Faculty Bibliography

OBJECTIVE:Tumors and other disease complications of neurofibromatosis (NF) can cause pain and negatively affect physical functioning. To document the clinical benefit of treatment in NF trials targeting these manifestations, patient-reported outcomes (PROs) assessing pain and physical functioning should be included as study endpoints. Currently, there is no consensus on the selection and use of such measures in the NF population. This article presents the recommendations of the PRO group of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration for assessing the domains of pain and physical functioning for NF clinical trials. METHODS:The REiNS PRO group reviewed and rated existing PRO measures assessing pain intensity, pain interference, and physical functioning using their systematic method. Final recommendations are based primarily on 4 main criteria: patient characteristics, item content, psychometric properties, and feasibility for clinical trials. RESULTS:The REiNS PRO group chose the Numeric Rating Scale-11 (≥8 years) to assess pain intensity, the Pain Interference Index (6-24 years) and the Patient-Reported Outcome Measurement Information System (PROMIS) Pain Interference Scale (≥18 years) to evaluate pain interference, and the PROMIS Physical Functioning Scale to measure upper extremity function and mobility (≥5 years) for NF clinical trials. CONCLUSIONS:The REiNS Collaboration currently recommends these PRO measures to assess the domains of pain and physical functioning for NF clinical trials; however, further research is needed to evaluate their use in individuals with NF. A final consensus recommendation for the pain interference measure will be disseminated in a future publication based on findings from additional published research.

OBJECTIVE:Plexiform neurofibromas (PNs) are complex, benign nerve sheath tumors that occur in approximately 25%-50% of individuals with neurofibromatosis type 1 (NF1). PNs that cause airway compromise or pulmonary dysfunction are uncommon but clinically important. Because improvement in sleep quality or airway function represents direct clinical benefit, measures of sleep and pulmonary function may be more meaningful than tumor size as endpoints in therapeutic clinical trials targeting airway PN. METHODS:The Response Evaluation in Neurofibromatosis and Schwannomatosis functional outcomes group reviewed currently available endpoints for sleep and pulmonary outcomes and developed consensus recommendations for response evaluation in NF clinical trials. RESULTS:For patients with airway PNs, polysomnography, impulse oscillometry, and spirometry should be performed to identify abnormal function that will be targeted by the agent under clinical investigation. The functional group endorsed the use of the apnea hypopnea index (AHI) as the primary sleep endpoint, and pulmonary resistance at 10 Hz (R10) or forced expiratory volume in 1 or 0.75 seconds (FEV1 or FEV0.75) as primary pulmonary endpoints. The group defined minimum changes in AHI, R10, and FEV1 or FEV0.75 for response criteria. Secondary sleep outcomes include desaturation and hypercapnia during sleep and arousal index. Secondary pulmonary outcomes include pulmonary resistance and reactance measurements at 5, 10, and 20 Hz; forced vital capacity; peak expiratory flow; and forced expiratory flows. CONCLUSIONS:These recommended sleep and pulmonary evaluations are intended to provide researchers with a standardized set of clinically meaningful endpoints for response evaluation in trials of NF1-related airway PNs.

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.

BACKGROUND:Obesity is prevalent among adolescents and is associated with serious health consequences. Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG) are bariatric procedures that cause significant weight loss in adults and are increasingly being performed in adolescents with morbid obesity. Data comparing outcomes of RYGB vs. SG in this age-group are scarce. This study aims to compare short-term (1-6 months) and longer-term (7-18 months) body mass index (BMI) and biochemical outcomes following RYGB and SG in adolescents/young adults. METHODS:A retrospective study using data extracted from medical records of patients 16-21 years who underwent RYGB or SG between 2012 and 2014 at a tertiary care academic medical center. RESULTS:Forty-six patients were included in this study: 24 underwent RYGB and 22 underwent SG. Groups did not differ for baseline age, sex, race, or BMI. BMI reductions were significant at 1-6 months and 7-18 months within groups (p < 0.0001), but did not differ by surgery type (p = 0.65 and 0.09, for 1-6 months and 7-18 months, respectively). Over 7-18 months, within-group improvement in low-density lipoprotein (LDL) (-24 ± 6 in RYGB, p = 0.003, vs. -7 ± 9 mg/dl in SG, p = 0.50) and non-high-density lipoprotein (non-HDL) cholesterol (-23 ± 8 in RYGB, p = 0.02, vs. -12 ± 7 in SG, p = 0.18) appeared to be of greater magnitude following RYGB. However, differences between groups did not reach statistical significance. When divided by non-alcoholic steatohepatitis stages (NASH), patients with Stage II-III NASH had greater reductions in alanine aminotransferase levels vs. those with Stage 0-I NASH (-45 ± 18 vs. -9 ± 3, p = 0.01) after 7-18 months. RYGB and SG groups did not differ for the magnitude of post-surgical changes in liver enzymes. CONCLUSION/CONCLUSIONS:RYGB and SG did not differ for the magnitude of BMI reduction across groups, though changes trended higher following RYGB. Further prospective studies are needed to confirm these findings.

The rates of diabetes, obesity, and metabolic disease have reached epidemic proportions worldwide. In recent years there has been renewed interest in combating these diseases not only by modifying energy intake and lifestyle factors, but also by inducing endogenous energy expenditure. This approach has largely been stimulated by the recent recognition that brown adipose tissue (BAT)-long known to promote heat production and energy expenditure in infants and hibernating mammals-also exists in adult humans. This landmark finding relied on the use of clinical fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography, and imaging techniques continue to play a crucial and increasingly central role in understanding BAT physiology and function. Herein, the authors review the origins of BAT imaging, discuss current preclinical and clinical strategies for imaging BAT, and discuss imaging methods that will provide crucial insight into metabolic disease and how it may be treated by modulating BAT activity. (©) RSNA, 2016.

