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Context: Obstructive sleep apnea (OSA) is strongly related to obesity. Weight loss is recommended as part of the overall management plan for obese patients diagnosed with OSA.Objective: To determine whether surgically induced weight loss is more effective than conventional weight loss therapy in the management of OSA.Design, Setting, and Patients: A randomized controlled trial of 60 obese patients (body mass index: >35 and <55) with recently diagnosed (<6 months) OSA and an apnea-hypopnea index (AHI) of 20 events/hour or more. These patients had been prescribed continuous positive airway pressure (CPAP) therapy to manage OSA and were identified via accredited community sleep clinics. The trial was conducted between September 2006 and March 2009 by university- and teaching hospital-based clinical researchers in Melbourne, Australia. Patients with obesity hypoventilation syndrome, previous bariatric surgery, contraindications to bariatric surgery, or significant cardiopulmonary, neurological, vascular, gastrointestinal, or neoplastic disease were excluded.Interventions: Patients were randomized to a conventional weight loss program that included regular consultations with a dietitian and physician, and the use of very low-calorie diets as necessary (n = 30) or to bariatric surgery (laparoscopic adjustable gastric banding; n = 30).Main Outcome Measures: The primary outcome was baseline to 2-year change in AHI on diagnostic polysomnography scored by staff blinded to randomization. Secondary outcomes were changes in weight, CPAP adherence, and functional status.Results: Patients lost a mean of 5.1 kg (95% CI, 0.8 to 9.3 kg) in the conventional weight loss program compared with 27.8 kg (95% CI, 20.9 to 34.7 kg) in the bariatric surgery group (P < .001). The AHI decreased by 14.0 events/hour (95% CI, 3.3 to 24.6 events/hour) in the conventional weight loss group and by 25.5 events/hour (95% CI, 14.2 to 36.7 events/hour) in the bariatric surgery group. The between-group difference was -11.5 events/hour (95% CI, -28.3 to 5.3 events/hour; P = .18). CPAP adherence did not differ between the groups. The bariatric surgery group had greater improvement in the Short Form 36 physical component summary score (mean, 9.3 [95% CI, 0.5 to 18.0]; P = .04).Conclusion: Among a group of obese patients with OSA, the use of bariatric surgery compared with conventional weight loss therapy did not result in a statistically greater reduction in AHI despite major differences in weight loss.Trial Registration: anzctr.org Identifier: 12605000161628. [ABSTRACT FROM AUTHOR]

Objective: Insulin resistance and other features of the metabolic syndrome have been causally linked to adipose tissue macrophages (ATMs) in mice with diet-induced obesity. We aimed to characterize macrophage phenotype and function in human subcutaneous and omental adipose tissue in relation to insulin resistance in obesity.Research Design and Methods: Adipose tissue was obtained from lean and obese women undergoing bariatric surgery. Metabolic markers were measured in fasting serum and ATMs characterized by immunohistology, flow cytometry, and tissue culture studies. RESULTS ATMs comprised CD11c(+)CD206(+) cells in "crown" aggregates and solitary CD11c(-)CD206(+) cells at adipocyte junctions. In obese women, CD11c(+) ATM density was greater in subcutaneous than omental adipose tissue and correlated with markers of insulin resistance. CD11c(+) ATMs were distinguished by high expression of integrins and antigen presentation molecules; interleukin (IL)-1beta, -6, -8, and -10; tumor necrosis factor-alpha; and CC chemokine ligand-3, indicative of an activated, proinflammatory state. In addition, CD11c(+) ATMs were enriched for mitochondria and for RNA transcripts encoding mitochondrial, proteasomal, and lysosomal proteins, fatty acid metabolism enzymes, and T-cell chemoattractants, whereas CD11c(-) ATMs were enriched for transcripts involved in tissue maintenance and repair. Tissue culture medium conditioned by CD11c(+) ATMs, but not CD11c(-) ATMs or other stromovascular cells, impaired insulin-stimulated glucose uptake by human adipocytes.Conclusions: These findings identify proinflammatory CD11c(+) ATMs as markers of insulin resistance in human obesity. In addition, the machinery of CD11c(+) ATMs indicates they metabolize lipid and may initiate adaptive immune responses. [ABSTRACT FROM AUTHOR]

