Rare Antagonistic Leptin Variants and Severe, Early-Onset Obesity.

Hormone absence or inactivity is common in congenital disease, but hormone antagonism remains controversial. Here, we characterize two novel homozygous leptin variants that yielded antagonistic proteins in two unrelated children with intense hyperphagia, severe obesity, and high circulating levels of leptin. Both variants bind to the leptin receptor but trigger marginal, if any, signaling. In the presence of nonvariant leptin, the variants act as competitive antagonists. Thus, treatment with recombinant leptin was initiated at high doses, which were gradually lowered. Both patients eventually attained near-normal weight. Antidrug antibodies developed in the patients, although they had no apparent effect on efficacy. No severe adverse events were observed. (Funded by the German Research Foundation and others.).

Nutritional Challenges and Treatment After Bariatric Surgery.

Bariatric surgery is an important weight loss tool in individuals with severe obesity. It is currently the most effective long-term weight loss treatment that lowers obesity-related comorbidities. It also has significant physiological and nutritional consequences that can result in gastrointestinal complications and micronutrient deficiencies. After gastric bypass, clinical events that negatively affect nutritional status include malabsorption, dumping syndrome, kidney stones, altered intestinal bile acid availability, bowel obstruction, ulcers, gastroesophageal reflux, and bacterial overgrowth. Risk factors for poor nutritional status and excessive loss of lean body mass and bone include reduced dietary quality and inadequate intake, altered nutrient absorption, and poor patient compliance with nutrient supplementation. There are unique concerns in adolescents, older individuals, and individuals who become pregnant postoperatively. With careful management, health-care professionals can assist with long-term weight loss success and minimize the risk of acute and long-term nutrition complications after bariatric surgery.

Antiretroviral Drug Exposure and Response in Obese and Morbidly Obese People With Human Immunodeficiency Virus (HIV): A Study Combining Modelling and Swiss HIV Cohort Data.

BACKGROUND: Obesity is increasingly prevalent among people with HIV (PWH) and can possibly result in suboptimal antiretroviral drug (ARV) exposure and response. However, this has not been thoroughly evaluated given that obese PWH are underrepresented in clinical trials. We performed virtual trials using physiologically based pharmacokinetic (PBPK) modelling combined with observed clinical data to provide ARV dosing guidance in obese individuals. METHODS: Each trial included a cohort of virtual adults with a body mass index (BMI) between 18.5 and 60 kg/m2. Therapeutic drug-monitoring data from the Swiss HIV Cohort Study (SHCS) were used to verify the predictive performance of the model. Subsequently, the model was applied to predict the pharmacokinetics of ARVs for different obesity classes. The association between ARV plasma concentrations and virological response was investigated in obese and nonobese individuals. RESULTS: The PBPK model predicted an average reduction in ARV exposure of ∼20% and trough concentrations of ∼6% in obese (BMI ≥30 kg/m2) compared with nonobese (BMI: 18.5-25 kg/m2) individuals, consistent with observed clinical data. Etravirine and rilpivirine were the most impacted, especially in individuals with BMI >40 kg/m2 whose trough concentrations were below the clinical target threshold. Obese PWH in the SHCS did not have a higher rate of unsuppressed viral load than nonobese PWH. CONCLUSIONS: The concentrations of ARVs are modestly reduced in obese individuals, with no negative impact on the virological response. Our data provide reassurance that standard doses of ARVs are suitable in obese PWH, including those who gained substantial weight with some of the first-line ARVs.

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.

Effect of resveratrol on insulin action in primary myotubes from lean individuals and individuals with severe obesity.

