Faculty Bibliography

PURPOSE/OBJECTIVE:The aim of this study is to evaluate the safety and effectiveness of CT-guided corticosteroid injection for the treatment of osseous Langerhans cell histiocytosis (LCH) in a multi-institutional study. MATERIALS AND METHODS/METHODS:This IRB-approved study included patients from three institutions. We retrospectively reviewed clinical, procedural, and imaging data for corticosteroid injections performed to treat osseous LCH. Location of the lesion, lesion maximum dimension and volume, corticosteroid type and dose, and time interval between injection and change in lesion size/volume and symptoms were recorded. Generalized estimating equations (accounting for multiple lesions per subject) were used to evaluate the association between predictors (dose, maximum lesion dimension, and lesion volume) and outcomes (time to partial and complete radiographic resolution, and time to pain control). This analysis was adjusted by anatomic site. RESULTS:. Imaging and clinical follow-up were available for 22/40 (55%) and 34/40 (85%) of injections, respectively. All lesions responded to corticosteroid injection. Times to partial and complete imaging resolution were 13 ± 9 and 32 ± 13 weeks, respectively, and time to pain resolution was 22 ± 14 weeks. There were no complications. CONCLUSION/CONCLUSIONS:CT-guided corticosteroid injection is a safe and effective treatment for LCH. Pain resolution was achieved in all patients and imaging did not show progressive disease in any of the patients.

INTRODUCTION:Body composition assessed using opportunistic CT has been recently identified as a predictor of outcome in patients with cancer. The purpose of this study was to determine whether the cross-sectional area (CSA) and the attenuation of abdominal subcutaneous adipose tissue, visceral adipose tissue (VAT), and paraspinous and abdominal muscles are the predictors of length of hospital stay, 30-day postoperative complications, and revision surgery in patients treated for long bone metastases. METHODS:A retrospective database of patients who underwent surgery for long bone metastases from 1999 to 2017 was used to identify 212 patients who underwent preoperative abdominal CT. CSA and attenuation measurements for subcutaneous adipose tissue, VAT, and muscles were taken at the level of L4 with the aid of an in-house segmentation algorithm. Bivariate and multivariate linear and logistic regression models were created to determine associations between body composition measurements and outcomes while controlling for confounders, including primary tumor, metastasis location, and preoperative albumin. RESULTS:On multivariate analysis, increased VAT CSA {regression coefficient (r) (95% confidence interval [CI]); 0.01 (0.01 to 0.02); P < 0.01} and decreased muscle attenuation (r [95% CI] -0.07 [-0.14 to -0.01]; P = 0.04) were associated with an increased length of hospital stay. In bivariate analysis, increased muscle CSA was associated with increased chance of revision surgery (odds ratio [95% CI]; 1.02 [1.01 to 1.03]; P = 0.04). No body composition measurements were associated with postoperative complications within 30 days. DISCUSSION:Body composition measurements assessed using opportunistic CT predict adverse postoperative outcomes in patients operated for long bone metastases.

PURPOSE/OBJECTIVE:To assess the perception of equity and respect in the workplace and within the SSR. We hypothesized that responses would differ by gender and minorities underrepresented in medicine (URiM) status. METHODS:An electronic survey was sent to 1,531 SSR members between January 2020 and March 2020 to determine perception of equity and respect. Descriptive statistics were calculated, and analysis of differences in response by gender/minority status was performed using the Fisher's exact test. The study was exempt from IRB approval. RESULTS:There were 176 responses (11.5%). Most respondents (61.9%) were between 30 and 50 years. Members identified as male (M) in 74.4%, as female (F) in 25.0%, and as "other" in 0.6%. URiM comprised 9.1% of members. Women worked more commonly in academia (p = 0.005), had the perception of unequal opportunities for leadership positions within the institution (p = 0.006), and emphasized the importance of having a mentor of the same gender (p = 0.001). URiM members were less likely to hold a leadership position (p = 0.1, trend), had a perception of unequal opportunities for leadership positions within the institution (p = 0.06, trend), and reported the importance of having a mentor of the same race (p = 0.06, trend). There were no significant differences between gender or URiM status and perception of the SSR to provide an inclusive environment and leadership opportunities (p ≥ 0.39). CONCLUSION/CONCLUSIONS:While survey participation was limited and potentially biased, respondents perceived that women and minorities have fewer opportunities and are treated with lower regard in the workplace compared to male, non-minority colleagues.

