miR-33 deletion in hepatocytes attenuates NAFLD-NASH-HCC progression.

The complexity of the mechanisms underlying non-alcoholic fatty liver disease (NAFLD) progression remains a significant challenge for the development of effective therapeutics. miRNAs have shown great promise as regulators of biological processes and as therapeutic targets for complex diseases. Here, we study the role of hepatic miR-33, an important regulator of lipid metabolism, during the progression of NAFLD and the development of hepatocellular carcinoma (HCC). We report that miR-33 is elevated in the livers of humans and mice with NAFLD and that its deletion in hepatocytes (miR-33 HKO) improves multiple aspects of the disease, including steatosis and inflammation, limiting the progression to non-alcoholic steatohepatitis (NASH), fibrosis and HCC. Mechanistically, hepatic miR-33 deletion reduces lipid synthesis and promotes mitochondrial fatty acid oxidation, reducing lipid burden. Additionally, absence of miR-33 alters the expression of several known miR-33 target genes involved in metabolism and results in improved mitochondrial function and reduced oxidative stress. The reduction in lipid accumulation and liver injury resulted in decreased YAP/TAZ pathway activation, which may be involved in the reduced HCC progression in HKO livers. Together, these results suggest suppressing hepatic miR-33 may be an effective therapeutic approach to temper the development of NAFLD, NASH, and HCC in obesity.

Core Set of Patient-Reported Outcome Measures for Measuring Quality of Life in Clinical Obesity Care.

PURPOSE: The focus of measuring success in obesity treatment is shifting from weight loss to patients' health and quality of life. The objective of this study was to select a core set of patient-reported outcomes and patient-reported outcome measures to be used in clinical obesity care. MATERIALS AND METHODS: The Standardizing Quality of Life in Obesity Treatment III, face-to-face hybrid consensus meeting, including people living with obesity as well as healthcare providers, was held in Maastricht, the Netherlands, in 2022. It was preceded by two prior multinational consensus meetings and a systematic review. RESULTS: The meeting was attended by 27 participants, representing twelve countries from five continents. The participants included healthcare providers, such as surgeons, endocrinologists, dietitians, psychologists, researchers, and people living with obesity, most of whom were involved in patient representative networks. Three patient-reported outcome measures (patient-reported outcomes) were selected: the Impact of Weight on Quality of Life-Lite (self-esteem) measure, the BODY-Q (physical function, physical symptoms, psychological function, social function, eating behavior, and body image), and the Quality of Life for Obesity Surgery questionnaire (excess skin). No patient-reported outcome measure was selected for stigma. CONCLUSION: A core set of patient-reported outcomes and patient-reported outcome measures for measuring quality of life in clinical obesity care is established incorporating patients' and experts' opinions. This set should be used as a minimum for measuring quality of life in routine clinical practice. It is essential that individual patient-reported outcome measure scores are shared with people living with obesity in order to enhance patient engagement and shared decision-making.

Patient and healthcare practitioner evaluation of patient-reported outcomes in bariatric surgery - a modified Delphi study.

