Intestinal epigenomic alterations are associated with a dysregulated nutrient absorption phenotype in obesity.

Obesity is an epidemic with myriad health effects, but little is understood regarding individual obese phenotypes and how they may respond to therapy. Epigenetic changes associated with obesity have been detected in blood, liver, pancreas, and adipose tissues. Previous work found that dietary glucose hyperabsorption occurs in some obese subjects, but detailed transcriptional or epigenomic features of the intestine associated with this phenotype are unknown. This study evaluated differentially expressed genes and relative chromatin accessibility in intestinal organoids established from donors classified as lean, obese, or obese hyperabsorptive by body mass index and glucose transport assays. Transcriptomic analysis indicated that obese hyperabsorptive subjects have significantly upregulated dietary nutrient absorption proteins and downregulated type I interferon targets. Chromatin accessibility and transcription factor footprinting suggested that enhanced binding of HNF4G promotes the obese hyperabsorption phenotype. Quantitative PCR assessment in a larger subject cohort suggested that intestinal epithelial expression of CUBN, GIP, and SLC2A5 have high correlation with hyperabsorption. The obese hyperabsorption phenotype is characterized by transcriptional changes that support increased nutrient uptake and may be driven by differentially accessible chromatin. Recognizing unique intestinal phenotypes in obesity provides new perspective in considering therapeutic targets and options to manage the disease.

Endoluminal bariatric and metabolic therapies: state-of-the-art.

PURPOSE OF REVIEW: The aim of this review is to present the current state of the field, highlight recent developments, and describe the clinical outcomes of these endoluminal bariatric and metabolic procedures. RECENT FINDINGS: The landscape of endoluminal devices and techniques for treating obesity has expanded significantly, with FDA-approved therapies currently available to patients with a body mass index values as high as 50 kg/m 2 . Although notable advancements have been made in this area, there is a need for further emphasis to be placed on the metabolic improvements resulting from these therapies, in addition to the conventional focus on weight loss outcomes. Some of these procedures are now FDA approved for the treatment of metabolic disease as opposed to weight loss. To achieve the most favorable results, it is imperative that all endoluminal interventions are combined with a moderately intensive diet and lifestyle program lasting at least 12 months. SUMMARY: Endoluminal metabolic and bariatric therapy represents a bridge between lifestyle counseling, pharmaceutical interventions, and the most efficacious treatment for obesity, bariatric surgery. By virtue of its minimally invasive approach, this therapy may be an appealing option for patients who are ineligible for, or averse to, bariatric surgery and who have experienced suboptimal outcomes or unable to afford medical treatments. Furthermore, these interventions may be particularly beneficial in the early stages of obesity.

Acute Pancreatitis Review.

Acute pancreatitis, a prevalent illness with devastating consequences, poses a grave threat to those affected. There has been a steady increase in the occurrence of acute pancreatitis at about 3% per year from 1961 to 2016. There are 3 main guidelines on acute pancreatitis, including the American College of Gastroenterology, the International Association of Pancreatology/American Pancreatic Association guideline in 2013, and the American Gastroenterological Association guideline in 2018. However, several milestone studies have been published since then. We hereby reviewed the current acute pancreatitis guidelines with an update on clinical practicechanging literature. The aggressive or moderate fluid resuscitation in acute pancreatitis (WATERFALL) trial recommended fluid resuscitation with lactated Ringer's solution at a moderate aggressive rate. All guidelines did not recommend prophylactic antibiotics use. Early enteral feeding reduces morbidity. A clear liquid diet is no longer recommended. Nutrition with nasogastric or nasojejunal feeding does not have a difference. The upcoming high vs. low-energy administration in the early phase of acute pancreatitis (GOULASH) trial will provide more information on the impact of calorie intake. Pain management should be individualized based on the degree of pain and severity of pancreatitis. In patients with moderate to severe and severe acute pancreatitis, a step-down approach with epidural analgesia can be considered for moderate to severe pain. The management of acute pancreatitis has evolved. New research on the impact of electrolytes, pharmacologic agents, the role of anticoagulants, and nutrition support will provide scientific and clinical evidence to improve patient care and decrease morbidity and mortality.

Impact of Adjunctive Pharmacotherapy With Intragastric Balloons for the Treatment of Obesity.

