Faculty Bibliography

In early March 2020 an outbreak of coronavirus disease 2019 (COVID-19) in New York City exerted sudden and extreme pressures on emergency medical services and quickly changed public health policy and clinical guidance. Recognizing this, New York City Health + Hospitals established a clinician-staffed COVID-19 hotline for all New Yorkers. The hotline underwent three phases as the health crisis evolved. As of May 1, 2020, the hotline had received more than ninety thousand calls and was staffed by more than a thousand unique clinicians. Hotline clinicians provided callers with clinical assessment and guidance, registered them for home symptom monitoring, connected them to social services, and provided a source of up-to-date answers to COVID-19 questions. By connecting New Yorkers with hotline clinicians, regardless of their regular avenues of accessing care, the hotline aimed to ease the pressures on the city's overtaxed emergency medical services. Future consideration should be given to promoting easy access to clinician hotlines by disadvantaged communities early in a public health crisis and to evaluating the impact of clinician hotlines on clinical outcomes.

BACKGROUND AND PURPOSE/OBJECTIVE:Patients with the Coronavirus Disease of 2019 (COVID-19) are at increased risk for thrombotic events and mortality. Various anticoagulation regimens are now being considered for these patients. Anticoagulation is known to increase the risk for adverse bleeding events, of which intracranial hemorrhage (ICH) is one of the most feared. We present a retrospective study of 33 patients positive for COVID-19 with neuroimaging-documented ICH and examine anticoagulation use in this population. METHODS:Patients over the age of 18 with confirmed COVID-19 and radiographic evidence of ICH were included in this study. Evidence of hemorrhage was confirmed and categorized by a fellowship trained neuroradiologist. Electronic health records were analyzed for patient information including demographic data, medical history, hospital course, laboratory values, and medications. RESULTS:We identified 33 COVID-19 positive patients with ICH, mean age 61.6 years (range 37-83 years), 21.2% of whom were female. Parenchymal hemorrhages with mass effect and herniation occurred in 5 (15.2%) patients, with a 100% mortality rate. Of the remaining 28 patients with ICH, 7 (25%) had punctate hemorrhages, 17 (60.7%) had small- moderate size hemorrhages, and 4 (14.3%) had a large single site of hemorrhage without evidence of herniation. Almost all patients received either therapeutic dose anticoagulation (in 22 [66.7%] patients) or prophylactic dose (in 3 [9.1] patients) prior to ICH discovery. CONCLUSIONS:Anticoagulation therapy may be considered in patients with COVID-19 though the risk of ICH should be taken into account when developing a treatment regimen.

Medical knowledge examinations employing open-ended (constructed response) items can be useful to assess medical students' factual and conceptual understanding. Modern day curricula that emphasize active learning in small groups and other interactive formats lend themselves to an assessment format that prompts students to share conceptual understanding, explain, and elaborate. The open-ended question examination format can provide faculty with insights into learners' abilities to apply information to clinical or scientific problems, and reveal learners' misunderstandings about essential content. To implement formative or summative assessments with open-ended questions in a rigorous manner, educators must design systems for exam creation and scoring. This includes systems for constructing exam blueprints, items and scoring rubrics, and procedures for scoring and standard setting. Information gained through review of students' responses can guide future educational sessions and curricular changes in a cycle of continuous improvement.

Introduction/UNASSIGNED:Microaggressions are connected to broader conceptualizations of the impact of implicit bias and systems of inequity. The body of evidence supporting the need for more-open discussions in medical education about race, racism, and their impact on health disparities continues to grow. Some have advocated for the importance of bringing anti-racist pedagogy into medical education curricula, which involves explicitly attempting to move beyond people's comfort zones and acknowledging that discomfort can be a catalyst for growth. To discuss the intent and impact of microaggressions in health care settings and how we might go about responding to them, we developed a workshop for third-year undergraduate medical students within a longitudinal undergraduate medical education diversity and inclusion curriculum. Methods/UNASSIGNED:= 154). Prior to the workshop, the students were asked to anonymously submit critical incident reports on any microaggressions experienced or witnessed to develop case studies for problem-based learning. Teaching modalities included lecture, problem-based learning with case studies, pair and share, and facilitated small- and large-group debriefs. Results/UNASSIGNED:The session was evaluated using a 4-point Likert scale to assess students' comfort in learning about the information presented. Ninety-eight percent felt confident in identifying microaggressions, and 85% felt confident in interrupting microaggressions when they occur. Discussion/UNASSIGNED:This personalized workshop exposes students to microaggressions personally experienced by colleagues with an attempt to interrupt them using empathy, awareness, and communication techniques.