Context: Adolescent obesity is a common and serious health problem affecting more than 5 million young people in the United States alone. Bariatric surgery is being evaluated as a possible treatment option. Laparoscopic adjustable gastric banding (gastric banding) has the potential to provide a safe and effective treatment.Objective: To compare the outcomes of gastric banding with an optimal lifestyle program on adolescent obesity.Design, Setting, and Patients: A prospective, randomized controlled trial of 50 adolescents between 14 and 18 years with a body mass index (BMI) higher than 35, recruited from the Melbourne, Australia, community, assigned either to a supervised lifestyle intervention or to undergo gastric banding, and followed up for 2 years. The study was performed between May 2005 and September 2008.Main Outcome Measures: Weight loss. Secondary outcomes included change in metabolic syndrome, insulin resistance, quality of life, and adverse outcomes.Results: Twenty-four of 25 patients in the gastric banding group and 18 of 25 in lifestyle group completed the study. Twenty-one (84%) in the gastric banding and 3 (12%) in the lifestyle groups lost more than 50% of excess weight, corrected for age. Overall, the mean changes in the gastric banding group were a weight loss of 34.6 kg (95% CI, 30.2-39.0), representing an excess weight loss of 78.8% (95% CI, 66.6%-91.0%), 12.7 BMI units (95% CI, 11.3-14.2), and a BMI z score change from 2.39 (95% CI, 2.05-2.73) to 1.32 (95% CI, 0.98-1.66). The mean losses in the lifestyle group were 3.0 kg (95% CI, 2.1-8.1), representing excess weight loss of 13.2% (95% CI, 2.6%-21.0%), 1.3 BMI units (95% CI, 0.4-2.9), and a BMI z score change from 2.41 (95% CI, 2.21-2.66) to 2.26 (95% CI, 1.91-2.43). At entry, 9 participants (36%) in the gastric banding group and 10 (40%) in the lifestyle group had the metabolic syndrome. At 24 months, none of the gastric banding group had the metabolic syndrome (P = .008; McNemar chi(2)) compared with 4 of the 18 completers (22%) in the lifestyle group (P = .13). The gastric banding group experienced improved quality of life with no perioperative adverse events. However, 8 operations (33%) were required in 7 patients for revisional procedures either for proximal pouch dilatation or tubing injury during follow-up.Conclusions: Among obese adolescent participants, use of gastric banding compared with lifestyle intervention resulted in a greater percentage achieving a loss of 50% of excess weight, corrected for age. There were associated benefits to health and quality of life.Trial Registration: ANZCTR Identifier: 12605000160639. [ABSTRACT FROM AUTHOR]

Objective: To determine the within-trial cost-efficacy of surgical therapy relative to conventional therapy for achieving remission of recently diagnosed type 2 diabetes in class I and II obese patients.Research Design and Methods: Efficacy results were derived from a 2-year randomized controlled trial. A health sector perspective was adopted, and within-trial intervention costs included gastric banding surgery, mitigation of complications, outpatient medical consultations, medical investigations, pathology, weight loss therapies, and medication. Resource use was measured based on data drawn from a trial database and patient medical records and valued based on private hospital costs and government schedules in 2006 Australian dollars (AUD). An incremental cost-effectiveness analysis was undertaken.Results: Mean 2-year intervention costs per patient were 13,400 AUD for surgical therapy and 3,400 AUD for conventional therapy, with laparoscopic adjustable gastric band (LAGB) surgery accounting for 85% of the difference. Outpatient medical consultation costs were three times higher for surgical patients, whereas medication costs were 1.5 times higher for conventional patients. The cost differences were primarily in the first 6 months of the trial. Relative to conventional therapy, the incremental cost-effectiveness ratio for surgical therapy was 16,600 AUD per case of diabetes remitted (currency exchange: 1 AUD = 0.74 USD).Conclusions: Surgical therapy appears to be a cost-effective option for managing type 2 diabetes in class I and II obese patients. [ABSTRACT FROM AUTHOR]

