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The Association Between IGF-1 Levels and the Histologic Severity of Nonalcoholic Fatty Liver Disease
Dichtel, Laura E; Corey, Kathleen E; Misdraji, Joseph; Bredella, Miriam A; Schorr, Melanie; Osganian, Stephanie A; Young, Brian J; Sung, Joshua C; Miller, Karen K
OBJECTIVES/OBJECTIVE:The mechanisms responsible for the development of nonalcoholic fatty liver disease (NAFLD) and progression to nonalcoholic steatohepatitis (NASH) are incompletely understood. Growing evidence suggests that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may have roles in the development and progression of NAFLD. We hypothesized that lower serum IGF-1 levels would be associated with increased liver fat accumulation, inflammation, and fibrosis in a group of meticulously phenotyped obese subjects with liver biopsies. METHODS:A retrospective, cross-sectional study was performed at Massachusetts General Hospital, Boston, MA, USA and St. Mary's Hospital, Richmond, VA, USA. Liver biopsies were performed in 142 subjects during NAFLD work-up or bariatric surgery and were graded by a single, blinded pathologist. Main outcome measures included liver histology and serum IGF-1. RESULTS:. Mean serum IGF-1 was lower in subjects with lobular inflammation (112±47 vs. 136±57 ng/ml, P=0.01), hepatocyte ballooning (115±48 vs. 135±57 ng/ml, P=0.05), higher fibrosis stage (stage 2-4 vs. 0-1; 96±40 vs. 125±51 ng/ml, P=0.005), and NASH (109±45 vs. 136±57 ng/ml, P=0.002). All results remained significant after controlling for age, BMI, and a diagnosis of diabetes, and all but hepatocyte ballooning (trend, P=0.06) remained significant after excluding individuals with cirrhosis. Steatosis was not significantly associated with mean serum IGF-1 levels. CONCLUSIONS:Low serum IGF-1 levels are associated with increased histologic severity of NAFLD when rigorously controlled for age, BMI, the presence of diabetes, and after the exclusion of subjects with cirrhosis. Further investigation is warranted to determine the differential effects of GH and IGF-1 on the development and progression of NAFLD, which could further elucidate pathophysiology and identify therapeutic targets.
PMCID:5288606
PMID: 28125073
ISSN: 2155-384x
CID: 5600912
Vertebral Volumetric Bone Density and Strength Are Impaired in Women With Low-Weight and Atypical Anorexia Nervosa
Bachmann, Katherine N; Schorr, Melanie; Bruno, Alexander G; Bredella, Miriam A; Lawson, Elizabeth A; Gill, Corey M; Singhal, Vibha; Meenaghan, Erinne; Gerweck, Anu V; Slattery, Meghan; Eddy, Kamryn T; Ebrahimi, Seda; Koman, Stuart L; Greenblatt, James M; Keane, Robert J; Weigel, Thomas; Misra, Madhusmita; Bouxsein, Mary L; Klibanski, Anne; Miller, Karen K
CONTEXT:Areal bone mineral density (BMD) is lower, particularly at the spine, in low-weight women with anorexia nervosa (AN). However, little is known about vertebral integral volumetric BMD (Int.vBMD) or vertebral strength across the AN weight spectrum, including "atypical" AN [body mass index (BMI) ≥18.5 kg/m2]. OBJECTIVE:To investigate Int.vBMD and vertebral strength, and their determinants, across the AN weight spectrum. DESIGN:Cross-sectional observational study. SETTING:Clinical research center. PARTICIPANTS:153 women (age 18 to 45): 64 with low-weight AN (BMI <18.5 kg/m2; 58% amenorrheic), 44 with atypical AN (18.5≤BMI<23 kg/m2; 30% amenorrheic), 45 eumenorrheic controls (19.2≤BMI<25 kg/m2). MEASURES:Int.vBMD and cross-sectional area (CSA) by quantitative computed tomography of L4; estimated vertebral strength (derived from Int.vBMD and CSA). RESULTS:Int.vBMD and estimated vertebral strength were lowest in low-weight AN, intermediate in atypical AN, and highest in controls. CSA did not differ between groups; thus, vertebral strength (calculated using Int.vBMD and CSA) was driven by Int.vBMD. In AN, Int.vBMD and vertebral strength were associated positively with current BMI and nadir lifetime BMI (independent of current BMI). Int.vBMD and vertebral strength were lower in AN with current amenorrhea and longer lifetime amenorrhea duration. Among amenorrheic AN, Int.vBMD and vertebral strength were associated positively with testosterone. CONCLUSIONS:Int.vBMD and estimated vertebral strength (driven by Int.vBMD) are impaired across the AN weight spectrum and are associated with low BMI and endocrine dysfunction, both current and previous. Women with atypical AN experience diminished vertebral strength, partially due to prior low-weight and/or amenorrhea. Lack of current low-weight or amenorrhea in atypical AN does not preclude compromise of vertebral strength.
