Faculty Bibliography

Over the last decade there has been tremendous growth in the development of accelerated MD pathways that allow medical students to graduate in three years. Developing an accelerated pathway program requires commitment from students and faculty with intensive re-thinking and altering of the curriculum to ensure adequate content to achieve competency in an accelerated timeline. A re-visioning of assessment and advising must follow and the application of AI and new technologies can be added to support teaching and learning. We describe the curricular revision to an accelerated pathway at NYU Grossman School of Medicine highlighting our thought process, conceptual framework, assessment methods and outcomes over the last ten years.

PURPOSE/OBJECTIVE:For accelerated 3-year MD (3YMD) pathways to be fully adopted in medical education, a comprehensive analysis of outcome data is needed. This study includes 7 accelerated 3YMD graduating classes at NYU Grossman School of Medicine (NYUGSOM) and reports on outcomes from both medical school and internship compared to their 4-year MD (4YMD) counterparts. METHOD/METHODS:Outcomes across the undergraduate-graduate medical education continuum for the first 7 classes of NYUGSOM graduates (matriculated from 2013-2019) from the accelerated 3YMD (n = 136) and 4YMD pathways (n = 681) were compared. For the internship outcomes, 3YMD interns were compared with 4YMD interns who graduated from NYUGSOM and all 4YMD interns (4YMD graduates from NYUGSOM and any other medical school) at NYUGSOM residencies. RESULTS:Accelerated 3YMD students were approximately 5 months older at admission and had higher multiple mini-interview scores than 4YMD students. Overall, accelerated 3YMD students performed similarly to 4YMD students during medical school and internship. Significant differences included higher performance by 3YMD students on preclerkship exams and lower performance on Steps 1 and 2 (average: 5.6 and 8.3 fewer points, respectively) and the physical examination portion of the NYUGSOM Comprehensive Clinical Skills Exam. Internship data indicated comparable team assessments across all residencies, statistically significant higher performance on Step 3 when compared to all 4YMD interns, and, in internal medicine, comparable clinical reasoning between 3YMD and all 4YMD interns. When comparing 3YMD interns to all 4YMD interns in the internal medicine residency program, 3YMD interns had a statistically significantly higher performance on milestones. CONCLUSIONS:The outcomes from 7 years of graduating accelerated 3YMD students at NYUGSOM show similar performance in medical school and early residency to 4YMD graduates. Long-term study of accelerated 3YMD students from NYUGSOM and other medical schools is needed to further validate the success of this innovative medical education pathway.

BACKGROUND:We examined effects of single-nucleotide variants (SNVs) of IL1RN, the gene encoding the anti-inflammatory interleukin 1 receptor antagonist (IL-1Ra), on the cytokine release syndrome (CRS) and mortality in patients with acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS:IL1RN CTA haplotypes formed from 3 SNVs (rs419598, rs315952, rs9005) and the individual SNVs were assessed for association with laboratory markers of inflammation and mortality. We studied 2589 patients hospitalized with SARS-CoV-2 between March 2020 and March 2021. RESULTS:Mortality was 15.3% and lower in women than men (13.1% vs 17.3%, P = .0003). Carriers of the CTA-1/2 IL1RN haplotypes exhibited decreased inflammatory markers and increased plasma IL-1Ra. Evaluation of the individual SNVs of the IL1RN, carriers of the rs419598 C/C SNV exhibited significantly reduced inflammatory biomarker levels and numerically lower mortality compared to the C/T-T/T genotype (10.0% vs 17.8%, P = .052) in men, with the most pronounced association observed in male patients ≤74 years old, whose mortality was reduced by 80% (3.1% vs 14.0%, P = .030). CONCLUSIONS:The IL1RN haplotype CTA and C/C variant of rs419598 are associated with attenuation of the CRS and decreased mortality in men with acute SARS-CoV-2 infection. The data suggest that the IL1RN pathway modulates the severity of coronavirus disease 2019 (COVID-19) via endogenous anti-inflammatory mechanisms.