BACKGROUND: Patient-reported outcomes are an important emerging metric increasingly utilised in clinical, research and registry settings. These outcomes, while vital, are underutilised and require refinement for the specific patient population of those undergoing bariatric surgery. This study aimed to investigate and compare how pre-surgical patients, post-surgical patients, and healthcare practitioners evaluate patient-reported outcomes of bariatric surgery to identify outcomes that are considered most important. METHODS: A modified Delphi survey was distributed to patients pre- and post-surgery, and to a variety of healthcare practitioners involved in bariatric care. Across two rounds, participants were asked to rate a variety of physical and psychosocial outcomes of bariatric surgery from 0 (Not Important) to 10 (Extremely Important). Outcomes rated 8-10 by at least 70% of participants were considered highly important (prioritised). The highest-rated outcomes were compared between the three groups as well as between medical and allied health practitioner subgroups. RESULTS: 20 pre-surgical patients, 95 post-surgical patients, and 28 healthcare practitioners completed both rounds of the questionnaire. There were 58 outcomes prioritised, with 21 outcomes (out of 90, 23.3%) prioritised by all three groups, 13 (14.4%) by two groups, and 24 (26.7%) prioritised by a single group or subgroup. Unanimously prioritised outcomes included 'Co-morbidities', 'General Physical Health', 'Overall Quality of Life' and 'Overall Mental Health'. Discordant outcomes included 'Fear of Weight Regain', 'Suicidal Thoughts', 'Addictive Behaviours', and 'Experience of Stigma or Discrimination'. CONCLUSION: While there was considerable agreement between stakeholder groups on many outcomes, there remain several outcomes with discordant importance valuations that must be considered. In particular, healthcare practitioners prioritised 20 outcomes that were not prioritised by patients, emphasising the range of priorities across stakeholder groups. Future work will consider these priorities to ensure resulting measures encompass all important outcomes and are beneficial and valid for end users.

Metabolic and Bariatric Surgeon Criteria-An International Experts' Consensus.

PURPOSE: With the global epidemic of obesity, the importance of metabolic and bariatric surgery (MBS) is greater than ever before. Performing these surgeries requires academic training and the completion of a dedicated fellowship training program. This study aimed to develop guidelines based on expert consensus using a modified Delphi method to create the criteria for metabolic and bariatric surgeons that must be mastered before obtaining privileges to perform MBS. METHODS: Eighty-nine recognized MBS surgeons from 42 countries participated in the Modified Delphi consensus to vote on 30 statements in two rounds. An agreement/disagreement among ≥ 70.0% of the experts was regarded to indicate a consensus. RESULTS: Consensus was reached on 29 out of 30 statements. Most experts agreed that before getting privileges to perform MBS, surgeons must hold a general surgery degree and complete or have completed a dedicated fellowship training program. The experts agreed that the learning curves for the various operative procedures are approximately 25-50 operations for the LSG, 50-75 for the OAGB, and 75-100 for the RYGB. 93.1% of experts agreed that MBS surgeons should diligently record patients' data in their National or Global database. CONCLUSION: MBS surgeons should have a degree in general surgery and have been enrolled in a dedicated fellowship training program with a structured curriculum. The learning curve of MBS procedures is procedure dependent. MBS surgeons must demonstrate proficiency in managing postoperative complications, collaborate within a multidisciplinary team, commit to a minimum 2-year patient follow-up, and actively engage in national and international MBS societies.

Modified One Anastomosis Gastric Bypass Following Sleeve Gastrectomy for Severe Reflux and Delayed Gastric Emptying: A Prospective Trial with Clinical and Physiological Outcome Measures.

BACKGROUND: Gastro-esophageal reflux (GORD) following sleeve gastrectomy (SG) is a central challenge, and precise indications for revisional surgery or the physiology have not been precisely defined. We aimed to determine whether OAGB performed for reflux post-SG (1) accelerates gastric emptying half-time, (2) reduces the frequency and severity of reflux events, and (3) improves reflux symptoms. METHODS: We undertook a prospective trial (ACTRN12616001089426). There were 22 participants who underwent measurement before and after revisional surgery with 29 optimal SG (patients with optimal outcome from their primary surgery) as controls. All participants underwent a protocolized nuclear scintigraphy, 24-h pH monitoring, and gastroscopy and completed objective questionnaires. RESULTS: Trial patients were 90.9% female, age 44.4 years. Conversion from SG to OAGB was at a median of 45.2 ± 19.6 months. Scintigraphy showed an increased rate of gastric emptying post-OAGB 34 (IQR 14) vs 24 (IQR 10.3) min, p-value 0.008, with decreased number of reflux events post-prandially (39 (IQR 13) vs 26 (IQR 7), p-value 0.001). This data correlated with the pH analysis; total acid events substantially reduced post-OAGB 58.5 (IQR 88) vs 12 (IQR 9.4) events, p-value 0.017. Endoscopic findings indicated a reduction in incidence of bile stasis 72.7% vs 40.9% post-OAGB, p-value < 0.00010. Post-OAGB, patients experienced less frequent regurgitation (12 ± 4.1 vs. 5.5 ± 3, p-value 0.012) and reflux (37.1 ± 15.7 vs. 16.8 ± 12.6, p-value 0.003). CONCLUSIONS: We found OAGB is an effective treatment for reflux associated with delayed gastric emptying post-SG. The likely mechanisms is by, an increase in the rate of gastric clearance and reduced reflux events and overall esophageal acid exposure. This suggests that some forms of post-SG reflux are driven by slower emptying of the residual stomach and are amenable to treatment with drainage above the incisura.

