Faculty Bibliography

The ability of research networks and individual institutions to effectively and efficiently prepare, respond, and adapt to emergent challenges is essential for the biomedical research enterprise. At the beginning of 2021, a special Working Group was formed by individuals in the Clinical and Translational Science Award (CTSA) consortium and approved by the CTSA Steering Committee to explore "Adaptive Capacity and Preparedness (AC&P) of CTSA Hubs." The AC&P Working Group took a pragmatic Environmental Scan (E-Scan) approach of utilizing the diverse data that had been collected through existing mechanisms. The Local Adaptive Capacity framework was adapted to illustrate the interconnectedness of CTSA programs and services, while exposing how the demands of the pandemic forced them to quickly pivot and adapt. This paper presents a synopsis of the themes and lessons learned that emerged from individual sections of the E-Scan. Lessons learned from this study may improve our understanding of adaptive capacity and preparedness at different levels, as well as help strengthen the core service models, strategies, and foster innovation in clinical and translational science research.

BACKGROUND/UNASSIGNED:Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease worldwide. There are limited biomarkers that can detect progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The purpose of our study was to utilize CT texture analysis to distinguish steatosis from NASH. METHODS/UNASSIGNED:) underwent liver biopsy and abdominal non-contrast CT. CT texture analysis was performed to quantify gray-level tissue summaries (e.g., entropy, kurtosis, skewness, and attenuation) using commercially available software (TexRad, Cambridge England). Logistic regression analyses were performed to quantify the association between steatosis/NASH status and CT texture. ROC curve analysis was performed to determine sensitivity, specificity, AUC, 95% CIs, and cutoff values of texture parameters to differentiate steatosis from NASH. RESULTS/UNASSIGNED: = 0.009) than those with simple steatosis. Entropy values below 4.73 predict NASH with 100% (95%CI: 67-100%) specificity and 80% (50-100%) sensitivity, AUC: 0.88. MPP values below 54.0 predict NASH with 100% (67-100%) specificity and 100% (50-100%) sensitivity, AUC 0.90. CONCLUSION/UNASSIGNED:Our study provides preliminary evidence that CT texture analysis may serve as a novel imaging biomarker for disease activity in NAFLD and the discrimination of steatosis and NASH.

The coronavirus disease 2019 (COVID-19) pandemic has dramatically changed our lives and the delivery of healthcare. The pandemic also led to widespread disruption in the research activities and training of pre-doctoral, post-doctoral, and early career faculty researchers. This mini-review uses the Local Adaptive Capacity Framework to describe successful practices, challenges, and lessons learned on how Clinical and Translational Science Award (CTSA) hubs have used their expertise, resources, and collaborations to advance clinical and translational science research and workforce development while facing and adapting to a pandemic. Data for this mini-review were taken from the scientific literature (23 articles) and the Research Performance Progress Reports of 50 unique CTSA hubs (40 TL1 and 50 KL2 awards). Institutions responded in innovative ways to the disruption of the COVID-19 pandemic. Electronic and virtual platforms were used to overcome challenges related to physical distancing, laboratory closures, and travel bans. The importance of mentorship and well-being led to the creation of new virtual programs to expand mentoring and networking beyond the home institution and to promote well-being and resilience. These solutions to translational workforce development can be implemented to address future public health emergencies.

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.

CONTEXT:Vertical sleeve gastrectomy (VSG) is an increasingly common tool to achieve weight loss and improve metabolic health in adolescents and young adults with obesity, although it may adversely affect bone health. OBJECTIVE:This work aimed to evaluate the effect of VSG on bone health in youth. METHODS:An observational 2-year study was conducted at a tertiary care center of 66 patients aged 13 to 24 years with moderate-to-severe obesity meeting criteria for VSG. The patients underwent VSG (n = 30) or nonsurgical (n = 36) management per the decision of patient and clinical team. Main outcome measures included dual-energy x-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HRpQCT) measures of bone mineral density (BMD), geometry, and microarchitecture. RESULTS:VSG patients achieved 25.3 ± 2.0% weight loss at 2 years (P < .001) while control subjects gained 4.0 ± 2.0% (P = .026). Total hip BMD declined 8.5 ± 1.0% following VSG compared with 0.1 ± 1.0% gain in controls (P < .001), with similar results at the femoral neck (P < .001). Total volumetric BMD (vBMD) decreased both at the distal radius and tibia following VSG (P < .001) driven primarily by trabecular vBMD loss (P < .001). Two-year changes in cortical vBMD did not differ between groups, though cortical porosity decreased following VSG both at the radius and tibia (P = .048 and P < .001). Cortical thickness increased in controls but not in VSG (P = .022 and P = .002 for between-group comparisons at the radius and tibia, respectively). Following VSG, estimated failure load decreased at the radius and did not demonstrate the physiologic increases at the tibia observed in controls. CONCLUSION:VSG leads to progressive changes in bone health over 2 years, and may lead to increased skeletal fragility in adolescents and young adults.