PMCID:5413107
PMID: 27732336
ISSN: 1945-7197
CID: 5600902
Long-term outcomes of percutaneous lumbar facet synovial cyst rupture
Huang, Ambrose J; Bos, Stijn A; Torriani, Martin; Simeone, F Joseph; Chang, Connie Y; Pomerantz, Stuart R; Bredella, Miriam A
OBJECTIVE:To evaluate the therapeutic value, safety, and long-term clinical outcomes of percutaneous lumbar facet synovial cyst (LFSC) rupture. MATERIALS AND METHODS/METHODS:Our study was institutional review board (IRB)-approved and Health Insurance Portability and Accountability Act (HIPAA)-compliant. The study group comprised 71 patients (44 women, mean age: 65 ± 17 years) who underwent CT- or fluoroscopy-guided percutaneous LFSC rupture. The technical success of LFSC rupture, the long-term clinical outcome, including repeat procedures or surgery, and imaging findings on MRI and CT were recorded. RESULTS:Seventy-nine LFSC ruptures were performed in 71 patients. CT guidance was used in 57 cases and fluoroscopy guidance in 22 cases. LFSC rupture was technically successful in 58 out of 79 cases (73 %). Mean injection volume for cyst rupture was 3.6 ± 2.2 mL and a combination of steroid and anesthetic was injected in all cases. Over a mean follow-up time of 44 months, 12 % of patients underwent repeat cyst rupture, and 46 % eventually underwent surgery, whereas the majority of patients (55 %) experienced symptomatic relief and did not undergo surgery. There was no significant association between a successful outcome and age, sex, level, or size of LFSC (p > 0.1). LFSCs with T2 hypointensity were more likely to require surgery (p = 0.02). There was one complication, a bacterial skin infection that completely resolved following antibiotic therapy. CONCLUSION/CONCLUSIONS:Percutaneous LFSC rupture is an effective and safe nonsurgical treatment option for LFSC. More than half of treated patients were able to avoid subsequent surgery. Therefore, percutaneous LFSC rupture should be considered before surgical intervention.
PMID: 27771754
ISSN: 1432-2161
CID: 5600972
Body composition in pituitary, adrenal and iatrogenic Cushing's syndrome and effects of DHEAS levels [Letter]
Dichtel, Laura E; Schorr, Melanie; Gill, Corey M; Economopoulos, Konstantinos P; Gerweck, Anu V; Swearingen, Brooke; Hodin, Richard; Bredella, Miriam A; Miller, Karen K
PMCID:5164987
PMID: 27696526
ISSN: 1365-2265
CID: 5600882
Idiopathic tumoral calcinosis-like lesion in the lower cervical spine causing acute central cord syndrome: case report [Case Report]
Al-Sukaini, Ahmad; Paulino Pereira, Nuno Rui; Yu, Elaine W; Chebib, Ivan; Bredella, Miriam A; Schwab, Joseph
A 57-year-old male presented with recurrent falls, bilateral lower-limb paresthesia, and severe neck pain. Imaging revealed a mass compressing his spinal cord. He was admitted for further workup for spinal cord compression. Within 24 hours of admission, he developed upper-extremity weakness while maintaining lower-extremity function. He underwent urgent decompression of his spinal cord. During exposure, a white, creamy odorless substance was noted. This same substance was found under pressure within the spinal canal. The mass was grossly removed, and the patient's weakness improved postoperatively. Based on the clinical picture, intraoperative presentation, and final histological examination, idiopathic tumoral calcinosis-like lesion was considered as the most appropriate diagnosis.
