Faculty Bibliography

OBJECTIVE:Obesity and diabetes are established risk factors for severe SARS-CoV-2 outcomes, but less is known about their impact on susceptibility to COVID-19 infection and general symptom severity. We hypothesized that those with obesity or diabetes would be more likely to self-report a positive SARS-CoV-2 test, and among those with a positive test, have greater symptom severity and duration. METHODS:Among 44,430 COVID-19 Community Research Partnership participants, we evaluated the association of self-reported and electronic health record obesity and diabetes with a self-reported positive COVID-19 test at any time. Among the 2,663 participants with a self-reported positive COVID-19 test during the study, we evaluated the association of obesity and diabetes with self-report of symptom severity, duration, and hospitalization. Logistic regression models were adjusted for age, sex, race/ethnicity, socioeconomic status, and healthcare worker status. RESULTS:We found a positive graded association between Body Mass Index (BMI) category and positive COVID-19 test (Overweight OR = 1.14 [1.05-1.25]; Obesity I OR = 1.29 [1.17-2.42]; Obesity II OR = 1.34 [1.19-1.50]; Obesity III OR = 1.53 [1.35-1.73]), and a similar but weaker association with COVID-19 symptoms and severity among those with a positive test. Diabetes was associated with COVID-19 infection but not symptoms after adjustment, with some evidence of an interaction between obesity and diabetes. CONCLUSIONS:While the limitations of this health system convenience sample include generalizability and selection around test-seeking, the strong graded association of BMI and diabetes with self-reported COVID-19 infection suggests that obesity and diabetes may play a role in risk for symptomatic SARS-CoV-2 beyond co-occurrence with socioeconomic factors.

Objective: The aim of this study was to describe the clinical impact of major diagnostic discrepancies in pathology reports of gynecologic malignancies for patients presenting for second opinion to a comprehensive cancer center.
Method(s): All cases of gynecologic malignancy submitted for second opinion review by gynecologic pathologists between 2010 and 2016 were evaluated. Cases with major discrepancies (deemed to have potential clinical impact) with outside diagnoses were self-identified by the specialized gynecologic pathologists. Cases were grouped according to pathologic disagreement with no impact on care and pathologic disagreement with clinical impact. Clinical impact was based on National Comprehensive Cancer Network (NCCN) guidelines and gynecologic oncologist expert opinion.
Result(s): Of the 8,475 gynecologic cases reviewed, 1,265 (15%) discrepancies with outside hospital diagnoses were identified. Of these, 198 (16%) were deemed to be major discrepancies. There were 77 (39%) endometrial cancers, 42 (21%) ovarian cancers, 32 (16%) sarcomas, 30 (15%) cervical cancers, and 18 (9%) other malignancies. Most cases (n = 78, 39%) resulted in change in histology, while 32 (16%) cases noted a different site of origin of disease compared to original diagnosis. Forty-three (22%) cases were downgraded from malignant to benign, and 33 (17%) upgraded from benign to malignant. There were 123 (62%) cases that were deemed to have a pathologic disagreement that had clinical sequelae (change in treatment). Of these, 53 (43%) were surgical (recommend for or against), and 70 (57%) were nonsurgical. Review of uterine sarcoma cases, although considered major discrepancies by expert pathology, had no clinical impact in 60% (n = 18) of cases.
Conclusion(s): Pathologic review of outside cases by specialized gynecologic pathologists identified a group of cases across all gynecologic tumor types that led to changes in clinical management. The impact on patient outcomes should be further explored.
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Chemotherapy-induced hand-foot syndrome and nail changes are common complications of many classic chemotherapeutic agents and the newer molecular targeted therapies. They significantly impact patient quality of life, and frequently necessitate chemotherapy dose intensity modification or reduction. We aim to describe the epidemiology, pathogenesis, clinical presentation, and current evidence-based treatment options for these entities.

BACKGROUND: There is no known association between the development of keratoacanthomas and prurigo nodules. OBJECTIVE: We report a case series of 7 patients with a long-standing history of actinic damage, pruritus, and prurigo nodularis who developed widespread keratoacanthomas within the same affected area. METHODS: This was a retrospective case series assessing the clinical characteristics of patients with multiple keratoacanthomas arising in association with prurigo nodules. RESULTS: All 7 patients were elderly Caucasian women (mean age 79 +/- 3.7 years) with actinically damaged skin and a long-standing history of widespread pruritus and prurigo nodules. All patients had histologically confirmed keratoacanthomas, or squamous cell carcinomas with the clinical appearance of a keratoacanthoma, that developed within the field of prurigo nodules. All 7 patients had a clinical response to acitretin with a decrease in the number of lesions. Four patients had an associated eczematous dermatitis and were also treated with cyclosporine with improvement in pruritus and prurigo nodules and no increase in keratoacanthomas. LIMITATIONS: The retrospective design and small number of patients are limitations to this study. CONCLUSION: Our case series represents a distinct subset of elderly individuals with extensive actinic damage who we believe are predisposed to developing both prurigo nodules and keratoacanthomas.

