADI-S. Similarly, OAGB showed lower rates of overall complications (1.9% vs 4.5% and 6.4%), blood transfusions (0.4% vs 1.1% and 1.8%), unplanned ICU admission (0.3% vs 0.8% and 1.4%), readmission (2.4% vs 4.9% and 5.0%), and reoperation (1.2% vs 1.9% and 3.1%). A multilogistic regression analysis was performed, RYGB and SADI-S demonstrated higher odds of 30-day complications. CONCLUSION: The incidence of primary OAGB has increased since its approval by ASMBS, from 0.05% reported between 2015 and 2019 to 0.78% between 2020 and 2021. OAGB had better 30-day outcomes and shorter operative times than RYGB and SADI-S and therefore, could be considered a viable alternative.

Conversion of one-anastomosis gastric bypass to Roux-En-Y gastric bypass: mid-term results from the United Arab Emirates.

BACKGROUND: One-Anastomosis Gastric Bypass (OAGB) is becoming popular, but some patients may need to convert to Roux-en-Y Gastric Bypass (RYGB) due weight-related difficulties or postoperative complications. The data on conversions is currently limited to 30-day or short-term follow-up studies. As such, the objective of this study was to evaluate the indications and mid-term outcomes for OAGB conversions to RYGB at a tertiary referral center in the United Arab Emirates. METHODS: A retrospective analysis was conducted on patients who underwent conversion from OAGB to RYGB between February 2016 and May 2023. Demographic information, indications for conversion, intraoperative details, and mid-term outcomes were collected and analyzed. RESULTS: Sixty-four patients underwent conversion from previous OAGB to RYGB. The cohort was 73.4% female (n = 47) with a mean age of 40.8 years. Indications for conversion included acid reflux (n = 28, 43.7%), intractable nausea/vomiting (n = 20, 31.2%), protein-calorie malnutrition (n = 7, 10.9%), anastomotic ulcer (n = 6, 9.3%) and weight recidivism (n = 3, 4.7%). The mean operative time was 238 ± 78.3 min. During the procedure, three intraoperative complications occurred: two cases of bleeding and one case of bowel perforation; all successfully addressed during surgery. The median hospital stay was 3 ± 15.8 days. Three patients (4.6%) experienced major postoperative complications comprising 2 anastomotic leaks and 1 small bowel obstruction. The mean follow-up time was 26.2 ± 19.7 months, with 96.2% of patients reporting resolution of symptoms. There were no mortalities. CONCLUSIONS: Acid reflux is representing 43.7% of the indications for conversion from OAGB to RYGB. The symptom resolution rate holds significance, standing at a remarkable 96.8%. Despite surgical technique advancements, the complication rate after conversions remains significant at 4.6%, with no mortality reported. OAGB patients should be informed about these risks prior to undergoing conversions from OAGB to RYGB.

Comparison of weight loss after Roux-en-Y gastric bypass in Helicobacter pylori-negative and Helicobacter pylori eradicated patients during five years follow-ups.

PURPOSE: Helicobacter pylori (HP) is the most common human infection that has affected up to 50% of the population worldwide. The relationship between HP eradication and weight loss is under debate. The present study aimed to compare weight loss outcomes after Roux-en-Y gastric bypass (RYGB) in HP-negative (HP-) and HP-eradicated (HPe) patients during five years follow-ups. METHODS: This retrospective cohort study was conducted on 305 patients aged 18 and more with severe obesity, who underwent primary RYGB from February 2014 to November 2017. The HP-negative and HP-eradicated patients were evaluated for weight loss outcomes during five years follow-ups. RESULTS: Patients' mean age, mean weight, and mean body mass index were 38.78 ± 9.9, 114.8 ± 13.6, and 43.37 ± 2.55, respectively. 27.2% of patients who were HP-positive were treated before RYGB. There was no significant difference between the HP- and HPe patients in terms of total weight loss percent (%TWL), 12 to 60 months after RYGB. Excess weight loss percent (%EWL) was higher in HPe patients compared to HP- patients (P = 0.04) at 12-month after RYGB. However, there was no difference in %EWL between these two groups of patients, 36 and 60 months after RYGB. CONCLUSION: The results of the present study showed that TWL% had no significant difference in HP- and HPe groups during five years follow-ups after RYGB. The %EWL was higher in HPe patients only at 12 months after RYGB and the difference did not persist over time.