BACKGROUND:Relevant clinical information is often missing when a patient sees a specialist after being referred by another physician in the ambulatory setting. This can result in missed or delayed diagnoses, delayed treatment, unnecessary testing, and drug interactions. Residents' attitudes toward providing clinical information at the time of referral and their perspectives toward training on referral skills are not clear. We sought to assess internal medicine residents' attitudes toward and experiences with outpatient referrals. METHODS:We conducted a cross-sectional survey in October-December 2018 of all internal medicine interns and residents affiliated with a large, urban internal medicine residency program in New York, NY. We used a novel survey instrument that included 13 questions about attitudes toward and experiences with outpatient referrals. We used descriptive statistics to characterize the results. RESULTS:Overall, 122 of 132 residents participated (92% response rate). Respondents were approximately equally distributed across post-graduate years 1-3. Although 83% of residents reported that it is "always" important to provide the clinical reason for a referral, only 11% stated that they "always" provide a sufficient amount of clinical information for the consulting provider when making a referral. Only 9% of residents "strongly agree" that residency provides sufficient training in knowing when to refer patients, and only 8% "strongly agree" that residency provides sufficient training in what information to provide the consulting physician. CONCLUSIONS:These results suggest a substantial discrepancy between the amount of information residents believe they should provide at the time of a referral and the amount they actually provide. Many residents report not receiving adequate training during residency on when to refer patients and what clinical information to provide at the time of referral. Improvements to medical education regarding outpatient referrals are urgently needed.

Twenty patients with carbapenem-resistant Enterobacteriaceae (CRE) infections were treated with meropenem-vaborbactam. Thirty-day clinical success and survival rates were 65% (13/20) and 90% (18/20), respectively. Thirty-five percent of patients had microbiologic failures within 90 days. One patient developed a recurrent infection due to meropenem-vaborbactam non-susceptible, ompK36 porin mutant Klebsiellapneumoniae.

Mycobacterium abscessus (Mab) is a highly drug-resistant nontuberculous mycobacteria (NTM). Efforts to discover new treatments for M. abscessus infections are accelerating with a focus on cell wall synthesis proteins (L, D-transpeptidases, Ldt_Mab1-5, and D,D-carboxypeptidase) that are targeted by β-lactam antibiotics. A challenge to this approach is the presence of chromosomally encoded β-lactamase, Bla_Mab Using a "mechanism based" approach, we show that a novel ceftaroline-imipenem combination effectively lowered the minimal inhibitory concentrations (MICs) of Mab isolates (MIC₅₀ ≤ 0.25, MIC₉₀ ≤ 0.5). Ceftaroline and imipenem combined with a β-lactamase inhibitor, relebactam or avibactam, demonstrated only a modest effect on susceptibility, compared to each of the beta-lactams alone. In steady state kinetic assays, Bla_Mab exhibited a lower K_{i app} (K_{i app} = 0.30 ± 0.03 μM, avibactam; 136 ± 14 μM, relebactam) and a faster acylation rate for avibactam (k₂/K = 3.4 ± 0.4 x 10⁵ M^-1s^-1, avibactam; 6 ± 0.6 x 10² M^-1s^-1, relebactam). The k_cat/K_m was nearly 10-fold lower for ceftaroline fosamil (0.007 ± 0.001 μM^-1s^-1) compared to imipenem (0.056 ± 0.006 μM^-1s^-1). Timed mass spectrometry captured complexes of avibactam and Bla_Mab, Ldt_{Mab1, 2, and 4}, and D,D-carboxypeptidase, whereas relebactam bound only Bla_Mab and Ldt_{Mab1 and 2} Interestingly, Ldt_{Mab1, 2, 4 and 5} and D, D-carboxypeptidase bound only to imipenem when incubated with imipenem and ceftaroline fosamil. We next determined the binding constants of imipenem and ceftaroline fosamil to Ldt_{Mab1, 2, 4 and 5} and showed that imipenem bound > 100 fold more avidly than ceftaroline fosamil for Ldt_Mab1 and Ldt_Mab2 (e.g. K_{i app} or K_m LdtMab1 = 0.01 ± 0.01 μM for imipenem vs 0.73 ± 0.08 μM for ceftaroline fosamil). Molecular modelling indicates that Ldt_Mab2 readily accommodates imipenem, but the active site must widen to ≥ 8Ã… for ceftaroline to enter. Our analysis demonstrates that ceftaroline and imipenem binding to multiple targets (L, D-transpeptidases and D, D-carboxypeptidase) provides mechanistic rationale for the effectiveness of this dual β-lactam combination in Mab infections.