Metabolic Bariatric Surgery Across the IFSO Chapters: Key Insights on the Baseline Patient Demographics, Procedure Types, and Mortality from the Eighth IFSO Global Registry Report.

INTRODUCTION: The International Federation for Surgery for Obesity and Metabolic Disorders (IFSO) Global Registry aims to provide descriptive data about the caseload and penetrance of surgery for metabolic disease and obesity in member countries. The data presented in this report represent the key findings of the eighth report of the IFSO Global Registry. METHODS: All existing Metabolic and Bariatric Surgery (MBS) registries known to IFSO were invited to contribute to the eighth report. Aggregated data was provided by each MBS registry to the team at the Australia and New Zealand Bariatric Surgery Registry (ANZBSR) and was securely stored on a Redcap™ database housed at Monash University, Melbourne, Australia. Data was checked for completeness and analyzed by the IFSO Global Registry Committee. Prior to the finalization of the report, all graphs were circulated to contributors and to the global registry committee of IFSO to ensure data accuracy. RESULTS: Data was received from 24 national and 2 regional registries, providing information on 502,150 procedures. The most performed primary MBS procedure was sleeve gastrectomy, whereas the most performed revisional MBS procedure was Roux-en-Y gastric bypass. Asian countries reported people with lower BMI undergoing MBS along with higher rates of diabetes. Mortality was a rare event. CONCLUSION: Registries enable meaningful comparisons between countries on the demographics, characteristics, operation types and approaches, and trends in MBS procedures. Reported outcomes can be seen as flags of potential issues or relationships that could be studied in more detail in specific research studies.

Impact of bariatric surgery on anthropometric, metabolic, and reproductive outcomes in polycystic ovary syndrome: a systematic review and meta-analysis.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in females. Modest weight loss improves reproductive and metabolic PCOS features. While lifestyle modifications and pharmacotherapies remain first-line weight loss strategies, bariatric surgery is emerging as a potentially effective treatment. We performed a systematic review and meta-analysis of published literature to examine the impact of bariatric surgery in PCOS to inform the 2023 International PCOS Evidence-based Guidelines. Electronic databases were searched for observational studies and trials comparing pharmacologic or lifestyle treatments to bariatric surgery in women with PCOS or bariatric surgery in women with or without PCOS. Anthropometric, reproductive, hormonal, and metabolic outcomes were included and, where possible, meta-analyzed using random-effects models. Risk of bias and evidence quality were assessed. Ten studies were included involving 432 women with and 590 women without PCOS. Comparisons between bariatric surgery and pharmacologic or lifestyle treatments were only reported in one study each, and most reproductive outcomes were limited to a single study; therefore, meta-analyses could not be performed. Meta-analysis found that women with PCOS experience similar improvements in anthropometric, hormonal, and metabolic outcomes after bariatric surgery compared to those without PCOS. Existing research is limited and of low quality with high risk of bias, especially in comparison to existing PCOS treatments and with respect to reproductive outcomes including pregnancy, highlighting the need for additional studies to inform clinical recommendations.

Emerging multi-port soft tissue robotic systems: a systematic review of clinical outcomes.