BACKGROUND:The presence of bone marrow edema (BME) on magnetic resonance imaging (MRI) has been used to evaluate for bone stress injuries in athletes. PURPOSE/OBJECTIVE:To examine the prevalence of MRI findings, including BME, in a single male collegiate basketball team before and after a single season and to assess its association with clinically symptomatic metatarsal bone stress injuries. STUDY DESIGN/METHODS:Cohort Study; Level of evidence, 3. METHODS:A total of 16 men on a single collegiate basketball team (mean age, 20.0 ± 1.8 years) underwent 1.5-T MRI focused on both midfeet during the preseason, and 13 underwent repeat MRI during the postseason. MRI findings included the presence of BME and the radiographic classification of the bone stress injury (grades 1-4). Injury surveillance performed by athletic trainers was used to identify metatarsal bone stress injuries over the course of the season. RESULTS:< .10), with the abnormalities persisting on postseason MRI in all players. CONCLUSION/CONCLUSIONS:Collegiate male basketball players may have a high prevalence of BME, often without associated symptoms. The absence of foot pain or a corresponding diagnosis of a metatarsal bone stress injury in this study suggests that MRI findings of BME in asymptomatic athletes should be interpreted with caution.

In addition to restrictions on conducting research, COVID-19-related travel bans and scientific meeting cancellations have negatively affected scholars in the Clinical and Translational Science Award (CTSA) Mentored Career Development Award (KL2) program. In response, a national virtual visiting scholar program was developed to provide opportunity for KL2 scholars to be virtual visiting professors at another CTSA hub, meet faculty and scholars, and expand networks and build collaborations. This article describes the design and short-term outcomes of the virtual CTSA Visiting Scholar Program. In 2020, a working group designed core program elements and developed an application and selection process. Anonymized surveys were sent to scholars post visit and to scholars and program directors 6 months post visit to evaluate their experience and solicit suggestions for improvements. Between November 2020 and May 2021, 56 KL2 scholars and 27 hubs participated. Forty-five (80.4%) participating scholars responded to the initial survey. Nearly all scholars (44, 97.7%) agreed their experience was valuable. All respondents indicated they would recommend the program to other KL2 scholars. For the 6-month survey, the response rate was 87.5% (49/56). Within 6 months of their visit, 36 (73.5%) respondents had contacted at least one person at the host hub and for 17 (34.7%) respondents, new collaborations with the host hub ensued. Twenty-five of 27 (92.6%) host hubs responded to the survey. Most (21, 84.0%) agreed that hearing visiting scholar talks was valuable to their own scholars and 23 (92%) indicated likelihood of their hub participating in future round of the program. The virtual Visiting Scholar Program provided KL2 scholars an opportunity to virtually visit another CTSA hub, present their research, and meet with faculty and other scholars to expand their networks. Although geared to KL2 scholars, this model is potentially generalizable to other nationally coordinated career development programs.

BACKGROUND:With the growing prevalence of severe obesity in adolescents, sleeve gastrectomy (SG), a type of metabolic bariatric surgery (MBS), is increasingly being performed at a younger age. Data regarding changes in homeostatic and hedonic appetite following SG are conflicting in adults, with some studies showing no change and others showing a decrease in appetite. Data evaluating the effect of SG on appetite during adolescence, when appetite is more plastic, are currently lacking. OBJECTIVE:To evaluate appetite changes one year after SG in adolescents with obesity vs. in non-surgical controls (NS). METHODS:Thirty-nine subjects 13-21 years old with severe obesity were followed for a year; 19 underwent SG, and 20 were followed without surgery. Subjects had fasting blood tests for appetite-regulating hormones and completed a visual analog scale for appetite assessment (VAS). RESULTS:= 0.011). Appetite changes were not associated with weight loss or final BMI. CONCLUSIONS:There were no changes in appetite measures one-year after SG from pre-surgery levels in adolescents with obesity, and appetite changes were not associated with changes in BMI. It is important to evaluate the impact of long-term appetite changes, if any, on weight loss after SG.

OBJECTIVE:The GH and IGF-1 axis is a candidate disease-modifying target in nonalcoholic fatty liver disease (NAFLD) given its lipolytic, anti-inflammatory and anti-fibrotic properties. IGF-1 receptor (IGF-1R) and GH receptor (GHR) expression in adult, human hepatic tissue is not well understood across the spectrum of NAFLD severity. Therefore, we sought to investigate hepatic IGF-1R and GHR expression in subjects with NAFLD utilizing gene expression analysis (GEA) and immunohistochemistry (IHC). DESIGN:GEA (n = 318) and IHC (n = 30) cohorts were identified from the Massachusetts General Hospital NAFLD Tissue Repository. GEA subjects were categorized based on histopathology as normal liver histology (NLH), steatosis only (Steatosis), nonalcoholic steatohepatitis (NASH) without fibrosis (NASH F0), and NASH with fibrosis (NASH F1-4) with GEA by the Nanostring nCounter assay. IHC subjects were matched for age, body mass index (BMI), sex, and diabetic status across three groups (n = 10 each): NLH, Steatosis, and NASH with fibrosis (NASH F1-3). IHC for IGF-1R, IGF-1 and GHR was performed on formalin-fixed, paraffin-embedded hepatic tissue samples. RESULTS:IGF-1R gene expression did not differ across NAFLD severity while IGF-1 gene expression decreased with increasing NAFLD severity, including when controlled for BMI and age. GHR expression did not differ by severity of NAFLD based on GEA or IHC. CONCLUSIONS:IGF-1R and GHR expression levels were not significantly different across NAFLD disease severity. However, expression of IGF-1 was lower with increasing severity of NAFLD. Additional research is needed regarding the contribution of the GH/IGF-1 axis to the pathophysiology of NAFLD and NASH.

