Dayyeh, Barham Abu

Objective: To develop and validate 2 predictive models, the Diabetes Remission Index (DRI) and the Weight loss–adjusted DRI (W-DRI), for assessing type 2 diabetes (T2D) remission following metabolic and bariatric surgery (MBS). Background: MBS, including Roux-en-Y gastric bypass and sleeve gastrectomy, is highly effective in achieving T2D remission, but outcomes vary across populations. Predicting remission remains critical for individualized patient care and optimizing surgical outcomes. Existing tools focus on general outcomes, and a specific model incorporating weight loss data has been lacking. Methods: This multicenter, retrospective cohort study included patients with T2D and overweight/obesity (body mass index: ≥27 kg/m 2 ) who underwent Roux-en-Y gastric bypass or sleeve gastrectomy between 2008 and 2018. Institution 1 (I-1) data (n = 503) were used to develop and internally validate the models, whereas Institution 2 (I-2) data (n = 409) were used for external validation. The DRI model incorporated preoperative variables, and the W-DRI model, in addition, included postsurgical weight loss. Predictive accuracy was assessed using area under the Receiver Operating Characteristic curve [area under the curve (AUC)], calibration plots, and stratified analyses. Results: In I-1, 44.7% of patients achieved T2D remission, with a DRI model AUC of 0.80. In I-2, 52.6% achieved remission, with a model AUC of 0.78. Incorporating weight loss improved W-DRI predictive accuracy (AUC: 0.82 in I-1, 0.79 in I-2). Calibration plots demonstrated strong agreement between predicted and observed remission rates. An online DRI and W-DRI calculator is available through the Mayo Clinic webpage (https://newsnetwork.mayoclinic.org/dri-calculator/). Conclusions: The DRI and W-DRI models accurately predict T2D remission post-MBS, enabling personalized patient care and informed decision-making. Further validation across diverse populations is warranted.

Background: Within the spectrum of gastroesophageal reflux disease (GERD), pathologic reflux applies to the subset of patients with either erosive esophagitis or abnormal esophageal acid exposure on pH-metry, consequences of a dysfunctional antireflux barrier (ARB). Methods: The American Foregut Society (AFS) tasked a 13-member working group of expert foregut surgeons and esophagologists (The ARB Cooperative) to develop a white paper on ARB function, dysfunction, and mechanisms of action of antireflux surgery through discussion of relevant literature summarized herein. Results: The ARB Cooperative concluded that pathologic reflux is a consequence of the interplay between progressive anatomical distortion of the ARB and physiology. Factors contributing to ARB dysfunction include (1) separation of crural diaphragm from the lower esophageal sphincter with widening of the hiatus and diminished crural diaphragm sphincteric function; (2) loss of the intra-abdominal lower esophageal sphincter segment with complete disabling of the flap valve component of the ARB; (3) axial hiatal hernia leading to reflux during swallow-induced lower esophageal sphincter (LES) relaxation, LES hypotension, inspiration related reflux, a lowered threshold for eliciting transient LES relaxations, and increased compliance of the gastroesophageal junction leading to greater diameter of sphincter opening during transient LES relaxations. With regard to antireflux surgery, the objectives include: (1) reduction of hiatal hernia and restoration of the intra-abdominal esophageal segment; (2) repair of the dilated hiatus; (3) restoring flap valve function by modifying gastroesophageal anatomy; and (4) restricting gastroesophageal junction opening during periods of relaxation. Conclusions: This ARB Cooperative white paper supports the concept of there being 3 major inter-related mechanisms promoting ARB competence: the LES as an intrinsic sphincter, the crural diaphragm as an extrinsic sphincter, and the gastroesophageal valve, a mechanical 1-way valve. Pathological reflux occurs with progressive anatomical disruption of the ARB which in turn leads to physiological dysfunction, the severity of which parallels the extent of anatomical disruption. The corollary of this is that the primary mechanism of antireflux surgery is to restore the ARB by eliminating or compensating for its anatomical disruption. It is the hope of the cooperative that understanding the proposed framework will help clinicians and researchers in improving antireflux procedures.

Abstract Satiation is the physiologic process that regulates meal size and termination, and it is quantified by the calories consumed to reach satiation. Given its role in energy intake, changes in satiation contribute to obesity's pathogenesis. Our study employed a protocolized approach to study the components of food intake regulation including a standardized breakfast, a gastric emptying study, appetite sensation testing, and a satiation measurement by an ad libitummeal test. These studies revealed that satiation is highly variable among individuals, and while baseline characteristics, anthropometrics, body composition and hormones, contribute to this variability, these factors do not fully account for it. To address this gap, we explored the role of a germline polygenic risk score, which demonstrated a robust association with satiation. Furthermore, we developed a machine-learning-assisted gene risk score to predict satiation and leveraged this prediction to anticipate responses to anti-obesity medications. Our findings underscore the significance of satiation, its inherent variability, and the potential of a genetic risk score to forecast it, ultimately allowing us to predict responses to different anti-obesity interventions.