BACKGROUND: We conducted this study to compare the weight loss outcome of intragastric balloons (IGBs) in conjunction with pharmacotherapy vs IGB and intensive lifestyle changes alone. METHODS: This was a multicenter, non-randomized, retrospective study involving 4 academic hospitals. Patients underwent IGB placement with or without concomitant anti-obesity pharmacotherapy. The primary outcome was percent total weight loss (TBWL) after IGB placement at 6 and 12 months. RESULTS: This study included 102 patients, with 23 patients (mean age 46.6 years, 82.6% female) treated with IGB/pharmacotherapy and 79 patients (mean age 46.0 years, 88.6% female) treated with IGB/lifestyle modifications. Patients had a 100% follow-up rate at 6 and 12 months. At 6 months following IGB placement, both groups achieved a similar %TBWL. At 12 months, %TBWL was greater in the IGB/pharmacotherapy group (12.6% ± 1.2 vs 9.7% ± 0.7, P = .04). 65.2% of patients achieved ≥10% TBWL at 12 months in the IGB/pharmacotherapy group, compared to 38.0% in the IGB/lifestyle group (P < .05). The proportion of patients that achieved ≥15% weight loss at 12 months was also significantly different between the IGB/pharmacotherapy and IGB/lifestyle groups (30.4% vs 20.3%, P < .05). DISCUSSION: IGB with concomitant use of pharmacotherapy did not improve weight loss while the IGB was in place compared to IGB and lifestyle changes. However, patients receiving IGB with pharmacotherapy did have greater weight loss and diminished weight regain after balloon removal compared to those receiving just IGB and lifestyle changes.

Challenges of developing and executing a multi-site registry for a novel device with evolving indications for use.

BACKGROUND: The introduction of new technologies in endoscopy has been met with uncertainty, skepticism, and lack of standardization or training parameters, particularly when disruptive devices or techniques are involved. The widespread availability of a novel endoscopic suturing device (OverStitch™) for tissue apposition has enabled the development of applications of endoscopic suturing. METHODS: The American Gastroenterological Association partnered with Apollo Endosurgery to develop a registry to capture in a pragmatic non-randomized study the safety, effectiveness, and durability of endoscopic suturing in approximating tissue in the setting of bariatric revision and fixation of endoprosthetic devices. RESULTS: We highlight the challenges of the adoption of novel techniques by examining the process of developing and executing this multicenter registry to assess real-world use of this endoscopic suturing device. We also present our preliminary data on the safety and effectiveness of the novel device as it is applied in the treatment of obesity. CONCLUSIONS: The Prospective Registry for Trans-Orifice Endoscopic Suturing Applications (ES Registry) was an effective Phase 4, postmarketing registry aimed at capturing pragmatic, real-world use of a novel device. These findings serve to solidify the role of endoscopic suturing in clinical practice.

Does endoscopic mean safer? A comparison of the short-term safety of endoscopic versus laparoscopic bariatric therapies.

Background and study aims There is minimal research on real-world, large-volume data comparing endoscopic bariatric therapy (EBT) to laparoscopic bariatric therapy (LBT). This study aimed to compare 30-day postoperative morbidity and mortality outcomes of primary EBT vs LBT using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program. Patients and methods Patients aged 18 to 80 with body mass index (BMI) 35 to 40 kg/m 2 undergoing primary procedures were included. Propensity score matching 1:50 was performed for EBT versus LBT based on age, sex, and BMI. Results We matched 211 EBTs with 9,059 LBTs. Operative length (63.9, 95 % confidence interval [CI]: 57.9, 69.8 versus 81.1, 95 % CI: 80.1, 82.1) and length of stay (0.49 days, 95 % CI: 0.29, 0.69 versus 1.43 days, 95 % CI: 1.41, 1.45) were significantly lower in the EBT group than the LBT group. There was no difference between EBT and LBT in the odds of readmission (odds ratio [OR] = 0.31, 95 % CI: 0.08, 1.25), reoperation (OR = 0.39, 95 % CI: 0.05, 2.84), or reintervention (OR = 0.98, 95 % CI: 0.24, 3.99). After controlling for chronic obstructive pulmonary disease, sleep apnea, history of myocardial infarction, hypertension requiring medications, and diabetes, EBT continued to be associated with lower odds of having any adverse event (AE) than LBT, with an OR of 0.34 (95 % CI: 0.16, 0.69). Subgroup analysis comparing EBT to laparoscopic sleeve gastrectomy (LSG) showed that EBT was associated with a lower risk having any AE than LSG, with an OR of 0.39 (95 % CI: 0.19, 0.79). Conclusions EBT is associated with a lower 30-day AE rate and shorter procedural length and length of stay than LBT, with similar rates of readmission, reintervention, and reoperation.