Context: Observational studies suggest that surgically induced loss of weight may be effective therapy for type 2 diabetes.Objective: To determine if surgically induced weight loss results in better glycemic control and less need for diabetes medications than conventional approaches to weight loss and diabetes control.Design, Setting, and Participants: Unblinded randomized controlled trial conducted from December 2002 through December 2006 at the University Obesity Research Center in Australia, with general community recruitment to established treatment programs. Participants were 60 obese patients (BMI >30 and <40) with recently diagnosed (<2 years) type 2 diabetes.Interventions: Conventional diabetes therapy with a focus on weight loss by lifestyle change vs laparoscopic adjustable gastric banding with conventional diabetes care.Main Outcome Measures: Remission of type 2 diabetes (fasting glucose level <126 mg/dL [7.0 mmol/L] and glycated hemoglobin [HbA1c] value <6.2% while taking no glycemic therapy). Secondary measures included weight and components of the metabolic syndrome. Analysis was by intention-to-treat.Results: Of the 60 patients enrolled, 55 (92%) completed the 2-year follow-up. Remission of type 2 diabetes was achieved by 22 (73%) in the surgical group and 4 (13%) in the conventional-therapy group. Relative risk of remission for the surgical group was 5.5 (95% confidence interval, 2.2-14.0). Surgical and conventional-therapy groups lost a mean (SD) of 20.7% (8.6%) and 1.7% (5.2%) of weight, respectively, at 2 years (P < .001). Remission of type 2 diabetes was related to weight loss (R2 = 0.46, P < .001) and lower baseline HbA1c levels (combined R2 = 0.52, P < .001). There were no serious complications in either group.Conclusions: Participants randomized to surgical therapy were more likely to achieve remission of type 2 diabetes through greater weight loss. These results need to be confirmed in a larger, more diverse population and have long-term efficacy assessed.Trial Registration: actr.org Identifier: ACTRN012605000159651. [ABSTRACT FROM AUTHOR]

Background: Obesity is a major, growing health problem. Observational studies suggest that bariatric surgery is more effective than nonsurgical therapy, but no randomized, controlled trials have confirmed this.Objective: To ascertain whether surgical therapy for obesity achieves better weight loss, health, and quality of life than nonsurgical therapy.Design: Randomized, controlled trial.Setting: University departments of medicine and surgery and an affiliated private hospital.Patients: 80 adults with mild to moderate obesity (body mass index, 30 kg/m2 to 35 kg/m2) from the general community.Interventions: Patients were assigned to a program of very-low-calorie diets, pharmacotherapy, and lifestyle change for 24 months (nonsurgical group) or to placement of a laparoscopic adjustable gastric band (LAP-BAND System, INAMED Health, Santa Barbara, California) (surgical group).Measurements: Outcome measures were weight change, presence of the metabolic syndrome, and change in quality of life at 2 years.Results: At 2 years, the surgical group had greater weight loss, with a mean of 21.6% (95% CI, 19.3% to 23.9%) of initial weight lost and 87.2% (CI, 77.7% to 96.6%) of excess weight lost, while the nonsurgical group had a loss of 5.5% (CI, 3.2% to 7.9%) of initial weight and 21.8% (CI, 11.9% to 31.6%) of excess weight (P < 0.001). The metabolic syndrome was initially present in 15 (38%) patients in each group and was present in 8 (24%) nonsurgical patients and 1 (3%) surgical patient at the completion of the study (P < 0.002). Quality of life improved statistically significantly more in the surgical group (8 of 8 subscores of Short Form-36) than in the nonsurgical group (3 of 8 subscores).Limitations: The study included mildly and moderately obese participants, was not powered for comparison of adverse events, and examined outcomes only for 24 months.Conclusions: Surgical treatment using laparoscopic adjustable gastric banding was statistically significantly more effective than nonsurgical therapy in reducing weight, resolving the metabolic syndrome, and improving quality of life during a 24-month treatment program. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA) is common in severely obese subjects (body mass index [BMI] > 35). Overnight polysomnography (OPS) is the "gold standard" method of evaluating this condition; however, it is time-consuming, inconvenient, and expensive. Selection of patients for OPS would be enhanced if we could better predict those likely to have clinically significant OSA.Study Objective: To look for clinical and biochemical predictors of OSA in symptomatic patients presenting for obesity surgery.Design and Patients: Symptoms suggestive of OSA were sought in a structured interview. We report OPS results of 99 consecutive subjects in whom OSA was clinically suspected. Predictors of apnea-hypopnea index (AHI) were sought from an extensive preoperative data collection. Multivariate linear and logistic analysis was used to identify independent predictors of AHI.Results: Symptoms were poor predictors of AHI, with observed sleep apnea the only positive predictor. Four clinical and two biochemical factors independently predicted AHI: observed sleep apnea, male sex, higher BMI, age, fasting insulin, and glycosylated hemoglobin A(Ic) (r(2) = 0.42). Neck circumference (the best single measure) could replace BMI and sex in the analysis (r(2) = 0.43). With cutoffs selected, a simple scoring system using these six factors provides a method of predicting those with moderate or severe OSA. A score > or = 3 provides a sensitivity and specificity of 89% and 81%, and 96% and 71% for AHIs of > or = 15 and > or = 30, respectively. None of the 31 subjects with scores of 0 or 1 were found to have an AHI > or = 15.Conclusion: We explore sleep disturbance and report a simple method of predicting OSA in severely obese symptomatic subjects. This should assist in limiting the use of OPS to those with greater risk and provide a method of assessing risk in those not presenting primarily with a sleep problem. [ABSTRACT FROM AUTHOR]