Resveratrol, a natural polyphenol compound contained in numerous plants, has been proposed as a treatment for obesity-related disease processes such as insulin resistance. However, in humans there are conflicting results concerning the efficacy of resveratrol in improving insulin action; the purpose of the present study was to determine whether obesity status (lean, severely obese) affects the response to resveratrol in human skeletal muscle. Primary skeletal muscle cells were derived from biopsies obtained from age-matched lean and insulin-resistant women with severe obesity and incubated with resveratrol (1 µM) for 24 h. Insulin-stimulated glucose oxidation and incorporation into glycogen, insulin signal transduction, and energy-sensitive protein targets [AMP-activated protein kinase (AMPK), Sirt1, and PGC1α] were analyzed. Insulin-stimulated glycogen synthesis, glucose oxidation, and AMPK phosphorylation increased with resveratrol incubation compared with the nonresveratrol conditions (main treatment effect for resveratrol). Resveratrol further increased IRS1, Akt, and TBC1D4 insulin-stimulated phosphorylation and SIRT1 content in myotubes from lean women, but not in women with severe obesity. Resveratrol improves insulin action in primary human skeletal myotubes derived from lean women and women with severe obesity. In women with obesity, these improvements may be associated with enhanced AMPK phosphorylation with resveratrol treatment.NEW & NOTEWORTHY A physiologically relevant dose of resveratrol increases insulin-stimulated glucose oxidation and glycogen synthesis in myotubes from individuals with severe obesity. Furthermore, resveratrol improved insulin signal transduction in myotubes from lean individuals but not from individuals with obesity. Activation of AMPK plays a role in resveratrol-induced improvements in glucose metabolism in individuals with severe obesity.

Body Contouring Surgery After Bariatric Surgery Improves Long-Term Health-Related Quality of Life and Satisfaction With Appearance: An International Longitudinal Cohort Study Using the BODY-Q.

OBJECTIVE: To examine health-related quality of life (HRQL) and satisfaction with appearance in patients who have undergone bariatric surgery (BS) with or without subsequent body contouring surgery (BCS) in relation to the general population normative for the BODY-Q. BACKGROUND: The long-term impact of BS with or without BCS has not been established using rigorously developed and validated patient-reported outcome measures. The BODY-Q is a patient-reported outcome measure developed to measure changes in HRQL and satisfaction with appearance in patients with BS and BCS. METHODS: Prospective BODY-Q data were collected from 6 European countries (Denmark, the Netherlands, Finland, Germany, Italy, and Poland) from June 2015 to February 2022 in a cohort of patients who underwent BS. Mixed-effects regression models were used to analyze changes in HRQL and appearance over time between patients who did and did not receive BCS and to examine the impact of patient-level covariates on outcomes. RESULTS: This study included 24,604 assessments from 5620 patients. BS initially led to improved HRQL and appearance scores throughout the first postbariatric year, followed by a gradual decrease. Patients who underwent subsequent BCS after BS experienced a sustained improvement in HRQL and appearance or remained relatively stable for up to 10 years postoperatively. CONCLUSIONS: Patients who underwent BCS maintained an improvement in HRQL and satisfaction with appearance in contrast to patients who only underwent BS, who reported a decline in scores 1 to 2 years postoperatively. Our results emphasize the pivotal role that BCS plays in the completion of the weight loss trajectory.

Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): a multicentre, open-label, randomised trial.

BACKGROUND: Observational studies suggest that bariatric-metabolic surgery might greatly improve non-alcoholic steatohepatitis (NASH). However, the efficacy of surgery on NASH has not yet been compared with the effects of lifestyle interventions and medical therapy in a randomised trial. METHODS: We did a multicentre, open-label, randomised trial at three major hospitals in Rome, Italy. We included participants aged 25-70 years with obesity (BMI 30-55 kg/m2), with or without type 2 diabetes, with histologically confirmed NASH. We randomly assigned (1:1:1) participants to lifestyle modification plus best medical care, Roux-en-Y gastric bypass, or sleeve gastrectomy. The primary endpoint of the study was histological resolution of NASH without worsening of fibrosis at 1-year follow-up. This study is registered at ClinicalTrials.gov, NCT03524365. FINDINGS: Between April 15, 2019, and June 21, 2021, we biopsy screened 431 participants; of these, 103 (24%) did not have histological NASH and 40 (9%) declined to participate. We randomly assigned 288 (67%) participants with biopsy-proven NASH to lifestyle modification plus best medical care (n=96 [33%]), Roux-en-Y gastric bypass (n=96 [33%]), or sleeve gastrectomy (n=96 [33%]). In the intention-to-treat analysis, the percentage of participants who met the primary endpoint was significantly higher in the Roux-en-Y gastric bypass group (54 [56%]) and sleeve gastrectomy group (55 [57%]) compared with lifestyle modification (15 [16%]; p<0·0001). The calculated probability of NASH resolution was 3·60 times greater (95% CI 2·19-5·92; p<0·0001) in the Roux-en-Y gastric bypass group and 3·67 times greater (2·23-6·02; p<0·0001) in the sleeve gastrectomy group compared with in the lifestyle modification group. In the per protocol analysis (236 [82%] participants who completed the trial), the primary endpoint was met in 54 (70%) of 77 participants in the Roux-en-Y gastric bypass group and 55 (70%) of 79 participants in the sleeve gastrectomy group, compared with 15 (19%) of 80 in the lifestyle modification group (p<0·0001). No deaths or life-threatening complications were reported in this study. Severe adverse events occurred in ten (6%) participants who had bariatric-metabolic surgery, but these participants did not require re-operations and severe adverse events were resolved with medical or endoscopic management. INTERPRETATION: Bariatric-metabolic surgery is more effective than lifestyle interventions and optimised medical therapy in the treatment of NASH. FUNDING: Fondazione Policlinico Universitario A Gemelli, Policlinico Universitario Umberto I and S Camillo Hospital, Rome, Italy.

