Overemphasis of USMLE and Its Potential Impact on Diversity in Otolaryngology

Objective: Applicant demographics during the 2019-2020 residency cycle were evaluated to determine if strict utilization of United States Medical Licensing Examination (USMLE) scores in applicant selection could lead to a restriction in diversity. Study design: Cross-sectional study. Setting: Otolaryngology residency applicants to a single institution. Methods: A total of 381 applicants were analyzed by age, gender, applicant type, race/ethnicity, USMLE scores, permanent zip code, and graduating medical school. Results: Among applicants, 37% were women; 9% were ≥30 years of age; 12% were underrepresented minorities (URMs); 71% to 81% had above-average socioeconomic surrogate markers; 22% were from a top 25 US News & World Report-ranked institution; and 81% were from an institution with an otolaryngology residency program. There was no increase in applicants who identified as URM from the 2015-2020 cycles. Multivariable regression analysis showed that applicants who were international medical graduates, URMs, and ≥30 years of age had lower Step 1 and Step 2 scores (P \u3c .05). Applicants who identified as women had a lower Step 1 score, and those from top 25 National Institutes of Health-funded institutions had a higher Step 1 score; however, there was no difference when Step 2 scores were compared (P \u3e .05). Conclusion: Our data suggest that in the pre-USMLE Step 1 pass/fail setting, strict adherence to USMLE scores may lead to disproportionally low recruitment of applicants who are women, ≥30 years of age, URMs, and from institutions without an otolaryngology residency program. We must implement measures against overemphasizing the absolute values of USMLE scores for a true holistic review of applicants, specifically to prevent an overemphasis on the USMLE Step 2 score

Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes

Most patients diagnosed with resected pancreatic adenocarcinoma (PDAC) survive less than 5 years, but a minor subset survives longer. Here, we dissect the role of the tumor microbiota and the immune system in influencing long-term survival. Using 16S rRNA gene sequencing, we analyzed the tumor microbiome composition in PDAC patients with short-term survival (STS) and long-term survival (LTS). We found higher alpha-diversity in the tumor microbiome of LTS patients and identified an intra-tumoral microbiome signature (Pseudoxanthomonas-Streptomyces-Saccharopolyspora-Bacillus clausii) highly predictive of long-term survivorship in both discovery and validation cohorts. Through human-into-mice fecal microbiota transplantation (FMT) experiments from STS, LTS, or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration. Our study demonstrates that PDAC microbiome composition, which cross-talks to the gut microbiome, influences the host immune response and natural history of the disease. The distinct tumor microbiome from pancreatic cancer long-term survivors can be used to predict PDAC survival in humans, and transfer of long-term survivor gut microbiomes can alter the tumor microbiome and tumor growth in mouse models

Interleukin-17-induced neutrophil extracellular traps mediate resistance to checkpoint blockade in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy with an immunosuppressive microenvironment that is resistant to most therapies. IL17 is involved in pancreatic tumorigenesis, but its role in invasive PDAC is undetermined. We hypothesized that IL17 triggers and sustains PDAC immunosuppression. We inhibited IL17/IL17RA signaling using pharmacological and genetic strategies alongside mass cytometry and multiplex immunofluorescence techniques. We uncovered that IL17 recruits neutrophils, triggers neutrophil extracellular traps (NETs), and excludes cytotoxic CD8 T cells from tumors. Additionally, IL17 blockade increases immune checkpoint blockade (PD-1, CTLA4) sensitivity. Inhibition of neutrophils or Padi4-dependent NETosis phenocopies IL17 neutralization. NMR spectroscopy revealed changes in tumor lactate as a potential early biomarker for IL17/PD-1 combination efficacy. Higher expression of IL17 and PADI4 in human PDAC corresponds with poorer prognosis, and the serum of patients with PDAC has higher potential for NETosis. Clinical studies with IL17 and checkpoint blockade represent a novel combinatorial therapy with potential efficacy for this lethal disease