CONTEXT:Obesity is a state of relative growth hormone (GH) deficiency, and GH has been identified as a candidate disease-modifying target in nonalcoholic fatty liver disease (NAFLD) because of its lipolytic and anti-inflammatory properties. However, the GH/IGF-1 axis has not been well characterized in NAFLD. OBJECTIVE:We aimed to investigate serum GH and IGF-1 levels in relation to intrahepatic lipid content (IHL) and markers of hepatocellular damage and fibrosis in NAFLD. METHODS:This cross-sectional study included 102 adults (43% women; age 19-67; BMI ≥ 25 kg/m2) without type 2 diabetes. IHL was measured by magnetic resonance spectroscopy; NAFLD was defined by ≥ 5% IHL. Peak-stimulated GH in response to GH releasing hormone and arginine was assessed as was serum IGF-1 (LC/MS). RESULTS:There was no difference in mean age, BMI, or sex distribution in NAFLD vs controls. Mean (± SD) IHL was higher in NAFLD vs controls (21.8 ± 13.3% vs 2.9 ± 1.1%, P < 0.0001). Mean peak-stimulated GH was lower in NAFLD vs controls (9.0 ± 6.3 vs 15.4 ± 11.2 ng/mL, P = 0.003), including after controlling for age, sex, visceral adipose tissue, and fasting glucose. In a stepwise model, peak-stimulated GH predicted 14.6% of the variability in IHL (P = 0.004). Higher peak-stimulated GH was also associated with lower ALT. Higher serum IGF-1 levels were associated with lower risk of liver fibrosis by Fibrosis-4 scores. CONCLUSION:Individuals with NAFLD have lower peak-stimulated GH levels but similar IGF-1 levels as compared to controls. Higher peak-stimulated GH levels are associated with lower IHL and less hepatocellular damage. Higher IGF-1 levels are associated with more favorable fibrosis risk scores. These data implicate GH and IGF-1 as potential disease modifiers in the development and progression of NAFLD.

BACKGROUND:States of chronic overnutrition and undernutrition are both associated with impaired bone health and increased fracture risk but there are no data on bone microarchitecture following short-term controlled nutritional challenges. OBJECTIVE:The purpose of our study was to evaluate the impact of short-term high-caloric feeding and fasting on bone microarchitecture. We hypothesized that both high-caloric feeding and fasting would have negative effects on microarchitecture. MATERIALS AND METHODS:). Subjects underwent an in-patient 10-day high-caloric visit (caloric intake with goal to achieve 7% weight gain), after which they went home to resume a normal diet for 13-18 days (stabilization period), and were then readmitted for a 10-day in-patient fasting stay (no caloric intake). All subjects underwent HRpQCT (XtremeCT, Scanco Medical AG, Brüttisellen, Switzerland) of the distal tibia and distal radius after each visit to assess volumetric bone mineral density (vBMD), trabecular and cortical microarchitecture, and strength estimates. The Wilcoxon signed rank test was used to perform within group comparisons. RESULTS:During the high-caloric period, there was a mean increase in weight by 6.3 + 1.7% (p < 0.0001). There were no significant changes in bone parameters in the distal tibia or distal radius (p > 0.05). During the stabilization period there was a significant reduction in weight by -2.7 + 1.9% (p < 0.0001) but no change in bone parameters (p > 0.05). During the fasting period there was a further reduction in weight by -8.8 + 1.2% (p < 0.0001). In the distal tibia, there was a significant increase in total and cortical vBMD, trabecular and cortical parameters as well as strength estimates (p < 0.05). In the distal radius there was an increase in total and trabecular vBMD (p < 0.05), while there were no changes in other microarchitecture parameters or strengths estimates. CONCLUSION:Short-term fasting after high-caloric feeding improves vBMD, bone microarchitecture and strength estimates of the distal tibia, while short-term high-caloric feeding does not change vBMD or microarchitecture. These results suggest that short-term fasting after high-caloric feeding in healthy individuals improves bone health and that these changes can be detected using HRpQCT in-vivo.