Transoral Outlet Reduction: Expert Tips, Tricks, and Troubleshooting.

Transoral outlet reduction (TORe) is an incisionless, endoscopic procedure to address weight recurrence after Roux-en-Y gastric bypass. Given the chronic, progressive nature of obesity and the minimally invasive, anatomy preserving technique of TORe, the procedure is expected to be met with high patient acceptance and widening clinical adoption. Nevertheless, the approach to TORe has been heterogeneous. As endoscopic bariatric therapies are increasingly incorporated into the multidisciplinary management of obesity, it is crucial to have a standardized, evidence-based framework for their implementation. In this review, based on the available literature and the authors' combined experience of over 1,000 TORe procedures, we present our approach to patient selection, procedural technique, troubleshooting, and patient aftercare unique to TORe.

Use of Impedance Planimetry in the Diagnosis of Gastric Sleeve Stenosis: The Establishment of New Benchmark Values.

INTRODUCTION: Gastric sleeve stenosis (GSS) is an increasingly common adverse event following sleeve gastrectomy for which objective diagnostic criteria are lacking. Impedance planimetry measurements show promise in characterizing GSS, though normal and abnormal benchmark values have never been established. METHODS: This was a retrospective analysis of upper endoscopies performed with impedance planimetry for suspected GSS. A bariatric endoscopist, blind to impedance planimetry measurements, assessed gastric sleeve anatomy and graded GSS severity. Impedance planimetry of diameter and distensibility index (DI) were obtained using 3 different balloon volumes (30, 40, and 50 mL). RESULTS: A total of 110 upper endoscopies were included. Distribution of GSS was graded as none, mild, moderate, and severe in 19 (17%), 27 (25%), 34 (31%), and 30 (27%) procedures, respectively. In normal gastric sleeve anatomy, mean (±SD) diameter and DI measurements using consecutive balloon volumes ranged from 19.1 (±5.5) to 23.2 (±1.7) and 16.8 (±4.9) to 23.1 (±10.9), respectively. In severe GSS, mean diameter and DI measurements ranged from 10.3 (±3.0) to 16.6 (±2.1) and 7.5 (±2.4) to 7.7 (±2.4), respectively. When stratified by severity, impedance planimetry measurements of diameter and DI were significantly lower with each subsequent increase in GSS grade regardless of balloon fill volumes ( P ≤ 0.001). DISCUSSION: Impedance planimetry measurements provide objective assessment in the diagnosis of GSS and correlate with luminal narrowing. A diameter ≥20 mm and a DI ≥15 mm 2 /mm Hg, as measured by impedance planimetry, are predictive of normal gastric sleeve anatomy. This study provides new benchmark values for the diagnosis and severity of GSS.

Lipid metabolic reprogramming mediated by circulating Nrg4 alleviates metabolic dysfunction-associated steatotic liver disease during the early recovery phase after sleeve gastrectomy.

