Faculty Bibliography

SHP2 is a phosphatase and a critical mediator of receptor tyrosine kinase (RTK)-driven RAS/mitogen-activated protein kinase (MAPK) signaling. Despite promising preclinical data, SHP2 inhibitors have shown minimal clinical efficacy, with no defined clinical mechanisms of primary resistance. Here, we elucidate phosphorylation of SHP2 at tyrosine 62 (pY62) as a hotspot phosphorylation site in the proteome and RTK-driven tumor types in patients. We demonstrate that SRC family kinases directly phosphorylate SHP2 at Y62, downstream of but not directly phosphorylated by RTKs. Using biochemical and biophysical analyses, we show that SHP2^Y62D enforces an open, active conformation, resulting in constitutive phosphatase activation that is sufficient to activate MAPK signaling and confer resistance to allosteric SHP2 inhibitors. These findings establish that SHP2 pY62 is a phosphorylation hotspot phenocopying mutational activation, a mechanism of primary resistance to SHP2 inhibitors, and a cancer drug target distinct from wildtype SHP2.

BACKGROUND/UNASSIGNED:Distinguishing between nursing competency and education in clinical health care is multidimensional. The NYU Langone Health Nursing Education and Competency Algorithm (NE-CA) was developed to guide competency identification. METHOD/UNASSIGNED:A qualitative study was conducted to elicit dialogue through focus groups to identify themes specifically related to use of the NE-CA. RESULTS/UNASSIGNED:The results of this qualitative research include four major themes: algorithm, competency, competency assessment process, and education. CONCLUSION/UNASSIGNED:Findings from the focus groups support the application of the NE-CA by clinical nurse educators, professional registered nurses, and organizational stakeholders guiding competency and education.

BACKGROUND/UNASSIGNED:The patient-specific instrumentation (PSI) used during corrective high tibial osteotomies and distal femoral osteotomies is based on 3-dimensional computed tomography (3D CT). Plain radiographs are typically used preoperatively to determine the need for an osteotomy; however, it is unclear how well measurements on plain radiographs correlate with 3D CT. PURPOSE/HYPOTHESIS/UNASSIGNED:The purpose of this study was to evaluate the correlation between coronal and sagittal alignment measurements on plain radiographs and 3D CT. It was hypothesized that there would be high agreement in the measurement of the mechanical medial tibial width ratio (mMTWr) and the medial posterior tibial slope (PTS) between both modalities. STUDY DESIGN/UNASSIGNED:Cohort study (diagnosis); Level of evidence, 3. METHODS/UNASSIGNED:Patients who underwent hip-to-ankle CT as part of the preoperative workup before a corrective osteotomy from October 2020 to November 2023 were reviewed. Coronal (mMTWr) and sagittal alignment (medial PTS) were evaluated preoperatively by 2 raters on standing whole-leg radiographs and a lateral radiograph of the knee, respectively, and by semi-automated PSI software on 3D CT. Intraclass correlation coefficients (ICC) were calculated to assess interrater reliability for each measurement and to evaluate agreement between raters and the PSI software. RESULTS/UNASSIGNED:Complete data sets were obtained for 91 cases. The ICC between raters for preoperative mMTWR was 0.99. The ICC between the raters' measurements and the PSI software measurements of mMTWr was 0.99. The ICC between raters for preoperative PTS was 0.82. The ICC between the raters' measurements and the PSI software's PTS measurements was 0.63. CONCLUSION/UNASSIGNED:This study found that coronal measurements performed on whole-leg radiographs and 3D CT were highly correlated, with near-perfect agreement, and that medial PTS measurements showed moderate agreement between modalities. These data suggest that measurements on plain radiographs are reproducible and accurate for evaluating coronal alignment and PTS preoperatively. Surgeons can confidently use plain radiographs to assess whether or not a patient is a candidate for a knee osteotomy.

CONTEXT/BACKGROUND:More health systems are establishing outpatient palliative care (PC) programs, increasing demand for ambulatory PC clinicians. However, existing outpatient training during hospice and palliative medicine (HPM) fellowship remains limited and suboptimal. Little is known about the outpatient-specific knowledge and skills PC trainees should acquire for competent outpatient practice. OBJECTIVES/OBJECTIVE:To identify and prioritize outpatient-focused educational topics for HPM fellows and clinicians new to ambulatory practice. METHODS:A cross-sectional survey of United States (U.S.) outpatient PC clinicians (physicians, advanced practice practitioners [APPs]). Using a list of 51 educational topics, respondents selected a maximum of 20 topics they would prioritize as essential to prepare learners for outpatient practice. RESULTS:Of 247 clinicians, 136 (55%) responded, including 115 physicians and 21 APPs from all U.S. regions. Seven of 51 topics were prioritized by more than two-thirds of respondents (n = 92-119, 68%-86%). Four focused on outpatient application of core PC skills (pain management [n = 113, 83%], nonpain symptom management [n = 117, 86%], depression/anxiety [n = 107, 79%], goals of care [n = 92, 68%]). The remaining three covered discrete topics related to pain and opioid management, including best practices for caring for patients with comorbid pain and substance use disorder (n = 104, 76%). CONCLUSION/CONCLUSIONS:This national survey identified foundational outpatient-focused educational topics for HPM learners and suggests that outpatient curricula prioritize deliberate education on the unique application of core PC skills in outpatient settings. This prioritized list provides education leaders a roadmap to enhance existing curricula and informs the development of outpatient educational resources that can be shared across institutions.

