Cortisol/Cortisone Ratio in Youth with Obesity One Year Following Sleeve Gastrectomy.

Background: Glucocorticoid metabolites are associated with body composition measures and are altered with weight status. Metabolic and bariatric surgery (MBS) results in significant changes in weight and body composition. However, MBS effects on glucocorticoid metabolites are unknown. Objective: To evaluate (i) changes in the cortisol/cortisone ratio in youth with obesity 12 months after sleeve gastrectomy (SG) compared with nonsurgical controls with obesity (NS), and (ii) associations of these changes with body composition changes. Methods: A total of 38 participants 13-25 years old with obesity (29 female) were followed for 12 months. Half underwent SG, and the other half were followed with routine care (nonsurgical, NS). Fasting blood was assessed for cortisol and cortisone using liquid chromatography-mass spectroscopy as part of metabolomic analysis, and the cortisol/cortisone ratio was calculated. A single-slice MRI of the abdomen was performed to assess subcutaneous and visceral adipose tissue (SAT, VAT). Hepatic steatosis was assessed by computed tomography (CT). Results: SG did not differ from NS for baseline clinical characteristics, other than the mean age (SG 18.0 ± 0.46 vs. NS 16.6 ± 0.50 years, P = 0.041), BMI (BMI, 47.23 ± 1.5 vs. 41.32 ± 1.1 kg/m2, P = 0.003) weight and VAT, which were higher in SG. Significant reductions were noted over 12 months in BMI, BMI z-score, VAT, and SAT within the SG versus NS groups (P ≤ 0.001). Over 12 months, groups did not differ for changes in cortisol/cortisone ratio after controlling for age at baseline (P = 0.293). The ratio trended to decrease within the SG group [-1.40 (-5.08, 0.06), P = 0.080], particularly among those that had completed puberty (P = 0.048). No associations were found between changes in the cortisol/cortisone ratio and changes in body composition. Conclusions: The cortisol/cortisone ratio trended to decrease 12 months following SG. However, no associations were found between changes in the cortisol/cortisone ratio and changes in body composition. Studies with larger numbers of participants are necessary to confirm these findings.

AI-based opportunistic quantitative image analysis of lung cancer screening CTs to reduce disparities in osteoporosis screening.

Osteoporosis is underdiagnosed, especially in ethnic and racial minorities who are thought to be protected against bone loss, but often have worse outcomes after an osteoporotic fracture. We aimed to determine the prevalence of osteoporosis by opportunistic CT in patients who underwent lung cancer screening (LCS) using non-contrast CT in the Northeastern United States. Demographics including race and ethnicity were retrieved. We assessed trabecular bone and body composition using a fully-automated artificial intelligence algorithm. ROIs were placed at T12 vertebral body for attenuation measurements in Hounsfield Units (HU). Two validated thresholds were used to diagnose osteoporosis: high-sensitivity threshold (115-165 HU) and high specificity threshold (<115 HU). We performed descriptive statistics and ANOVA to compare differences across sex, race, ethnicity, and income class according to neighborhoods' mean household incomes. Forward stepwise regression modeling was used to determine body composition predictors of trabecular attenuation. We included 3708 patients (mean age 64 ± 7 years, 54 % males) who underwent LCS, had available demographic information and an evaluable CT for trabecular attenuation analysis. Using the high sensitivity threshold, osteoporosis was more prevalent in females (74 % vs. 65 % in males, p < 0.0001) and Whites (72 % vs 49 % non-Whites, p < 0.0001). However, osteoporosis was present across all races (38 % Black, 55 % Asian, 56 % Hispanic) and affected all income classes (69 %, 69 %, and 91 % in low, medium, and high-income class, respectively). High visceral/subcutaneous fat-ratio, aortic calcification, and hepatic steatosis were associated with low trabecular attenuation (p < 0.01), whereas muscle mass was positively associated with trabecular attenuation (p < 0.01). In conclusion, osteoporosis is prevalent across all races, income classes and both sexes in patients undergoing LCS. Opportunistic CT using a fully-automated algorithm and uniform imaging protocol is able to detect osteoporosis and body composition without additional testing or radiation. Early identification of patients traditionally thought to be at low risk for bone loss will allow for initiating appropriate treatment to prevent future fragility fractures. CLINICALTRIALS.GOV IDENTIFIER: N/A.

