Faculty Bibliography

BACKGROUND:Hidradenitis suppurativa (HS) is a debilitating dermatologic condition presenting with recurrent abscesses. While there are multiple scales to determine HS severity, none are designed for self-administration. A validated severity self-assessment tool may facilitate survey research and improve communication by allowing patients to objectively report their HS severity between clinic visits. OBJECTIVES/OBJECTIVE:The purpose of this study was to assess a self-administered HS measure. METHODS:An HS self-assessment tool (HSSA) with 10 photographs of different Hurley stages was developed. The tool was administered to patients diagnosed with HS who visited the Wake Forest Baptist Health dermatology clinic over a span of 2 months. Physician-administered Hurley stage was recorded to determine criterion validity. To assess test-retest reliability of the measure, patients completed the HSSA again at least 30 minutes after the first completion. RESULTS:Twenty-four patients completed the measure, and 20 of these patients completed it twice. Agreement between physician-determined Hurley stage and self-determined Hurley stage was 66.7% with a weighted kappa of 0.57 (95% confidence interval [CI]: 0.30-0.84). The weighted kappa for agreement between patients' initial and second completion of the HSSA was 0.81 (95% CI: 0.64-0.99). CONCLUSIONS:The self-administered measure provides moderate agreement with physician-determined Hurley stage and good test-retest reliability.

Background We hypothesized that neo-epitope-based prediction using an advanced in silico T cell epitope screening system (AncerTM) may better identify patients with improved prognosis than tumor mutation burden. Analysis of genomic data derived from the muscle-invasive bladder cancer (BLCA) cohort of The Cancer Genome Atlas (TCGA) database for CD4, CD8, and Treg neo-epitopes was performed to determine whether AncerTM would improve prognostic stratification compared to tumor mutational burden (TMB). Methods BLCA patient mutanomes (n=412) were retrieved from the TCGA and evaluated with AncerTM, an innovative and automated neo-epitope screening platform that combines proprietary machine learningbased HLA I and HLA II neo-epitope identification tools with removal of inhibitory regulatory T cell epitopes for neo-epitope ranking and personalized cancer vaccine design. BLCA patients were separated based on median TMB or neo-epitope burdens. We investigated the effect of integrating both CD8 and CD4 neo-epitope burdens as most mutanome pipelines exclusively focus on the identification of Class I neo-epitopes. Overall survival was analyzed using the Kaplan-Meier method and differences analyzed by log-rank testing. Results Compared to low TMB, high TMB was significantly associated with improved survival (p = 0.0001, difference of 38.5 months in median survival, Figure 1). Improved differentiation of median survival times was obtained when separating patients based on their Class I neoepitope content, as estimated by AncerTM (p < 0.0001, difference of 59.8 months in median survival). Adding Class II neo-epitope burden further increased separation of OS times, showcased by a 69.6-month increase in median survival for BLCA patients with both high CD8 and high CD4 neo-epitope contents compared to other patients (p = 0.0001). Since we discovered that Class II neo-epitopes can induce inhibitory responses, we further evaluated whether the screening of these detrimental sequences could improve our analysis. Upon identifying Class II neo-epitopes likely to induce T effector (Teff) responses, we found that the median survival of patients with high CD8 and high CD4 Teff contents was extended by nearly 4 months to 73.4 months compared, to the remainder of the cohort (p < 0.0001, Figure 2). Conclusions Our analysis suggests that optimal host-immune recognition of CD8+, CD4+, and Treg epitopes plays a key role in cancer survival. While defining CD8 neo-epitope burden enhanced associations with OS, the inclusion of CD4 Teff neo-epitope burden substantially helped identify long-term survivors. These results suggest that defining the number of true neo-epitopes using AncerTM may represent a novel prognostic or predictive biomarker

Heart failure (HF) is a devastating condition characterized by poor quality of life, numerous complications, high rate of readmission and increased mortality. HF is the most common cause of hospitalization in the United States especially among people over the age of 64 years. The number of people grappling with the ill effects of HF is on the rise as the number of people living to an old age is also on the increase. Several factors have been attributed to these high readmission and mortality rates among which are; poor adherence with therapy, inability to keep up with clinic appointments and even failure to recognize early symptoms of HF deterioration which may be a result of cognitive impairment. Therefore, this review seeks to compile the most recent information about the links between HF and dementia or cognitive impairment. We also assessed the prognostic consequences of cognitive impairment complicating HF, therapeutic strategies among patients with HF and focus on future areas of research that would reduce the prevalence of cognitive impairment, reduce its severity and also ameliorate the effect of cognitive impairment coexisting with HF.

