Bariatric surgery partially reverses subclinical proarrhythmic structural, electrophysiological, and autonomic changes in obesity.

BACKGROUND: Obesity confers higher risks of cardiac arrhythmias. The extent to which weight loss reverses subclinical proarrhythmic adaptations in arrhythmia-free obese individuals is unknown. OBJECTIVE: The purpose of this study was to study structural, electrophysiological, and autonomic remodeling in arrhythmia-free obese patients and their reversibility with bariatric surgery using electrocardiographic imaging (ECGi). METHODS: Sixteen arrhythmia-free obese patients (mean age 43 ± 12 years; 13 (81%) female participants; BMI 46.7 ± 5.5 kg/m2) had ECGi pre-bariatric surgery, of whom 12 (75%) had ECGi postsurgery (BMI 36.8 ± 6.5 kg/m2). Sixteen age- and sex-matched lean healthy individuals (mean age 42 ± 11 years; BMI 22.8 ± 2.6 kg/m2) acted as controls and had ECGi only once. RESULTS: Obesity was associated with structural (increased epicardial fat volumes and left ventricular mass), autonomic (blunted heart rate variability), and electrophysiological (slower atrial conduction and steeper ventricular repolarization time gradients) remodeling. After bariatric surgery, there was partial structural reverse remodeling, with a reduction in epicardial fat volumes (68.7 cm3 vs 64.5 cm3; P = .0010) and left ventricular mass (33 g/m2.7 vs 25 g/m2.7; P < .0005). There was also partial electrophysiological reverse remodeling with a reduction in mean spatial ventricular repolarization gradients (26 mm/ms vs 19 mm/ms; P = .0009), although atrial activation remained prolonged. Heart rate variability, quantified by standard deviation of successive differences in R-R intervals, was also partially improved after bariatric surgery (18.7 ms vs 25.9 ms; P = .017). Computational modeling showed that presurgical obese hearts had a larger window of vulnerability to unidirectional block and had an earlier spiral-wave breakup with more complex reentry patterns than did postsurgery counterparts. CONCLUSION: Obesity is associated with adverse electrophysiological, structural, and autonomic remodeling that is partially reversed after bariatric surgery. These data have important implications for bariatric surgery weight thresholds and weight loss strategies.

Bariatric surgery for spontaneous ovulation in women living with polycystic ovary syndrome: the BAMBINI multicentre, open-label, randomised controlled trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Obesity exacerbates the reproductive complications of PCOS; however, the management of obesity in women with PCOS remains a large unmet clinical need. Observational studies have indicated that bariatric surgery could improve the rates of ovulatory cycles and prospects of fertility; however, the efficacy of surgery on ovulation rates has not yet been compared with behavioural modifications and medical therapy in a randomised trial. The aim of this study was to compare the safety and efficacy of bariatric surgery versus medical care on ovulation rates in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. METHODS: In this multicentre, open-label, randomised controlled trial, 80 women older than 18 years, with a diagnosis of PCOS based on the 2018 international evidence-based guidelines for assessing and managing PCOS, and a BMI of 35 kg/m2 or higher, were recruited from two specialist obesity management centres and via social media. Participants were randomly assigned at a 1:1 ratio to either vertical sleeve gastrectomy or behavioural interventions and medical therapy using a computer-generated random sequence (PLAN procedure in SAS) by an independent researcher not involved with any other aspect of the clinical trial. The median age of the entire cohort was 31 years and 79% of participants were White. The primary outcome was the number of biochemically confirmed ovulatory events over 52 weeks, and was assessed using weekly serum progesterone measurements. The primary endpoint included the intention-to-treat population and safety analyses were per-protocol population. This study is registered with the ISRCTN registry (ISRCTN16668711). FINDINGS: Participants were recruited from Feb 20, 2020 to Feb 1, 2021. 40 participants were assigned to each group and there were seven dropouts in the medical group and ten dropouts in the surgical group. The median number of ovulations was 6 (IQR 3·5-10·0) in the surgical group and 2 (0·0-4·0) in the medical group. Women in the surgical group had 2.5 times more spontaneous ovulations compared with the medical group (incidence rate ratio 2·5 [95% CI 1·5-4·2], p<0·0007). There were more complications in the surgical group than the medical group, although without long-term sequelae. There were 24 (66·7%) adverse events in the surgical group and 12 (30·0%) in the medical group. There were no treatment-related deaths. INTERPRETATION: Bariatric surgery was more effective than medical care for the induction of spontaneous ovulation in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. Bariatric surgery could, therefore, enhance the prospects of spontaneous fertility in this group of women. FUNDING: The Jon Moulton Charity Trust.