Prospective evaluation of transoral outlet reduction (TORe) after Roux-en-Y gastric bypass (RYGB) failure.

BACKGROUND AND AIMS: Weight regain after RYGB is multifactorial including dilatation of the gastro-jejunal anastomosis. Transoral outlet reduction (TORe) procedure is a minimally invasive alternative to surgical anastomotic revision. METHODS: We conducted a prospective, multicenter, simple blind, randomized study in patients with weight regain following RYGB, comparing the efficacy of conventional nutritional and behavioral management associated with a TORe procedure (TORe group) with conventional management alone and a Sham procedure (Sham group). The main objective of this study was to evaluate the percentage of excess weight loss (%EWL) at 12 months after endoscopy. RESULTS: From January 2015 to January 2019, 73 subjects were randomized in four French Bariatric centers. The final analysis involved 50 subjects, 25 in each group, 44 women, 6 men, with an average BMI of 40.6 kg/m2. At 12 months, the average %EWL was significantly higher in the TORe group than in the Sham group (13.5 ± 14.1 vs. - 0.77 ± 17.1; p = 0.002). Cohen's d was 0.91, indicating a large effect size of the procedure on the %EWL. There was no significant difference between groups concerning the improvement of obesity-related comorbidities (diabetes and dyslipidemia) and quality of life at 12 months. We report frequent adverse events in the TORe group (20% had adverse events related to the procedure). Three adverse events were serious, including two perforations of the gastro-jejunal anastomosis after TORe group that led to the premature termination of the study. CONCLUSIONS: After RYGBP failure linked to the dilatation of the gastro-jejunal anastomosis, TORe procedure with nutritional management results in significantly higher %EWL at 12 months compared to patients with nutritional management alone. As surgery, this minimally invasive endoscopic procedure can be associated with severe adverse events.

Comparison between total weight loss and other metrics after bariatric surgery using a multilevel mixed-effects linear regression model.

BACKGROUND: Several tools are used to assess postoperative weight loss after bariatric surgery, including the percentage of excess body weight loss (%EWL), percentage of total weight loss (%TWL), and percentage of excess body mass index (BMI) loss (%EBMIL). A repeated series of measurements should be considered to assess weight loss as accurately as possible. This study aimed to test weight loss metrics. METHODS: Data were obtained from a prospective database of patients with obesity who underwent laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) between 2016 and 2017 in a French tertiary referral bariatric center. A multilevel mixed-effects linear regression model with repeated measures was used to analyze repeated weight measurements over time. RESULTS: A total of 435 patients underwent LRYGB (n = 266) or LSG (n = 169). At 2 years, the average %EWL, %EBMIL, and %TWL were 56.8%, 61.3%, and 26.6%, respectively. Patients who underwent LSG experienced lower weight loss (ß: - 4233 in %TWL model, ß: - 6437 in %EWL model, and ß: - 6989 in %EBMIL model) than those who underwent LRYGB. In multivariate mixed analysis, preoperative BMI was not significantly associated with %TWL at 2 years (ß, - 0.09 [- 0.22-0.03] p = 0.1). Preoperative BMI was negatively associated with both %EWL (ß, - 1.61 [- 1.84-- 1.38] p < 0.0001) and %EBMIL (ß, - 1.91 [- 2.16-- 1.66] p < 0.0001). CONCLUSION: This is the first study to assess %TWL use for postoperative weight measurement, using a multilevel mixed-effects linear regression model %TWL is the measure of choice to assess weight loss following bariatric surgery.

1- and 2-year outcomes and predictors of weight loss after gastric sleeve to Roux-en-Y gastric bypass conversion: a retrospective cohort study.

