Uncovering the Burden of Immune-Related Adverse Events in Immunotherapy: Insights from a Nationally Representative Sample.

BACKGROUND: Immune checkpoint inhibitors have shown promising efficacy in multiple malignancies and, therefore, have been increasingly used over the past decade. Clinical data have suggested anti-cancer efficacy associated with immune-related adverse events that could have added healthcare resource utilization and costs. OBJECTIVE: We used a nationwide dataset to investigate the association between immune-related adverse events and healthcare resource utilization, charges, and mortality among patients receiving various immune checkpoint inhibitors for indicated cancers. METHODS: We performed a retrospective analysis of the National Inpatient Sample to identify patients hospitalized in the USA for immunotherapy between October 2015 and 2018. Data between patients who developed immune-related adverse events were compared to those who did not. Baseline characteristics, inpatient complications, and associated charges were collected and analyzed between these two groups. RESULTS: Patients who developed immune-related adverse events in the hospital had high incidences of acute kidney injury, non-septic shock, and pneumonia, and managing these complications significantly contributed to higher healthcare resource utilization. The average charge of admission was highest in patients who developed an infusion reaction, followed by colitis, and adrenal insufficiency. In terms of cancer type, renal cell carcinoma had the highest charges, followed by Merkel cell carcinoma. CONCLUSIONS: Immune checkpoint inhibitor-based regimens have shifted the treatment landscape among multiple malignancies and their use continues to expand. However, a significant proportion of patients still develop severe adverse effects leading to increased healthcare costs and impacting patients' quality of life. Closer attention should be given to recognizing and managing immune-related adverse events according to guidelines across healthcare facilities and clinical practice settings.

Metastatic Testicular Seminoma in a Patient With Down Syndrome Presenting As Extensive Deep Venous Thrombosis.

Testicular cancer, particularly seminoma, is associated with Down syndrome. In cognitively impaired patients, the typical presenting signs of testicular cancer may be missed, and atypical presenting features may be the only clue to the diagnosis. In this report, we present the case of a 38-year-old male who presented with extensive deep vein thrombosis in the setting of seminoma.

Medical Student Confidence in Diagnosis of Dermatologic Diseases in Skin of Color.

Purpose: To evaluate medical student confidence in diagnosing dermatologic diseases in skin of color. Methods: A voluntary supplemental module was implemented as part of the second-year dermatology curriculum at Wayne State University School of Medicine (WSU SOM) in Detroit, Michigan. The goal of the module was to ascertain whether it may increase confidence in students with their approach to diagnosing diseases in darker skin tones. Results: Seventy-seven of 295 students (26%) completed a "Skin of Color" optional module consisting of thirteen cases of common skin pathologies in African American patients. A pre- and post-survey performed to assess students' confidence using a five-point Likert scale. After completing the module, medical students demonstrated a statistically significant increase in confidence in diagnosing skin pathologies in skin of color. Conclusion: Dermatology pre-clinical course work should include supplementary materials to increase student confidence in diagnosing skin diseases in darker skin tones.

Bile acid: a potential inducer of colon cancer stem cells.

BACKGROUND: Although the unconjugated secondary bile acids, specifically deoxycholic acid (DCA) and lithocholic acid (LCA), are considered to be risk factors for colorectal cancer, the precise mechanism(s) by which they regulate carcinogenesis is poorly understood. We hypothesize that the cytotoxic bile acids may promote stemness in colonic epithelial cells leading to generation of cancer stem cells (CSCs) that play a role in the development and progression of colon cancer. METHODS: Normal human colonic epithelial cells (HCoEpiC) were used to study bile acid DCA/LCA-mediated induction of CSCs. The expression of CSC markers was measured by real-time qPCR. Flow cytometry was used to isolate CSCs. T-cell factor/lymphoid-enhancing factor (TCF/LEF) luciferase assay was employed to examine the transcriptional activity of ß-catenin. Downregulation of muscarinic 3 receptor (M3R) was achieved through transfection of corresponding siRNA. RESULTS: We found DCA/LCA to induce CSCs in normal human colonic epithelial cells, as evidenced by the increased proportion of CSCs, elevated levels of several CSC markers, as well as a number of epithelial-mesenchymal transition markers together with increased colonosphere formation, drug exclusion, ABCB1 and ABCG2 expression, and induction of M3R, p-EGFR, matrix metallopeptidases, and c-Myc. Inhibition of M3R signaling greatly suppressed DCA/LCA induction of the CSC marker ALDHA1 and also c-Myc mRNA expression as well as transcriptional activation of TCF/LEF. CONCLUSIONS: Our results suggest that bile acids, specifically DCA and LCA, induce cancer stemness in colonic epithelial cells by modulating M3R and Wnt/ß-catenin signaling and thus could be considered promoters of colon cancer.