Antarctic climate warming and atmospheric CO 2 rise during the last deglaciation may be attributed in part to sea ice reduction in the Southern Ocean. Yet, glacial-interglacial Antarctic sea ice dynamics and underlying mechanisms are poorly constrained, as robust sea ice proxy evidence is sparse. Here, we present a molecular biomarker-based sea ice record that resolves the spring/summer sea ice variability off East Antarctica during the past 40 thousand years (ka). Our results indicate that substantial sea ice reduction culminated rapidly and contemporaneously with upwelling of carbon-enriched waters in the Southern Ocean at the onset of the last deglaciation but began at least ~2 ka earlier probably driven by an increasing local integrated summer insolation. Our findings suggest that sea ice reduction and associated feedbacks facilitated stratification breakup and outgassing of CO 2 in the Southern Ocean and warming in Antarctica but may also have played a leading role in initializing these deglacial processes in the Southern Hemisphere.

Aim: Randomized trials reporting 5-year outcomes have shown bariatric surgery  to induce diabetes remission and improve cardiovascular risk. However, the longer-term effects of surgery are uncertain, with only one randomized trial reporting 10-year diabetes outcomes in people with obesity. We aimed to compare 10-year diabetes outcomes of people who are overweight but not obese, randomly assigned to receive either multidisciplinary diabetes care, or multidisciplinary diabetes care combined with gastric band (GB) surgery., Methods: Between 2009 and 2011, 51 adults were randomized. After 5 years, they were discharged to receive community care and reassessed after 10 years. The primary outcome was diabetes remission, defined as glycated haemoglobin (HbA1c) <6.5% (48 mmol/mol) without glucose-lowering medication., Results: Forty-one participants (20 medical and 21 GB) completed the 10-year assessment. The median (Q1, Q3) weight loss in the GB group was 9.8 (6.7, 16.3)% at 10 years compared with 5.6 (3.4, 7.6)% in the medical group (median difference 4.2%; p = .008). Diabetes remission occurred in five GB participants and no medical participants (relative risk 0.76, 95% CI: 0.55-0.93, p = .048). GB participants used fewer glucose-lowering medications at 10 years but HbA1c, fasting glucose, calculated cardiovascular risk, quality-of-life and incident diabetes complications did not differ significantly between the groups., Conclusion: When compared with medical care, GB surgery achieved greater weight loss and modestly increased the likelihood of diabetes remission. However, it did not improve HbA1c, cardiovascular risk or quality of life., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Preoperative opioid use strongly correlates with greater postoperative opioid use and complications following total joint arthroplasty (TJA). However, there is a lack of information regarding the effect of opioid consumption during the hospital stay and within the operating room on postoperative opioid use., Methods: We retrospectively reviewed 369 consecutive patients undergoing primary TJA at an academic center over a 9-month period. Ninety-day preoperative and postoperative opioid prescriptions were obtained from the state's drug monitoring database. In-hospital opioid consumption data was obtained from the preoperative unit, operating room, postanesthesia care unit (PACU), and hospital floor. Multivariate analysis was utilized to compare patients' total in-hospital opioid consumption with their preoperative and postoperative use, along with opioid use throughout the hospitalization., Results: Total in-hospital opioid consumption was independently associated with postoperative opioid use (r s  = 0.17, P = .0010). Opioids consumed on the hospital floor correlated with opioid use in the preoperative unit (r s  = 0.11, P = .0338) and PACU (r s  = 0.15, P = .0032). Increased preoperative opioid consumption was the greatest risk factor for excessive postoperative use (r s  = 0.44, P < .0001). A greater proportion of patients <65 years of age were high posthospital opioid consumers (P = .0146) and significantly more TKA patients were in the higher use groups (P = .0006)., Conclusion: In-hospital opioid use is independently associated with preoperative and postoperative consumption. Preoperative opioid use remains the greatest risk factor for increased opioid consumption after TJA. Multimodal approaches to decrease reliance on opioids for pain control during hospitalization may offer hope to further decrease postoperative usage., Level of Evidence: III., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: A principal mechanism of action in bariatric surgery is reduction in calorie consumption due to decreased hunger and increased satiety. Patients' ability to perceive post-operative changes to their hunger is therefore central to optimal results. This study examined factors that may impact how patients perceive post-operative hunger and how perception of hunger impacts eating and subsequent weight loss after laparoscopic adjustable gastric banding (LAGB)., Methods: Patients undertaking LAGB (n = 147) provided pre-surgery and 2-year weight loss data and pre-surgery and 12-month psychological data (perception of hunger, disinhibition related to eating, emotional eating)., Results: Path analysis demonstrated that patients with lower levels of pre-surgery cognitive restraint over eating experienced significantly greater reduction in perception of hunger at 12 months post-surgery. Perceived reduction in hunger was significantly associated with lower levels of both emotional eating and disinhibited eating. Finally, reduced emotional eating at 12 months significantly predicted 9% of the variance in percentage of total weight loss (%TWL) at 2 years after surgery., Conclusion: These initial findings suggest that preparation for bariatric surgery may be enhanced by psychoeducation regarding cognitive restraint over eating and its effect on hunger perception. In addition, psychological treatment that focuses on identifying and responding to changes in hunger may contribute to improved outcomes for those who have difficulty adjusting to post-operative eating behaviours.

