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Skeletal Effects of Sleeve Gastrectomy in Adolescents and Young Adults: A 2-Year Longitudinal Study
Mitchell, Deborah M; Singhal, Vibha; Animashaun, Abisayo; Bose, Amita; Carmine, Brian; Stanford, Fatima C; Inge, Thomas H; Kelsey, Megan M; Lee, Hang; Bouxsein, Mary L; Yu, Elaine W; Bredella, Miriam A; Misra, Madhusmita
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.
PMCID:10211497
PMID: 36314507
ISSN: 1945-7197
CID: 5602082
Ten-Year Follow-up of Internal Neurofibroma Growth Behavior in Adult Patients With Neurofibromatosis Type 1 Using Whole-Body MRI
Ly, K Ina; Merker, Vanessa L; Cai, Wenli; Bredella, Miriam A; Muzikansky, Alona; Thalheimer, Raquel D; Da, Jennifer Liwei; Orr, Christina C; Herr, Hamilton P; Morris, Mary E; Chang, Connie Y; Harris, Gordon J; Plotkin, Scott R; Jordan, Justin T
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.
PMCID:9969927
PMID: 36332985
ISSN: 1526-632x
CID: 5602102
Changes in serum cortisol levels after 10 days of overfeeding and fasting
Colling, Caitlin; Bredella, Miriam A; Fazeli, Pouneh K; Pachón-Peña, Gisela; Singh, Ravinder J; Rosen, Clifford J; Miller, Karen K
Chronic caloric deprivation and obesity are complicated by hypercortisolemia. The effects of acute overfeeding and fasting on circulating free cortisol levels and conversion of cortisone to free cortisol are unknown. We hypothesized that serum-free cortisol and free cortisol-to-cortisone ratio would increase after both overfeeding and fasting. This is a prospective study of 22 healthy volunteers who completed a 10-day high-calorie protocol followed by a 10-day fast, separated by a 2-wk washout. Morning free and total cortisol and free cortisone levels (LC/MS) were measured at baseline and after 10 days of each intervention. Both high-calorie feeding and fasting increased total and free cortisol and the free cortisol-to-free cortisone ratio (P = 0.001 to P = 0.046). There were sex interactions, with significant effects in men (P < 0.001), but not in women (P = 0.898 and 1.000, respectively) in subset analyses examining the effects of fasting on free cortisol and the free-to-total cortisol ratio. Overfeeding and fasting both increase circulating free cortisol levels and appear to alter the balance between cortisol and its inactive metabolite, cortisone. Further study is warranted to determine whether elevated cortisol levels contribute to complications of starvation and obesity, such as bone fragility.NEW & NOTEWORTHY Overfeeding and fasting both increase circulating free cortisol levels and appear to alter the balance between cortisol and its inactive metabolite, cortisone. The effect of fasting on free cortisol levels is modified by sex. Further study is needed to determine the mechanisms driving the increases in cortisol.
PMCID:10228666
PMID: 37053050
ISSN: 1522-1555
CID: 5602112
Whole body imaging in musculoskeletal oncology: when, why, and how
Vicentini, Joao R T; Bredella, Miriam A
The use of whole-body imaging has become increasingly popular in oncology due to the possibility of evaluating total tumor burden with a single imaging study. This is particularly helpful in cases of widespread disease where dedicated regional imaging would make the evaluation more expensive, time consuming, and prone to more risks. Different techniques can be used, including whole-body MRI, whole-body CT, and PET-CT. Common indications include surveillance of cancer predisposing syndromes, evaluation of osseous metastases and clonal plasma cell disorders such as multiple myeloma, and evaluation of soft tissue lesions, including peripheral nerve sheath tumors. This review focuses on advanced whole-body imaging techniques and their main uses in musculoskeletal oncology.