BACKGROUND: The metabolic benefits of bariatric surgery that contribute to the alleviation of metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. However, the processes and mechanisms underlying the contribution of lipid metabolic reprogramming after bariatric surgery to attenuating MASLD remain elusive. METHODS: A case-control study was designed to evaluate the impact of three of the most common adipokines (Nrg4, leptin, and adiponectin) on hepatic steatosis in the early recovery phase following sleeve gastrectomy (SG). A series of rodent and cell line experiments were subsequently used to determine the role and mechanism of secreted adipokines following SG in the alleviation of MASLD. RESULTS: In morbidly obese patients, an increase in circulating Nrg4 levels is associated with the alleviation of hepatic steatosis in the early recovery phase following SG before remarkable weight loss. The temporal parameters of the mice confirmed that an increase in circulating Nrg4 levels was initially stimulated by SG and contributed to the beneficial effect of SG on hepatic lipid deposition. Moreover, this occurred early following bariatric surgery. Mechanistically, gain- and loss-of-function studies in mice or cell lines revealed that circulating Nrg4 activates ErbB4, which could positively regulate fatty acid oxidation in hepatocytes to reduce intracellular lipid deposition. CONCLUSIONS: This study demonstrated that the rapid effect of SG on hepatic lipid metabolic reprogramming mediated by circulating Nrg4 alleviates MASLD.

Severe obesity among patients with left ventricular assist devices.

BACKGROUND: Patients with obesity and advanced heart failure requiring left ventricular assist device (LVAD) support are more likely to experience LVAD complications and may be disproportionately Black and/or female when compared to patients without obesity. Among these patients, obesity may represent a barrier to transplant eligibility and a marker of inequity in heart transplantation and health outcomes in advanced heart failure. METHODS: To better understand this issue at our institution, we examined our active LVAD cohort and found that almost one-third of all patients had severe obesity with BMI ≥ 35 kg/m2. RESULTS: Patients with LVADs and severe obesity were significantly younger and more likely to self-identify as Black, and numerically more likely to be female. CONCLUSION: Weight management in this group represents a vital area for improved equity in health outcomes and barriers to heart transplantation. TRIAL REGISTRATION: NA.

The association of obesity with post-cesarean inpatient opioid consumption.

BACKGROUND: Obesity and prescription opioid misuse are important public health concerns in the United States. A common intersection occurs when women with obesity undergo cesarean birth and receive narcotic medications for postpartum pain. OBJECTIVE: To examine the association between obesity and inpatient opioid use after cesarean birth. METHODS: A retrospective cohort study of patients that underwent cesarean birth in 2015-2018. Primary outcome was post-cesarean delivery opioid consumption starting 24 h after delivery measured as morphine milliequivalents per hour (MME/h). Secondary outcome was MME/h consumption in the highest quartile of all subjects. Opioid consumption was compared between three BMI groups: non-obese BMI 18.5-29.9 kg/m2; obese BMI 30.0-39.9 kg/m2; and morbidly obese BMI ≥ 40.0 kg/m2 using univariable and multivariable analyses. RESULTS: Of 1620 patients meeting inclusion criteria, 496 (30.6%) were in the non-obese group, 753 (46.5%) were in the obese group, and 371 (22.9%) were in the morbidly obese group. In the univariate analysis, patients with obesity and morbid obesity required higher MME/h than patients in the non-obese group [1.3 MME/h (IQR 0.1, 2.4) vs. 1.6 MME/h (IQR 0.5, 2.8) vs. 1.8 MME/h (IQR 0.8, 2.9), for non-obese, obese, and morbidly obese groups respectively, p < 0.001]. In the multivariable analysis, this association did not persist. In contrast, subjects in the obese and morbidly obese groups were more likely to be in the highest quartile of MME/h opioid consumption compared with those in the non-obese group (23.5% vs. 48.1% vs. 28.4%, p < 0.001, respectively); with aOR 1.42 (95% CI 1.07-1.89, p = 0.016) and aOR 1.60 (95% CI 1.16-2.22, p = 0.005) for patients with obesity and morbid obesity, respectively. CONCLUSION: Maternal obesity was not associated with higher hourly MME consumption during inpatient stay after cesarean birth. However, patients with obesity and morbid obesity were significantly more likely to be in the top quartile of MME hourly consumption.

Visceral adipose tissue adiponectin predicts excess weight loss after bariatric surgery in females with severe obesity.

