Faculty Bibliography

BACKGROUND:Sleeve gastrectomy (SG) is the most common metabolic and bariatric surgery (MBS) procedure in adolescents and adults. Only few studies have assessed bone outcomes following SG and it is unknown whether skeletal changes differ by age group. Recent studies have identified marrow adipose tissue (MAT) as a novel biomarker for bone quality with studies in adults showing high MAT in those with visceral adiposity and a reciprocal increase in MAT with bone loss. OBJECTIVE:To determine the impact of SG on volumetric BMD (vBMD) and MAT in adolescents and adults with obesity. We hypothesized that SG would lead to a decrease in vBMD and increase in MAT but that these changes would be less pronounced in adolescents compared to adults. MATERIALS AND METHODS:), before and 12 months after SG. At baseline and 12 months, subjects underwent quantitative CT of the lumbar spine (L1-L2) to assess trabecular vBMD, single voxel proton MR spectroscopy at 3 T (PRESS pulse sequence without water suppression) at L1-L2 to quantify MAT, and MRI of the abdomen to assess visceral (VAT) and subcutaneous adipose tissue (SAT). RESULTS:At baseline, adolescents had lower MAT (p = 0.0002) and higher vBMD (p = 0.050) compared to adults. Adolescents and adults lost 27.9 ± 6.5 vs. 25.0 ± 11.2% of body weight (p < 0.0001 for within group change), while there was no significant difference between groups (p = 0.455). There was a significant reduction in vBMD in adults (-3.9 ± 3.9%, p = 0.005) and a trend for a reduction in adolescents (-3.7 ± 7.5%, p = 0.119), with no significant difference between groups (p = 0.944). Lumbar MAT content increased in both adults and adolescents (p ≤ 0.034), while the difference was not significant between groups (p = 0.281). In adolescents and adults, 12-month percent change in weight and BMI was positively associated with % change in MAT (p ≤ 0.042). 12-month percent change in MAT was positively associated with 12-month % change in SAT in adolescents and 12-month percent change in VAT in adults (p ≤ 0.045). CONCLUSION:SG in adolescents and adults with severe obesity is associated with a reduction in lumbar vBMD and an increase in lumbar MAT, although the reduction in adolescents did not reach statistical significance, with no significant differences in these endpoints between groups. Our results suggest detrimental effects of bariatric surgery on bone for patients across the life span.

Research examining bone marrow adipose tissue (BMAT) has rapidly expanded during the last two decades, leading to advances in knowledge on the role of BMAT in the pathogenesis of bone loss and endocrine disorders. Clinical imaging has played a crucial role for the in vivo assessment of BMAT, allowing non-invasive quantification and evaluation of BMAT composition. In the present work, we review different imaging methods for assessing properties of BMAT. Our aim is to review conventional magnetic resonance imaging (MRI), water-fat imaging, and single-voxel proton magnetic resonance spectroscopy (¹H-MRS), as well as computed tomography (CT)-based techniques, including single energy and dual energy CT. We will also discuss the clinical applications of these methods in type 2 diabetes mellitus, obesity and anorexia nervosa.

There is a global increase in the prevalence of severe obesity in females during adolescence, which is a critical period for neurocognitive development. An increasing number of adolescents and young adults are now undergoing weight loss surgery as a treatment strategy for obesity. In addition to metabolic complications, obesity has been linked to neurocognitive comorbidity, and studies exploring cognitive performance in adolescents with severe obesity and the impact of bariatric surgery on cognitive abilities are limited. Verbal memory and executive function were assessed cross-sectionally in 69 females with moderate to severe obesity and 24 females without obesity, 13-24 years old. In an exploratory analysis, cognitive changes were also assessed longitudinally over 12 months in a subset of 35 females with moderate to severe obesity following weight loss surgery (n = 21) or following usual care without surgery (n = 14). In cross-sectional analysis, females with moderate to severe obesity showed lower scores for short-term and long-term recall (verbal memory) and response inhibition and cognitive flexibility (executive function) than the comparison group, when adjusted for age and baseline intelligence. Females with moderate to severe obesity who underwent surgery showed significant weight loss but no improvement in verbal memory and executive function scores over 12 months compared with those who did not have surgery. Females with moderate to severe obesity demonstrate worse performance in tests of verbal memory and executive function than the comparison group without obesity. In addition, exploratory analyses provide no indication that weight loss surgery improves these observed cognitive decrements over a period of 12 months. Further studies are necessary to comprehensively evaluate changes in cognitive function following bariatric surgery.