PMID: 27611507
ISSN: 1547-5646
CID: 5600862
Treatment of aneurysmal bone cysts by percutaneous CT-guided injection of calcitonin and steroid
Chang, Connie Y; Kattapuram, Susan V; Huang, Ambrose J; Simeone, F Joseph; Torriani, Martin; Bredella, Miriam A
OBJECTIVES/OBJECTIVE:To determine the efficacy and safety of percutaneous calcitonin and steroid injection in the treatment of aneurysmal bone cysts (ABCs). MATERIALS AND METHODS/METHODS:Our study was IRB-approved and HIPAA-compliant. We reviewed pre- and post-procedural imaging studies and medical records of all CT-guided percutaneous injections of ABCs with calcitonin and steroid performed at our institution between 2003 and 2015. RESULTS:Treatment success based on imaging was categorized as substantial (51-100 %), partial (1-50 %), or none (0 %) by comparing radiographs of the lesion before and after treatment. Our study group comprised 9 patients (7 female, 2 male; mean age 19 ± 5 (range 12-25) years). ABCs were located in the pubis (n = 3), femur (n = 2), and humerus/scapula/ilium/sacrum (n = 1 for each). One patient did not have any clinical or imaging follow-up. For the other 8 patients, clinical and imaging follow-up ranged from 1 to 93 months (mean 16 ± 29 months). One patient had two injections, and 1 patient had three injections. Six out of eight patients (75 %) had complete symptomatic relief and 2 patients (25 %) had partial symptomatic relief after initial injection. Imaging follow-up revealed substantial imaging response in 4 out of 8 patients (50 %). There was a partial imaging response in 2 patients (25 %) and no imaging response in 2 out of 8 patients (25 %), and all 4 of these patients had local recurrence. There were no complications. CONCLUSION/CONCLUSIONS:Percutaneous CT-guided injection of ABCs with calcitonin and steroid is a safe and effective treatment. Lack of imaging response may necessitate more aggressive treatment to minimize local recurrence.
PMID: 27743037
ISSN: 1432-2161
CID: 5600952
Sex Differences in Body Composition
Bredella, Miriam A
Body composition differs between men and women. Men have more lean mass, and women have more fat mass than men. Men are more likely to accumulate adipose tissue around the trunk and abdomen, whereas women usually accumulate adipose tissue around the hips and thighs. Less is known about sex differences in ectopic fat depots. Advances in imaging allow the noninvasive assessment of abdominal and femorogluteal fat compartments, intramyocellular lipids, intrahepatic lipids, pericardial adipose tissue, and neck adipose tissue including brown adipose tissue and tongue adipose tissue. In this review, sex differences of regional adipose tissue, muscle mass, ectopic lipids, and brown adipose tissue and their effects on cardiometabolic risk will be discussed. In addition, novel imaging techniques to quantify these body composition compartments noninvasively will be described.