OBJECTIVE: Bariatric surgery not always results in satisfactory excess weight loss (EWL) in severe obesity. Given the economic and clinical costs of bariatric surgery failure, defining predictors of successful EWL represents a relevant clinical issue for the health system to select patients benefiting from operation. METHODS: By ELISA and Western blot analyses, we assessed the predicting value of pre-operative adiponectin (APN) locally produced in abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue versus plasma levels as a novel sex-linked biomarker of EWL at different time points of follow up (6-24 months) after bariatric surgery in 43 patients (56% females) affected by severe obesity undergoing a small pilot observational study. RESULTS: VAT-APN was lower in females and represented the only marker significantly correlated with EWL. In females, VAT-APN in the distribution upper quartile but not baseline BMI retained a statistically significant correlation with EWL at any time points (6-24 months) at multivariate analysis. The best VAT-APN cut-off value to predict 95% EWL at 12 months from surgery (98% accuracy, 100% sensitivity, 94% specificity, p = 0.010) was 5.1 µg/mg. CONCLUSIONS: In this very preliminary study, APN in VAT rather than its circulating or subcutaneous levels predicts EWL after bariatric surgery as an independent factor in the female sex only, thus contributing to identify those patients who could much benefit from surgery.

The effects of bariatric surgery on cardiac function: a systematic review and meta-analysis.

INTRODUCTION: Obesity is associated with alterations in cardiac structure and haemodynamics leading to cardiovascular mortality and morbidity. Culminating evidence suggests improvement of cardiac structure and function following bariatric surgery. OBJECTIVE: To evaluate the effect of bariatric surgery on cardiac structure and function in patients before and after bariatric surgery. METHODS: Systematic review and meta-analysis of studies reporting pre- and postoperative cardiac structure and function parameters on cardiac imaging in patients undergoing bariatric surgery. RESULTS: Eighty studies of 3332 patients were included. Bariatric surgery is associated with a statistically significant improvement in cardiac geometry and function including a decrease of 12.2% (95% CI 0.096-0.149; p < 0.001) in left ventricular (LV) mass index, an increase of 0.155 (95% CI 0.106-0.205; p < 0.001) in E/A ratio, a decrease of 2.012 mm (95% CI 1.356-2.699; p < 0.001) in left atrial diameter, a decrease of 1.16 mm (95% CI 0.62-1.69; p < 0.001) in LV diastolic dimension, and an increase of 1.636% (95% CI 0.706-2.566; p < 0.001) in LV ejection fraction after surgery. CONCLUSION: Bariatric surgery led to reverse remodelling and improvement in cardiac geometry and function driven by metabolic and haemodynamic factors.

Bone mineral density in young adults 5 to 11 years after adolescent metabolic and bariatric surgery for severe obesity compared to peers.

OBJECTIVE: Metabolic and bariatric surgery (MBS) is associated with decreased bone mineral density (BMD) in adults. The long-term impact of MBS during adolescence on BMD is unknown. We report bone health status 5 to 11 years after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) from the Teen-LABS study cohort. METHODS: Between 2016 and 2022, BMD was measured by dual energy x-ray absorptiometry (DXA) in 106 young adults who had undergone MBS as adolescents. Volumetric BMD by peripheral quantitative computed tomography was measured on a subset. Ninety-one controls who had not undergone MBS were recruited for comparison. RESULTS: In cases (RYGB: mean age 26.8 ± 1.9 years, mean BMI 42.1 ± 9.9 kg/m2, VSG: mean age 25.1 ± 2.1 years, mean BMI 37.1 ± 8.4 kg/m2), compared to controls (mean age 26.5 ± 2.7 years, mean BMI 40.2 ± 8.7 kg/m2) (age p < 0.001, BMI p = 0.02), adjusted mean DXA-BMD (g/cm2) of the RYGB (n = 58) and VSG (n = 48) groups were lower at the hip (-10.0% and -6.3%), femoral neck (-9.6% and -5.7%) and ultra-distal radius (-7.9% and -7.0%; all p < 0.001), respectively. DXA-BMD did not differ between RYGB and VSG groups. Trabecular volumetric BMD at the radius and tibia were lower in the RYGB (-30% and -26%) and VSG (-15% and -14%) groups compared to the control group (p < 0.001). Greater time since MBS was associated with lower BMD Z-scores at the hip (p = 0.05) and femoral neck (p = 0.045). Percent change in body mass index (BMI) from baseline or in the first year after MBS were not associated with bone measures at a median of 9.3 years post MBS. CONCLUSION: BMD, especially of the hip and femoral neck, was lower in young adults who underwent MBS during adolescence compared to matched peers who had not undergone MBS. BMD Z-scores of the femoral neck were inversely associated with time since MBS but were not associated with BMI change.