The Attitude of Practitioners Towards Endoscopic Sleeve Gastroplasty.

BACKGROUND AND AIM: Despite widespread adoption and encouraging results seen over the last 5 years, no consensus exists regarding the endoscopic sleeve gastroplasty (ESG) technique, training, or preprocedure and postprocedure management of the patient. The aim of our survey was to assess practice trends and preferences of bariatric endoscopists with respect to ESG. METHODS: Using a digital platform, we conducted a worldwide survey by emailing a link with an electronic questionnaire to 1200 bariatric endoscopists trained to perform endoscopic suturing using the Apollo Overstitch suturing device (Apollo Endosurgery). RESULTS: We received 221 responses that were included in the analysis. Fifty-one responders (36.4%) required 1 to 10 procedures, and 37 (26.4%) needed 11 to 20 procedures to become proficient at ESG. Ninety-six (68.6%) stated that lower body mass index thresholds should be adopted for Asian and Arab patients. There was no consensus on the ideal number of sutures, with 45 (32.1%), 42 (30%), 36 (25.7%), 13 (9.3%), and 4 (2.9%) recommending 4 to 6, 5 to 7, 6 to 8, 7 to 9, and 8 to 12 sutures, respectively. The primary barriers to establishing an endobariatric program were the inability to establish a cash pay model, 77 (95.1%); lack of institutional support, 61 (75.3%); and difficulty in establishing an ambulatory surgical center/hospital to perform ESG, 73 (90.1%). CONCLUSIONS: ESG practice trends remain heterogenous among practitioners in regard to indication, technique, and preprocedure and postprocedure management. Specific ESG guidelines are warranted, and this survey will assist in providing the framework for these guidelines to be written.

Gastric Mucosal Devitalization (GMD): Using the Porcine Model to Develop a Novel Endoscopic Bariatric Approach.

BACKGROUND AND AIMS: As the pig model has similar gastrointestinal anatomy and physiology to humans, we used pigs to create a gastric mucosal devitalization (GMD) model in preparation for clinical translation of this technique as an endoscopic bariatric therapy (EBT). The aims of this study were to determine the ablation parameters and technique for a successful, safe, and feasible large surface area GMD that produces weight loss. METHODS: We performed GMD using argon plasma coagulation (APC) in 3 phases. Phase 1 assessed the ablation energy required to accomplish selective mucosal ablation using ex vivo pig stomachs (n = 2). Phase 2 assessed the optimal percentage of mucosal surface area to be treated and was performed on 10 pigs. Phase 3 assessed feasibility, efficacy, and safety with 8 pigs randomized into GMD (n = 4) or sham (SH, n = 4) and survived for 1 month. Body weights (GMD, n = 4, SH, n = 4) were measured daily in phase 3 for 1 month, and relative body weights were calculated and analyzed using one-tailed Student's t-test. Percent body fat was compared between GMD and SH at baseline and 1 month post-GMD. RESULTS: Phase 1 identified the optimal ablation parameters (120 W) that were then used in phase 2. Phase 2 revealed a trend that was suggestive that the optimal percent surface area to ablate was similar to that which is removed at laparoscopic sleeve gastrectomy. In phase 3, GMD was performed over 70% surface area of the greater curvature of the stomach in four pigs. GMD pigs had significantly lower relative body weight increase compared to SH at 1 month (1.375 ± 0.085 vs 1.575 ± 0.047, p = 0.0435). MRI showed a significantly lower body fat mass at 1 month in GMD pigs (5.9 ± 0.4% vs 12.7 ± 2.3%, p = 0.026) compared to SH. CONCLUSIONS: GMD resulted in decreased weight gain in the GMD group as evidenced by a lower relative body weight at 1 month. GMD in an animal model appears to show promise as a potential weight loss therapy.