Multiple novel multi-port robotic surgical systems have been introduced into clinical practice. This systematic review aims to evaluate the clinical outcomes of these novel robotic systems to conventional laparoscopic technique and established da Vinci robotic surgical platforms. A literature search of Embase, Medline, Pubmed, Cochrane library, and Google Scholar was performed according to the PRISMA guidelines from 2012 to May 2023. Studies comparing clinical outcomes of novel multi-port robotic surgical systems with laparoscopic or the da Vinci platforms were included. Case series with no comparison groups were excluded. Descriptive statistics were used to report patient and outcome data. A systematic narrative review was provided for each outcome. Twelve studies comprised of 1142 patients were included. A total of 6 novel multi-port robotic systems: Micro Hand S, Senhance, Revo-i MSR-5000, KangDuo, Versius, and Hugo™ RAS were compared against the laparoscopic or the da Vinci robotic platforms. Clinical outcomes of these novel robotic platforms were comparable to the established da Vinci platforms. When compared against conventional laparoscopic approaches, the robotic platforms demonstrated lower volume of blood loss, shorter length of stay but longer operative time. This systematic review highlighted the safe implementation and efficacy of 6 new robotic systems. The clinical outcomes achieved by these new robotic systems are comparable to the established da Vinci robotic system in simple to moderate case complexities. There is emerging evidence that these new robotic systems provide a viable alternative to currently available robotic platforms.

Robotic versus laparoscopic gastric bypass in bariatric surgery: a systematic review and meta-analysis on perioperative outcomes.

BACKGROUND: Robotic-assisted surgery has emerged as a compelling approach to bariatric surgery. However, current literature has not consistently demonstrated superior outcomes to laparoscopic bariatric surgery to justify its higher cost. With its mechanical advantages, the potential gains from the robotic surgical platform are likely to be apparent in more complex cases such as gastric bypass, especially revisional cases. OBJECTIVE: This systematic review and meta-analysis aimed to summarize the literature and evaluate the peri-operative outcomes of patients with obesity undergoing robotic gastric bypass versus laparoscopic gastric bypass surgery. SETTING: Systematic review. METHODS: A literature search of Embase, Medline, Pubmed, Cochrane library, and Google Scholar was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies comparing outcomes of robotic and laparoscopic gastric bypass for obesity were included. RESULTS: Twenty-eight eligible studies comprised a total of 82,155 patients; 9051 robotic bypass surgery (RBS) versus 73,104 laparoscopic bypass surgery (LBS) were included. All included studies compared Roux-en-Y gastric bypass. RBS was noted to have higher reoperation rate within 30 days (4.4% versus 3.4%; odds ratio 1.31 [95% CI, 1.04-1.66]; P = .027; I2 = 43.5%) than LBS. All other endpoints measured (complication rate, anastomotic leak, anastomotic stricture, surgical site infections, hospital readmission, length of stay, operative time, conversion rate and mortality) did not show any difference between RBS and LBS. CONCLUSION: This systematic review and meta-analysis showed that there was no significant difference in key outcome measures in robotic versus laparoscopic gastric bypass. RBS was associated with a slightly higher reoperation rate and there was no reduction in overall complication rate with the use of robotic platform.

Mitochondria- and NOX4-dependent antioxidant defense mitigates progression to nonalcoholic steatohepatitis in obesity.