OBJECTIVE/UNASSIGNED:To further validate a serum proteomics panel for predicting radiographic (structural) knee OA progression. DESIGN/UNASSIGNED:Serum peptides were targeted by multiple-reaction-monitoring mass spectrometry in the New York University cohort (n ​= ​104). Knee OA progression was defined as joint space narrowing ≥1 in the tibiofemoral compartment of one knee per study participant over a 24-month follow-up. The discriminative ability of an 11-peptide panel was evaluated by multivariable logistic regression and area under the receiver operating characteristic curve (AUC), without and with demographic characteristics of age, sex, and body mass index. The association of each peptide with OA progression was assessed by odds ratios (OR) in multivariable logistic regression models adjusted for demographics. RESULTS/UNASSIGNED:The cohort included 46 (44%) knee OA progressors. The panel of 11 peptides alone yielded AUC ​= ​0.66 (95% CI [0.55, 0.77]) for discriminating progressors from non-progressors; demographic traits alone yielded AUC ​= ​0.66 (95% CI [0.55, 0.77]). Together the 11 peptides and demographics yielded AUC ​= ​0.72 (95% CI [0.62, 0.83]). CRAC1 had the highest odds for predicting OA progression (OR 2.014, 95% CI [0.996, 4.296], p ​= ​0.058). CONCLUSIONS/UNASSIGNED:We evaluated a parsimonious serum proteomic panel and found it to be a good discriminator of knee radiographic OA progression from non-progression. Since these biomarkers are quantifiable in serum, they could be deployed relatively easily to provide a simple, cost-effective strategy for identifying and monitoring individuals at high risk of knee OA progression.

PURPOSE/OBJECTIVE:To explore whether a machine-learning algorithm could accurately perform the initial screening of medical school applications. METHOD/METHODS:Using application data and faculty screening outcomes from the 2013 to 2017 application cycles (n = 14,555 applications), the authors created a virtual faculty screener algorithm. A retrospective validation using 2,910 applications from the 2013 to 2017 cycles and a prospective validation using 2,715 applications during the 2018 application cycle were performed. To test the validated algorithm, a randomized trial was performed in the 2019 cycle, with 1,827 eligible applications being reviewed by faculty and 1,873 by algorithm. RESULTS:The retrospective validation yielded area under the receiver operating characteristic (AUROC) values of 0.83, 0.64, and 0.83 and area under the precision-recall curve (AUPRC) values of 0.61, 0.54, and 0.65 for the invite for interview, hold for review, and reject groups, respectively. The prospective validation yielded AUROC values of 0.83, 0.62, and 0.82 and AUPRC values of 0.66, 0.47, and 0.65 for the invite for interview, hold for review, and reject groups, respectively. The randomized trial found no significant differences in overall interview recommendation rates according to faculty or algorithm and among female or underrepresented in medicine applicants. In underrepresented in medicine applicants, there were no significant differences in the rates at which the admissions committee offered an interview (70 of 71 in the faculty reviewer arm and 61 of 65 in the algorithm arm; P = .14). No difference in the rate of the committee agreeing with the recommended interview was found among female applicants (224 of 229 in the faculty reviewer arm and 220 of 227 in the algorithm arm; P = .55). CONCLUSIONS:The virtual faculty screener algorithm successfully replicated faculty screening of medical school applications and may aid in the consistent and reliable review of medical school applicants.

BACKGROUND/UNASSIGNED:The lack of disease modifying drugs in Osteoarthritis (OA) may be attributed to the difficulty in robust response based on patient-reported outcomes (PROs) linked to drug mechanism of action. Joint tissue turnover biomarkers are associated with disease progression. A subset of patients has elevated serum levels of CRP metabolite (CRPM). This explorative study investigates the associations between PROs and joint tissue turnover markers in patients with high or low CRPM. METHODS/UNASSIGNED:Serum of 146 knee OA patients of the New York Inflammation cohort and 21 healthy donors were assessed for biomarkers of collagen degradation (C1M, C2M, C3M, C4M), formation (PRO-C1, PRO-C2, PRO-C3, PRO-C4), and CRPM. Mean (SD) age was 62.5 (10.1); BMI, 26.6 (3.6); 62% women; and, 67.6% had symptomatic OA. WOMAC pain, stiffness, function, and total were recorded at baseline and at two-year follow-up. Associations were adjusted for race, sex, age, BMI, and NSAID. RESULTS/UNASSIGNED:group. The best predictive models for improvement were found for function and total with AUCs of 0.74 (p ​< ​0.01) and 0.78 (p ​< ​0.01). The best predictive models for worsening were found for function and total with AUCs of 0.84 (p ​< ​0.01) and 0.80 (p ​< ​0.05). CONCLUSION/UNASSIGNED:We hypothesize that collagen markers are prognostic tools for segregating patient populations in clinical trials.