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.

The effect of bariatric surgery type on cardiac reverse remodelling.

INTRODUCTION: Bariatric surgery is effective in reversing adverse cardiac remodelling in obesity. However, it is unclear whether the three commonly performed operations; Roux-en-Y Gastric Bypass (RYGB), Laparoscopic Sleeve Gastrectomy (LSG) and Laparoscopic Adjustable Gastric Band (LAGB) are equal in their ability to reverse remodelling. METHODS: Fifty-eight patients underwent CMR to assess left ventricular mass (LVM), LV mass:volume ratio (LVMVR) and LV eccentricity index (LVei) before and after bariatric surgery (26 RYGB, 22 LSG and 10 LAGB), including 46 with short-term (median 251-273 days) and 43 with longer-term (median 983-1027 days) follow-up. Abdominal visceral adipose tissue (VAT) and epicardial adipose tissue (EAT) were also assessed. RESULTS: All three procedures resulted in significant decreases in excess body weight (48-70%). Percentage change in VAT and EAT was significantly greater following RYGB and LSG compared to LAGB at both timepoints (VAT:RYGB -47% and -57%, LSG -47% and -54%, LAGB -31% and -25%; EAT:RYGB -13% and -14%, LSG -16% and -19%, LAGB -5% and -5%). Patients undergoing LAGB, whilst having reduced LVM (-1% and -4%), had a smaller decrease at both short (RYGB: -8%, p < 0.005; LSG: -11%, p < 0.0001) and long (RYGB: -12%, p = 0.009; LSG: -13%, p < 0.0001) term timepoints. There was a significant decrease in LVMVR at the long-term timepoint following both RYGB (-7%, p = 0.006) and LSG (-7%, p = 0.021), but not LAGB (-2%, p = 0.912). LVei appeared to decrease at the long-term timepoint in those undergoing RYGB (-3%, p = 0.063) and LSG (-4%, p = 0.015), but not in those undergoing LAGB (1%, p = 0.857). In all patients, the change in LVM correlated with change in VAT (r = 0.338, p = 0.0134), while the change in LVei correlated with change in EAT (r = 0.437, p = 0.001). CONCLUSIONS: RYGB and LSG appear to result in greater decreases in visceral adiposity, and greater reverse LV remodelling with larger reductions in LVM, concentric remodelling and pericardial restraint than LAGB.

Intersection of sepsis, atrial fibrillation, and severe obesity: a population-based analysis in the United States.

BACKGROUND: Atrial fibrillation (AF) is an indicator of poor prognosis in patients with sepsis and can increase the risk of stroke and mortality. Data on the impact of severe obesity on the outcomes of sepsis complicated by AF remains poorly understood. METHODS: National Inpatient Sample (2018) and ICD-10 CM codes were used to identify the principal sepsis admissions with AF. We assessed comorbidities and outcomes of sepsis in people without obesity (BMI < 30) vs. non-severe obesity (BMI 30-35) and severe obesity (BMI > 35) cohorts. We also did a subgroup analysis to further stratify obesity based on metabolic health and analyzed the findings. The primary outcomes were the prevalence and adjusted odds of AF, AF-associated stroke, and all-cause mortality in sepsis by obesity status. Multivariable regression analyses were adjusted for patient- and hospital-level characteristics and comorbidities. RESULTS: Our main analysis showed that of the 1,345,595 sepsis admissions, the severe obesity cohort was the youngest (median age 59 vs. non-severe 64 and people without obesity 68 years). Patients with obesity, who were often female, were more likely to have hypertension, diabetes, congestive heart failure, chronic pulmonary disease, and chronic kidney disease. The crude prevalence of AF was highest in non-severe obesity (19.9%). The adjusted odds of AF in non-severe obesity (OR 1.21; 95% CI:1.16-1.27) and severe obesity patients with sepsis (OR 1.49; 95% CI:1.43-1.55) were significantly higher than in people without obesity (p < 0.001). Paradoxically, the rates of AF-associated stroke (1%, 1.5%, and 1.7%) and in-hospital mortality (3.3%, 4.9%, and 7.1%) were lowest in the severe obesity cohort vs. the non-severe and people without obesity cohorts, respectively. On multivariable regression analyses, the all-cause mortality revealed lower odds in sepsis-AF patients with severe obesity (OR 0.78; 95% CI:0.67-0.91) or non-severe obesity (OR 0.63; 95% CI:0.54-0.74) vs. people without obesity. There was no significant difference in stroke risk. CONCLUSIONS: A higher prevalence of cardiovascular comorbidities can be linked to a higher risk of AF in people with obesity and sepsis. Paradoxically, lower rates of stroke and all-cause mortality secondary to AF in people with obesity and sepsis warrant further investigation.