PMID: 35809098
ISSN: 1432-2161
CID: 5601992
Relationship of Imaging-guided Corticosteroid Injections to COVID-19 Incidence in the Pandemic Recovery Period
Vicentini, Joao R T; Habibollahi, Sina; Staffa, Steven J; Simeone, Frank J; Kheterpal, Arvin B; Graeber, Adam R; Bredella, Miriam A; Chang, Connie Y
Background Corticosteroids injected for the treatment of musculoskeletal pain are systemically absorbed and can affect the immune response to viral infections. Purpose To determine the incidence of symptomatic COVID-19 disease in individuals receiving image-guided corticosteroid injections for musculoskeletal pain compared with the general population during the pandemic recovery period. Materials and Methods In this prospective cohort multicenter study, adults with a history of musculoskeletal pain who underwent imaging-guided intra-articular and spine corticosteroid injections from April 2020 to February 2021 were consecutively enrolled. Participants were followed for a minimum of 28 days through their electronic medical record (EMR) or by direct phone communication to screen for COVID-19 test results or symptoms. Clinical data, including body mass index (BMI), were also obtained from the EMR. The incidence of COVID-19 in the state was obtained using the Massachusetts COVID-19 Response Reporting website. The Student t test was used for continuous variable comparisons. Univariable analyses were performed using the Fisher exact test. Results A total of 2714 corticosteroid injections were performed in 2190 adult participants (mean age, 59 years ± 15 [SD]; 1031 women). Follow-up was available for 1960 participants (89%) who received 2484 injections. Follow-up occurred a mean of 97 days ± 33 (range, 28-141 days) after the injection. Of the 1960 participants, 10 had COVID-19 within 28 days from the injection (0.5% [95% CI: 0.24, 0.94]) and 43 had COVID-19 up to 4 months after the injection (2.2% [95% CI: 1.6, 2.9]). These incidence rates were lower than that of the population of Massachusetts during the same period (519 195 of 6 892 503 [7.5%], P < .001 for both 28 days and 4 months). Participants diagnosed with COVID-19 (n = 10) within 28 days from the injection had a higher BMI than the entire cohort (n = 1960) (mean, 32 kg/m2 ± 10 vs 28 kg/m2 ± 6; P = .04). Conclusion Adults who received image-guided corticosteroid injections for pain management during the pandemic recovery period had a lower incidence of symptomatic COVID-19 compared with the general population. © RSNA, 2022 Online supplemental material is available for this article.
PMCID:9341274
PMID: 35787202
ISSN: 1527-1315
CID: 5601962
Two-year Skeletal Effects of Sleeve Gastrectomy in Adolescents with Obesity Assessed with Quantitative CT and MR Spectroscopy
Huber, Florian A; Singhal, Vibha; Tuli, Shubhangi; Becetti, Imen; López López, Ana Paola; Bouxsein, Mary L; Misra, Madhusmita; Bredella, Miriam A
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.
PMID: 37310246
ISSN: 1527-1315
CID: 5602192
Training and cultivating the translational science workforce: Responses of Clinical and Translational Science Awards program hubs to the COVID-19 pandemic
Bredella, Miriam A; Volkov, Boris B; Doyle, Jamie M
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.
PMCID:9841297
PMID: 36448246
ISSN: 1752-8062
CID: 5602122
Bone marrow adipose tissue is associated with fracture history in anorexia nervosa
Dang, T; Faje, A T; Meenaghan, E; Bredella, M A; Bouxsein, M L; Klibanski, A; Fazeli, P K
UNLABELLED:Although bone mineral density (BMD) is decreased and fracture risk increased in anorexia nervosa, BMD does not predict fracture history in this disorder. We assessed BMD, bone microarchitecture, and bone marrow adipose tissue (BMAT) in women with anorexia nervosa and found that only BMAT was associated with fracture history. INTRODUCTION/BACKGROUND:Anorexia nervosa (AN) is a psychiatric disorder characterized by low body weight, low BMD, and increased risk of fracture. Although BMD is reduced and fracture risk elevated, BMD as assessed by DXA does not distinguish between individuals with versus those without prior history of fracture in AN. Despite having decreased peripheral adipose tissue stores, individuals with AN have enhanced bone marrow adipose tissue (BMAT), which is inversely associated with BMD. Whether increased BMAT is associated with fracture in AN is not known. METHODS:H-MRS, and parameters of bone microarchitecture by HR-pQCT. RESULTS:Sixteen women (47.1%) with AN reported prior history of fracture compared to 11 normal-weight women (39.3%, p = 0.54). In the entire group and also the subset of women with AN, there were no significant differences in BMD or parameters of bone microarchitecture in women with prior fracture versus those without. In contrast, women with AN with prior fracture had greater BMAT at the spine and femur compared to those without (p = 0.01 for both). CONCLUSION/CONCLUSIONS:In contrast to BMD and parameters of bone microarchitecture, BMAT is able to distinguish between women with AN with prior fracture compared to those without. Prospective studies will be necessary to understand BMAT's potential pathophysiologic role in the increased fracture risk in AN.