Increased investment in primary care is associated with lower healthcare costs and improved population health. The allocation of scarce resources should be driven by robust models that adequately describe primary care activities and spending within a health system, and allow comparisons within and across health systems. However, disparate definitions result in wide variations in estimates of spending on primary care. We propose a new model that allows for a dynamic assessment of primary care spending (PC Spend) within the context of a system's total healthcare budget. The model articulates varied definitions of primary care through a tiered structure which includes overall spending on primary care services, spending on services delivered by primary care professionals and spending delivered by providers that can be characterised by the '4Cs' (first contact, continuous, comprehensive and coordinated care). This unifying framework allows a more refined description of services to be included in any estimate of primary care spend and also supports measurement of primary care spending across nations of varying economic development, accommodating data limitations and international health system differences. It provides a goal for best accounting while also offering guidance, comparability and assessments of how primary care expenditures are associated with outcomes. Such a framework facilitates comparison through the creation of standard definitions and terms, and it also has the potential to foster new areas of research that facilitate robust policy analysis at the national and international levels.

Background: The risk-benefit ratio of ACE-I/ARB therapy after an AKI episode is unclear.
Method(s): We studied 1570 patients recently discharged from hospital and enrolled in a multi-center prospective cohort study (ASSESS-AKI). Follow-up began 3 months after index hospitalization and continued through November 2018. Half of the participants had AKI during the index hospitalization. ACE-I/ARB use and covariates were ascertained 3 months after discharge from the index hospitalization. We used multivariable Cox regression adjusting for demographics, cardiovascular disease, diabetes mellitus, heart failure (HF), blood pressure, urine protein to creatinine ratio, and eGFR to examine the association between ACE-I/ARB use and subsequent death, AKI (>=50% difference between peak and nadir inpatient serum creatinine), renal progression (ESRD or halving of eGFR), and adjudicated HF events.
Result(s): Among study participants who did not have AKI during index hospitalization (N=806), mean age was 65 years, mean eGFR 74 ml/min/1.73m2, and 45% self-reported use of ACE-I/ARB 3 months after hospitalization. Among study participants who did have AKI during index hospitalization (N=764), mean age was 64 years, mean eGFR 65 ml/min/1.73m2, and 50% self-reported use of ACE-I/ARB 3 months after hospitalization. Mean follow-up time was 3.6 years. ACE-I/ARB therapy 3 months after an AKI hospitalization was associated with a lower risk of another hospitalized AKI event and a lower risk of death (Table).
Conclusion(s): Use of ACE-I/ARB in survivors of hospitalized AKI was not associated with increased risk of subsequent AKI but was associated with lower risk of death

INTRODUCTION:The United States Medical Licensing Examination (USMLE) Step 1 and Step 2 Clinical Knowledge (CK) are important for trainee medical knowledge assessment and licensure, medical school program assessment, and residency program applicant screening. Little is known about how USMLE performance varies between institutions. This observational study attempts to identify institutions with above-predicted USMLE performance, which may indicate educational programs successful at promoting students' medical knowledge. METHODS:Self-reported institution-level data was tabulated from publicly available US News and World Report and Association of American Medical Colleges publications for 131 US allopathic medical schools from 2012-2014. Bivariate and multiple linear regression were performed. The primary outcome was institutional mean USMLE Step 1 and Step 2 CK scores outside a 95% prediction interval (≥2 standard deviations above or below predicted) based on multiple regression accounting for students' prior academic performance. RESULTS:Eighty-nine US medical schools (54 public, 35 private) reported complete USMLE scores over the three-year study period, representing over 39,000 examinees. Institutional mean grade point average (GPA) and Medical College Admission Test score (MCAT) achieved an adjusted R2 of 72% for Step 1 (standardized βMCAT 0.7, βGPA 0.2) and 41% for Step 2 CK (standardized βMCAT 0.5, βGPA 0.3) in multiple regression. Using this regression model, 5 institutions were identified with above-predicted institutional USMLE performance, while 3 institutions had below-predicted performance. CONCLUSIONS:This exploratory study identified several US allopathic medical schools with significant above- or below-predicted USMLE performance. Although limited by self-reported data, the findings raise questions about inter-institutional USMLE performance parity, and thus, educational parity. Additional work is needed to determine the etiology and robustness of the observed performance differences.