Intranasal Oxytocin for Obesity.

BACKGROUND: Accumulating preclinical and preliminary translational evidence shows that the hypothalamic peptide oxytocin reduces food intake, increases energy expenditure, and promotes weight loss. It is currently unknown whether oxytocin administration is effective in treating human obesity. METHODS: In this randomized, double-blind, placebo-controlled trial, we randomly assigned adults with obesity 1:1 (stratified by sex and obesity class) to receive intranasal oxytocin (24 IU) or placebo four times daily for 8 weeks. The primary end point was change in body weight (kg) from baseline to week 8. Key secondary end points included change in body composition (total fat mass [g], abdominal visceral adipose tissue [cm2], and liver fat fraction [proportion; range, 0 to 1; higher values indicate a higher proportion of fat]), and resting energy expenditure (kcal/day; adjusted for lean mass) from baseline to week 8 and caloric intake (kcal) at an experimental test meal from baseline to week 6. RESULTS: Sixty-one participants (54% women; mean age ± standard deviation, 33.6 ± 6.2 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 36.9 ± 4.9) were randomly assigned. There was no difference in body weight change from baseline to week 8 between oxytocin and placebo groups (0.20 vs. 0.26 kg; P=0.934). Oxytocin (vs. placebo) was not associated with beneficial effects on body composition or resting energy expenditure from baseline to week 8 (total fat: difference [95% confidence interval], 196.0 g [-1036 to 1428]; visceral fat: 3.1 cm2 [-11.0 to 17.2]; liver fat: -0.01 [-0.03 to 0.01]; resting energy expenditure: -64.0 kcal/day [-129.3 to 1.4]). Oxytocin compared with placebo was associated with reduced caloric intake at the test meal (-31.4 vs. 120.6 kcal; difference [95% confidence interval], -152.0 kcal [-302.3 to -1.7]). There were no serious adverse events. Incidence and severity of adverse events did not differ between groups. CONCLUSIONS: In this randomized, placebo-controlled trial in adults with obesity, intranasal oxytocin administered four times daily for 8 weeks did not reduce body weight. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT03043053.).

Opportunistic CT for Prediction of Adverse Postoperative Events in Patients with Spinal Metastases.

The purpose of this study was to assess the value of body composition measures obtained from opportunistic abdominal computed tomography (CT) in order to predict hospital length of stay (LOS), 30-day postoperative complications, and reoperations in patients undergoing surgery for spinal metastases. 196 patients underwent CT of the abdomen within three months of surgery for spinal metastases. Automated body composition segmentation and quantifications of the cross-sectional areas (CSA) of abdominal visceral and subcutaneous adipose tissue and abdominal skeletal muscle was performed. From this, 31% (61) of patients had postoperative complications within 30 days, and 16% (31) of patients underwent reoperation. Lower muscle CSA was associated with increased postoperative complications within 30 days (OR [95% CI] = 0.99 [0.98-0.99], p = 0.03). Through multivariate analysis, it was found that lower muscle CSA was also associated with an increased postoperative complication rate after controlling for the albumin, ASIA score, previous systemic therapy, and thoracic metastases (OR [95% CI] = 0.99 [0.98-0.99], p = 0.047). LOS and reoperations were not associated with any body composition measures. Low muscle mass may serve as a biomarker for the prediction of complications in patients with spinal metastases. The routine assessment of muscle mass on opportunistic CTs may help to predict outcomes in these patients.

Implementation and Evaluation of a National Well-Being Curriculum for KL2 Scholars.

