Faculty Bibliography

INTRODUCTION/UNASSIGNED:Addressing systemic bias in medical school assessment is an urgent task for medical education. This paper outlines recommendations on topic areas for further research on systemic bias, developed from a workshop discussion at the 2023 annual meeting of the Society of Directors of Research in Medical Education. MATERIALS AND METHODS/UNASSIGNED:During the workshop, directors engaged in small-group discussions on guidelines to address bias in assessment practices following a proposed categorization of 'Do's,' 'Don'ts,' and 'Don't knows' and listed their insights using anonymous sticky notes, which were shared and discussed with the larger group of participants. The authors performed a content analysis of the notes through deductive and inductive coding. We reviewed and discussed our analysis to reach consensus. RESULTS/UNASSIGNED:The workshop included 31 participants from 28 institutions across the US and Canada, generating 51 unique notes. Participants identified 23 research areas in need of further study. The inductive analysis of proposed research areas revealed four main topics: 1) The role of interventions, including pre-medical academic interventions, medical-education interventions, assessment approaches, and wellness interventions; 2) Professional development, including the definition and assessment of professionalism and professional identity formation; 3) Context, including patient care and systemic influences; and 4) Research approaches. DISCUSSION/UNASSIGNED:While limited to data from a single workshop, the results offered perspectives about areas for further research shared by a group of directors of medical education research units from diverse backgrounds. The workshop produced valuable insights into the need for more evidence-based interventions that promote more equitable assessment practices grounded in real-world situations and that attenuate the effects of bias.

OBJECTIVES/OBJECTIVE:TERT promoter mutations are not infrequently encountered in thyroid carcinomas; however, it is unclear if additional molecular alterations may play a role in determining tumor behavior. METHODS:Fine-needle aspiration (FNA) specimens from 32 patients with TERT promoter mutations detected by ThyroSeq v3 from 4 institutions were included in the study. FNA diagnoses, molecular results, and surgical follow-up were retrospectively reviewed and analyzed. RESULTS:There were 5 benign and 27 malignant neoplasms, including 7 high-grade thyroid carcinomas (HGCs) on histopathologic follow-up. Of 4 cases with an isolated TERT mutation, 3 (75%) cases were malignant. Of 17 cases harboring a co-occurring TERT mutation with 1 additional molecular alteration, 13 (76%) displayed malignancy on histopathologic follow-up. All 11 cases with TERT mutations plus 2 or more additional molecular alterations were malignant on follow-up. Furthermore, HGC was not seen in cases with an isolated TERT mutation, while 80% of cases harboring TERT mutations plus 3 additional molecular alterations showed HGC. CONCLUSIONS:TERT promoter mutations are commonly associated with malignancy, particularly HGCs, when multiple co-occurring molecular alterations are present. However, TERT promoter mutations may occasionally be detected in benign thyroid neoplasms when encountered in isolation or with fewer than 2 additional molecular alterations.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is pivotal in development, metabolic homeostasis, and immune responses. While recent research has highlighted AhR's significant role in modulating oxidative stress responses, its mechanistic relationship with ferroptosis-an iron-dependent, non-apoptotic cell death-remains to be fully elucidated. In our study, we discovered that AhR plays a crucial role in ferroptosis, in part by transcriptionally regulating the expression of the solute carrier family 7 member 11 (SLC7A11). Our findings indicate that both pharmacological inactivation and genetic ablation of AhR markedly enhance erastin-induced ferroptosis. This enhancement is achieved by suppressing SLC7A11, leading to increased lipid peroxidation. We also obtained evidence of post-translational modifications of SLC7A11 during ferroptosis. Additionally, we observed that indole 3-pyruvate (I3P), an endogenous ligand of AhR, protects cells from ferroptosis through an AhR-dependent mechanism. Based on these insights, we propose that AhR transcriptionally regulates the expression of SLC family genes, which in turn play a pivotal role in mediating ferroptosis. This underscores AhR's essential role in suppressing lipid oxidation and ensuring cell survival under oxidative stress.

Monogenic diseases of immune dysregulation should be considered in the evaluation of children presenting with recurrent neutrophilic dermatoses in association with systemic signs of inflammation, autoimmune disease, hematologic abnormalities, and opportunistic or recurrent infections. We report the case of a 2-year-old boy presenting with a neutrophilic dermatosis, found to have a novel likely pathogenic germline variant of the IKAROS Family Zinc Finger 1 (IKZF1) gene; the mutation likely results in a loss of function dimerization defective protein based on reports and studies of similar variants. IKZF1 variants could potentially lead to aberrant neutrophil chemotaxis and development of neutrophilic dermatoses. Long-term surveillance is required to monitor the development of hematologic malignancy, autoimmunity, immunodeficiency, and infection in patients with pathogenic IKZF1 germline variants.

