Faculty Bibliography

PURPOSE/UNASSIGNED:To develop a deep learning algorithm capable of extracting pectoralis muscle and adipose measurements and to longitudinally investigate associations between these measurements and incident heart failure (HF) in participants from the Multi-Ethnic Study of Atherosclerosis (MESA). MATERIALS AND METHODS/UNASSIGNED:MESA is a prospective study of subclinical cardiovascular disease characteristics and risk factors for progression to clinically overt disease approved by institutional review boards of six participating centers (ClinicalTrials.gov identifier: NCT00005487). All participants with adequate imaging and clinical data from the fifth examination of MESA were included in this study. Hence, in this secondary analysis, manual segmentations of 600 chest CT examinations (between the years 2010 and 2012) were used to train and validate a convolutional neural network, which subsequently extracted pectoralis muscle and adipose (intermuscular adipose tissue (IMAT), perimuscular adipose tissue (PAT), extramyocellular lipids and subcutaneous adipose tissue) area measurements from 3031 CT examinations using individualized thresholds for adipose segmentation. Next, 1781 participants without baseline HF were longitudinally investigated for associations between baseline pectoralis muscle and adipose measurements and incident HF using crude and adjusted Cox proportional hazards models. The full models were adjusted for variables in categories of demographic (age, race, sex, income), clinical/laboratory (including physical activity, BMI, and smoking), CT (coronary artery calcium score), and cardiac MRI (left ventricular ejection fraction and mass (% of predicted)) data. RESULTS/UNASSIGNED:In 1781 participants (median age, 68 (IQR,61, 75) years; 907 [51%] females), 41 incident HF events occurred over a median 6.5-year follow-up. IMAT predicted incident HF in unadjusted (hazard ratio [HR]:1.14; 95% CI: 1.03-1.26) and fully adjusted (HR:1.16, 95% CI: 1.03-1.31) models. PAT also predicted incident HF in crude (HR:1.19; 95% CI: 1.06-1.35) and fully adjusted (HR:1.25; 95% CI: 1.07-1.46) models. CONCLUSION/UNASSIGNED:The study demonstrates that fast and reliable deep learning-derived pectoralis muscle and adipose measurements are obtainable from conventional chest CT, which may be predictive of incident HF.©RSNA, 2023.

Sleeve gastrectomy (SG) has many metabolic benefits and leads to improvements in testosterone levels, which means improvement in the Leydig cell function of the testis. However, data about the effects of SG on Sertoli cell function (as assessed by inhibin B) are not available. In this preliminary study, we evaluate, for the first time, the effect of SG in adolescents after SG. We evaluate 16 adolescent and young adult males, six of whom underwent SG and followed them for 2 years. We report that Leydig cell function (as assessed by testosterone levels) improved and was associated with degree of weight loss. Sertoli cell function improved only slightly in SG group and did not change compared to the nonsurgical controls, and these changes were not associated with degree of weight loss. Thus, we conclude that larger and long-term follow-up studies are required to evaluate the changes in Sertoli cell function after SG as that is integral to male fertility.Clinical Trial Registration: NCT02557438.

OBJECTIVE:To determine mechanisms contributing to impaired bone health in youth 24 months following sleeve gastrectomy (SG). DESIGN/METHODS:Twenty-four-month longitudinal observational study. METHODS:Participants included 23 youth undergoing SG and 30 non-surgical controls (NS) 13-25 years old with moderate-to-severe obesity. Subjects underwent fasting labs for bone turnover markers (N-terminal propeptide of type 1 procollagen, C-telopeptide (CTX)), sex hormones, sex hormone binding globulin (SHBG), and enteric peptides, DXA for areal bone mineral density (aBMD) and body composition, high-resolution peripheral quantitative CT for volumetric BMD (vBMD) at the distal radius and tibia, and microfinite element analysis for strength estimates. RESULTS:Groups did not differ for mean age or BMI z-scores. Over 24 months, compared to NS, SG had greater reductions in BMI z-scores, and spine, hip, and femoral neck aBMD Z-scores (P ≤ .012), greater increases in serum CTX and SHBG (P ≤ .039), and greater decreases in estrone and ghrelin (P ≤ .021). Among females, estrone and free androgen index (FAI) decreased (P ≤ .022) in SG vs NS groups. After controlling for age and sex, decreases in BMI and lean mass were associated with decreases in total hip and femoral neck aBMD Z-scores, and decreases in radial total and trabecular vBMD and failure load, and tibial total and trabecular vBMD. Among females, after controlling for age, decreases in estrone were associated with decreases in spine aBMD Z-scores and radial total and trabecular vBMD, and decrease in FAI with decreases in radial failure load. CONCLUSION/CONCLUSIONS:Reductions in BMI, lean mass, and sex steroids over 24 months post-SG are associated with bone loss and could be targeted for preventative or therapeutic interventions. Clinical trial registration number: The study is registered in ClinicalTrials.gov (NCT02557438).