Purpose: We studied the impact of mTOR signaling inhibition with rapamycin in head and neck squamous cell carcinoma (HNSCC) in the neoadjuvant setting. The goals were to evaluate the mTOR pathway as a therapeutic target for patients with advanced HNSCC, and the clinical safety, antitumor, and molecular activity of rapamycin administration on HNSCC., Patients and Methods: Patients with untreated stage II-IVA HNSCC received rapamycin for 21 days (day 1, 15 mg; days 2-12, 5 mg) prior to definitive treatment with surgery or chemoradiation. Treatment responses were assessed clinically and radiographically with CT and FDG-PET. Pre- and posttreatment biopsies and blood were obtained for toxicity, immune monitoring, and IHC assessment of mTOR signaling, as well as exome sequencing., Results: Sixteen patients (eight oral cavity, eight oropharyngeal) completed rapamycin and definitive treatment. Half of patients were p16 positive. One patient had a pathologic complete response and four (25%) patients met RECIST criteria for response (1 CR, 3 PR, 12 SD). Treatment was well tolerated with no grade 4 or unexpected toxicities. No significant immune suppression was observed. Downstream mTOR signaling was downregulated in tumor tissues as measured by phosphorylation of S6 ( P < 0.0001), AKT ( P < 0.0001), and 4EBP ( P = 0.0361), with a significant compensatory increase in phosphorylated ERK in most patients ( P < 0.001). Ki67 was reduced in tumor biopsies in all patients ( P = 0.013)., Conclusions: Rapamycin treatment was well tolerated, reduced mTOR signaling and tumor growth, and resulted in significant clinical responses despite the brief treatment duration, thus supporting the potential role of mTOR inhibitors in treatment regimens for HNSCC., (©2018 American Association for Cancer Research.)

Introduction: Durability is a key requirement for the broad acceptance of bariatric surgery. We report on durability at and beyond 10 years with a systematic review and meta-analysis of all reports providing data at 10 or more years and a single-centre study of laparoscopic adjustable gastric banding (LAGB) with 20 years of follow-up., Methods: Systematic review with meta-analysis was performed on all eligble reports containing 10 or more years of follow-up data on weight loss after bariatric surgery. In addition, a prospective cohort study of LAGB patients measuring weight loss and reoperation at up to 20 years is presented., Results: Systematic review identified 57 datasets of which 33 were eligible for meta-analysis. Weighted means of the percentage of excess weight loss (%EWL) were calculated for all papers included in the systematic review. Eighteen reports of gastric bypass showed a weighted mean of 56.7%EWL, 17 reports of LAGB showed 45.9%EWL, 9 reports of biliopancreatic bypass +/- duodenal switch showed 74.1%EWL and 2 reports of sleeve gastrectomy showed 58.3%EWL. Meta-analyses of eligible studies demonstrated comparable results. Reoperations were common in all groups. At a single centre, 8378 LAGB patients were followed for up to 20 years with an overall follow-up rate of 54%. No surgical deaths occurred. Weight loss at 20 years (N = 35) was 30.1 kg, 48.9%EWL and 22.2% total weight loss (%TWL). Reoperation rate was initially high but reduced markedly with improved band and surgical and aftercare techniques., Conclusion: All current procedures are associated with substantial and durable weight loss. More long-term data are needed for one-anastomosis gastric bypass and sleeve gastrectomy. Reoperation is likely to remain common across all procedures.