Impact of insulin sensitization on metabolic and fertility outcomes in women with polycystic ovary syndrome and overweight or obesity-A systematic review, meta-analysis, and meta-regression.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. This systematic review, meta-analysis, and meta-regression aims to compare the effect of insulin sensitizer pharmacotherapy on metabolic and reproductive outcomes in women with PCOS and overweight or obesity. We searched online databases MEDLINE via OVID, EMBASE, Clinicaltrials.gov, and EudraCT for trials published from inception to November 13, 2023. Inclusion criteria were double-blind, randomized controlled trials in women diagnosed with PCOS, body mass index (BMI) ≥ 25 kg/m2, which reported metabolic or reproductive outcomes. The intervention was insulin sensitization pharmacotherapy versus placebo or other agents. The primary outcomes were changes from baseline BMI, fasting blood glucose, and menstrual frequency. Nineteen studies were included in this review. Metformin had the most significant effect on the fasting plasma glucose and body mass index. Insulin sensitizer pharmacotherapy significantly reduced fasting plasma glucose, body mass index, fasting serum insulin, HOMA-IR, sex hormone binding globulin, and total testosterone, but the effect size was small. There was a lack of menstrual frequency and live birth data. The results indicate a role for insulin sensitizers in improving the metabolic and, to a lesser degree, reproductive profile in these women. Further research should examine insulin sensitizers' effects on objective measures of fecundity.

Risk Factors for Chronic Abdominal Pain After RYGB: Are Patients Adequately Selected Beforehand?

PURPOSE: Chronic abdominal pain after RYGB is a known issue. Identifying the potential patient-related and modifiable risk factors might contribute to diminish the risk for this undesirable outcome. METHODS: A single-center retrospective cohort study with prospective data collection was conducted with inclusion of all patients who underwent RYGB surgery between 2015 and 2021. Data from the NBSR and medical records were used. Patients with chronic abdominal pain were defined when pain lasting or recurring for more than 3 to 6 months. RESULTS: Six hundred sixty-four patients who underwent RYGB surgery were included with a median follow-up of 60.5 months. Forty-nine patients (7.3%) presented with chronic abdominal pain. Postoperative complications (OR 13.376, p = 0.020) and diagnosis of depression (OR 1.971, p = 0.037) were associated with developing abdominal pain. On the other hand, ex-smokers (OR 0.222, p = 0.040) and older age (0.959, p = 0.004) presented as protective factors. CONCLUSION: Postoperative complications and diagnosis of depression are risk factors for chronic pain after RYGB. The role of the bariatric MDT remains crucial to select these patients adequately beforehand.

Multi-tissue profiling of oxylipins reveal a conserved up-regulation of epoxide:diol ratio that associates with white adipose tissue inflammation and liver steatosis in obesity.