BACKGROUND: Sleeve gastrectomy to Roux-en-Y bypass conversion is a commonly performed procedure, yet data are limited on outcomes and their predictors. The purpose of this study is to characterize the long-term outcomes of patients after sleeve-to-bypass conversion and identify predictors of post-conversion outcomes. METHODS: We performed a retrospective cohort study of patients who underwent sleeve-to-bypass conversion for obesity across four hospitals from 06/2017 to 04/2023. Predictors of the below-average percent excess weight loss (%EWL; relative to pre-conversion weight) at 1 and 2 years following conversion were identified using multivariate logistic regression models adjusting for comorbidities, demographics, and neighborhood socioeconomic status. RESULTS: 150 Patients undergoing sleeve-to-bypass conversion were identified. 99 had 1-year data and 63 had 2-year data. Mean %EWL at 1- and 2-years following conversion were 40.2% and 37.4%, respectively. EWL > 40% after sleeve gastrectomy was an independent predictor of the below-average %EWL 1-year post-conversion (OR 10.0, 95% CI 2.2-63.0, p < 0.01), and BMI > 40 kg/m2 at the time of conversion was an independent predictor of both 1- and 2-year below-average %EWL post-conversion (p = 0.01 and 0.05, respectively). Insignificant predictors of the below-average %EWL after conversion included: weight regain after sleeve, time between sleeve and conversion, alimentary limb length, and any bariatric surgery prior to sleeve gastrectomy. CONCLUSION: Patients should be counseled that the typical expected %EWL for sleeve-to-bypass conversion is less than the 50% EWL benchmark of success for index bariatric operations. The main predictors of a suboptimal conversion outcome are > 40% EWL after sleeve or > 40 BMI kg/m2 at the time of conversion. Most variables in our analysis were not predictors of post-conversion %EWL, including weight regain between sleeve and conversion, alimentary limb length, and time interval between procedures, which suggests that these factors should not play a large role when considering sleeve-to-bypass conversion.

Late-"de novo" paraesophageal hernia after Roux-en-Y gastric bypass (RYGB)-should it be repaired?

BACKGROUND: This study presents a case series of "de novo" paraesophageal hernia (dnPEH) in post-Roux-en-Y gastric bypass (RYGB) patients and analyzes the predisposing factors, symptoms, and outcomes after repair. This is a lesser known complication after RYGB and when symptomatic, may warrant surgery. METHODS: A retrospective review of data from a single academic institution from 2002 to 2022 was performed identifying patients who developed dnPEH after RYGB and compared them to patients with primary RYGB without post-operative symptomatic dnPEH. Patient characteristics from initial RYGB were analyzed to identify predisposing factors for dnPEH development. Additional information analyzed included time to dnPEH repair, indications for surgery, types of herniation, type of surgical repair, and symptom resolution. RESULTS: There were 6975 RYGB in the study period of which 6619 underwent RYGB alone at index surgery, with 31 of those patients developing late stage PEH requiring repair. Patients with older age (51.8 years with dnPEH vs 45.2 years without, p = 0.001) and increased weight loss at 1 year (33.4% vs 30.5%, p = 0.048) from index RYGB were more likely to develop dnPEH. The incidence of dnPEH was 31/6619 (0.47%). Late dnPEH after RYGB took an average of 74 months (45-102 months IQR) to develop symptoms and undergo repair. The most common symptoms were heartburn/reflux 19/31 (61.3%) and epigastric pain 13/31 (41.9%). Symptom resolution rate after repair was highest with 100% for globus and 89.5% heartburn/reflux. The most common form of dnPEH was pouch herniation in 25/31. Surgical repair most commonly included primary cruroplasty alone in 25/31 with additional mesh in 1 case. Recurrence rate was 2/31 (6.54%). CONCLUSION: Late dnPEH after RYGB is an emerging entity typically occurring years after index RYGB. Symptomatic patients with dnPEH warrant hernia repair and responded well to surgical repair in this case series.

Safety and factors associated with early discharge in revisional laparoscopic Roux-en-Y gastric bypass: analysis of the MBSAQIP database.