OBJECTIVES/OBJECTIVE:The 2019 American Society of Colposcopy and Cervical Pathology management guidelines recommend that patients with an unsatisfactory Papanicolaou (Pap) test (UPT) and negative human papillomavirus (HPV) cotest undergo repeat age-based screening in 2 to 4 months. The rationale is that a negative HPV test in the setting of an UPT may reflect an inadequate sample and therefore should not be interpreted as truly "negative." For patients 25 years and older who are cotested, if HPV is positive for the 16 or 18 genotypes, direct referral for colposcopy is recommended. Our study aimed to determine if a negative HPV cotest result is predictive of the absence of a high-grade squamous intraepithelial lesion (HSIL) and whether these patients may be called back for repeat testing at an interval longer than 2 to 4 months. METHODS:Follow-up cervical cytology and biopsy results in women with UPT and HPV cotests from January 2017 to December 2021 were collected. Original UPT and HPV cotest results were correlated with the follow-up Pap and biopsy results. RESULTS:There were 1,496 (2.28%) UPT cases out of 65,641 total Pap tests. Among the 1,496 UPT cases, 1,010 (67.5%) had HPV cotesting; 676 (45.1%) were followed by repeat Pap or biopsy within 4 months and 850 (56.8%) within 12 months. The total follow-up rate was 81%, with a range of 3 days to 36 months. The HSIL rate in HPV-positive cases was 5.7% (3/53) vs 0.4% (2/539) (P = .006) in HPV-negative cases. In UPT, HPV cotesting showed negative predictive values for low-grade and high-grade squamous intraepithelial lesion detection of 98.5% and 99.6%, respectively, while positive predictive values were 19% and 5.7%. CONCLUSIONS:A negative HPV cotest in individuals with UPT predicted the lack of HSIL in our study. Compliance with the recommended follow-up time of 2 to 4 months for women with UPT was low (45.1%). Our study suggests that women with UPT and negative HPV cotest may be safely called back at an interval longer than 4 months.

Clonorchis sinensis, a liver fluke parasite, infects humans through ingestion of raw or undercooked fish, crabs, or crayfish in endemic areas where the parasite is found. Clonorchis sinensis infects the liver, gallbladder, and bile duct in humans, causing Clonorichiasis. Although the majority of patients are asymptomatic, long-lasting infections may cause severe disease. Without treatment, human infection may persist for the parasite's lifespan (25-30 years). Pathologic diagnosis can be challenging as sampling may demonstrate limited cellularity with minuscule eggs that may be overlooked. Here, we report a rare case of liver fluke eggs diagnosed in bile duct brush cytology.

BACKGROUND:Prostate cancer (PCa) is the most common malignant tumor found among men in the United States. Incidence rates of PCa have recently grown in Asian countries, partially due to the comprehensive implementation of early detection systems. Interestingly, a prospective cohort study showed that adopting a westernized dietary pattern was associated with a higher risk of being diagnosed with PCa among Korean and Japanese men. However, a comparison of current clinicopathological features of PCa between American and Chinese men is lacking. In this study, we report the current clinicopathological features of PCa in Chinese men and compare them to those of patients in the USA. MATERIALS AND METHODS/METHODS:Case cohorts included, in total, 871 PCa cases with prostatectomy sequentially treated since 2017, including 299 cases from USA and 572 cases from two different academic hospitals in China. The parameters, including patient's age, preoperative Prostate-Specific Antigen (PSA) level, Gleason score, Grade Group, stage and tumor focality, were collected, analyzed and compared using two sample t-test, Wilcoxon rank sum test, Pearson's Chi-squared test and Fisher's exact test. RESULTS:Significant differences were demonstrated in the mean age of patients, preoperative PSA levels, extra-prostatic extension, Gleason scores, and Grade Groups (p < 0.05). PCa patients in the Chinese group were older than patients in the USA group (67.81 vs. 63.53, p < 0.01). The preoperative PSA levels in the Chinese group were higher than those in the USA group (11.69 v.s 6.30, p < 0.01). A higher percentage of high Grade Groups (Groups 4 and 5) was observed in the Chinese group (25.7%) compared to the USA cohort (17.11%), while Grade Group 2 was more common in the USA group than in the Chinese group (51.68% vs. 32.52%, p < 0.01). CONCLUSIONS:All these data suggest that the clinicopathologic features of PCa are different between the USA and Chinese populations, which may be influenced by treatment strategies (including surgical case selection criteria).