BACKGROUND: Obesity drives maladaptive changes in the white adipose tissue (WAT) which can progressively cause insulin resistance, type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated liver disease (MASLD). Obesity-mediated loss of WAT homeostasis can trigger liver steatosis through dysregulated lipid pathways such as those related to polyunsaturated fatty acid (PUFA)-derived oxylipins. However, the exact relationship between oxylipins and metabolic syndrome remains elusive and cross-tissue dynamics of oxylipins are ill-defined. METHODS: We quantified PUFA-related oxylipin species in the omental WAT, liver biopsies and plasma of 88 patients undergoing bariatric surgery (female N = 79) and 9 patients (female N = 4) undergoing upper gastrointestinal surgery, using UPLC-MS/MS. We integrated oxylipin abundance with WAT phenotypes (adipogenesis, adipocyte hypertrophy, macrophage infiltration, type I and VI collagen remodelling) and the severity of MASLD (steatosis, inflammation, fibrosis) quantified in each biopsy. The integrative analysis was subjected to (i) adjustment for known risk factors and, (ii) control for potential drug-effects through UPLC-MS/MS analysis of metformin-treated fat explants ex vivo. FINDINGS: We reveal a generalized down-regulation of cytochrome P450 (CYP)-derived diols during obesity conserved between the WAT and plasma. Notably, epoxide:diol ratio, indicative of soluble epoxide hydrolyse (sEH) activity, increases with WAT inflammation/fibrosis, hepatic steatosis and T2DM. Increased 12,13-EpOME:DiHOME in WAT and liver is a marker of worsening metabolic syndrome in patients with obesity. INTERPRETATION: These findings suggest a dampened sEH activity and a possible role of fatty acid diols during metabolic syndrome in major metabolic organs such as WAT and liver. They also have implications in view of the clinical trials based on sEH inhibition for metabolic syndrome. FUNDING: Wellcome Trust (PS3431_WMIH); Duke-NUS (Intramural Goh Cardiovascular Research Award (Duke-NUS-GCR/2022/0020); National Medical Research Council (OFLCG22may-0011); National Institute of Environmental Health Sciences (Z01 ES025034); NIHR Imperial Biomedical Research Centre.

Society for Endocrinology guidelines for the diagnosis and management of post-bariatric hypoglycaemia.

Post bariatric hypoglycaemia (PBH) is typically a post-prandial hypoglycaemia occurring about 2-4 hours after eating in people who have undergone bariatric surgery. PBH develops relatively late after surgery and often after discharge from post-surgical follow-up by bariatric teams, leading to variability in diagnosis and management in non-specialist centres. AIM: to improve and standardise clinical practice in the diagnosis and management of PBH. OBJECTIVES: (1) to undertake an up-to-date review of the current literature; (2) to formulate practical and evidence-based guidance with regards on the diagnosis and treatment of PBH; (3) to recommend future avenues for research in this condition. METHOD: A scoping review was undertaken after an extensive literature search. A consensus on the guidance and confidence in the recommendations was reached by the steering group authors prior to review by key stakeholders. OUTCOME: We make pragmatic recommendations for the practical diagnosis and management of PBH including criteria for diagnosis and recognition, as well as recommendations for research areas that should be explored.

Oligogenic inheritance in severe adult obesity.

BACKGROUND/OBJECTIVE: The genetic architecture of extreme non-syndromic obesity in adults remains to be elucidated. A range of genes are known to cause monogenic obesity, but even when pathogenic mutations are present, there may be variable penetrance. METHODS: Whole-exome sequencing (WES) was carried out on a 15-year-old male proband of Pakistani ancestry who had severe obesity. This was followed by family segregation analysis, using Sanger sequencing. We also undertook re-analysis of WES data from 91 unrelated adults with severe obesity (86% white European ancestry) from the Personalised Medicine for Morbid Obesity (PMMO) cohort, recruited from the UK National Health Service. RESULTS: We identified an oligogenic mode of inheritance of obesity in the proband's family-this provided the impetus to reanalyze existing sequence data in a separate dataset. Analysis of PMMO participant data revealed two further patients who carried more than one rare, predicted-deleterious mutation in a known monogenic obesity gene. In all three cases, the genes involved had known autosomal dominant inheritance, with incomplete penetrance. CONCLUSION: Oligogenic inheritance may explain some of the variable penetrance in Mendelian forms of obesity. We caution clinicians and researchers to avoid confining sequence analysis to individual genes and, in particular, not to stop looking when the first potentially-causative mutation is found.

Increased glycemic variability in pregnant women with Roux-en-Y gastric bypass compared with sleeve gastrectomy.

