Faculty Bibliography

Clinical and Translational Science Award (CTSA) TL1 trainees and KL2 scholars were surveyed to determine the immediate impact of the COVID-19 pandemic on training and career development. The most negative impact was lack of access to research facilities, clinics, and human subjects, plus for KL2 scholars lack of access to team members and need for homeschooling. TL1 trainees reported having more time to think and write. Common strategies to maintain research productivity involved time management, virtual connections with colleagues, and shifting to research activities not requiring laboratory/clinic settings. Strategies for mitigating the impact of the COVID-19 pandemic on training and career development are described.

OBJECTIVE:The aim of the study was to determine abdominal and breast adipose tissue parameters on 18-fluorodeoxyglucose positron emission tomography/computed tomography (CT) that may serve as outcome predictors in breast angiosarcoma patients. MATERIALS/METHODS:Women with breast angiosarcoma (n = 13) who underwent 18-fluorodeoxyglucose positron emission tomography/CT were identified. A control group was selected (n = 25). Abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) were assessed on unenhanced computed tomographies. Breast adipose tissue (BAT) volumes of the uninvolved breast were quantified. Metabolic activity of VAT, SAT, and BAT was calculated (standardized uptake value [SUV]). RESULTS:Breast angiosarcoma patients had higher metabolic activity of VAT compared with controls (SUV 0.93 ± 0.39 vs 0.64 ± 0.11, P = 0.044). Within the patient group, there were 6 deaths (46.2%). Patients who died had higher SAT activity (SUV 0.52 ± 0.24 vs 0.29 ± 0.06, P = 0.027) and higher BAT metabolic activity (SUV 0.48 ± 0.20 vs 0.27 ± 0.11, P = 0.045) compared with nondeceased patients. CONCLUSIONS:Patients with breast angiosarcoma have higher metabolic activity of VAT. Higher abdominal SAT and higher BAT metabolic activity of the uninvolved breast might predict mortality.

Chondroblastoma is currently classified as a benign neoplasm; however, chondroblastoma and chondroblastoma-like osteosarcoma have morphologic overlap, raising the possibility that some tumors diagnosed as chondroblastoma-like osteosarcoma might actually represent malignant chondroblastoma. The H3F3B K36M point mutation, which has not been reported in osteosarcoma, is identified in 95% of chondroblastomas and is reliably detectable by immunohistochemistry (IHC). We reviewed 11 tumors diagnosed as atypical chondroblastoma, malignant chondroblastoma, or chondroblastoma-like osteosarcoma (median follow-up: 8.8 years; range: 4 months-26.4 years). Seven chondroblastomas with cytologic atypia and permeative growth were designated "malignant chondroblastoma"; six were H3K36M-positive by IHC. Relative to conventional chondroblastoma, malignant chondroblastoma occurred in older individuals (median: 52 years; range: 29-57 years) and arose at unusual sites. Three of four tumors with long-term follow-up recurred, and one patient died of widespread metastases. One was found to have chromosomal copy number alter4ations and a SETD2 mutation in addition to H3F3B K36M. The four remaining tumors were classified as chondroblastoma-like osteosarcoma. Chondroblastoma-like osteosarcoma occurred in younger patients (median: 21 years; range: 19-40 years) than malignant chondroblastoma. In contrast to malignant chondroblastoma, all had regions of malignant cells forming bone. Two of three patients with long-term follow-up developed recurrences, and two died of disease, one with widespread metastases. No mutations in H3F3A/H3F3B were detected by Sanger sequencing. While malignant chondroblastoma and chondroblastoma-like osteosarcoma show significant morphologic overlap, they have distinct clinical presentations and genetic findings. When considering this challenging differential diagnosis, IHC using histone H3 mutation-specific antibodies is a critical diagnostic adjunct.

OBJECTIVE:To evaluate organ dose and total effective dose of whole-body low-dose CT (WBLDCT) performed on different CT-scanner models in patients with multiple myeloma (MM) and to compare it to the effective dose of radiographic skeletal survey and representative diagnostic CTs. MATERIAL AND METHODS/METHODS:We retrospectively analyzed data from 228 patients (47.4% females, mean age 67.9 ± 10.4 years, mean weight 81.8 ± 22.4 kg) who underwent WBLDCT for the work-up or surveillance of MM. Patients were scanned using one of six multi-detector CT-scanners. Organ doses and total effective doses per scan were calculated using a commercially available dose-management platform (Radimetrics, Bayer Healthcare, Leverkusen, Germany). The median effective dose was compared to radiographic skeletal survey and representative diagnostic CTs. RESULTS:The mean effective dose of our WBLDCT-protocol was 4.82 mSv. A significantly higher effective dose was observed in females compared to males (4.95 vs. 4.70 mSv, P = 0.002). Mean organ dose ranged from 3.72 mSv (esophagus) to 13.09 mSv (skeleton). Mean effective dose varied amongst different CT-scanners (range 4.34-8.37 mSv). The median effective dose of WBLDCT was more than twice the dose of a skeletal survey (4.82 vs. 2.04 mSv), 23% higher than a diagnostic contrast-enhanced chest CT (3.9 mSv), 46% lower than a diagnostic contrast-enhanced abdomen/pelvis CT (9.0 mSv), and 45% lower than a lumbar spine CT (8.7 mSv). CONCLUSIONS:WBLDCT in MM has a higher effective dose than a radiographic skeletal survey, but a lower effective dose than diagnostic CTs of lumbar spine, abdomen and pelvis. This underlines the broad applicability of WBLDCT in the management of MM patients.

