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.

Liver-derived extracellular vesicles improve whole-body glycaemic control via inter-organ communication.

Small extracellular vesicles (EVs) are signalling messengers that regulate inter-tissue communication through delivery of their molecular cargo. Here, we show that liver-derived EVs are acute regulators of whole-body glycaemic control in mice. Liver EV secretion into the circulation is increased in response to hyperglycaemia, resulting in increased glucose effectiveness and insulin secretion through direct inter-organ EV signalling to skeletal muscle and the pancreas, respectively. This acute blood glucose lowering effect occurs in healthy and obese mice with non-alcoholic fatty liver disease, despite marked remodelling of the liver-derived EV proteome in obese mice. The EV-mediated blood glucose lowering effects were recapitulated by administration of liver EVs derived from humans with or without progressive non-alcoholic fatty liver disease, suggesting broad functional conservation of liver EV signalling and potential therapeutic utility. Taken together, this work reveals a mechanism whereby liver EVs act on peripheral tissues via endocrine signalling to restore euglycaemia in the postprandial state.

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.

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.

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.

dsMTL: a computational framework for privacy-preserving, distributed multi-task machine learning.

MOTIVATION: In multi-cohort machine learning studies, it is critical to differentiate between effects that are reproducible across cohorts and those that are cohort-specific. Multi-task learning (MTL) is a machine learning approach that facilitates this differentiation through the simultaneous learning of prediction tasks across cohorts. Since multi-cohort data can often not be combined into a single storage solution, there would be the substantial utility of an MTL application for geographically distributed data sources. RESULTS: Here, we describe the development of 'dsMTL', a computational framework for privacy-preserving, distributed multi-task machine learning that includes three supervised and one unsupervised algorithms. First, we derive the theoretical properties of these methods and the relevant machine learning workflows to ensure the validity of the software implementation. Second, we implement dsMTL as a library for the R programming language, building on the DataSHIELD platform that supports the federated analysis of sensitive individual-level data. Third, we demonstrate the applicability of dsMTL for comorbidity modeling in distributed data. We show that comorbidity modeling using dsMTL outperformed conventional, federated machine learning, as well as the aggregation of multiple models built on the distributed datasets individually. The application of dsMTL was computationally efficient and highly scalable when applied to moderate-size (n < 500), real expression data given the actual network latency. AVAILABILITY AND IMPLEMENTATION: dsMTL is freely available at https://github.com/transbioZI/dsMTLBase (server-side package) and https://github.com/transbioZI/dsMTLClient (client-side package). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Comprehensive Analysis of Improvements in Health-Related Quality of Life and Establishment of QALY Gains in a Government-Funded Bariatric Surgical Program with 5-Year Follow-up.

PURPOSE: Bariatric surgery is an efficacious intervention for substantial and sustained weight reduction in individuals with morbid obesity resulting in health improvements. However, the changes to a patient's health related quality of life (HRQoL) in the medium to longer term after bariatric surgery have not been adequately characterized. Our aim was to evaluate the change to patient HRQoL 5 years following bariatric surgery in an Australian government-funded hospital system and determine the significance of relationships between change in physical and mental assessment scores and HRQoL utility scores. MATERIALS AND METHODS: We performed a longitudinal panel study of 81 adult patients who underwent primary bariatric surgery at an Australian tertiary government-funded hospital and completed multi-attribute utility (MAU), multi-attribute non-utility (MA), and disease-specific adjusted quality of life (AQoL) questionnaires before and after bariatric surgery. RESULTS: At a mean (SD) 5.72 (1.07) years postbariatric surgery, participants demonstrated statistically significant improvements in mean AQoL-8D utility (0.135 (0.21); P < 0.0001), yielding a mean 3.2 (1.67) QALYs gained. Beck Depression Inventory-II scores improved (baseline mean 17.35 (9.57); 5-year mean 14.7 (11.57); P = 0.037). Short Form-36 scores improved in the domains of physical functioning and role limitations due to physical health and general health. Change in depression scores and patient satisfaction with surgery were found to be significant predictors of follow up AQoL utility scores. CONCLUSIONS: Bariatric surgery improves physical and psychological quality of life measures over 5 years. The improvement of patient QALYs provide insight to the potential cost utility of publicly funded bariatric surgery in the medium term.

Effect of Bariatric Surgery on Risk of Complications After Total Knee Arthroplasty: A Randomized Clinical Trial.