INTRODUCTION: Bariatric surgery is associated with adverse pregnancy outcomes such as reduced birth weight and premature birth. One possible mechanism for this is increased glycemic variability (GV) which occurs after bariatric surgery. The objective of this study was to compare the effect of Roux-en-Y gastric bypass (RYGB) versus vertical sleeve gastrectomy (SG) on GV during pregnancy and to investigate the relationships of GV, type of bariatric surgery and maternal and neonatal outcomes. RESEARCH DESIGN AND METHODS: Fourteen pregnant women after RYGB and 14 after SG were investigated with continuous glucose monitoring in their second or third trimester in this observational study carried out as part of routine clinical care. RESULTS: Pregnant women with RYGB had similar mean interstitial glucose values but significantly increased indices of GV and a lower %time in range 3.9-7.8 mmol/L (70-140 mg/dL), compared with SG. CONCLUSIONS: Pregnant women who have undergone RYGB have greater GV during pregnancy compared with those who have undergone SG. Further research is needed to establish the relationship between GV and pregnancy outcomes to determine the preferred bariatric operation in women of reproductive age, and whether interventions to reduce GV might improve outcomes.

Improvements in Sperm Motility Following Low- or High-Intensity Dietary Interventions in Men With Obesity.

INTRODUCTION: Obesity increases risks of male infertility, but bariatric surgery does not improve semen quality. Recent uncontrolled studies suggest that a low-energy diet (LED) improves semen quality. Further evaluation within a randomized, controlled setting is warranted. METHODS: Men with obesity (18-60 years) with normal sperm concentration (normal count) (n = 24) or oligozoospermia (n = 43) were randomized 1:1 to either 800 kcal/day LED for 16 weeks or control, brief dietary intervention (BDI) with 16 weeks' observation. Semen parameters were compared at baseline and 16 weeks. RESULTS: Mean age of men with normal count was 39.4 ± 6.4 in BDI and 40.2 ± 9.6 years in the LED group. Mean age of men with oligozoospermia was 39.5 ± 7.5 in BDI and 37.7 ± 6.6 years in the LED group. LED caused more weight loss than BDI in men with normal count (14.4 vs 6.3 kg; P < .001) and men with oligozoospermia (17.6 vs 1.8 kg; P < .001). Compared with baseline, in men with normal count total motility (TM) increased 48 ± 17% to 60 ± 10% (P < .05) after LED, and 52 ± 8% to 61 ± 6% (P < .0001) after BDI; progressive motility (PM) increased 41 ± 16% to 53 ± 10% (P < .05) after LED, and 45 ± 8% to 54 ± 65% (P < .001) after BDI. In men with oligozoospermia compared with baseline, TM increased 35% [26] to 52% [16] (P < .05) after LED, and 43% [28] to 50% [23] (P = .0587) after BDI; PM increased 29% [23] to 46% [18] (P < .05) after LED, and 33% [25] to 44% [25] (P < .05) after BDI. No differences in postintervention TM or PM were observed between LED and BDI groups in men with normal count or oligozoospermia. CONCLUSION: LED or BDI may be sufficient to improve sperm motility in men with obesity. The effects of paternal dietary intervention on fertility outcomes requires investigation.

Perceptions and priorities of perioperative staff and the public for sustainable surgery: a validated questionnaire study.