OBJECTIVE:The purpose of our study was to determine the role of brown adipose tissue (BAT) in cancer progression. MATERIALS AND METHODS/METHODS:Our study was approved by our institutional review board and Health Insurance Portability and Accountability Act-compliant. Our study group comprised 132 cancer patients (116 f, 16 m; mean age 50 ± 16 years) who underwent F18-FDG PET/CT per standard clinical protocol, for staging or surveillance of cancer. We included patients who were BAT-positive on PET/CT and had clinical follow-up data available for at least 12 months or until tumor recurrence or tumor-related death, whichever occurred first. BAT volume by PET/CT was quantified by PET-CT Viewer shareware. Clinical information including tumor type, tumor recurrence, survival, and outside temperature at time of scan were recorded. Cox proportional hazard models were used to determine longitudinal associations between BAT volume and tumor recurrence/mortality. RESULTS:There were 55 tumor recurrences/tumor-related deaths over a median follow-up period of 71 (33; 110 interquartile range) months. Higher BAT volume was associated with an increased likelihood of tumor recurrence/tumor-associated mortality after adjustment for covariates (p = 0.03). CONCLUSION/CONCLUSIONS:BAT volume, assessed using routine PET/CT, is a predictor of tumor recurrence/mortality in patients with cancer, independent of other factors that can influence BAT activity, such as sex, age, BMI, or tumor type.

This paper summarizes the highlights of the Scientific Sessions of the 46th Annual Scientific Meeting of the International Skeletal Society (ISS) which was hosted in Vancouver, Canada, in September 2019.

BACKGROUND:Sleeve gastrectomy is the most commonly performed weight loss surgery in adolescents with moderate-to-severe obesity. While studies in adults have reported on the deleterious effects of gastric bypass surgery on bone structure and strength estimates, data are lacking for the impact of sleeve gastrectomy on these measures in adolescents. OBJECTIVE:To evaluate the impact of sleeve gastrectomy on bone outcomes in adolescents and young adults over 12 months using dual energy X-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HRpQCT). PARTICIPANTS AND METHODS:We enrolled 44 youth 14-22 years old with moderate to severe obesity; 22 underwent sleeve gastrectomy and 22 were followed without surgery (16 females and 6 males in each group). At baseline and 12 months, DXA was used to assess areal bone mineral density (aBMD), HRpQCT of the distal radius and tibia was performed to assess bone geometry, microarchitecture and volumetric BMD (vBMD), and finite element analysis to assess strength estimates (stiffness and failure load). These analyses were adjusted for age, sex, race and the bone measure at baseline. Fasting blood samples were assessed for calcium, phosphorus, and 25(OH) vitamin D (25OHD) levels. RESULTS:Over 12-months, the surgical group lost 27.2% of body weight compared to 0.1% in the non-surgical (control) group. Groups did not differ for changes in 25OHD levels (p = 0.186). Compared to controls, the surgical group had reductions in femoral neck and total hip aBMD Z-scores (p ≤ 0.0006). At the distal tibia, compared to controls, the surgical group had reductions in cortical area and thickness and trabecular number, and increases in trabecular area and separation (p ≤ 0.026). At the distal radius, the surgical group had greater reductions in trabecular vBMD, than controls (p = 0.010). The surgical group had an increase in cortical vBMD at both sites (p ≤ 0.040), possibly from a decrease in cortical porosity (p ≤ 0.024). Most, but not all, differences were attenuated after adjusting for 12-month change in BMI. Groups did not differ for changes in strength estimates over time, except that increases in tibial stiffness were lower in the surgical group (p = 0.044) after adjusting for 12-month change in BMI. CONCLUSIONS:Over 12 months, weight loss associated with sleeve gastrectomy in adolescents had negative effects on areal BMD and certain HRpQCT parameters. However, bone strength estimates remained stable, possibly because of a simultaneous decrease in cortical porosity and increase in cortical volumetric BMD. Additional research is necessary to determine the relative contribution(s) of weight loss and the metabolic effects of surgery on bone outcomes, and whether the observed effects on bone stabilize or progress over time.

PURPOSE/OBJECTIVE:To determine (i) whether intra-articular gadolinium from MR arthrography (MRA) results in gadolinium deposition in the brain and (ii) whether there is a correlation between intra-articular gadolinium dose and intracranial gadolinium deposition. MATERIALS AND METHODS/METHODS:This retrospective study was institutional review board (IRB) approved and HIPAA compliant. The study group included consecutive adult patients who had undergone MRA of the hip or shoulder and subsequent MRI of the brain. None of the patients had a history of intravenous gadolinium exposure. A control group of patients of similar age and sex who were never exposed to gadolinium and had brain MRIs available was included. Signal intensities (SI) of four brain regions: pons, dentate nuclei (DN), globus pallidi (GP), and thalamus (Thal) normalized to cerebrospinal fluid (CSF) and expressed in SI ratios were measured on T1-weighted non-contrast MR images. Groups were compared using the student's t test. Linear correlation analysis of gadolinium dose and brain SI ratios was performed, and Pearson correlation coefficients (r) are reported. RESULTS:We identified 109 patients (mean age 44 ± 14 years, 54% men) who had undergone MRA and 149 controls of similar age and sex distribution. There was no significant difference in mean SI ratios of the brain regions between patients and controls: pons/CSF (p = 0.7), DN/CSF (p = 0.4), GP/CSF (p > 0.99), Thal/CSF (p = 0.3). Within the MRA group, gadolinium dose was not associated with SI ratios (p > 0.2). CONCLUSION/CONCLUSIONS:Our study found no MR evidence of intracranial gadolinium deposition following MRA. In addition, there was no association between intra-articular gadolinium dose and SI ratios in commonly affected regions of the brain.