Introduction: The study aimed to pilot test a well-being curriculum for KL2 scholars to be used across the Clinical and Translational Science Award consortium. Methods: Between November 2022, and May 2023, 36 KL2 scholars from 25 hubs participated in the program. The General Well-Being Index for U.S. Workers and the Patient Reported Outcomes Measurement Information System (PROMIS-29) were completed by scholars before and after the program. Results: Postparticipation, there was a trend of improvement in the domains of well-being, sleep, anxiety, and fatigue. Conclusion: Implementing a virtual synchronous well-being curriculum allowed the scholars to connect across the consortium and improve their well-being.

Two-Year Study on the Impact of Sleeve Gastrectomy on Depressive and Anxiety Symptoms in Adolescents and Young Adults with Moderate to Severe Obesity.

PURPOSE: Sleeve gastrectomy (SG), the most commonly performed weight loss surgery in adolescents and young adults with moderate to severe obesity, is highly effective for weight loss. Current literature regarding depressive and anxiety symptomatology following SG in youth is sparse and conflicting. We evaluated changes in depressive and anxiety symptoms in adolescents and young adults with moderate to severe obesity 2 years following SG compared with non-surgical controls (NS) followed for a similar duration. MATERIALS AND METHODS: Forty-six youth 13-25 years old with moderate-severe obesity (33 female) were followed for 2 years; 21 underwent SG, and 25 were NS. Subjects underwent anthropometric measurements and completed self-report questionnaires. Beck Depression Inventory-II (BDI-II) was used to assess depressive symptoms and the State-Trait Anxiety Inventory (STAI)-X2 for anxiety symptoms. RESULTS: Groups did not differ for age (18.4 ± 0.4 vs. 17.8 ± 0.5 years, p = 0.456). The SG group had a higher mean BMI vs. NS (47.5 (42.1, 52.4) vs. 41.6 (37.8, 46.5) kg/m2; p = 0.011). At 2-year follow-up, SG had greater reductions in weight and BMI vs. NS (p < 0.0001). Groups did not differ for changes in BDI-II and STAI scores (BDI-II: - 1.0 (- 6.0, 10.0) in SG vs. - 1.0 (- 6.0, 3.5) in NS, p = 0.37; STAI: 3.1 ± 3.2 in SG vs. - 1.1 ± 1.5 in NS, p = 0.24). CONCLUSION: No change was found in depressive and anxiety symptomatology following surgery despite marked weight reduction over a 2-year period, underscoring the need to better evaluate psychopathology in youth undergoing SG to develop supportive therapeutic strategies. GOV IDENTIFIER: NCT02557438 https://clinicaltrials.gov/ct2/show/NCT02557438?id=NCT02557438&draw=2&rank=1 ; The study was registered on 23 September 2015.

Bone marrow adipocytes fuel emergency hematopoiesis after myocardial infarction.

After myocardial infarction (MI), emergency hematopoiesis produces inflammatory myeloid cells that accelerate atherosclerosis and promote heart failure. Since the balance between glycolysis and mitochondrial metabolism regulates hematopoietic stem cell homeostasis, metabolic cues may influence emergency myelopoiesis. Here, we show in humans and female mice that hematopoietic progenitor cells increase fatty acid metabolism after MI. Blockade of fatty acid oxidation by deleting carnitine palmitoyltransferase (Cpt1A) in hematopoietic cells of Vav1Cre/+Cpt1Afl/fl mice limited hematopoietic progenitor proliferation and myeloid cell expansion after MI. We also observed reduced bone marrow adiposity in humans, pigs and mice following MI. Inhibiting lipolysis in adipocytes using AdipoqCreERT2Atglfl/fl mice or local depletion of bone marrow adipocytes in AdipoqCreERT2iDTR mice also curbed emergency hematopoiesis. Furthermore, systemic and regional sympathectomy prevented bone marrow adipocyte shrinkage after MI. These data establish a critical role for fatty acid metabolism in post-MI emergency hematopoiesis.