Surgery is a substantial contributor to healthcare-related emissions. Despite a drive to improve sustainability, few interventions have been adopted. Stakeholder engagement is considered a key barrier to implementation. This study aimed to determine the attitudes and beliefs of the perioperative staff and the public regarding sustainability initiatives in surgery, and whether differences exist between the two groups. Materials and Methods: Separate validated healthcare professional and public questionnaires were developed using a stepwise process. A systematic review was undertaken using Medline, Embase and Cochrane to identify key domains pertaining to sustainability and ensure content validity. Initial questionnaires were developed and refined using an iterative process of feedback from focus groups. Psychometric validation was conducted to remove question ambiguity. The final validated questionnaire was distributed to perioperative staff and the public using a multimodal approach involving online tools and in person. Results: Only 37.1% of perioperative staff reported the implementation of sustainability initiatives in their departments. Yet, staff (45.7%) and the public (48.2%) somewhat agreed that sustainability should influence a surgeon's procedural decision-making. Insufficient staff education regarding sustainability was a potential cause for the lack of adoption, with 71.4% reporting they had no formal training. Moreover, discrepancies in the perceived importance of sustainability may have contributed. Staff and the public agreed that outcomes (38.6 vs. 42.7%, P=0.767) and surgeon experience with a technique (28.6 vs. 40.0%, P=0.082) were more important than sustainability. However, 40.9% of the public did not consider operative time an important factor compared to sustainability, while 45.7% of staff would only tolerate procedures 25% longer. Conclusions: Engaging stakeholders is central to implementing long-term environmentally sustainable initiatives in surgery without compromising patient outcomes. More work is needed to understand the relative trade-offs considered by perioperative staff and the public, as well as provide both groups with more pertinent education on ecological outcomes.

Interventions for sustainable surgery: a systematic review.

OBJECTIVE: To systematically evaluate interventions designed to improve the sustainability of surgical practice with respect to their environmental and financial impact. BACKGROUND: Surgery contributes significantly to emissions attributed to healthcare due to its high resource and energy use. Several interventions across the operative pathway have, therefore, been trialed to minimize this impact. Few comparisons of the environmental and financial effects of these interventions exist. MATERIALS AND METHODS: A search of studies published up to 2nd February 2022 describing interventions to increase surgical sustainability was undertaken. Articles regarding the environmental impact of only anesthetic agents were excluded. Data regarding environmental and financial outcomes were extracted with a quality assessment completed dependent upon the study design. RESULTS: In all, 1162 articles were retrieved, of which 21 studies met inclusion criteria. Twenty-five interventions were described, which were categorized into five domains: 'reduce and rationalize', 'reusable equipment and textiles', 'recycling and waste segregation', 'anesthetic alternatives', and 'other'. Eleven of the 21 studies examined reusable devices; those demonstrating a benefit reported 40-66% lower emissions than with single-use alternatives. In studies not showing a lower carbon footprint, the reduction in manufacturing emissions was offset by the high environmental impact of local fossil fuel-based energy required for sterilization. The per use monetary cost of reusable equipment was 47-83% of the single-use equivalent. CONCLUSIONS: A narrow repertoire of interventions to improve the environmental sustainability of surgery has been trialed. The majority focuses on reusable equipment. Emissions and cost data are limited, with longitudinal impacts rarely investigated. Real-world appraisals will facilitate implementation, as will an understanding of how sustainability impacts surgical decision-making.

Tripeptide gut hormone infusion does not alter food preferences or sweet taste function in volunteers with obesity and prediabetes/diabetes but promotes restraint eating: A secondary analysis of a randomized single-blind placebo-controlled study.

AIMS: To investigate whether the elevation in postprandial concentrations of the gut hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM) and peptide YY (PYY) accounts for the beneficial changes in food preferences, sweet taste function and eating behaviour after Roux-en-Y gastric bypass (RYGB). MATERIALS AND METHODS: This was a secondary analysis of a randomized single-blind study in which we infused GLP-1, OXM, PYY (GOP) or 0.9% saline subcutaneously for 4 weeks in 24 subjects with obesity and prediabetes/diabetes, to replicate their peak postprandial concentrations, as measured at 1 month in a matched RYGB cohort (ClinicalTrials.gov NCT01945840). A 4-day food diary and validated eating behaviour questionnaires were completed. Sweet taste detection was measured using the method of constant stimuli. Correct sucrose identification (corrected hit rates) was recorded, and sweet taste detection thresholds (EC50s: half maximum effective concencration values) were derived from concentration curves. The intensity and consummatory reward value of sweet taste were assessed using the generalized Labelled Magnitude Scale. RESULTS: Mean daily energy intake was reduced by 27% with GOP but no significant changes in food preferences were observed, whereas a reduction in fat and increase in protein intake were seen post-RYGB. There was no change in corrected hit rates or detection thresholds for sucrose detection following GOP infusion. Additionally, GOP did not alter the intensity or consummatory reward value of sweet taste. A significant reduction in restraint eating, comparable to the RYGB group was observed with GOP. CONCLUSION: The elevation in plasma GOP concentrations after RYGB is unlikely to mediate changes in food preferences and sweet taste function after surgery but may promote restraint eating.

