Assessment of the Murine Tumor Microenvironment by Multiplex Immunofluorescence.

We describe the staining methods used for simultaneous detection of tumor microenvironment components as well as the automated quantification methodologies. This method uses mouse formalin-fixed paraffin-embedded tissues and multiplex immunofluorescence (Multiplex IF) followed by multispectral imaging. Currently, this methodology has shown to have a valuable role in murine immunoprofiling, and can be useful when evaluating the changes incurred on the tumor microenvironment upon various immunopreventive strategies.

Development of the National Otolaryngology Interest Group: Conception to Implementation.

Otolaryngology is a small and highly sought-after surgical subspecialty with sparse residency positions, making it competitive to match into. Allopathic (MD) students without home otolaryngology residency programs, osteopathic (DO) medical students, and underrepresented minorities have historically faced additional challenges in matching into otolaryngology. These specific populations generally experience limited opportunities in establishing mentors, engaging in scholarly activity, and gaining early exposure to clinical settings. Even though the American Osteopathic Association and the Accreditation Council for Graduate Medical Education merger was in part established to create equity among applicants, there remains a substantial disparity among the match rates of medical students of various educational and cultural backgrounds. The National Otolaryngology Interest Group is a student-led interest group created to provide all medical students, especially those facing barriers, with the resources needed to best prepare for matching into an otolaryngology residency program and ultimately a career in otolaryngology.

Current Barriers in Pursuing Otolaryngology as an Osteopathic Applicant and Proposed Goals for the Future.

The osteopathic (DO) medical profession has seen a substantial increase in popularity, evident by the drastic increase in the DO physician workforce and increasing number of DO graduates in the United States. Osteopathic medical schools have historically been primary care focused, resulting in a majority of their graduates pursuing practice in those specialties. This focus may be inadvertently creating a disadvantageous environment for DO students who aim to pursue specialized or traditionally competitive fields in medicine. Otolaryngology is a prime example of osteopathic underrepresentation, as there is currently a significantly low percentage of DO residents in otolaryngology residency programs and practicing DO otolaryngologists. Given the recent American Council on Graduate Medical Education (ACGME) and American Osteopathic Association (AOA) merger between osteopathic and allopathic (MD) residency programs, it is of great value to further discuss avenues for progress and mitigation of barriers.

Pathways and Barriers to Careers in Academic Clinical Cancer Prevention: a Qualitative Study.

National surveys document steady declines over time in interest in academic medicine and cancer prevention careers (Am J Prev Med 54(3):444-8, 2018). Through interviews with 16 academic cancer prevention physicians at one comprehensive cancer center, this study identifies motivations and barriers to physician careers in academic cancer prevention and proposes recommendations to increase recruitment. Participants reported that cancer prevention was vague to them early in training, impairing career exploration. Further, without role models and opportunities to learn about cancer prevention, many were ignorant of career options. Many had incorrect views about cancer prevention practice being mainly within the scope of primary care physicians, and some reported colleagues viewing the rigor of cancer prevention skeptically. However, all described notable experiences-in classes, with mentors, on research projects, or from encounters with patients, motivating them to pursue academic clinical cancer prevention regardless of challenges. Clearly, a lack of both information and guidance towards careers in clinical cancer prevention has been critical barriers to robust recruitment of physicians to the field and must be addressed urgently. Helping physicians earlier during training to both understand the value of prevention and cultivate their interests in it, particularly for clinical cancer prevention, would have widespread benefits.

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 < .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 > .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.

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.

Applicant-to-Residency Program Communication: Does It Matter?

OBJECTIVES: To elucidate the frequency and types of pre- and post-interview communication that applicants engage with programs, to garner the perceptions of both applicants and program directors (PDs), and determine if communication influences outcomes. SUBJECTS AND METHODS: Electronic surveys were distributed to otolaryngology residency applicants, and to PDs of ACGME-accredited otolaryngology programs after the 2018 to 2019 application cycle. RESULTS: 93 of 324 applicants (28.7%) and 33 of 106 PDs (31.3%) responded. In the pre-interview period, 58.1% of applicants sent emails of interest, and 41.9% had a mentor initiate communication. In the post-interview period, the majority of applicants (82.8%) sent notes of intent to their number one choice, and 32.3% had a faculty mentor communicate this on their behalf. The majority of PDs (84.8%) were undecided or did not believe that emails of interest influence decisions to offer an interview, whereas 81.8% believed that communication initiated by an applicant's mentor has an impact on interview offers. No PD agreed that declarations of intent from applicants have an impact on their rank lists, while only 33.3% of PDs believed that a mentor communicating this for an applicant has some impact. Our statistical findings are in agreement with these perceptions as neither applicant-initiated pre-interview (P = .54), mentor-initiated pre-interview (P = .62), applicant-initiated post-interview (P = .11) nor mentor-initiated post-interview (P = .78) communications influenced the number of interviews received or ultimate match outcome. CONCLUSION: Pre- and post-interview communication practices vary widely among otolaryngology applicants. Applicant-initiated communication has no impact on outcomes, while mentor-initiated communication is perceived to have more benefit, despite not impacting interview or match outcomes in this study.

Otolaryngology Residency Application during the SARS-CoV-2 (COVID-19) Pandemic.

The escalation of the COVID-19 pandemic has affected health care at every level, including medical education. As some fourth-year medical students graduate early to join the front lines, we must now turn our attention to those trainees in their penultimate year. In this commentary, we address the unique dilemmas facing otolaryngology residency candidates for the 2020-2021 cycle, with a focus on those applicants with no institutional otolaryngology department.