Do patients with obesity undergoing bariatric surgery modify their objectively measured physical activity? A systematic review and meta-analysis.

BACKGROUND: Obesity is a chronic disease associated with adverse outcomes and its prevalence is increasing, which makes it a concern. One of the obesity treatment options is bariatric surgery, which effectively reduces calorie absorption and total body mass, but its effects on physical activity (PA) levels need to be clarified, considering the protective effect of the PA against cardiovascular disease, independently of the weight loss alone. OBJECTIVES: To carry out a systematic review and meta-analysis of observational studies that evaluated PA in pre- and post-bariatric surgery periods through objective evaluation. METHODS: A systematic search was carried out following the PRISMA criteria of studies with adult individuals who underwent bariatric surgery and were objectively evaluated for PA pre- and post-surgery. Studies with interventions were excluded. RESULTS: A total of 419 records were found, and after excluding duplicates and applying the eligibility criteria, 10 studies remained. This meta-analysis found a significant increase in the steps by day (MD = 1340; 95% CI = 933.90; 1745.35, p < 0.001) and the light physical activity level (MD = 16.8 min/day; 95% CI = 2.60; 30.98, p = 0.02), but not in moderate to vigorous physical activity (MD = 0.24; 95% CI = -0.08; 1.57, p = 0.92). CONCLUSIONS: Patients undergoing bariatric surgery increased their steps by day and light physical activity but did not increase moderate to vigorous physical activity.

Clinical characteristics and outcomes of children, adolescents and young adults with overweight or obesity and mental health disorders.

BACKGROUND: Mental disorders are important comorbidities in youth with obesity. Aim was to describe the clinical characteristics and outcome of youth with overweight or obesity having comorbid mental disorders. METHODS: Data from children, adolescents, and young adults (age 6-30 years) with overweight or obesity and mental disorders (depression, anxiety disorder, eating disorder, attention deficit disorder (ADHD)) from 226 centers in Germany and Austria participating in the Adiposity Patient Registry (APV) were analyzed and compared with those without reported mental disorders using regression modeling. RESULTS: Mental health comorbidity was reported in a total of 3969 out of 114,248 individuals with overweight or obesity: 42.5% had ADHD, 31.3% anxiety disorders, 24.3% depression, and 12.9% eating disorders. Being male (OR 1.39 (95%CI 1.27;1.52)), of older age (1.42 (1.25;1.62)), or with extreme obesity (1.45 (1.30;1.63)) were most strongly associated with mental health comorbidity. Regression analysis showed that mean BMI-SDS was significantly higher in the group of individuals with depression and eating disorders (BMI-SDS 2.13 (lower; upper mean:2.09;2.16) and 2.22 (2.17;2.26)) compared to those without reported mental health comorbidity (BMI-SDS 2.008 (2.005;2.011); p < 0.001). In youth with ADHD, BMI-SDS was lower compared to those without reported mental disorders (BMI-SDS 1.91 (1.89;1.93) vs 2.008 (2.005;2.011); p < 0.001). Proportion of severe obesity was higher in individuals with depression (23.7%), anxiety disorders (17.8%), and eating disorders (33.3%), but lower in ADHD (10.3%), compared to those without reported mental disorders (13.5%, p < 0.002). Proportions of dyslipidaemia and abnormal carbohydrate metabolism were not different in youth with and without reported mental health comorbidity. BMI-SDS change after one year of lifestyle intervention program ranged between -0.22 and -0.16 and was similar in youth without and with different mental disorders. CONCLUSION: Health care professionals caring for youth with overweight or obesity should be aware of comorbid mental disorders and regular mental health screening should be considered.