Bariatric Surgery and Incident Heart Failure: a Propensity Score Matched Nationwide Cohort Study.

BACKGROUND: Bariatric surgery results in significant weight loss and a reduction in the incidence of cardiovascular disease in patients with obesity; however, relatively little research considers its effect on the incidence of heart failure (HF). We aimed to determine whether bariatric surgery reduces the incidence of HF in patients with obesity, compared to non-surgical management. METHODS: A propensity-score matched, retrospective cohort study using patients records from the nationwide Clinical Practice Research Database (CPRD) was conducted. 3052 patients who received bariatric surgery were matched with 3052 patients who did not, according to propensity to receive bariatric surgery, determined through a logistic regression model. Patients were eligible if >18 years old, BMI > 35 kg/m2, and no prior diagnosis of HF. The pre-defined primary endpoint was the development of new HF, and secondary endpoints were all-cause mortality and hospitalisations due to HF. RESULTS: Patients who received bariatric surgery had a significantly lower incidence of new HF (hazard ratio 0.45, 95% confidence interval 0.28-0.73, p = 0.0011) and all-cause mortality (hazard ratio 0.56, 95% confidence interval 0.38-0.83, p = 0.0036). CONCLUSIONS: This study provides evidence of lower rates of HF and all-cause mortality in patients who undergo bariatric surgery, compared to propensity-score matched controls. Future studies to understand the mechanism(s) involved in this reduction and explore the lifetime benefits in high-risk cohorts are paramount.

The postprandial secretion of peptide YY1-36 and 3-36 in obesity is differentially increased after gastric bypass versus sleeve gastrectomy.

OBJECTIVES: Peptide tyrosine tyrosine (PYY) exists as two species, PYY1-36 and PYY3-36 , with distinct effects on insulin secretion and appetite regulation. The detailed effects of bariatric surgery on PYY1-36 and PYY3-36 secretion are not known as previous studies have used nonspecific immunoassays to measure total PYY. Our objective was to characterize the effect of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on fasting and postprandial PYY1-36 and PYY3-36 secretion using a newly developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. DESIGN AND SUBJECTS: Observational study in 10 healthy nonobese volunteers and 30 participants with obesity who underwent RYGB (n = 24) or SG (n = 6) at the Imperial Weight Centre [NCT01945840]. Participants were studied using a standardized mixed meal test (MMT) before and 1 year after surgery. The outcome measures were PYY1-36 and PYY3-36 concentrations. RESULTS: Presurgery, the fasting and postprandial levels of PYY1-36 and PYY3-36 were low, with minimal responses to the MMT, and these did not differ from healthy nonobese volunteers. The postprandial secretion of both PYY1-36 and PYY3-36 at 1 year was amplified after RYGB, but not SG, with the response being significantly higher in RYGB compared with SG. CONCLUSIONS: There appears to be no difference in PYY secretion between nonobese and obese volunteers at baseline. At 1 year after surgery, RYGB, but not SG, is associated with increased postprandial secretion of PYY1-36 and PYY3-36 , which may account for long-term differences in efficacy and adverse effects between the two types of surgery.

Apnoeic oxygenation in morbid obesity: a randomised controlled trial comparing facemask and high-flow nasal oxygen delivery.