Adults with obesity have a reduction in branched-chain amino acid (BCAA) levels following metabolic and bariatric surgery (MBS), which is hypothesized to contribute to the metabolic advantages of MBS. We examined this relationship in 62 youth 13-24 years old with severe obesity (47 female) over 12 months. Thirty had sleeve gastrectomy (SG) and 32 were non-surgical controls (NS). We measured fasting insulin, glucose, glycated hemoglobin (HbA1c), isoleucine, leucine, and valine concentrations, and post-prandial insulin and glucose, following a mixed meal tolerance test. Twenty-four-hour food recalls were collected. At baseline, groups did not differ in the intake or the serum levels of BCAAs, HbA1C, HOMA-IR, Matsuda index, insulinogenic index, or oral Disposition index (oDI). Over 12 months, SG vs. NS had greater reductions in serum BCAAs, and SG had significant reductions in BCAA intake. SG vs. NS had greater reductions in HbA1c and HOMA-IR, with increases in the Matsuda index and oDI. In SG, baseline leucine and total BCAA concentrations were negatively correlated with the baseline Matsuda index. Reductions in serum leucine were positively associated with the reductions in HOMA-IR over 12 months. These associations suggest a potential role of BCAA in regulating metabolic health. Reducing dietary intake and serum BCAA concentrations may reduce insulin resistance.

The purpose of this study was to develop a machine learning model to reconstruct time series kinematic and kinetic profiles of the ankle and knee joint across six different tasks using an ankle-mounted IMU. Four male collegiate basketball players performed repeated tasks, including walking, jogging, running, sidestep cutting, max-height jumping, and stop-jumping, resulting in a total of 102 movements. Ankle and knee flexion-extension angles and moments were estimated using motion capture and inverse dynamics and considered 'actual data' for the purpose of model fitting. Synchronous acceleration and angular velocity data were collected from right ankle-mounted IMUs. A time-series feature extraction model was used to determine a set of features used as input to a random forest regression model to predict the ankle and knee kinematics and kinetics. Five-fold cross-validation was performed to verify the model accuracy, and statistical parametric mapping was used to determine the difference between the predicted and experimental time series. The random forest regression model predicted the time-series profiles of the ankle and knee flexion-extension angles and moments with high accuracy (Kinematics: R2 ranged from 0.782 to 0.962, RMSE ranged from 2.19° to 11.58°; Kinetics: R2 ranged from 0.711 to 0.966, RMSE ranged from 0.10 Nm/kg to 0.41 Nm/kg). There were differences between predicted and actual time series for the knee flexion-extension moment during stop-jumping and walking. An appropriately trained feature-based regression model can predict time series knee and ankle joint angles and moments across a wide range of tasks using a single ankle-mounted IMU.

Sleeve gastrectomy (SG) is effective in treating cardiometabolic complications of obesity but is associated with bone loss. Our aim was to determine the effect of SG on the lumbar spine by biomechanical CT analysis in adolescents/young adults with obesity. We hypothesized that SG would lead to a decrease in strength and bone mineral density (BMD) compared with nonsurgical controls. In a 12-month prospective nonrandomized study, adolescents/young adults with obesity underwent SG (n = 29, 18.0 ± 2.1 years, 23 female) or were followed without surgery (controls, n = 30, 17.95 ± 3.0 years, 22 female). At baseline and 12 months, participants underwent quantitative computed tomography (QCT) of L₁ and L₂ for biomechanical assessment and MRI of the abdomen and mid-thigh for body composition assessment. Twelve-month changes between groups and within groups were assessed. Analyses were controlled for baseline and 12-month changes in body mass index (BMI) by multivariable analyses. Regression analysis was performed to evaluate the effect of body composition on bone parameters. Our institutional review board (IRB) approved the study, and informed consent/assent was obtained. Participants in the SG group had a higher baseline BMI than controls (p = 0.01) and lost an average of 34.3 ± 13.6 kg 12 months after surgery, whereas weight was unchanged in controls (p < 0.001). There were significant reductions in abdominal adipose tissue and thigh muscle area in the SG group compared with controls (p < 0.001). Bone strength, bending stiffness, and average and trabecular volumetric BMD decreased in the SG group compared with controls (p < 0.001). After controlling for change in BMI, a 12-month reduction in cortical BMD was significant in the SG group compared with controls (p = 0.02). Reductions in strength and trabecular BMD were associated with reductions in BMI, visceral adipose tissue, and muscle (p ≤ 0.03). In conclusion, SG in adolescents decreased strength and volumetric BMD of the lumbar spine compared with nonsurgical controls. These changes were associated with decreases in visceral fat and muscle mass. © 2023 American Society for Bone and Mineral Research (ASBMR).

Despite higher bone mineral density (BMD), women with obesity are at an increased risk of fracture compared to normal-weight women. Optimal adolescent bone accrual is critical for normal peak bone mass acquisition and future bone health. Whereas several studies have examined the impact of low body weight on bone accrual in youth, data are lacking regarding the impact of obesity on bone accrual. We examined bone accrual over one year in young women with moderate to severe obesity (OB) (n = 21) versus normal-weight controls (NWC) (n = 50). Participants were 13-25 years old. We used dual-energy X-ray absorptiometry to assess areal BMD (aBMD) and high resolution peripheral quantitative computed tomography (distal radius and tibia) to assess volumetric BMD (vBMD), bone geometry, and microarchitecture. Analyses were controlled for age and race. The mean age was 18.7 ± 2.7 years. OB and NWC were similar for age, race, height, and physical activity. OB had a higher BMI (p < 0.0001) and younger menarchal age (p = 0.022) than NWC. Over one year, OB did not demonstrate the increase in total hip BMD observed in NWC (p = 0.03). Increases in percent cortical area and cortical thickness, and cortical and total vBMD at the radius were lower in OB than in NWC (p ≤ 0.037). Groups did not differ for tibial bone accrual. We demonstrate that longitudinal bone accrual is impaired at the total hip and radial cortex in young women with obesity, raising concerns regarding their future bone health.