Serum phosphate is associated with mortality among patients admitted to ICU for acute pancreatitis.

BACKGROUND AND AIMS: Routine laboratory tests can be useful predictors in the early assessment of the severity and mortality of acute pancreatitis (AP). The aim of this study was to evaluate the accuracy of clinical and laboratory parameters for the prediction of mortality among patients admitted to the intensive care unit (ICU) for AP. METHODS: We conducted a retrospective analysis of prospectively collected data from Beth Israel Deaconess Hospital made publicly available to examine the relationship between routine clinical and laboratory parameters with respect to mortality for AP. Cox proportional hazard ratio was used to evaluate the impact of several routine laboratory markers on mortality. Receiver operation characteristic (ROC) curve was performed to determine the accuracy of diagnosis of laboratory tests by using area under curve (AUC) for the respective analysis. RESULTS: In total, 499 patients were admitted to the ICU for AP. Several factors for predicting mortality in AP at admission were identified in the multivariate analysis: alkaline phosphatase hazard ratio (HR) = 1.00 (1.00-1.00, p = 0.024), anion gap HR = 1.09 (1.00-1.20, p = 0.047), bilirubin total HR = 1.11 (1.06-1.17, p < 0.001), calcium total HR = 0.59 (0.42-0.84, p = 0.004), phosphate HR = 1.51 (1.18-1.94, p = 0.001), potassium HR = 1.91 (1.03-3.55, p = 0.041), white blood cells HR = 1.04 (1.00-1.07, p = 0.028). The AUC of serum phosphate level for mortality was 0.7 in the ROC analysis. The optimal cut-off value of serum phosphate level for prediction of mortality was 3.78 mg/dl (sensitivity, 0.58; specificity, 0.78). CONCLUSION: In this large cohort, we identified baseline serum phosphate as the most valuable single routine laboratory test for predicting mortality in AP. Future prospective studies are required to confirm these results.

The Utility of EndoFLIP for Measuring Gastrojejunal Anastomosis Diameter and Distensibility in Patients Experiencing Weight Regain Post Roux-en-Y Gastric Bypass.

A dilated gastrojejunal anastomosis (GJA) diameter is an independent predictor of weight regain following Roux-en-Y gastric bypass (RYGB). Despite this, there is no standardized method for GJA diameter measurement. We performed a retrospective analysis to compare endoscopic visual estimation and endoluminal functional impedance planimetry (EndoFLIP) for measuring GJA diameter in patients with weight regain post-RYGB. Visual estimation was found to overestimate GJA diameter by a mean of 4.2mm ± 4.6mm when compared with EndoFLIP. Furthermore, we identified symptomatic patients with normal GJA diameter but increased distensibility, which may represent a previously unrecognized subgroup. Our findings suggest the potential utility of EndoFLIP in the evaluation of post-RYGB weight regain and support the need for prospective studies to investigate the relationship between GJA distensibility and weight regain.

Endoscopic sleeve gastroplasty: suturing the gastric fundus does not confer benefit.

BACKGROUND : There is heterogeneity regarding the technical aspects of endoscopic sleeve gastroplasty (ESG), such as applying fundal sutures. Our aim was to determine whether ESG with fundal suturing (ESG-FS) affects weight loss and the serious adverse event (SAE) rate when compared with ESG with no fundal suturing (ESG-NFS). METHODS: We conducted a two-center retrospective analysis of 247 patients who underwent ESG with or without fundal suturing. The primary outcome was percentage excess weight loss (%EWL) at 3, 6, and 12 months post-ESG. The secondary outcomes included the SAE rate and procedure duration. RESULTS: At 3, 6, and 12-months, ESG-NFS had a significantly greater mean %EWL compared with ESG-FS (38.4 % [standard deviation (SD) 15.3 %] vs. 31.2 % [SD 13.9 %], P = 0.001; 54.7 % [SD 19.2 %] vs. 37.7 % [SD 17.3 %], P < 0.001; 65.3 % [SD 21.1 %] vs. 40.6 % [SD 23.5 %], P < 0.001, respectively). There was no statistically significant difference in the SAE rates for ESG-NFS (n = 2; 2.0 %) and ESG-FS (n = 4; 2.6 %; P > 0.99). The mean procedure time was significantly shorter in the ESG-NFS group at 59.1 minutes (SD 32.7) vs. 93.0 minutes (35.5; P < 0.001), and a lower mean number of sutures were used, with 5.7 (SD 1.1) vs. 8.4 (SD 1.6; P < 0.001). CONCLUSION : ESG-NFS demonstrated greater efficacy and shorter procedure duration. Therefore, fundal suturing should not be performed.