Introduction: Dyslipidemia affects up to 75% of morbidly obese individuals and is a key driver of cardiovascular disease. Weight loss is an established strategy to improve metabolic risk, including dyslipidemia. We aimed to determine weight loss goals for resolution of serum lipid abnormalities, by measuring improvements during progressive weight loss in obese individuals., Methods: We performed a prospective cohort study of obese individuals with the metabolic syndrome undergoing adjustable gastric banding. Lipid levels were monitored monthly for 9 months, then three monthly until 24 months., Results: There were 101 participants included, age 47.4 ± 10.9 years with body mass index 42.6 ± 5.9 kg/m 2 . At 24 months, total body weight loss (TBWL) was 18.3 ± 7.9%. This was associated with significant improvements in high-density lipoprotein (HDL) (1.18 vs 1.47, p < 0.001), triglyceride (2.0 vs 1.4, p < 0.001), and total cholesterol to HDL ratio (TC:HDL) (4.6 vs 3.6, p < 0.001). Over this time, progressive and linear improvements in HDL, triglycerides, and TC:HDL were seen with incremental weight loss (observed at 2.5% TBWL intervals). Significant improvements occurred after a threshold weight loss of 7.5-12.5% TBWL was achieved, with odds ratio (OR) 1.48-2.50 for normalization. These odds improved significantly with increasing weight loss (OR 18.2-30.4 with > 25% TBWL). Despite significant weight loss, there was no significant change in low-density lipoprotein (LDL)., Conclusion: Significant improvements in triglycerides, HDL, and TC:HDL occur after 7.5-12.5% TBWL, with ongoing benefit after greater weight loss. LDL needs to be addressed independently, as this was not observed to respond to weight loss alone., Trial Registration Number: Australian Clinical Trials Registry (ACTRN12610000049077).

Background: Long-term outcome data are needed to define the role of bariatric surgery in type 2 diabetes (T2D). To address this, we collated diabetes outcomes more than a decade after laparoscopic adjustable gastric band (LAGB) surgery., Method: Clinical and biochemical measures from 113 obese T2D patients who underwent LAGB surgery in 2003 and 2004 were analyzed. Diabetes remission was defined as HbA1c < 6.2% (44 mmol/mol) and fasting glucose < 7.0 mmol/L., Results: Seventy-nine patients had weight data at 10 years and attained a median [Q1, Q3] weight loss of 16 [10, 21] percent. Sixty patients attended a follow-up assessment. Their baseline HbA1c of 7.8 [7.1, 9.3] percentage units (62 [54, 78] mmol/mol) had decreased to 6.6 [6.1, 8.4] (49 [43, 68] mmol/mol) despite no significant change in glucose-lowering therapy. Eleven patients (18%) were in diabetes remission and another 18 had HbA1c ≤ 6.5%. Significant improvements in physical measures of quality of life, blood pressure, and lipid profile were also observed but there was no change in the proportion of patients with albuminuria and a significant decline in estimated glomerular filtration rate. Twelve patients in the follow-up cohort (20%) required anti-reflux medication after surgery and 26 (43%) underwent gastric band revision surgery., Conclusion: Weight loss for over 10 years after LAGB surgery delivers clinically meaningful improvements in HbA1c, blood pressure, lipids, and quality of life at the cost of a high rate of revision surgery and increased use of anti-reflux medication. These findings support the use of bariatric surgery as a long-term treatment for weight loss and wellbeing in patients with T2D., Study Registration: Registered with the Australian Clinical trials registry as ACTRN12615000089538.

Background: Inflammatory factors derived from adipose tissue have been implicated in mediating insulin resistance in obesity. We sought to identify these using explanted human adipose tissue exposed to innate and adaptive immune stimuli., Methods: Subcutaneous and omental adipose tissue from obese, insulin-resistant donors was cultured in the presence of macrophage and T-cell stimuli, and the conditioned medium tested for its ability to inhibit insulin-stimulated glucose uptake into human Simpson-Golabi-Behmel Syndrome (SGBS) adipocytes. The nature of the inhibitory factor in conditioned medium was characterized physicochemically, inferred by gene microarray analysis and confirmed by antibody neutralization., Results: Conditioned medium from omental adipose tissue exposed to a combination of macrophage- and T-cell stimuli inhibited insulin action and adiponectin secretion in SGBS adipocytes. This effect was associated with a pronounced change in adipocyte morphology, characterized by a decreased number of lipid droplets of increased size. The bioactivity of conditioned medium was abolished by trypsin treatment and had a molecular weight of 46 kDa by gel filtration. SGBS adipocytes exposed to a bioactive medium expressed multiple gene transcripts regulated by interferon-gamma (IFN-γ). Recombinant human IFN-γ recapitulated the effects of the bioactive medium and neutralizing antibody against IFN-γ but not other candidate factors abrogated medium bioactivity., Conclusions: IFN-γ released from inflamed omental adipose tissue may contribute to the metabolic abnormalities seen in human obesity.