AbstractBackgroundFood intake is regulated by homeostatic and hedonic systems that interact in a complex neuro‐hormonal network. Dysregulation in energy intake can lead to obesity (OB) or anorexia nervosa (AN). However, little is known about the neurohormonal response patterns to food intake in normal weight (NW), OB, and AN.Material & MethodsDuring an ad libitum nutrient drink (Ensure®) test (NDT), participants underwent three pseudo‐continuous arterial spin labeling (pCASL) MRI scans. The first scan was performed before starting the NDT after a > 12 h overnight fast (Hunger), the second after reaching maximal fullness (Satiation), and the third 30‐min after satiation (postprandial fullness). We measured blood levels of ghrelin, cholecystokinin (CCK), glucagon‐like peptide (GLP‐1), and peptide YY (PYY) with every pCASL‐MRI scan. Semiquantitative cerebral blood flow (CBF) maps in mL/100 gr brain/min were calculated and normalized (nCBF) with the CBF in the frontoparietal white matter. The hypothalamus (HT), nucleus accumbens [NAc] and dorsal striatum [DS] were selected as regions of interest (ROIs).ResultsA total of 53 participants, 7 with AN, 17 with NW (body‐mass index [BMI] 18.5–24.9 kg/m2), and 29 with OB (BMI ≥30 kg/m2) completed the study. The NW group had a progressive decrease in all five ROIs during the three stages of food intake (hunger, satiation, and post‐prandial fullness). In contrast, participants with OB showed a minimal change from hunger to postprandial fullness in all five ROIs. The AN group had a sustained nCBF in the HT and DS, from hunger to satiation, with a subsequent decrease in nCBF from satiation to postprandial fullness. All three groups had similar hormonal response patterns with a decrease in ghrelin, an increase in GLP‐1 and PYY, and no change in CCK.ConclusionConditions of regulated (NW) and dysregulated (OB and AN) energy intake are associated with distinctive neurohormonal activity patterns in response to hunger, satiation, and postprandial fullness.

Background: Gastrojejunal (GJ) anastomotic stenosis is a well-described complication after Roux-en-Y gastric bypass (RYGB); however, its impact on weight loss outcomes is not well elucidated. Methods: We performed a retrospective cohort study of adult patients who underwent RYGB at our institution between 2008 and 2020. Propensity score matching was used to match 30 patients who developed GJ stenosis within the first 30 days post-RYGB with 120 control patients who did not develop this outcome. Short and long-term complications and mean percentage of total body weight loss (TWL) were recorded at 3 months, 6 months, 1 year, 2 years, 3 to 5 years, and 5 to 10 years postoperatively. Hierarchical linear regression modeling was used to analyze the association between early GJ stenosis and the mean percentage of TWL. Results: Patients who developed early GJ stenosis had a 13.6% increase in the mean percentage of TWL when compared with controls in the hierarchical linear model [P < 0.001 (95% CI: 5.7; 21.5)]. These patients were also more likely to present to an intravenous infusion center (70% vs 4%; P < 0.01), require readmission within 30 days (16.7% vs 2.5%; P < 0.01), and/or develop an internal hernia (23.3% vs 5.0%) postoperatively. Conclusions: Patients who develop early GJ stenosis after RYGB have a greater degree of long-term weight loss compared with patients who do not develop this complication. Although our findings support the key contribution that restrictive mechanisms play in maintaining weight loss after RYGB, GJ stenosis remains a complication associated with significant morbidity.

Abstract Background Obesity is associated with an increased incidence of at least 13 types of cancer. Although bariatric surgery has been associated with a reduced risk of hormonal cancers, data for non-hormonal cancers are scarce. The aim of this study was to evaluate the effect of bariatric surgery on the incidence of non-hormonal cancers. Methods Cochrane, Embase, PubMed, Scopus, and Web of Science were searched for articles between 1984 and 2018, following the PRISMA system. Meta-analysis was conducted using a random-effect model with subgroup analysis by procedure and cancer type. Results From 2526 studies screened, 15 were included. There were a total of 18 583 477 patients, 947 787 in the bariatric group and 17 635 690 in the control group. In comparison to the non-surgical group, the bariatric group had a lower incidence of cancer (OR .65 (95 per cent c.i. 0.53 to 0.80); P &lt; 0.002). In the subgroup analysis, Roux-en-Y gastric bypass and sleeve gastrectomy were associated with decreased risk of developing cancer, while no difference was observed with adjustable gastric banding. When evaluated by cancer type, liver (OR 0.417 (95 per cent c.i. 0.323 to 0.538)), colorectal (OR 0.64 (95 per cent c.i. 0.49 to 0.84)), kidney and urinary tract cancer (OR 0.77 (95 per cent c.i. 0.72 to 0.83)), oesophageal (OR 0.60 (95 per cent c.i. 0.43 to 0.85)), and lung cancer (OR 0.796 (95 per cent c.i. 0.45 to 0.80)) also presented a lower cancer incidence in the bariatric group. Conclusion Bariatric surgery is related to an almost 50 per cent reduction in the risk of non-hormonal cancers.