Safety of different electrocautery modes for endoscopic sphincterotomy: a Bayesian network meta-analysis.

BACKGROUND AND AIMS: Post-endoscopic retrograde cholangiopancreatography acute pancreatitis (PAP) and post-sphincterotomy hemorrhage are known adverse events of post-endoscopic retrograde cholangiopancreatography. Various electrosurgical currents can be used for endoscopic sphincterotomy. The extent to which this influences adverse events remains unclear. We assessed the comparative safety of different electrosurgical currents, through a Bayesian network meta-analysis of published studies merging direct and indirect comparison of trials. METHODS: We performed a Bayesian random-effects network meta-analysis of randomized controlled trials that compared the safety of different electrocautery modes for endoscopic sphincterotomy. RESULTS: Nine studies comparing four electrocautery modes (blended cut, pure cut, endocut, and pure cut followed by blended cut) with a combined enrollment of 1615 patients were included. The pooled results of the network meta-analysis did not show a significant difference in preventing post-sphincterotomy pancreatitis when comparing electrocautery modes. However, pure cut was associated with a statistically significant increased risk of bleeding compared with endocut [relative risk = 4.30; 95% confidence interval (1.53-12.87)]. On the other hand, the pooled results of the network meta-analysis showed no significant difference in prevention of bleeding when comparing blended cut versus endocut, pure cut followed by blended cut versus endocut, pure cut followed by blended cut versus blended cut, pure cut versus blended cut, and pure cut versus pure cut followed by blended cut. The results of rank probability found that endocut was most likely to be ranked the best. CONCLUSION: No electrocautery mode was superior to another with regard to preventing PAP. Endocut was superior with respect to preventing bleeding. Therefore, we suggest performing endoscopic sphincterotomy with endocut.

Transoral outlet reduction: could additional sutures cause more harm?

BACKGROUND: The double purse-string pattern (DPSP) of transoral outlet reduction (TORe) should conceivably result in a more robust scaffolding for the gastrojejunal anastomosis (GJA). However, there is a paucity of literature pertaining to post-TORe stenosis as an adverse event. Our aim was to determine the rate of stenosis, its potential predictors, and other complications of DPSP TORe. METHODS: We performed a retrospective analysis of a prospectively maintained database of 129 consecutive patients who underwent DPSP TORe between December 2015 and August 2019. RESULTS: The adverse event rate of TORe was 17.1 % (n = 22), with a 13.3 % (n = 17) rate of stenosis. Stenosis was not significantly associated with any baseline characteristics. GJA diameter pre- and post-TORe, the difference between these values, and procedure duration were not predictive of stenosis. Of patients who developed stenosis, 10 (58.8 %) responded to endoscopic balloon dilation and 7 (41.2 %) required stent placement. CONCLUSION: As the DPSP technique is a challenging procedure, with high complication rate and limited benefit, it should not be used for TORe.

Efficacy of Liraglutide to Prevent Weight Regain After Retrieval of an Adjustable Intra-gastric Balloon-a Case-Matched Study.