BACKGROUND AND OBJECTIVES:Internal neurofibromas, including plexiform neurofibromas (PNF), can cause significant morbidity in patients with neurofibromatosis type 1 (NF1). PNF growth is most pronounced in children and young adults, with more rapid growth thought to occur in a subset of PNF termed distinct nodular lesions (DNL). Growth behavior of internal neurofibromas and DNL in older adults is not well documented; yet knowledge thereof is important for patient risk stratification and clinical trial design. The primary objective of this study was to evaluate the long-term growth behavior of internal neurofibromas in adults with NF1. Secondary objectives were to correlate tumor growth behavior with patient-specific, tumor-specific, and patient-reported variables. METHODS:In this prospective cohort study, internal neurofibromas were identified on coronal short TI inversion recovery sequences on baseline and follow-up whole-body MRIs (WBMRIs). Tumor growth and shrinkage were defined as a volume change ≥20%. The association between tumor growth and patient-specific (baseline age, sex, and genotype), tumor-specific (morphology, location, DNL presence on baseline WBMRI, and maximum standardized uptake value on baseline PET imaging), and patient-reported variables (endogenous and exogenous hormone exposure, pain intensity, and quality of life) was assessed using the Spearman correlation coefficient and Kruskal-Wallis test. RESULTS:Of 106 patients with a baseline WBMRI obtained as part of a previous research study, 44 had a follow-up WBMRI. Three additional patients with WBMRIs acquired for clinical care were included, generating 47 adults for this study. The median age during baseline WBMRI was 42 years (range 18-70). The median time between WBMRIs was 10.4 years. Among 324 internal neurofibromas, 62.8% (56% of PNF and 62.1% of DNL) shrank spontaneously without treatment and 17.1% (17.9% of PNF and 13.8% of DNL) grew. Growth patterns were heterogeneous within participants. Patient-specific, tumor-specific, and patient-reported variables (including endogenous and exogenous hormone exposure) were not strong predictors of tumor growth. DISCUSSION:Internal neurofibroma growth behavior in older adults differs fundamentally from that in children and young adults, with most tumors, including DNL, demonstrating spontaneous shrinkage. Better growth models are needed to understand factors that influence tumor growth. These results will inform clinical trial design for internal neurofibromas.

Background Sleeve gastrectomy (SG) is effective in the treatment of cardiometabolic complications of obesity but is associated with bone loss. Purpose To determine the long-term effects of SG on vertebral bone strength, density, and bone marrow adipose tissue (BMAT) in adolescents and young adults with obesity. Materials and Methods This 2-year prospective nonrandomized longitudinal study enrolled adolescents and young adults with obesity who underwent either SG (SG group) or dietary and exercise counseling without surgery (control group) at an academic medical center from 2015 to 2020. Participants underwent quantitative CT of the lumbar spine (L1 and L2 levels) to assess bone density and strength, proton MR spectroscopy to assess BMAT (L1 and L2 levels), and MRI of the abdomen and thigh to assess body composition. Student t and Wilcoxon signed-rank tests were used to compare 24-month changes between and within groups. Regression analysis was performed to evaluate associations between body composition, vertebral bone density, strength, and BMAT. Results A total of 25 participants underwent SG (mean age, 18 years ± 2 [SD], 20 female), and 29 underwent dietary and exercise counseling without surgery (mean age, 18 years ± 3, 21 female). Body mass index (BMI) decreased by a mean of 11.9 kg/m² ± 5.21 [SD] after 24 months in the SG group (P < .001), while it increased in the control group (mean increase, 1.49 kg/m² ± 3.10; P = .02). Mean bone strength of the lumbar spine decreased after surgery compared with that in control subjects (mean decrease, -728 N ± 691 vs -7.24 N ± 775; P < .001). BMAT of the lumbar spine increased after SG (mean lipid-to-water ratio increase, 0.10 ± 0.13; P = .001). Changes in vertebral density and strength correlated positively with changes in BMI and body composition (R = 0.34 to R = 0.65, P = .02 to P < .001) and inversely with vertebral BMAT (R = -0.33 to R = -0.47, P = .03 to P = .001). Conclusion SG in adolescents and young adults reduced vertebral bone strength and density and increased BMAT compared with those in control participants. Clinical trial registration no. NCT02557438 © RSNA, 2023 See also the editorial by Link and Schafer in this issue.