BACKGROUND: Obesity is a risk factor for airway-related incidents during anaesthesia. High-flow nasal oxygen has been advocated to improve safety in high-risk groups, but its effectiveness in the obese population is uncertain. This study compared the effect of high-flow nasal oxygen and low-flow facemask oxygen delivery on duration of apnoea in morbidly obese patients. METHODS: Morbidly obese patients undergoing bariatric surgery were randomly allocated to receive either high-flow nasal (70 L min-1) or facemask (15 L min-1) oxygen. After induction of anaesthesia, the patients were apnoeic for 18 min or until peripheral oxygen saturation decreased to 92%. RESULTS: Eighty patients were studied (41 High-Flow Nasal Oxygen, 39 Facemask). The median apnoea time was 18 min in both the High-Flow Nasal Oxygen (IQR 18-18 min) and the Facemask (inter-quartile range [IQR], 4.1-18 min) groups. Five patients in the High-Flow Nasal Oxygen group and 14 patients in the Facemask group desaturated to 92% within 18 min. The risk of desaturation was significantly lower in the High-Flow Nasal Oxygen group (hazard ratio=0.27; 95% confidence interval [CI], 0.11-0.65; P=0.007). CONCLUSIONS: In experienced hands, apnoeic oxygenation is possible in morbidly obese patients, and oxygen desaturation did not occur for 18 min in the majority of patients, whether oxygen delivery was high-flow nasal or low-flow facemask. High-flow nasal oxygen may reduce desaturation risk compared with facemask oxygen. Desaturation risk is a more clinically relevant outcome than duration of apnoea. Individual physiological factors are likely to be the primary determinant of risk rather than method of oxygen delivery. CLINICAL TRIAL REGISTRATION: NCT03428256.

Multi-omic phenotyping reveals host-microbe responses to bariatric surgery, glycaemic control and obesity.

Background: Resolution of type 2 diabetes (T2D) is common following bariatric surgery, particularly Roux-en-Y gastric bypass. However, the underlying mechanisms have not been fully elucidated. Methods: To address this we compare the integrated serum, urine and faecal metabolic profiles of participants with obesity ± T2D (n = 80, T2D = 42) with participants who underwent Roux-en-Y gastric bypass or sleeve gastrectomy (pre and 3-months post-surgery; n = 27), taking diet into account. We co-model these data with shotgun metagenomic profiles of the gut microbiota to provide a comprehensive atlas of host-gut microbe responses to bariatric surgery, weight-loss and glycaemic control at the systems level. Results: Here we show that bariatric surgery reverses several disrupted pathways characteristic of T2D. The differential metabolite set representative of bariatric surgery overlaps with both diabetes (19.3% commonality) and body mass index (18.6% commonality). However, the percentage overlap between diabetes and body mass index is minimal (4.0% commonality), consistent with weight-independent mechanisms of T2D resolution. The gut microbiota is more strongly correlated to body mass index than T2D, although we identify some pathways such as amino acid metabolism that correlate with changes to the gut microbiota and which influence glycaemic control. Conclusion: We identify multi-omic signatures associated with responses to surgery, body mass index, and glycaemic control. Improved understanding of gut microbiota - host co-metabolism may lead to novel therapies for weight-loss or diabetes. However, further experiments are required to provide mechanistic insight into the role of the gut microbiota in host metabolism and establish proof of causality.

Length of biliopancreatic limb in Roux-en-Y gastric bypass and its impact on post-operative outcomes in metabolic and obesity surgery-systematic review and meta-analysis.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is a gold-standard procedure for treatment of obesity and associated comorbidities. No consensus on the optimal design of this operation has been achieved, with various lengths of bypassed small bowel limb lengths being used by bariatric surgeons. This aim of this systematic review and meta-analysis was to determine whether biliopancreatic limb (BPL) length in RYGB affects postoperative outcomes including superior reduction in weight, body mass index (BMI), and resolution of metabolic comorbidities associated with obesity. METHODS: A systematic search of the literature was conducted up until 1st June 2021. Meta-analysis of primary outcomes was performed utilising a random-effects model. Statistical significance was determined by p value < 0.05. RESULTS: Ten randomised controlled trials were included in the final quantitative analysis. No difference in outcomes following short versus long BLP in RYGB was identified at 12-72 months post-operatively, namely in BMI reduction, remission or improvement of type 2 diabetes mellitus, hypertension, dyslipidaemia, and complications (p > 0.05). Even though results of four studies showed superior total body weight loss in the long BPL cohorts at 24 months post-operatively (pooled mean difference -6.92, 95% CI -12.37, -1.48, p = 0.01), this outcome was not observed at any other timepoint. CONCLUSION: Based on the outcomes of the present study, there is no definitive evidence to suggest that alteration of the BPL affects the quantity of weight loss or resolution of co-existent metabolic comorbidities associated with obesity.