Nonalcoholic fatty liver disease (NAFLD) is prevalent in the majority of individuals with obesity, but in a subset of these individuals, it progresses to nonalcoholic steatohepatitis (0NASH) and fibrosis. The mechanisms that prevent NASH and fibrosis in the majority of patients with NAFLD remain unclear. Here, we report that NAD(P)H oxidase 4 (NOX4) and nuclear factor erythroid 2-related factor 2 (NFE2L2) were elevated in hepatocytes early in disease progression to prevent NASH and fibrosis. Mitochondria-derived ROS activated NFE2L2 to induce the expression of NOX4, which in turn generated H2O2 to exacerbate the NFE2L2 antioxidant defense response. The deletion or inhibition of NOX4 in hepatocytes decreased ROS and attenuated antioxidant defense to promote mitochondrial oxidative stress, damage proteins and lipids, diminish insulin signaling, and promote cell death upon oxidant challenge. Hepatocyte NOX4 deletion in high-fat diet-fed obese mice, which otherwise develop steatosis, but not NASH, resulted in hepatic oxidative damage, inflammation, and T cell recruitment to drive NASH and fibrosis, whereas NOX4 overexpression tempered the development of NASH and fibrosis in mice fed a NASH-promoting diet. Thus, mitochondria- and NOX4-derived ROS function in concert to drive a NFE2L2 antioxidant defense response to attenuate oxidative liver damage and progression to NASH and fibrosis in obesity.

Barriers to progression through Australian obesity management pathways: Survey data from the ACTION-IO study.

BACKGROUND AND OBJECTIVES: Our previous work uncovered a nine-year delay, from when Australian people with obesity (PwO) first began struggling with excess weight and first discussed weight with a healthcare professional (HCP). In this study we explore barriers to having an obesity consultation, making and discussing the diagnosis of obesity and arranging a management plan, including a follow-up appointment. METHOD: Australian PwO (n = 1000) and HCPs (n = 200; 50% general practitioners [GPs]), completed the Awareness, Care & Treatment In Obesity Management - An International Observation (ACTION-IO) online survey. RESULTS: Of Australian PwO, 53% had discussed weight with an HCP in the past five years, 25% were informed of their obesity diagnosis and 15% had weight-related follow-up appointments scheduled. Fewer GPs than other specialists reported recording obesity diagnoses, but GPs scheduled more follow-up appointments. Receiving formal obesity training was reported by 22% of GPs and 44% of other specialists. DISCUSSION: Barriers to obesity care in Australia include unrealistic expectations from both PwO and HCPs, lack of evidence-based strategies and insufficient training. Further exploration of barriers is required.

Infrared photodesorption of CO from astrophysically relevant ices studied with a free-electron laser.

The infrared excitation and photodesorption of carbon monoxide (CO) and water-containing ices have been investigated using the FEL-2 free-electron laser light source at the FELIX laboratory, Radboud University, The Netherlands. CO-water mixed ices grown on a gold-coated copper substrate at 18 K were investigated. No CO photodesorption was observed, within our detection limits, following irradiation with light resonant with the C-O vibration (4.67 µm). CO photodesorption was seen as a result of irradiation with infrared light resonant with water vibrational modes at 2.9 µm and 12 µm. Changes to the structure of the water ice, which modifies the environment of the CO in the mixed ice, were also seen subsequent to irradiation at these wavelengths. No water desorption was observed at any wavelength of irradiation. Photodesorption at both wavelengths is due to a single-photon process. Photodesorption arises due to a combination of fast and slow processes of indirect resonant photodesorption (fast), and photon-induced desorption resulting from energy accumulation in the librational heat bath of the solid water (slow) and metal-substrate-mediated laser-induced thermal desorption (slow). Estimated cross-sections for the slow processes at 2.9 µm and 12 µm were found to be ∼7.5 × 10-18 cm2 and ∼4.5 × 10-19 cm2, respectively.

Incidence of adverse mental health outcomes after sleeve gastrectomy compared with gastric bypass and restrictive bariatric procedures: a retrospective cohort study.