PMID: 29224088
ISSN: 0065-2598
CID: 5601162
Corrigendum: Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues
Scheller, Erica L; Doucette, Casey R; Learman, Brian S; Cawthorn, William P; Khandaker, Shaima; Schell, Benjamin; Wu, Brent; Ding, Shi-Ying; Bredella, Miriam A; Fazeli, Pouneh K; Khoury, Basma; Jepsen, Karl J; Pilch, Paul F; Klibanski, Anne; Rosen, Clifford J; MacDougald, Ormond A
PMID: 27929114
ISSN: 2041-1723
CID: 5600852
Adipose tissue and muscle attenuation as novel biomarkers predicting mortality in patients with extremity sarcomas
Veld, Joyce; Vossen, Josephina A; De Amorim Bernstein, Karen; Halpern, Elkan F; Torriani, Martin; Bredella, Miriam A
OBJECTIVES/OBJECTIVE:To assess CT-attenuation of abdominal adipose tissue and psoas muscle as predictors of mortality in patients with sarcomas of the extremities. METHODS:Our study was IRB approved and HIPAA compliant. The study group comprised 135 patients with history of extremity sarcoma (mean age: 53 ± 17 years) who underwent whole body PET/CT. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and psoas muscle attenuation (HU) was assessed on non-contrast, attenuation-correction CT. Clinical information including survival, tumour stage, sarcoma type, therapy and pre-existing comorbidities were recorded. Cox proportional hazard models were used to determine longitudinal associations between adipose tissue and muscle attenuation and mortality. RESULTS:There were 47 deaths over a mean follow-up period of 20 ± 17 months. Higher SAT and lower psoas attenuation were associated with increased mortality (p = 0.03 and p = 0.005, respectively), which remained significant after adjustment for age, BMI, sex, tumor stage, therapy, and comorbidities (p = 0.002 and p = 0.02, respectively). VAT attenuation was not associated with mortality. CONCLUSION/CONCLUSIONS:Attenuation of SAT and psoas muscle, assessed on non-contrast CT, are predictors of mortality in patients with extremity sarcomas, independent of other established prognostic factors, suggesting that adipose tissue and muscle attenuation could serve as novel biomarkers for mortality in patients with sarcomas. KEY POINTS/CONCLUSIONS:• CT-attenuation of adipose tissue and muscle predict mortality in sarcoma patients • CT-attenuation predicts mortality independent of established prognostic factors • Patients with sarcomas often undergo CT for staging or surveillance • Adipose tissue and muscle attenuation could serve as biomarkers for mortality.
PMID: 26960539
ISSN: 1432-1084
CID: 5600662
Fat accumulation in the tongue is associated with male gender, abnormal upper airway patency and whole-body adiposity
Godoy, Ivan R B; Martinez-Salazar, Edgar Leonardo; Eajazi, Alireza; Genta, Pedro R; Bredella, Miriam A; Torriani, Martin
OBJECTIVE:To examine associations between tongue adiposity with upper airway measures, whole-body adiposity and gender. We hypothesized that increased tongue adiposity is higher in males and positively associated with abnormal upper airway measures and whole-body adiposity. METHODS:We studied subjects who underwent whole-body positron emission tomography/computed tomography to obtain tongue attenuation (TA) values and cross-sectional area, pharyngeal length (PL) and mandibular plane to hyoid distance (MPH), as well as abdominal circumference, abdominal subcutaneous and visceral (VAT) adipose tissue areas, neck circumference (NC) and neck adipose tissue area. Metabolic syndrome was determined from available clinical and laboratory data. RESULTS:). Males had lower TA values (P=0.0002) and higher upper airway measures (P<0.0001) independent of age and BMI (P<0.001). In all subjects, TA was negatively associated with upper airway measures (P<0.001). TA was negatively associated with body composition parameters (all P<0.0001), most notably with VAT (r=-0.53) and NC (r=-0.47). TA values were lower in subjects with metabolic syndrome (P<0.0001). CONCLUSION/CONCLUSIONS:Increased tongue adiposity is influenced by gender and is associated with abnormal upper airway patency and body composition parameters.
PMCID:5367267
PMID: 27733254
ISSN: 1532-8600
CID: 5600922