OBJECTIVE:Obesity has been associated with cognitive decline in longitudinal studies of older individuals. We hypothesized that the cognitive sequelae of obesity may be detectable in the reproductive years. In addition, we explored the hypothesis that these associations may be mediated by the hormonal milieu. DESIGN AND METHODS/METHODS:Of 49 young healthy lean and overweight women aged 20-45, we investigated the association between performance on a battery of cognitive tests, body composition parameters [body mass index, total fat, abdominal (visceral, subcutaneous, and total) adipose tissue, and muscle], and hormone levels (insulin, adiponectin, leptin, insulin-like growth factor 1 (IGF-1), estrogen, testosterone, and vitamin D). RESULTS:We found a significant negative association between both visceral adiposity and muscle, and performance in the domain of verbal learning and memory, after controlling for age and education. Other body composition parameters showed similar trends (0.05 < P < 0.10). Additionally, the degree of insulin resistance was negatively associated with executive function domain. None of the associations between the other hormones examined (adipokines, IGF-1, gonadal hormones, and vitamin D) and cognitive function were significant. CONCLUSION/CONCLUSIONS:These preliminary findings suggest a possible association between obesity and cognitive function in healthy young women of reproductive age. More research is warranted into the potential modulatory effect of insulin resistance on this association.

Bone histomorphometry measurements require high spatial resolution that may not be feasible using multidetector CT (MDCT). This study evaluated the trabecular microarchitecture of lumbar spine using MDCT and C-arm CT in a series of young adult patients with anorexia nervosa (AN). 11 young females with AN underwent MDCT (anisotropic resolution with a slice thickness of ~626 μm) and C-arm CT (isotropic resolution of ~200 µm). Standard histomorphometric parameters the of L1 vertebral body, namely the apparent trabecular bone volume fraction (BV/TV), trabecular thickness (TbTh), trabecular number (TbN) and trabecular separation (TbSp), were analysed using MicroView software (GE Healthcare, Piscataway, NJ). Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Trabecular parameters derived from MDCT and C-arm CT were compared, and their association with BMD parameters was evaluated. Histomorphometric parameters derived from C-arm CT, namely TbTh, TbN and TbSp, were significantly different from the corresponding MDCT parameters. There were no significant correlations between C-arm CT-derived parameters and the corresponding MDCT-derived parameters. C-arm CT-derived parameters were significantly (p<0.001) correlated with anteroposterior L1 spine BMD and Z-scores: TbTh (r=0.723, r=0.744, respectively), TbN (r=-0.720, r=-0.712, respectively) and TbSp (r=0.656, r=0.648, respectively). BV/TV, derived from C-arm CT, was significantly associated with body mass index (r=0.636) and ideal body weight (r=0.730) (p<0.05). These associations were not present in MDCT-derived parameters. This study suggests that the spatial resolution offered by C-arm CT more accurately captures the histomorphometric parameters of trabecular morphology than MDCT in patients with AN.

OBJECTIVE:We previously reported improved body composition and cardiovascular risk markers plus a small decrease in glucose tolerance with GH administration vs placebo for 6 months to abdominally obese premenopausal women. The objective of this study was to determine whether the effects of GH treatment on cardiovascular risk markers, body composition and glucose tolerance in obese women persist 6 months after GH withdrawal. DESIGN AND PATIENTS/METHODS:Fifty abdominally obese premenopausal women completed a trial of rhGH vs placebo for 6 months; thirty-nine women completed a subsequent 6-month withdrawal observation period. MEASUREMENTS/METHODS:IGF-I, body composition by CT, (1) H-MRS and DXA, serum cardiovascular risk markers, oral glucose tolerance test (OGTT). RESULTS:IGF-I standard deviation scores (SDS) within the GH group were -1.7 ± 0.1 (pretreatment),-0.1 ± 0.3 (after 6 months of GH) and -1.7 ± 0.1 (6 months post-GH withdrawal). Six months after GH withdrawal, total abdominal and subcutaneous adipose tissue, total fat, trunk fat, trunk/extremity fat, hsCRP, apoB, LDL, and tPA were higher than at the 6-month (GH discontinuation) timepoint (P ≤ 0.05). All body composition and cardiovascular risk markers that had improved with GH returned to baseline levels by 6 months after GH discontinuation, as did fasting and 2-h OGTT glucose levels. CONCLUSION/CONCLUSIONS:The effects of GH administration to abdominally obese premenopausal women have a short time-course. The beneficial effects on body composition and cardiovascular risk markers, and the side effect of altered glucose tolerance returned to pretreatment levels after GH withdrawal. There was no suppression of endogenous IGF-I levels, which returned to baseline after GH withdrawal.