OBJECTIVE: This study examined rates of suicide and hospitalization with psychiatric diagnoses after sleeve gastrectomy compared with gastric bypass and restrictive procedures (gastric banding/gastroplasty). METHODS: This was a longitudinal retrospective cohort study comprising all patients who underwent primary bariatric surgery in New South Wales or Queensland, Australia, between July 2001 and December 2020. Hospital admission records, death registration, and cause of death records (if applicable) within these dates were extracted and linked. Primary outcome was death by suicide. Secondary outcomes were admissions with self-harm; substance-use disorder, schizophrenia, mood, anxiety, behavioral, and personality disorders; any of these; and psychiatric inpatient admission. RESULTS: A total of 121,203 patients were included, with median follow-up of 4.5 years per patient. There were 77 suicides, with no evidence of difference in rates by surgery type (rates [95% CI] per 100,000 person years: 9.6 [5.0-18.4] restrictive, 10.8 [8.4-13.9] sleeve gastrectomy, 20.4 [9.7-42.8] gastric bypass; p = 0.18). Rates of admission with self-harm declined after restrictive and sleeve procedures. Admission with anxiety disorders, any psychiatric diagnosis, and as a psychiatric inpatient increased after sleeve gastrectomy and gastric bypass, but not restrictive procedures. Admissions with substance-use disorder increased after all surgery types. CONCLUSIONS: Variable associations between bariatric surgeries and hospitalization with psychiatric diagnoses might indicate distinct vulnerabilities among patient cohorts or that differing anatomical and/or functional changes may contribute to effects on mental health.

Malnutrition defined by GLIM criteria identifies a higher incidence of malnutrition and is associated with pulmonary complications after oesophagogastric cancer surgery, compared to ICD-10-defined malnutrition.

BACKGROUND & OBJECTIVES: Low muscle mass, measured using computed tomography (CT), is associated with poor surgical outcomes. We aimed to include CT-muscle mass in malnutrition diagnosis using the Global Leadership Initiative on Malnutrition (GLIM) criteria, compare it to the International Classification of Diseases 10th Revision (ICD-10) criteria, and assess the impact on postoperative outcomes after oesophagogastric (OG) cancer surgery. METHODS: One hundred and eight patients who underwent radical OG cancer surgery and had preoperative abdominal CT imaging were included. GLIM and ICD-10 malnutrition data were assessed against complication and survival outcomes. Low CT-muscle mass was determined using predefined cut-points. RESULTS: GLIM-defined malnutrition prevalence was significantly higher than ICD-10-malnutrition (72.2% vs. 40.7%, p < 0.001). Of the 78 patients with GLIM-defined malnutrition, low muscle mass (84.6%) was the predominant phenotypic criterion. GLIM-defined malnutrition was associated with pneumonia (26.9% vs. 6.7%, p = 0.010) and pleural effusions (12.8% vs. 0%, p = 0.029). Postoperative complications did not correlate with ICD-10 malnutrition. Severe GLIM (HR: 2.51, p = 0.014) and ICD-10 (HR: 2.15, p = 0.039) malnutrition were independently associated with poorer 5-year survival. CONCLUSIONS: GLIM criteria appear to identify more malnourished patients and more closely relate to surgical risk than ICD-10 malnutrition, likely due to incorporating objective muscle mass assessment.

The length of hospital stay following bariatric surgery in Australia: the impact of patient, procedure, system and surgeon.

BACKGROUND: The length of a patient's stay (LOS) in a hospital is one metric used to compare the quality of care, as a longer LOS may flag higher complication rates or less efficient processes. A meaningful comparison of LOS can only occur if the expected average length of stay (ALOS) is defined first. This study aimed to define the expected ALOS of primary and conversion bariatric surgery in Australia and to quantify the effect of patient, procedure, system, and surgeon factors on ALOS. METHODS: This was a retrospective observational study of prospectively maintained data from the Bariatric Surgery Registry of 63 604 bariatric procedures performed in Australia. The primary outcome measure was the expected ALOS for primary and conversion bariatric procedures. The secondary outcome measures quantified the change in ALOS for bariatric surgery resulting from patient, procedure, hospital, and surgeon factors. RESULTS: Uncomplicated primary bariatric surgery had an ALOS (SD) of 2.30 (1.31) days, whereas conversion procedures had an ALOS (SD) of 2.71 (2.75) days yielding a mean difference (SEM) in ALOS of 0.41 (0.05) days, P < 0.001. The occurrence of any defined adverse event extended the ALOS of primary and conversion procedures by 1.14 days (CI 95% 1.04-1.25), P < 0.001 and 2.33 days (CI 95% 1.54-3.11), P < 0.001, respectively. Older age, diabetes, rural home address, surgeon operating volume and hospital case volume increased the ALOS following bariatric surgery. CONCLUSIONS: Our findings have defined Australia's expected ALOS following bariatric surgery. Increased patient age, diabetes, rural living, procedural complications and surgeon and hospital case volume exerted a small but significant increase in ALOS. STUDY TYPE: Retrospective observational study of prospectively collected data.