PMCID:9940017
PMID: 35999286
ISSN: 1433-2965
CID: 5602602
Distal Triceps Tendon Tears: Magnetic Resonance Imaging Patterns Using a Systematic Classification
Vicentini, Joao R T; Hilgersom, Nicolaas F J; Martinez-Salazar, Edgar L; Simeone, F Joseph; Bredella, Miriam A; Palmer, William E; Oh, Luke S; Torriani, Martin
OBJECTIVE:This study aimed to evaluate distal triceps tendon tear patterns using a systematic classification based on the tendon's layered structure. METHODS:We retrospectively identified Magnetic resonance imaging (MRI) examinations with triceps tendon tears that underwent reconstructive surgery. Magnetic resonance images were reviewed independently by 2 musculoskeletal radiologists to determine tendon layer involvement and ancillary findings, including tear size, involvement of triceps lateral expansion, and presence of olecranon bursal fluid. Surgical reports were scrutinized for level of anatomic detail and correlation with imaging findings. RESULTS:We identified 69 triceps tendon tears in 68 subjects (61 men, 7 women; mean age, 45 ± 12 years) who underwent surgical reconstruction. On MRI, the superficial layer was always involved with either a partial or full-thickness tear. The most common tear pattern was a combination of superficial layer full-thickness tear with deep layer partial tear (25 of 69 [36%]). Mean tear length was 24 ± 12 mm. We found no cases of isolated deep layer tears. Involvement of triceps lateral expansion and presence of bursal fluid correlated positively with tear severity of superficial and deep layers (P < 0.001). Detailed surgical correlation was limited, with only 9 of 69 (13%) of surgical reports containing information specifically addressing individual tendon layers. CONCLUSIONS:Triceps tendon tears show tear patterns following its layered structure and can be assessed by MRI. Radiologists and surgeons are encouraged to describe tear patterns considering both superficial and deep tendon layers.
PMID: 35081601
ISSN: 1532-3145
CID: 5601952
Impact of GH administration on skeletal endpoints in adults with overweight/obesity
Dichtel, Laura E; Haines, Melanie S; Gerweck, Anu V; Bollinger, Bryan; Kimball, Allison; Schoenfeld, David; Bredella, Miriam A; Miller, Karen K
OBJECTIVE/UNASSIGNED:Overweight/obesity is associated with relative growth hormone (GH) deficiency and increased fracture risk. We hypothesized that GH administration would improve bone endpoints in individuals with overweight/obesity. DESIGN/UNASSIGNED:An 18-month, randomized, double-blind, placebo-controlled study of GH, followed by 6-month observation. METHODS/UNASSIGNED:In this study, 77 adults (53% men), aged 18-65 years, BMI ≥ 25 kg/m2, and BMD T- or Z-score ≤ -1.0 were randomized to daily subcutaneous GH or placebo, targeting IGF1 in the upper quartile of the age-appropriate normal range. Forty-nine completed 18 months. DXA, volumetric quantitative CT, and high-resolution peripheral quantitative CT were performed. RESULTS/UNASSIGNED:Pre-treatment mean age (48 ± 12 years), BMI (33.1 ± 5.7 kg/m2), and BMD were similar between groups. P1NP, osteocalcin, and CTX increased (P < 0.005) and visceral adipose tissue decreased (P = 0.04) at 18 months in the GH vs placebo group. Hip and radius aBMD, spine and tibial vBMD, tibial cortical thickness, and radial and tibial failure load decreased in the GH vs placebo group (P < 0.05). Between 18 and 24 months (post-treatment observation period), radius aBMD and tibia cortical thickness increased in the GH vs placebo group. At 24 months, there were no differences between the GH and placebo groups in bone density, structure, or strength compared to baseline. CONCLUSIONS/UNASSIGNED:GH administration for 18 months increased bone turnover in adults with overweight/obesity. It also decreased some measures of BMD, bone microarchitecture, and bone strength, which all returned to pre-treatment levels 6 months post-therapy. Whether GH administration increases BMD with longer treatment duration, or after mineralization of an expanded remodeling space post-treatment, requires further investigation.
PMCID:9400128
PMID: 35315344
ISSN: 1479-683x
CID: 5601862