BACKGROUNDAdipocytes were long considered inert components of the bone marrow niche, but mouse and human models suggest bone marrow adipose tissue (BMAT) is dynamic and responsive to hormonal and nutrient cues.METHODSIn this study of healthy volunteers, we investigated how BMAT responds to acute nutrient changes, including analyses of endocrine determinants and paracrine factors from marrow aspirates. Study participants underwent a 10-day high-calorie protocol, followed by a 10-day fast.RESULTSWe demonstrate (a) vertebral BMAT increased significantly during high-calorie feeding and fasting, suggesting BMAT may have different functions in states of caloric excess compared with caloric deprivation; (b) ghrelin, which decreased in response to high-calorie feeding and fasting, was inversely associated with changes in BMAT; and (c) in response to high-calorie feeding, resistin levels in the marrow sera, but not the circulation, rose significantly. In addition, TNF-α expression in marrow adipocytes increased with high-calorie feeding and decreased upon fasting.CONCLUSIONHigh-calorie feeding, but not fasting, induces an immune response in bone marrow similar to what has been reported in peripheral adipose tissue. Understanding the immunomodulatory regulators in the marrow may provide further insight into the homeostatic function of this unique adipose tissue depot.FUNDINGNIH grant R24 DK084970, Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH, award UL 1TR002541), and NIH grants P30 DK040561 and U19 AG060917S1.

BACKGROUND:Musculoskeletal pain is a debilitating problem treated with image-guided corticosteroid injections. During the COVID-19 pandemic, multiple societies issued caution statements because of the unknown effect of corticosteroids on the patient's immune system. The purpose is to determine if image-guided corticosteroid injections administered during the COVID-19 lockdown phase were associated with a higher infection rate compared to the general population. MATERIALS AND METHODS/METHODS:In a prospective study, patients undergoing image-guided corticosteroid injections for pain management during the lockdown phase between April 15 and May 22, 2020, were enrolled. One month after the injection, patients were surveyed by telephone for any COVID-19-related symptoms, and the electronic medical record (EMR) was reviewed for symptoms and test results. RESULTS:Seventy-one subjects were recruited, 31 (44%) females, 40 (56%) males, ages 58 ± 17 (20-92) years. Follow-up was available in 66 (93%) of subjects, 60 (91%) by phone survey and EMR, 6 (9%) by EMR only, 45 ± 22 (19-83) days after injection. One (1/66, 1.52%; 95% CI 0.04-8.2%) 25-year-old male subject developed symptomatic infection 19 days after a tibiotalar injection. The prevalence of COVID-19 cases in the state of Massachusetts was 0.91% (62,726/6,892,503) during the study period. There was no significant difference in the rate of occurrence of new cases of COVID-19 infection between the corticosteroid injection group and the general population (p = 0.44). CONCLUSION/CONCLUSIONS:Image-guided corticosteroid injections for pain management performed during the lockdown phase of the COVID-19 pandemic were not associated with a higher infection rate compared to the general population.

OBJECTIVE:To implement a multifaceted wellness program in an academic radiology department to prevent burnout and to assess initial outcomes with special focus on the challenges related to the coronavirus disease 2019 (COVID-19) pandemic. METHODS:A wellness program was established to address institutional and personal factors of burnout. The program focused on interventions to improve efficiency of practice, provide personal and career support, and create a culture of wellness. The components of the program were designed with input from radiology faculty, and the program was financially supported by the hospital's physician organization. A survey was performed 6 months after the initiation of the program to determine radiologist engagement and satisfaction. With the onset of the COVID-19 pandemic, a new survey was administered to identify needs of faculty and adjust initiatives. This study was exempt from institutional review board approval. RESULTS:The majority of radiologists (79%) agreed or strongly agreed that the wellness program provided opportunities to connect with coworkers. All radiologists agreed that the program was helpful and should be continued. During the COVID-19 pandemic, 49% of physicians requested initiatives focused on well-being, emotional health, and mindfulness to support them during the crisis. CONCLUSIONS:The implementation of a faculty wellness program in an academic radiology department addressed institutional and personal factors of burnout, allowed faculty to connect with coworkers, and was found to be helpful by all radiologists. The COVID-19 pandemic shifted needs to well-being and emotional health initiatives. Follow-up data are necessary to assess its effect on burnout reduction.