PURPOSE/OBJECTIVE:To compare the lateral mortise and anterior midline approaches to fluoroscopically guided tibiotalar joint injections with respect to successful intra-articular needle placement, fluoroscopy time, radiation dose, and dose area product (DAP). MATERIALS AND METHODS/METHODS:This retrospective study was IRB-approved and HIPAA-compliant. 498 fluoroscopically guided tibiotalar joint injections were performed or supervised by one of nine staff radiologists from 11/1/2010-12/31/2013. The injection approach was determined by operator preference. Images were reviewed on a PACS workstation to determine the injection approach (lateral mortise versus anterior midline) and to confirm intra-articular needle placement. Fluoroscopy time (minutes), radiation dose (mGy), and DAP (μGy-m(2)) were recorded and compared using the student's t-test (fluoroscopy time) or the Wilcoxon rank sum test (radiation dose and DAP). RESULTS:There were 246 lateral mortise injections and 252 anterior midline injections. Two lateral mortise injections were excluded from further analysis because no contrast was administered. Intra-articular location of the needle tip was documented in 242/244 lateral mortise injections and 252/252 anterior midline injections. Mean fluoroscopy time was shorter for the lateral mortise group than the anterior midline group (0.7 ± 0.5 min versus 1.2 ± 0.8 min, P < 0.0001). Mean radiation dose and DAP were less for the lateral mortise group than the anterior midline group (2.1 ± 3.7 mGy versus 2.5 ± 3.5 mGy, P = 0.04; 11.5 ± 15.3 μGy-m(2) versus 13.5 ± 17.3 μGy-m(2), P = 0.006). CONCLUSION/CONCLUSIONS:Both injection approaches resulted in nearly 100% rates of intra-articular needle placement, but the lateral mortise approach used approximately 40% less fluoroscopy time and delivered 15% lower radiation dose and DAP to the patient.

OBJECTIVE:The purpose of this study was (1) to evaluate the association of trunk muscle density assessed by computed tomography (CT) with age, gender, and BMI and (2) to evaluate the association between trunk muscle CT density and degenerative disc and facet joint disease of the lumbar spine. MATERIAL AND METHODS/METHODS:The study was IRB approved and HIPAA compliant. The study group comprised 100 subjects (mean age 44.4 ± 22.2 years, 51 % male) who underwent CT of the abdomen and pelvis without intravenous contrast. Exclusion criteria included prior abdominal or spine surgery, active malignancy and scoliosis. CTs were reviewed and the attenuation of the rectus abdominis, transverse abdominis, internal and external obliques, psoas, multifidus, longissimus and gluteus maximus were measured bilaterally at consistent levels. Degenerative disc and bilateral facet joint disease were scored using established methods. Univariate analyses were performed using linear regression. Multivariate linear regression was performed to adjust for age, gender and BMI. RESULTS:CT density of each trunk muscle correlated inversely with age (p < 0.001) and BMI (p < 0.001). CT density of each trunk muscle correlated inversely with degenerative disc and facet joint disease in the univariate analyses (p < 0.001); however, only the gluteus maximus and the transverse abdominis remained significant predictors of degenerative disc and facet joint disease respectively in the multivariate analysis. CONCLUSION/CONCLUSIONS:Fatty infiltration of trunk musculature increases with age and BMI. Fatty infiltration of the gluteus maximus and transverse abdominis are associated with degenerative disc and facet joint disease, independent of age, gender and BMI.

OBJECTIVE:The purpose of this study was to determine whether CT attenuation thresholds can be used to distinguish untreated osteoblastic metastases from enostoses. MATERIALS AND METHODS/METHODS:The study group comprised 62 patients with 279 sclerotic bone lesions found at CT (126 enostoses in 37 patients and 153 metastases in 25 patients). The cause of sclerotic lesions was assessed histologically or by clinical and imaging follow-up. None of the patients had undergone prior treatment for the metastases. The mean and maximum attenuation were measured in Hounsfield units. ROC analysis was performed to determine sensitivity, specificity, AUC, 95% CIs, and cutoff values of CT attenuation to differentiate metastases from enostoses. Interreader reproducibility was assessed using an intraclass correlation coefficient with 95% CI. RESULTS:The mean and maximum CT attenuation values of enostoses were 1190 ± 239 HU and 1323 ± 234 HU, respectively, and those of osteoblastic metastases were 654 ± 176 HU and 787 ± 194 HU, respectively. Using a cutoff of 885 HU for mean attenuation, the AUC was 0.982, sensitivity was 95%, and specificity was 96%. Using a cutoff of 1060 HU for maximum CT attenuation, the AUC was 0.976, sensitivity was 95%, and specificity was 96%. The mean attenuation intraclass correlation coefficient was 0.987 for enostoses and 0.81 for metastases. The maximum attenuation intraclass correlation coefficient was 0.814 for enostoses and 0.980 for metastases. CONCLUSION/CONCLUSIONS:CT attenuation measurements can be used to distinguish untreated osteoblastic metastases from enostoses. A mean attenuation of 885 HU and a maximum attenuation of 1060 HU provide reliable thresholds below which a metastatic lesion is the favored diagnosis.