PURPOSE: Weight regain after balloon retrieval is a concern with all intra-gastric balloons (IGBs). The aim of this study was to evaluate the efficacy of liraglutide, a glucagon-like peptide-1 (GLP-1) agonist, to prevent weight regain following IGB retrieval. MATERIALS AND METHODS: This was a case-matched study of patients undergoing Spatz3 adjustable IGB (Spatz FGIA, Inc. NY, USA) at three outpatient clinics in Brazil between November 2015 and January 2019. Seventy-seven patients that opted to take liraglutide following IGB retrieval (IGB-L) were matched 1:1 to 198 patients that declined the medication-IGB-Alone (IGB-A). Propensity score adjustment was performed at the time of balloon retrieval on factors known to influence the choice of liraglutide. Weight and percent body fat (%BF) was measured at baseline and 9 months after IGB retrieval. % BF is defined as the total mass of fat divided by total body mass, multiplied by 100. The primary outcome was weight regain, and the secondary outcome was change in %BF 9 months after IGB retrieval. RESULTS: Propensity score matching yielded 53 matched pairs. Weight regain to the starting point was not observed in either group. There was significantly less weight regain in IGB-L compared to IGB-A, - 1.15 ± 0.94 kg versus - 0.66 ± 0.99 kg (p = 0.010) 9 months after balloon retrieval. Additionally, %BF decline in IGB-L was superior to IGB-A - 10.83 ± 1.50 versus - 7.94 ± 2.02 (p < 0.01). There was no difference in weight regain or decline in %BF based on liraglutide dose. CONCLUSION: Liraglutide has an additive benefit with respect to efficacy and a reduction in body fat when commenced after IGB retrieval. Future randomized control studies will be needed to determine the optimal dose and duration of liraglutide to achieve superior outcomes.

Endoscopic sleeve gastroplasty plus liraglutide versus endoscopic sleeve gastroplasty alone for weight loss.

BACKGROUND AND AIMS: Endoscopic sleeve gastroplasty (ESG) has been shown to be effective for inducing weight loss. The efficacy of liraglutide, a glucagon-like peptide-1 agonist, to augment weight loss after ESG is unknown. This study aims to evaluate the efficacy of ESG and liraglutide (ESG-L) compared with ESG alone. METHODS: This was a retrospective study of prospectively collected data from patients undergoing ESG at 3 outpatient clinics in Brazil between November 2017 and July 2018. Liraglutide was offered to all patients 5 months after ESG. Patients who opted to take liraglutide (ESG-L) were matched 1:1 to patients who declined it (ESG). The primary outcome was percent total body weight loss (%TBWL), and percent excess weight loss (%EWL) 7 months after initiation of liraglutide (12 months after ESG). The secondary outcome was change in percent body fat 12 months after ESG. ESG technique and postprocedure follow-up were identical at all 3 sites. RESULTS: Propensity score matching yielded 26 matched pairs. Adjusted comparisons between the 2 groups showed that patients who opted to take liraglutide had a superior mean %TBWL 7 months after initiation of liraglutide (ESG-L) compared with those who declined it (ESG) (24.72% ± 2.12% vs 20.51% ± 1.68%, respectively; P < .001). ESG-L had a statistically greater reduction in percent body fat compared with ESG (7.85% ± 1.26% vs 10.54% ± 1.88%, respectively; P < .001) at 12 months. CONCLUSIONS: Addition of liraglutide at 5 months results in superior weight loss and improved efficacy as demonstrated by decreased body fat 12 months after ESG. Further studies are imperative to determine optimal dose, timing, and duration of liraglutide.

Endobariatrics and Metabolic Endoscopy: Can We Solve the Obesity Epidemic with Our Scope?

PURPOSE OF REVIEW: Obesity is a chronic relapsing disease that results in cardiovascular disease, diabetes mellitus, and non-alcoholic fatty liver disease. Currently, surgery represents the most effective treatment. However, the advent of minimally invasive endoscopic bariatric therapy (EBT) has shifted the treatment paradigm to less invasive, cost-effective procedures with minimal complications and recovery time that are preferred by patients. In this review, we will describe current and future EBTs, focusing on outcomes and safety. RECENT FINDINGS: The endoscope has provided an incisionless portal into the gastrointestinal tract for placement of space-occupying devices and intraluminal procedures. EBTs are no longer solely manipulating anatomic alterations; instead, they aim to improve metabolic parameters such as glycated hemoglobin, low-density lipoprotein, cholesterol, and hepatic indices by targeting the mucosal layer of the gastrointestinal tract. The endoscope has succeeded in facilitating clinically meaningful weight loss and improvement of metabolic parameters. Future, solutions to the obesity epidemic will likely entail genetic testing, evaluation of the microbiome, and delivery of personalized therapy, utilizing combination endoscopic modalities that change the anatomy and physiology of individual patients, with new targets such as the abnormal metabolic signal.