Bariatric Surgery Efficiency, Safety and Health Outcomes in Government Versus Privately Funded Hospitals.

PURPOSE: This study aims to determine if the hospital efficiency, safety and health outcomes are equal in patients who receive bariatric surgery in government-funded hospitals (GFH) versus privately funded hospitals (PFH). MATERIALS AND METHODS: This is a retrospective observational study of prospectively maintained data from the Australia and New Zealand Bariatric Surgery Registry of 14,862 procedures (2134 GFH and 12,728 PFH) from 33 hospitals (8 GFH and 25 PFH) performed in Victoria, Australia, between January 1st, 2015, and December 31st, 2020. Outcome measures included the difference in efficacy (weight loss, diabetes remission), safety (defined adverse event and complications) and efficiency (hospital length of stay) between the two health systems. RESULTS: GFH treated a higher risk patient group who were older by a mean (SD) 2.4 years (0.27), P < 0.001; had a mean 9.0 kg (0.6) greater weight at time of surgery, P < 0.001; and a higher prevalence of diabetes at day of surgery OR = 2.57 (CI95%2.29-2.89), P < 0.001. Despite these baseline differences, both GFH and PFH yielded near identical remission of diabetes which was stable up to 4 years post-operatively (57%). There was no statistically significant difference in defined adverse events between the GFH and PFH (OR = 1.24 (CI95% 0.93-1.67), P = 0.14). Both healthcare settings demonstrated that similar covariates affect length of stay (LOS) (diabetes, conversion bariatric procedures and defined adverse event); however, these covariates had a greater effect on LOS in GFH compared to PFH. CONCLUSIONS: Bariatric surgery performed in GFH and PFH yields comparable health outcomes (metabolic and weight loss) and safety. There was a small but statistically significant increased LOS following bariatric surgery in GFH.

Long-term impact of weight loss for people with overweight but not obesity, and with type 2 diabetes: 10-year outcomes of a randomized trial of gastric band surgery.

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.

Liver-Secreted Hexosaminidase A Regulates Insulin-Like Growth Factor Signaling and Glucose Transport in Skeletal Muscle.

Nonalcoholic fatty liver disease (NAFLD) and impaired glycemic control are closely linked; however, the pathophysiological mechanisms underpinning this bidirectional relationship remain unresolved. The high secretory capacity of the liver and impairments in protein secretion in NAFLD suggest that endocrine changes in the liver are likely to contribute to glycemic defects. We identify hexosaminidase A (HEXA) as an NAFLD-induced hepatokine in both mice and humans. HEXA regulates sphingolipid metabolism, converting GM2 to GM3 gangliosides-sphingolipids that are primarily localized to cell-surface lipid rafts. Using recombinant murine HEXA protein, an enzymatically inactive HEXA(R178H) mutant, or adeno-associated virus vectors to induce hepatocyte-specific overexpression of HEXA, we show that HEXA improves blood glucose control by increasing skeletal muscle glucose uptake in mouse models of insulin resistance and type 2 diabetes, with these effects being dependent on HEXA's enzymatic action. Mechanistically, HEXA remodels muscle lipid raft ganglioside composition, thereby increasing IGF-1 signaling and GLUT4 localization to the cell surface. Disrupting lipid rafts reverses these HEXA-mediated effects. In this study, we identify a pathway for intertissue communication between liver and skeletal muscle in the regulation of systemic glycemic control.