Importance: People with severe obesity who undergo a total knee arthroplasty (TKA) for osteoarthritis (OA) are at higher risk of short-term and long-term complications compared with people with reference (<30) body mass index (BMI; weight in kilograms divided by height in meters squared). It is not known whether weight loss before TKA modifies this risk. Objective: To determine whether outcomes are improved by undergoing bariatric surgery before TKA in people with BMI greater than or equal to 35 and end-stage OA. Design, Setting, and Participants: This parallel-group, assessor-blinded, randomized clinical trial was conducted between May 2012 and June 2020 with a minimum follow-up of 12 months after TKA. TKA was performed at a tertiary referral university-affiliated public hospital, and bariatric surgery was performed at a private hospital facility and a university-affiliated private practice. Data analysis was performed from February to July 2021. Interventions: Bariatric surgery compared with usual weight management advice (treatment as usual [TAU]) in people scheduled for TKA. Main Outcomes and Measures: The primary outcome was complications of TKA measured by a composite of death from any cause, perioperative or postoperative complications resulting in a discharge delay, unplanned procedure, or readmission for at least 12 months after TKA. Secondary outcomes included hospital bed day utilization, anthropomorphic measures, and patient-reported outcomes. Results: Eighty-two patients waiting for TKA were randomized to undergo bariatric surgery (41 patients) or TAU (41 patients). Of the 82 participants, 66 (80.5%) were women, the mean (SD) age was 57.8 (4.9) years, and the mean (SD) BMI was 43.8 (5.5). Thirty-nine participants (95.1%) in the intervention group underwent laparoscopic adjustable gastric banding, and 29 (70.7%) subsequently underwent TKA. Thirty-nine patients (95.1%) in the TAU group underwent TKA. Six patients (14.6%) in the intervention group incurred the primary outcome (median follow-up, 24 months), compared with 15 (36.6%) in the TAU group (median follow-up, 27 months) (difference, 22.0%; 95% CI, 3.7% to 40.3%; P = .02). The between-group difference in BMI at 12 months was -6.32 (95% CI, -7.90 to -4.50; P < .001) in favor of the intervention group. TKA was declined by 12 participants (29.3%) in the intervention group because of symptom improvement, whereas 2 participants (4.9%) in the TAU group declined TKA (difference, 24.4%; 95% CI, 9.0% to 39.8%; P = .003). Conclusions and Relevance: Weight loss following bariatric surgery reduced the risk of complications of TKA in people with BMI greater than or equal to 35. Significantly fewer participants required TKA following weight loss, contributing to this finding. Trial Registration: Australian New Zealand Clinical Trials Registry Number: ACTRN12611001178932.

Deep proteomic profiling unveils arylsulfatase A as a non-alcoholic steatohepatitis inducible hepatokine and regulator of glycemic control.

Non-alcoholic steatohepatitis (NASH) and type 2 diabetes are closely linked, yet the pathophysiological mechanisms underpinning this bidirectional relationship remain unresolved. Using proteomic approaches, we interrogate hepatocyte protein secretion in two models of murine NASH to understand how liver-derived factors modulate lipid metabolism and insulin sensitivity in peripheral tissues. We reveal striking hepatokine remodelling that is associated with insulin resistance and maladaptive lipid metabolism, and identify arylsulfatase A (ARSA) as a hepatokine that is upregulated in NASH and type 2 diabetes. Mechanistically, hepatic ARSA reduces sulfatide content and increases lysophosphatidylcholine (LPC) accumulation within lipid rafts and suppresses LPC secretion from the liver, thereby lowering circulating LPC and lysophosphatidic acid (LPA) levels. Reduced LPA is linked to improvements in skeletal muscle insulin sensitivity and systemic glycemic control. Hepatic silencing of Arsa or inactivation of ARSA's enzymatic activity reverses these effects. Together, this study provides a unique resource describing global changes in hepatokine secretion in NASH, and identifies ARSA as a regulator of liver to muscle communication and as a potential therapeutic target for type 2 diabetes.

Low muscularity increases the risk for post-operative pneumonia and delays recovery from complications after oesophago-gastric cancer resection.