Introduction: The effect of the laparoscopic adjustable gastric band (LAGB) on esophageal acid exposure and reflux is poorly understood. Optimal technique and normative values for acid exposure have not been established in this group., Methods: High-resolution manometry (HRM) and 24-h ambulatory esophageal pH monitoring were performed in three groups: asymptomatic LAGB, symptomatic LAGB, and pre-operative reflux patients. This technique utilized intraluminal pressure signatures during HRM to guide accurate pH sensor placement., Results: The LAGB groups were well matched: age 48 vs 51 years (p = 0.249), weight loss 27.3 vs 26.7 kg (p = 0.911). The symptomatic group had a larger gastric pouch (5.2 vs 3.3 cm, p = 0.012), with higher esophageal acid exposure (10.8 vs 0.9%, p < 0.001). Two acidification patterns were observed: irritant and volume acidification, associated with substantial supine acidification. Symptomatic LAGB had altered esophageal motility, with poorer lower esophageal sphincter basal tone (8.0 vs 17.7 mmHg, p = 0.022) and impaired contractility of the lower esophageal segment (90 vs 40%, p = 0.009). Compared to pre-operative reflux patients, symptomatic LAGB patients demonstrated higher total and supine esophageal acid exposure (10.8 vs 7.0%, p = 0.010; 14.9 vs 5.1%, p < 0.001), less symptoms (2 vs 6, p = 0.001) and lower symptom index (0.7 vs 0.9, p = 0.010)., Conclusions: Ambulatory pH monitoring is an effective technique if the pH sensor is positioned appropriately using HRM. The correctly positioned LAGB appears associated with low esophageal acidification. In contrast, patients with symptoms or pouch dilatation can have markedly elevated esophageal acidification, particularly when supine. This is a different pattern compared to pre-operative patients and importantly can be disproportionate to symptoms.

The use of laparoscopic adjustable gastric banding (LAGB) is on the decline around the world despite the evidence base suggesting that it is a safe, effective and durable short-stay procedure which can be safely revised and is well tolerated by patients when they are appropriately supported. Currently, less than 1% of eligible obese persons are choosing to undergo bariatric surgery. If we are to improve uptake of bariatric surgery we need a raft of therapeutic options, including the LAGB, which sit between the relative impotence of medical therapies and the aggression of stapling procedures. This brief communication discusses what some of the drivers may be that are leading surgeons to abandon the band.

Aim: To determine the cost-effectiveness of gastric band surgery in overweight but not obese people who receive standard diabetes care., Method: A microsimulation model (United Kingdom Prospective Diabetes Study outcomes model) was used to project diabetes outcomes and costs from a two-year Australian randomized trial of gastric band (GB) surgery in overweight but not obese people (BMI 25 to 30kg/m 2 ) on to a comparable population of U.S. adults from the National Health and Nutrition Examination Survey (N=254). Estimates of cost-effectiveness were calculated based on the incremental cost-effectiveness ratios (ICERs) for different treatment scenarios. Costs were inflated to 2015 U.S. dollar values and an ICER of less than $50,000 per QALY gained was considered cost-effective., Results: The incremental cost-effectiveness ratio for GB surgery at two years exceeded $90,000 per quality-adjusted life year gained but decreased to $52,000, $29,000 and $22,000 when the health benefits of surgery were assumed to endure for 5, 10 and 15 years respectively. The cost-effectiveness of GB surgery was sensitive to utility gained from weight loss and, to a lesser degree, the costs of GB surgery. However, the cost-effectiveness of GB surgery was affected minimally by improvements in HbA1c, systolic blood pressure and cholesterol., Conclusions: GB surgery for overweight but not obese people with T2D appears to be cost-effective in the U.S. setting if weight loss endures for more than five years. Health utility gained from weight loss is a critical input to cost-effectiveness estimates and therefore should be routinely measured in populations undergoing bariatric surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Substantial weight loss in the setting of obesity has considerable metabolic benefits. Yet some studies have shown improvements in obesity-related metabolic comorbidities with more modest weight loss. By closely monitoring patients undergoing bariatric surgery, we aimed to determine the effects of weight loss on the metabolic syndrome and its components and determine the weight loss required for their resolution., Methods: We performed a prospective observational study of obese participants with metabolic syndrome (Adult Treatment Panel III criteria) who underwent laparoscopic adjustable gastric banding. Participants were assessed for all criteria of the metabolic syndrome monthly for the first 9 months, then 3-monthly until 24 months., Results: There were 89 participants with adequate longitudinal data. Baseline body mass index was 42.4±6.2 kg m -2 with an average age was 48.2±10.7 years. There were 56 (63%) women. Resolution of the metabolic syndrome occurred in 60 of the 89 participants (67%) at 12 months and 60 of the 75 participants (80%) at 24 months. The mean weight loss when metabolic syndrome resolved was 10.9±7.7% total body weight loss (TBWL). The median weight loss at which prevalence of disease halved was 7.0% TBWL (17.5% excess weight loss (EWL)) for hypertriglyceridaemia; 11% TBWL (26.1-28% EWL) for high-density lipoprotein cholesterol and hyperglycaemia; 20% TBWL (59.5% EWL) for hypertension and 29% TBWL (73.3% EWL) for waist circumference. The odds ratio for resolution of the metabolic syndrome with 10-12.5% TBWL was 2.09 (P=0.025), with increasing probability of resolution with more substantial weight loss., Conclusions: In obese participants with metabolic syndrome, a weight loss target of 10-12.5% TBWL (25-30% EWL) is a reasonable initial goal associated with significant odds of having metabolic benefits. If minimal improvements are seen with this initial target, additional weight loss substantially increases the probability of resolution.

