Faculty Bibliography

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

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: 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

We describe a case of immune reconstitution inflammatory syndrome (IRIS) secondary to reactivation of Mycobacterium tuberculosis in an HIV-infected patient with a high CD4+ cell count, who presented with a generalized seizure 6 weeks after starting antiretroviral therapy (ART). In our patient, the inflammatory response resulted in radiological features of neurological, pulmonary, and lymph node (LN) tuberculosis- (TB) IRIS, without the typical symptoms. Diagnosis was confirmed by LN biopsy and acid-fast bacilli (AFB) culture of LN and sputum. Treatment with isoniazid, rifabutin, ethambutol, and pyrazinamide was started in addition to continuation of ART. To our knowledge, we describe the first case of an atypical clinical presentation of an unmasking reaction of disseminated TB-IRIS in an HIV infected patient without acquired immune deficiency syndrome (AIDS), with restoring immunity during ART. Clinical and radiological predictors of TB-IRIS in co-infected patients starting ART are therefore essential in anticipating complications and facilitating expeditious management and prompt therapy.

Racial and ethnic minorities in the U.S. experience higher incidence of and greater morbidity from chronic disease. Limited English proficiency (LEP) is a known contributor to these health disparities. The Culturally and Linguistically Appropriate Services (CLAS) standards of the U.S. Department of Health and Human Services promote health equity through the incorporation of professional interpreter services. While such services have been shown to improve quality of care, limited data exist on patient perspectives regarding these services. Better understanding patient experiences with telephone interpreter services (TIS), an increasingly used modality for professional interpretation, could elucidate ways of improving care for this population. This study explored Spanish-speaking patient experiences with TIS at an urban community clinic. Qualitative data collected via focus groups was analyzed using content analysis and grounded theory methods. Our findings suggest that TIS are generally well accepted by Spanish-speaking LEP patients. Limited relationship development with providers and physician attitudes toward TIS were among reported barriers to the use of these services.