BACKGROUND: Low muscularity is associated with adverse surgical outcomes. We aimed to determine whether low muscularity is associated with an increased risk of post-operative complications and reduced long-term survival after oesophago-gastric cancer surgery. METHODS: Patients who underwent radical oesophago-gastric cancer surgery with preoperative abdominal computed tomography (CT) imaging were included. Low skeletal muscle index (SMI), measured by CT, was determined using pre-defined cut-points. Oncological, surgical, complications and outcome data were obtained from a prospective database. RESULTS: Of 108 patients, 61% (n = 66) had low SMI preoperatively. Patients with low SMI had a higher rate of post-operative pneumonia (30 vs. 7% normal muscularity, P = 0.004). Median length of stay (LOS) was higher in patients with low SMI if they had any complication (19.5 vs. 14 days, P = 0.026) or pneumonia (21 vs. 13 days, P = 0.018). On multivariate analysis, low SMI (OR 3.85, CI 1.10-13.4, P = 0.025), preoperative weight loss (OR 1.13, CI 1.01-1.25, P = 0.027), and smoking (OR 5.08, CI 1.24-20.9, P = 0.024) were independent predictors of having a severe complication. There was no difference in 5-year overall (62% vs. 69%, P = 0.241) and disease-free (11% vs. 21.4%, P = 0.110) survival between low SMI and normal muscle mass groups. CONCLUSION: Low SMI is associated with a significantly increased risk of pneumonia and increased LOS for patients with complications. Assessment of muscle mass may require additional muscle quality, strength, and physical performance measures to enhance preoperative risk assessment.

Potential positive effects of bariatric surgery on healthcare resource utilisation.

BACKGROUND: To determine whether a bariatric surgical procedure is associated with a reduction in healthcare utilisation among patients with obesity and high pre-procedural healthcare needs. METHODS: Design: Retrospective cohort study. SETTING: Tertiary Victorian public hospital. PARTICIPANTS: Twenty-nine adults who underwent publicly funded primary bariatric surgery between 2008 and 2018 at the Alfred Hospital, Melbourne and had high resource use over the year prior to surgery, defined as at least two of ≥3 hospital admissions, ≥7 inpatient bed days for obesity-related co-morbidities or inpatient hospital costs ≥$10 000. MAIN OUTCOME MEASURES: Change in inpatient and outpatient resource use. RESULTS: After 1 year following bariatric surgery, total hospital bed days decreased from 663 to 80 and the median (Q1, Q3) per patient decreased from 7 (4.5, 15) to 5 (2.25, 9.75) (p = 0.001) and the total number of hospital admissions fell from 118 to 67 (p < 0.001). The median cost of inpatient care decreased from $11 405 ($4408, $22251) to $3974 ($0, $4325) per annum (p < 0.001). The total and median number of outpatient attendances did not significantly change 12 months after bariatric surgery, but the demand for outpatient services unrelated to bariatric surgery declined by a median of four visits per patient (p = 0.013). CONCLUSIONS: The evidence from this small pilot study suggests that Bariatric surgery has the potential to decrease resource use and inpatient hospital costs over a 1-year time frame for obese patients with high resource use. These data will be used to design a prospective randomised controlled trial to provide more definitive information on this important issue.

Proteome analysis of human adipocytes identifies depot-specific heterogeneity at metabolic control points.

Adipose tissue is a primary regulator of energy balance and metabolism. The distribution of adipose tissue depots is of clinical interest because the accumulation of upper-body subcutaneous (ASAT) and visceral adipose tissue (VAT) is associated with cardiometabolic diseases, whereas lower-body glutealfemoral adipose tissue (GFAT) appears to be protective. There is heterogeneity in morphology and metabolism of adipocytes obtained from different regions of the body, but detailed knowledge of the constituent proteins in each depot is lacking. Here, we determined the human adipocyte proteome from ASAT, VAT, and GFAT using high-resolution Sequential Window Acquisition of all Theoretical (SWATH) mass spectrometry proteomics. We quantified 4,220 proteins in adipocytes, and 2,329 proteins were expressed in all three adipose depots. Comparative analysis revealed significant differences between adipocytes from different regions (6% and 8% when comparing VAT vs. ASAT and GFAT, 3% when comparing the subcutaneous adipose tissue depots, ASAT and GFAT), with marked differences in proteins that regulate metabolic functions. The VAT adipocyte proteome was overrepresented with proteins of glycolysis, lipogenesis, oxidative stress, and mitochondrial dysfunction. The GFAT adipocyte proteome predicted the activation of peroxisome proliferator-activated receptor α (PPARα), fatty acid, and branched-chain amino acid (BCAA) oxidation, enhanced tricarboxylic acid (TCA) cycle flux, and oxidative phosphorylation, which was supported by metabolomic data obtained from adipocytes. Together, this proteomic analysis provides an important resource and novel insights that enhance the understanding of metabolic heterogeneity in the regional adipocytes of humans.NEW & NOTEWORTHY Adipocyte metabolism varies depending on anatomical location and the adipocyte protein composition may orchestrate this heterogeneity. We used SWATH proteomics in patient-matched human upper- (visceral and subcutaneous) and lower-body (glutealfemoral) adipocytes and detected 4,220 proteins and distinguishable regional proteomes. Upper-body adipocyte proteins were associated with glycolysis, de novo lipogenesis, mitochondrial dysfunction, and oxidative stress, whereas lower-body adipocyte proteins were associated with enhanced PPARα activation, fatty acid, and BCAA oxidation, TCA cycle flux, and oxidative phosphorylation.