The first international Delphi consensus statement on Laparoscopic Gastrointestinal surgery.

BACKGROUND: Laparoscopic surgery has almost replaced open surgery in many areas of Gastro-Intestinal (GI) surgery. There is currently no published expert consensus statement on the principles of laparoscopic GI surgery. This may have affected the training of new surgeons. This exercise aimed to achieve an expert consensus on important principles of laparoscopic GI surgery. METHODS: A committee of 38 international experts in laparoscopic GI surgery proposed and voted on 149 statements in two rounds following a strict modified Delphi protocol. RESULTS: A consensus was achieved on 133 statements after two rounds of voting. All experts agreed on tailoring the first port site to the patient, whereas 84.2% advised avoiding the umbilical area for pneumoperitoneum in patients who had a prior midline laparotomy. Moreover, 86.8% agreed on closing all 15 mm ports irrespective of the patient's body mass index. There was a 100% consensus on using cartridges of appropriate height for stapling, checking the doughnuts after using circular staplers, and keeping the vibrating blade of the ultrasonic energy device in view and away from vascular structures. An 84.2% advised avoiding drain insertion through a ≥10 mm port site as it increases the risk of port-site hernia. There was 94.7% consensus on adding laparoscopic retrieval bags to the operating count and ensuring any surgical specimen left inside for later removal is added to the operating count. CONCLUSION: Thirty-eight experts achieved a consensus on 133 statements concerning various aspects of laparoscopic GI Surgery. Increased awareness of these could facilitate training and improve patient outcomes.

Increasing Adiposity Is Associated With QTc Interval Prolongation and Increased Ventricular Arrhythmic Risk in the Context of Metabolic Dysfunction: Results From the UK Biobank.

Background: Small-scale studies have linked obesity (Ob) and metabolic ill-health with proarrhythmic repolarisation abnormalities. Whether these are observed at a population scale, modulated by individuals' genetics, and confer higher risks of ventricular arrhythmias (VA) are not known. Methods and Results: Firstly, using the UK Biobank, the association between adiposity and QTc interval was assessed in participants with a resting 12-lead ECG (n = 23,683), and a polygenic risk score (PRS) was developed to investigate any modulatory effect of genetics. Participants were also categorised into four phenotypes according to the presence (+) or absence (-) of Ob, and if they were metabolically unhealthy (MU+) or not (MU-). QTc was positively associated with body mass index (BMI), body fat (BF), waist:hip ratio (WHR), and hip and waist girths. Individuals' genetics had no significant modulatory effect on QTc-prolonging effects of increasing adiposity. QTc interval was comparably longer in those with metabolic perturbation without obesity (Ob-MU+) and obesity alone (Ob+MU-) compared with individuals with neither (Ob-MU-), and their co-existence (Ob+MU+) had an additive effect on QTc interval. Secondly, for 502,536 participants in the UK Biobank, odds ratios (ORs) for VA were computed for the four clinical phenotypes above using their past medical records. Referenced to Ob-MU-, ORs for VA in Ob-MU+ men and women were 5.96 (95% CI: 4.70-7.55) and 5.10 (95% CI: 3.34-7.80), respectively. ORs for Ob+MU+ were 6.99 (95% CI: 5.72-8.54) and 3.56 (95% CI: 2.66-4.77) in men and women, respectively. Conclusion: Adiposity and metabolic perturbation increase QTc to a similar degree, and their co-existence exerts an additive effect. These effects are not modulated by individuals' genetics. Metabolic ill-health is associated with a higher OR for VA than obesity.