BACKGROUND: Improvements in bariatric surgery outcomes have prompted policy initiatives that explore shifting bariatric surgery toward outpatient procedures. While the safety of early discharge after primary laparoscopic Roux-en-Y gastric bypass (LRYGB) has been reported, its safety for revisional LRYGB remains uncertain. Our study aimed to investigate the safety and patient factors associated with early discharge in patients undergoing revisional LRYGB compared with primary LRYGB. METHODS: We identified adult patients who underwent primary and revisional LRYGB from 2020 to 2022 in the MBSAQIP database. Patients discharged early, i.e., same-day discharge (SDD) and next-day discharge (NDD) were compared to inpatients. Outcomes included 30-day complications (minor = Clavien-Dindo 1-2; major = Clavien-Dindo 3-4), mortality, readmissions, and reoperations. Multivariable logistic regression models adjusting for patient demographics, comorbidities, and operative time were fitted to assess the study outcomes. RESULTS: SDD rate was similar after primary (3,422/137,406; 2.5%) and revisional LRYGB (781/32,721; 2.4%), while NDD rate was higher in primary LRYGB (59.8% vs 54.7%, respectively; p < 0.001). SDD patients had lower odds of major complications compared to inpatients following primary (2% vs 7%, aOR: 0.30, 95%CI 0.24-0.38) and revisional LRYGB (3.7% vs 9.3%, aOR: 0.43, 95%CI 0.29-0.62, respectively). NDD patients had similarly lower odds of morbidity outcomes. ASA Classification IV/V was associated with lower odds of SDD compared to Class I/II (Primary: 0.9% vs. 3%, aOR: 0.61, 95% CI 0.48-0.78; Revisions: 0.9% vs. 3%, aOR: 0.24, 95%CI 0.10-0.55). CONCLUSION: Early discharge after revisional LRYGB, particularly after an overnight stay, can be accomplished safely in carefully selected patients. However, SDD rates remain low limiting its safety assessment. Further, almost half of the patients stay more than 48 h in the hospital suggesting that policy initiatives toward outpatient management after bariatric surgery may be inappropriate for this patient population.

Predictors of postoperative bleeding after minimally invasive bariatric surgery.

BACKGROUND: Minimally invasive bariatric surgeries provide effective weight loss with fewer complications. However, postoperative bleeding remains a significant concern due to its potential for serious morbidity and mortality. This study aimed to identify factors predicting postoperative bleeding following laparoscopic and robotic sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). METHODS: We analyzed patients who underwent SG and RYGB using the MBSAQIP database from 2015 to 2021. Four multivariate logistic regression analyses were conducted to investigate the relationship between postoperative bleeding and 24 independent factors for laparoscopic SG (lapSG), robotic SG (rSG), laparoscopic RYGB (lapRYGB), and robotic RYGB (rRYGB). RESULTS: We analyzed 659,294 lapSG, 53,548 rSG, 267,171 lapRYGB, and 22,492 rRYGB patients. In lapSG, the most significant factors included anticoagulation (OR 3.76; 95% CI 3.13-4.51), renal insufficiency (OR 2.06; 95% CI 1.37-3.09), history of DVT (OR 1.87; 95% CI 1.23-2.85), history of PE (OR 1.69; 95% CI 1.04-2.76, and BMI ≤ 40 (OR 1.22; 95% CI 1.09-1.38). In the rSG group, anticoagulation (OR 4.95; 95% CI 2.83-8.66), COPD (OR 2.80; 95% CI 1.29-6.05), and hyperlipidemia (OR 1.90; 95% CI 1.29-6.05) were significant factors. In lapRYGB, the most significant factors included anticoagulation (OR 3.68; 95% CI 3.11-4.35), renal insufficiency (OR 1.60; 95% CI 1.04-2.44), history of DVT (OR 1.70; 95% CI 1.09-2.07), cardiac stent (OR 1.51; 95% CI 1.09-2.07), and BMI ≤ 40 (OR 1.16; 95% CI 1.03-1.29). For rRYGB, anticoagulation (OR 4.69; 95% CI 2.86-7.70), history of PE (OR 4.28; 95% CI 1.53-12.00), and cardiac stent (OR 2.15; 95% CI 0.06-4.34) were significant. CONCLUSION: Preoperative anticoagulation, renal insufficiency, history of DVT and PE, a cardiac stent, and BMI ≤ 40 are associated with an increased risk of postoperative bleeding. The predictive factors were consistent across laparoscopic and robotic approaches in SG and RYGB procedures.