Dietary Macronutrient Composition in Relation to Circulating HDL and Non-HDL Cholesterol: A Federated Individual-Level Analysis of Cross-Sectional Data from Adolescents and Adults in 8 European Studies.

BACKGROUND: Associations between increased dietary fat and decreased carbohydrate intake with circulating HDL and non-HDL cholesterol have not been conclusively determined. OBJECTIVE: We assessed these relations in 8 European observational human studies participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) using harmonized data. METHODS: Dietary macronutrient intake was recorded using study-specific dietary assessment tools. Main outcome measures were lipoprotein cholesterol concentrations: HDL cholesterol (mg/dL) and non-HDL cholesterol (mg/dL). A cross-sectional analysis on 5919 participants (54% female) aged 13-80 y was undertaken using the statistical platform DataSHIELD that allows remote/federated nondisclosive analysis of individual-level data. Generalized linear models (GLM) were fitted to assess associations between replacing 5% of energy from carbohydrates with equivalent energy from total fats, SFAs, MUFAs, or PUFAs with circulating HDL cholesterol and non-HDL cholesterol. GLM were adjusted for study source, age, sex, smoking status, alcohol intake and BMI. RESULTS: The replacement of 5% of energy from carbohydrates with total fats or MUFAs was statistically significantly associated with 0.67 mg/dL (95% CI: 0.40, 0.94) or 0.99 mg/dL (95% CI: 0.37, 1.60) higher HDL cholesterol, respectively, but not with non-HDL cholesterol concentrations. The replacement of 5% of energy from carbohydrates with SFAs or PUFAs was not associated with HDL cholesterol, but SFAs were statistically significantly associated with 1.94 mg/dL (95% CI: 0.08, 3.79) higher non-HDL cholesterol, and PUFAs with -3.91 mg/dL (95% CI: -6.98, -0.84) lower non-HDL cholesterol concentrations. A statistically significant interaction by sex for the association of replacing carbohydrates with MUFAs and non-HDL cholesterol was observed, showing a statistically significant inverse association in males and no statistically significant association in females. We observed no statistically significant interaction by age. CONCLUSIONS: The replacement of dietary carbohydrates with fats had favorable effects on lipoprotein cholesterol concentrations in European adolescents and adults when fats were consumed as MUFAs or PUFAs but not as SFAs.

Ectodysplasin A Is Increased in Non-Alcoholic Fatty Liver Disease, But Is Not Associated With Type 2 Diabetes.

Ectodysplasin A (EDA) was recently identified as a liver-secreted protein that is increased in the liver and plasma of obese mice and causes skeletal muscle insulin resistance. We assessed if liver and plasma EDA is associated with worsening non-alcoholic fatty liver disease (NAFLD) in obese patients and evaluated plasma EDA as a biomarker for NAFLD. Using a cross-sectional study in a public hospital, patients with a body mass index >30 kg/m2 (n=152) underwent liver biopsy for histopathology assessment and fasting liver EDA mRNA. Fasting plasma EDA levels were also assessed. Non-alcoholic fatty liver (NAFL) was defined as >5% hepatic steatosis and nonalcoholic steatohepatitis (NASH) as NAFLD activity score ≥3. Patients were divided into three groups: No NAFLD (n=45); NAFL (n=65); and NASH (n=42). Liver EDA mRNA was increased in patients with NASH compared with No NAFLD (P=0.05), but not NAFL. Plasma EDA levels were increased in NAFL and NASH compared with No NAFLD (P=0.03). Plasma EDA was related to worsening steatosis (P=0.02) and fibrosis (P=0.04), but not inflammation or hepatocellular ballooning. ROC analysis indicates that plasma EDA is not a reliable biomarker for NAFL or NASH. Plasma EDA was not increased in patients with type 2 diabetes and did not correlate with insulin resistance. Together, we show that plasma EDA is increased in NAFL and NASH, is related to worsening steatosis and fibrosis but is not a reliable biomarker for NASH. Circulating EDA is not associated with insulin resistance in human obesity. Clinical Trial Registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12615000875505, identifier ACTRN12615000875505.