Objectives: Nonalcoholic fatty liver disease (NAFLD) affects over 80% of obese patients and is fueled by the metabolic syndrome. Weight loss is strongly advocated as a central treatment for NAFLD and has been shown to induce histological improvement. We aimed to define the patterns of improvement in NAFLD with weight loss and determine target weight goals for NAFLD resolution., Methods: A prospective study of 84 morbidly obese patients with NAFLD undergoing bariatric surgery was conducted. Intraoperative liver biopsies were taken. Monthly follow-up, including blood tests and measurements, was performed. We monitored improvements in NAFLD by monthly alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) levels over 1 year., Results: There was rapid improvement in ALT, particularly in the first 6 months following surgery, with statistically significant reduction in ALT at 2 months (35 vs 27 IU/L, p < 0.001). In multivariate analysis, there were significantly increased odds of ALT normalization after a %TBWL of 10-15% (odds ratio 2.49, p = 0.005). The odds of resolution increased with increasing weight loss. Triglyceride levels (odds ratio 0.59, p = 0.021) and baseline NAFLD activity score (odds ratio 0.28, p < 0.001) were also significantly related to ALT normalization. Improvements in ALT occurred prior to metabolic improvement and well before traditional ideal weight goals were reached., Conclusion: Improvements in NAFLD occurred rapidly after bariatric surgery and were closely related to weight loss and metabolic factors. A 10-15% reduction in body weight is an appropriate target to achieve substantial improvement in ALT levels., Trial Registration Number: Australian Clinical Trials Registry (ACTRN12610000049077).

Background: Patient-reported outcomes and perceptions are critical to the overall efficacy and acceptability of a surgical procedure. Outcomes, such as patient satisfaction and perceived success of the surgery and adverse symptoms, have not been described in detail following bariatric surgery. The associations and predictors of patient satisfaction have not been defined. This study aimed to examine long-term outcomes and perceptions after laparoscopic adjustable gastric banding (LAGB)., Methods: We conducted a prospective study of outcomes, satiety and adverse upper gastrointestinal symptoms, as well as quality of life and subjective patient satisfaction in LAGB patients. Data were collected at 3 years (T1) and 8 years post-operatively (T2)., Results: One-hundred and sixty patients completed follow-up at T1 and T2. The average age was 44.0 ± 11.2 years. At T2, the total body weight loss was 17.8 ± 11.9 %. Satisfaction decreased significantly between time points (8.6 ± 1.8 vs 7.2 ± 2.9, p < 0.01), and quality of life reduced slightly across all domains. Hunger scores remained low (3.8 ± 1.8 vs 3.9 ± 1.8, p = 0.61). The dysphagia score did not change significantly (p = 0.54). There was minimal change in frequency of regurgitation, although there was significant increase in patient assessment of how bothered they were by regurgitation. Multivariate analysis identified increased awareness of regurgitation as a principal driver of reduced satisfaction., Conclusions: Weight loss, satiety and adverse symptoms demonstrated only slight changes between 3 and 8 years post-operatively. Despite this, overall satisfaction and perception of success of the procedure reduced markedly. This appeared mediated by reduced tolerance of adverse symptoms. These data inform follow-up practises aimed at optimizing outcomes.