AIMS/OBJECTIVE:Simple bone cysts are benign intramedullary tumours primarily involving the long bones in skeletally immature individuals. Several mechanisms have been proposed for their pathogenesis. Although the diagnosis is typically straightforward, the interpretation can be problematic, because of superimposed fracture causing them to resemble aneurysmal bone cysts and other tumours. EWSR1-NFATC2 or FUS-NFATC2 fusions, which are characteristic of a subset of aggressive round cell sarcomas, have been recently detected in simple bone cysts. The aim of this study was to examine the clinicopathological and molecular features in a series of simple bone cysts. METHODS AND RESULTS/RESULTS:Using RNA-based next-generation sequencing and/or fluorescence in-situ hybridisation, we investigated the presence of EWSR1 or FUS rearrangements in nine simple bone cysts. The patients were five females and four males, aged 3-23 years (median, 14 years); the tumours ranged from 19 mm to 160 mm (median, 46 mm) in size, and involved the femur (n = 3), humerus (n = 2), fibula (n = 2), tibia (n = 1), and iliac wing (n =1). We identified three cases with EWSR1-NFATC2 fusion (showing identical breakpoints to those in EWSR1-NFATC2 sarcomas) and one additional case with FUS rearrangement. Unlike in EWSR1-NFATC2 sarcomas, immunohistochemical expression of NKX3.1 and NKX2.2 was absent in two simple bone cysts tested. CONCLUSIONS:More than 40% of simple bone cysts harbour genetic alterations confirming that they are neoplastic, investigation of EWSR1 and/or FUS rearrangement may help to distinguish simple bone cysts from mimics, and NFATC2 rearrangement is not pathognomonic of malignancy.

CONTEXT:Low energy availability causes disruption of hypothalamic gonadotropin-releasing hormone secretion leading to functional hypothalamic amenorrhea (FHA) and hypoestrogenism, which in turn contributes to decreased bone mineral density (BMD) and increased bone marrow adipose tissue (MAT). Transdermal estradiol administration in physiologic doses increases BMD in adolescents and adults with FHA. However, the impact of estrogen replacement on MAT in relation to changes in BMD has not been studied in adolescents and young adults. We hypothesized that physiologic estrogen replacement would lead to decreases in MAT, associated with increases in BMD. METHODS AND MATERIALS:We studied 15 adolescent and young adult females with FHA (14-25 years). All participants received a17β- estradiol transdermal patch at a dose of 0.1 mg/day (applied twice weekly) for 12 months. Participants also received cyclic progestin for 10-12 days each month. We quantified MAT (lipid/water ratio) of the fourth lumbar (L4) vertebral body and femoral diaphysis by single proton (1H)-magnetic resonance spectroscopy, and compartmental volumetric BMD of the distal radius and tibia using high-resolution peripheral quantitative computed tomography. RESULTS:Transdermal estradiol therapy over 12 months resulted in a decrease in MAT at the lumbar (L4) vertebra from 0.92 ± 0.55 at baseline to 0.63 ± 0.29 at 12-months (p = 0.008), and an increase in radial and tibial cortical vBMD (p = 0.006, p = 0.0003). Changes in L4 MAT trended to be inversely associated with changes in radial cortical vBMD (rho = -0.47, p = 0.08). CONCLUSION:We show that in adolescent and young adult girls with FHA, MAT decreases following transdermal estrogen therapy and these changes are associated with increased cortical vBMD.