Myosteatosis predicts higher complications and reduced overall survival following radical oesophageal and gastric cancer surgery.

INTRODUCTION: Low muscle attenuation, as governed by increased intramuscular fat infiltration (myosteatosis), may associate with adverse surgical outcomes. We aimed to determine whether myosteatosis is associated with an increased risk of postoperative complications and reduced long-term survival after oesophago-gastric (OG) cancer surgery. METHODS: Patients who underwent radical OG cancer surgery with preoperative abdominal computed tomography (CT) imaging were included. Myosteatosis was evaluated using previously defined cut-points for low skeletal muscle attenuation measured by CT. Oncological, surgical, complications, and outcome data were obtained from a prospective database. RESULTS: Of 108 patients, 56% (n = 61) had myosteatosis. Patients with myosteatosis were older (69.1 ±â€¯9.1 vs. 62.8 ±â€¯9.8 years, p = 0.001) and had a similar body mass index (BMI) (23.4 ±â€¯5.3 vs. 25.9 ±â€¯6.7 kg/m2, p = 0.766) compared to patients with normal muscle attenuation. Patients with myosteatosis had a higher rate of anastomotic leaks (15% vs. 2%, p = 0.041). On multivariate analysis, myosteatosis was an independent predictor of overall (OR 3.03, 95% CI 1.31-6.99, p = 0.009) and severe complications (OR 4.33, 95% CI 1.26-14.9, p = 0.020). Patients with myosteatosis had reduced 5 year overall (54.1% vs. 83%, p = 0.004) and disease-free (55.2% vs. 87.2%, p = 0.007) survival. CONCLUSION: Myosteatosis is associated with a significantly increased risk of overall and severe complications as well as substantially reduced long-term survival. Assessment of muscle attenuation provides analysis beyond standard anthropometrics and may form part of preoperative physiological staging tools used to improve surgical outcomes.

Mental Health Services in a U.S. Prison During the COVID-19 Pandemic.

Pandemics pose unique risks to people in correctional facilities. Among other vulnerabilities, incarcerated populations often have high rates of mental disorders and substance use disorders, which may increase risks for morbidity and mortality during a pandemic. California's San Quentin State Prison (SQSP) experienced multiple outbreaks during the 1918 influenza pandemic, and, a century later, the prison faces a new pandemic. This Open Forum describes the modification of mental health services in SQSP during the early stages of the COVID-19 pandemic. The authors explore the challenges of reducing risks of viral contagion while maintaining high-quality mental health care in a correctional setting.

Evaluation of the histological variability of core and wedge biopsies in nonalcoholic fatty liver disease in bariatric surgical patients.

BACKGROUND: Liver biopsy remains the gold standard for characterizing and evaluating treatment response in nonalcoholic fatty liver disease (NAFLD). Liver heterogeneity and sampling variability can affect the reliability of results. This study aimed to compare histological variability of intraoperative wedge and core liver biopsies from different lobes in bariatric patients, to better inform surgeons on biopsy method and guide interpretation of results. METHODS: We prospectively recruited bariatric surgical patients. Intraoperative core biopsies were taken from the left and right lobe, with a wedge biopsy taken from the left. All biopsies were graded by a specialist liver pathologist, blinded to clinical details and biopsy site. Concordance of histological findings between sites was evaluated. RESULTS: There were 91 participants (72.2% female), mean age 46.8 ± 12.0 years, body mass index 45.9 ± 9.4 kg/m2. There was no significant pattern for up- or down-grading disease dependent on biopsy technique. Moderate to strong agreement was seen in the presence of NAFLD and nonalcoholic steatohepatitis (NASH, κ = 0.609-0.865, p < 0.001) between biopsy sites. Individual components (steatosis, inflammation, ballooning) showed weaker agreement (κ = 0.386-0.656, p < 0.01). Fibrosis showed particularly poor agreement (κ = 0.223-0.496, p < 0.01). Detection of pathology improved with a combination of biopsy techniques, compared to a single biopsy method. CONCLUSION: Overall diagnosis of NAFLD or NASH shows good agreement between biopsy sites, but individual components, particularly fibrosis stage, vary significantly. Clinicians should consider biopsies from varied sites, to better assess liver disease severity. These data have important implications in fibrosis assessment of NAFLD and are relevant in the interpretation of histological efficacy of investigational pharmacotherapies. TRIAL REGISTRATION: ACTRN12615000875505 (Australian Clinical Trials Register).