Objectives: To determine links between objectively and subjectively measured physical function and cognitive function among HIV-positive older adults, a growing yet understudied group with elevated risk for multimorbidity. Methods: At a biomedical research visit, 162 participants completed objective tests of gait speed (4-m walk), grip strength (dynamometer), and cognitive function (Montreal Cognitive Assessment, MoCA) and reported their well-being (Medical Outcomes Study-HIV survey). Results: Those with faster gait speed had better overall cognitive function than those with slower gait speed (b = 3.98, SE = 1.30, p = .003) in an adjusted regression model controlling for age, sex, race, height, preferred language, and assistive device use. Grip strength was not significantly associated with overall cognitive function. Self-rated cognitive function was weakly related to MoCA scores (r = .26) and gait speed (r = .14) but was strongly associated with emotional well-being (r = .53). Discussion: These observed, expected connections between physical and cognitive function could inform intervention strategies to mitigate age-related declines for older adults with HIV.

BACKGROUND:We previously identified two acute kidney injury (AKI) sub-phenotypes (AKI-SP1 and AKI-SP2) with different risk of poor clinical outcomes and response to vasopressor therapy. Plasma biomarkers of endothelial dysfunction (tumor necrosis factor receptor-1, angiopoietin-1 and 2) differentiated the AKI sub-phenotypes. However, it is unknown whether these biomarkers are simply markers or causal mediators in the development of AKI sub-phenotypes. METHODS:We tested for associations between single-nucleotide polymorphisms within the Angiopoietin-1, Angiopoietin-2, and Tumor Necrosis Factor Receptor 1A genes and AKI- SP2 in 421 critically ill subjects of European ancestry. Top performing single-nucleotide polymorphisms (FDR < 0.05) were tested for cis-biomarker expression and whether genetic risk for AKI-SP2 is mediated through circulating biomarkers. We also completed in vitro studies using human kidney microvascular endothelial cells. Finally, we calculated the renal clearance of plasma biomarkers using 20 different timed urine collections. RESULTS:A genetic variant, rs2920656C > T, near ANGPT2 was associated with reduced risk of AKI-SP2 (odds ratio, 0.45; 95% CI, 0.31-0.66; adjusted FDR = 0.003) and decreased plasma angiopoietin-2 (p = 0.002). Causal inference analysis showed that for each minor allele (T) the risk of developing AKI-SP2 decreases by 16%. Plasma angiopoietin-2 mediated 41.5% of the rs2920656 related risk for AKI-SP2. Human kidney microvascular endothelial cells carrying the T allele of rs2920656 produced numerically lower levels of angiopoietin-2 although this was not statistically significant (p = 0.07). Finally, analyses demonstrated that angiopoietin-2 is minimally renally cleared in critically ill subjects. CONCLUSION/CONCLUSIONS:Genetic mediation analysis provides supportive evidence that angiopoietin-2 plays a causal role in risk for AKI-SP2.