OBJECTIVE/UNASSIGNED:, the gene encoding the anti-inflammatory IL-1 receptor antagonist (IL-1Ra), on the cytokine release syndrome and mortality. METHODS/UNASSIGNED:gene were assessed for association with laboratory markers of the cytokine release syndrome (CRS) and mortality. RESULTS/UNASSIGNED:rs419598 CC SNV exhibited lower inflammatory biomarker levels, and was associated with reduced mortality compared to the CT/TT genotype in men (OR 0.49 (0.23 - 1.00); 0.052), with the most pronounced effect observed between the ages of 55-74 [5.5% vs. 18.4%, p<0.001]. CONCLUSION/UNASSIGNED:modulates the COVID-19 cytokine release syndrome via endogenous " anti-inflammatory" mechanisms. SIGNIFICANCE STATEMENT/UNASSIGNED:merits further evaluation in severe SARS-CoV-2 infection.

Rheumatoid arthritis is a chronic systemic immune-mediated disease caused by genetic and environmental factors. It is often characterized by the generation of autoantibodies that lead to synovial inflammation and eventual multi-joint destruction. A growing number of studies have shown significant differences in the gut microbiota composition of rheumatoid arthritis (RA) patients compared to healthy controls. Environmental factors, and changes in diet and nutrition are thought to play a role in developing this dysbiosis. This review aims to summarize the current knowledge of intestinal dysbiosis, the role of nutritional factors, and its implications in the pathogenesis of rheumatoid arthritis and autoimmunity. The future direction focuses on developing microbiome manipulation therapeutics for RA disease management.

Type I interferon (IFN) is critical in our defense against viral infections. Increased type I IFN pathway activation is a genetic risk factor for systemic lupus erythematosus (SLE), and a number of common risk alleles contribute to the high IFN trait. We hypothesized that these common gain-of-function IFN pathway alleles may be associated with protection from mortality in acute COVID-19. We studied patients admitted with acute COVID-19 (756 European-American and 398 African-American ancestry). Ancestral backgrounds were analyzed separately, and mortality after acute COVID-19 was the primary outcome. In European-American ancestry, we found that a haplotype of interferon regulatory factor 5 (IRF5) and alleles of protein kinase cGMP-dependent 1 (PRKG1) were associated with mortality from COVID-19. Interestingly, these were much stronger risk factors in younger patients (OR=29.2 for PRKG1 in ages 45-54). Variants in the IRF7 and IRF8 genes were associated with mortality from COVID-19 in African-American subjects, and these genetic effects were more pronounced in older subjects. Combining genetic information with blood biomarker data such as C-reactive protein, troponin, and D-dimer resulted in significantly improved predictive capacity, and in both ancestral backgrounds the risk genotypes were most relevant in those with positive biomarkers (OR for death between 14 and 111 in high risk genetic/biomarker groups). This study confirms the critical role of the IFN pathway in defense against COVID-19 and viral infections, and supports the idea that some common SLE risk alleles exert protective effects in anti-viral immunity. BACKGROUND: We find that a number of IFN pathway lupus risk alleles significantly impact mortality following COVID-19 infection. These data support the idea that type I IFN pathway risk alleles for autoimmune disease may persist in high frequency in modern human populations due to a benefit in our defense against viral infections. TRANSLATIONAL SIGNIFICANCE: We develop multivariate prediction models which combine genetics and known biomarkers of severity to result in greatly improved prediction of mortality in acute COVID-19. The specific associated alleles provide some clues about key points in our defense against COVID-19.

Background/UNASSIGNED:Little outcome data exist on 3-year MD (3YMD) programs to guide residency program directors (PDs) in deciding whether to select these graduates for their programs. Objective/UNASSIGNED:To compare performance outcomes of 3YMD and 4-year MD (4YMD) students at New York University Grossman School of Medicine. Methods/UNASSIGNED:In 2020, using the Kirkpatrick 4-level evaluation model, outcomes from 3 graduating cohorts of 3YMD students (2016-2018) were compared with the 4YMD counterparts. Results/UNASSIGNED:=.03), other metrics and overall intern ratings did not differ by pathway. Conclusions/UNASSIGNED:Exploratory findings from a single institution suggest that 3YMD students performed similarly to 4YMD students in medical school and the first year of residency.