BACKGROUND:Age-related hearing loss is highly prevalent, underrecognized, and consequently, undertreated. Hearing loss can have a substantial negative impact on communication and biopsychosocial health. We hypothesize that offering validated hearing assessments and a point-of-care counseling program in an older, underserved population will be more accessible and acceptable than the traditional pathway for audiology care, particularly in marginalized communities. METHODS:This convergent mixed methods feasibility study will assess the implementation of a hearing program embedded in a quality improvement initiative within the Geriatric Clinic of New York City Health and Hospital's Bellevue Hospital Center and the feasibility of recruiting for a future efficacy trial to test the intervention. Adult patients ≥ 60 years who are proficient in English or Spanish and not currently using hearing rehabilitation are eligible for initial screening. Hearing level, including individual ear severity, is identified using a validated tablet-based measure of pure tone audiometry and a self-report measure of hearing disability. We define hearing loss subjectively based on a score of 8 or greater on the Hearing Handicap Inventory-Screen (HHI-S) or using a four-frequency pure tone average > 25 dB hearing level in the better ear, representing at least a mild hearing loss. Patients who are determined to have measurable hearing loss and provide informed consent will be invited to participate in a pilot study and randomized to one of two approaches: (1) a counseling on alternative rehabilitation strategies intervention arm or (2) usual care with referral to the audiology pathway. Primary feasibility outcomes include recruitment and retention rates, intervention adherence, acceptability, and the ability to collect outcome measurements. We will also explore changes in HHI-S scores over 3 months and assess subsequent audiology service utilization in both groups. In addition to the quantitative data, we will include key participant interviews with staff and patients to assess feasibility from participant attitudes. DISCUSSION/CONCLUSIONS:This study will provide insights into the feasibility of offering hearing screening/assessments and counseling in primary care and its potential to improve access to hearing care for underserved older adults. Findings will inform the design of future trials evaluating the impact of primary care-based tailored hearing interventions on patient health and quality of life. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT05943509, Trial registration date: July 13, 2023, Protocol Version: 1.

The convergence of artificial intelligence (AI) and neuroscience represents one of medicine's most profound intellectual partnerships. Neuronal architecture has inspired computational methods, while computational models, evolving from theoretical constructs to transformative clinical tools, are reshaping neurological practice. As AI systems attempt to augment diagnostic accuracy, treatment planning, and patient care, neurologists must develop fluency in these technologies to harness their potential while navigating their limitations and dangers. AI-related publications have exponentially increased in recent years, yet many neurologists lack the foundational computer science background needed to critically evaluate and most safely and effectively implement these tools in clinical practice. This article serves to outline the historical foundations linking neuroscience to computing, examine core concepts of the past and current AI landscape in neurology, and describe methodologies that aim to revolutionize neurological care.

In 2007, the American Society for Apheresis (ASFA) published guidance for physician documentation related to oversight of therapeutic apheresis (TA). Due to 21st century changes in healthcare delivery, the ASFA Board of Directors (BOD) charged its Public Affairs and Advocacy Committee (PAAC) to coordinate a review and update of the guidance. PAAC members reviewed minutes from various ASFA committees' earlier deliberations and sought additional information from the medical and general literature and regulatory/professional organizations involved with medical records documentation as well as from ASFA membership. A draft document was developed, reviewed, and approved by pertinent parties with changes incorporated into the guidance revision. Major change agents impacting TA documentation were identified including the importance of multidisciplinary care teams, the adoption of telemedicine in TA delivery, and the challenges highlighted by the SARS-CoV-2 pandemic. Formats involving TA documentation scenarios related to initial TA consultations and subsequent care activities by TA staff were developed. The introduction of new technologies, the advancing and mandating of electronic medical records (EMRs) adoption and a renewed emphasis on the team-based nature of healthcare delivery have all impacted TA services. Revised documentation formatting practices related to these changes, not only for physicians' involvement but recognition and inclusion of other members of multidisciplinary teams participating in TA, should be incorporated into TA operations. Such revisions can potentially enhance patient care and provide a foundation for TA-related biovigilance activities.

BACKGROUND AND AIMS/OBJECTIVE:The opioid crisis is still a public health emergency in the United States, despite recent declines in opioid overdose deaths (OODs) and increased availability of evidence-based practices (EBPs) for opioid use disorder (OUD). The geographic variability in OODs drives the need for localized decision-making, where interventions are tailored to the unique needs of communities. This study aimed to develop and calibrate a simulation model that evaluates the impact of enhanced implementation of EBP on OODs at the community-level. DESIGN/METHODS:We developed OPSiM (Opioid Policy Simulation Model), a community-level microsimulation model that simulates the course of opioid use, OUD, treatment, recovery and overdose-related events. The model was parameterized with data from the HEALing Communities Study and looked at six scenarios of EBPs implemented in 2025 with sustainment through 2030: (1) maintain 2024 EBP levels (status quo); (2) increase initiation of medications for opioid use disorder (MOUD); (3) increase MOUD retention; (4) increase MOUD initiation and retention; (5) increase distribution of naloxone; and (6) both scenarios 4 and 5. SETTING/METHODS:Twenty-nine communities in Massachusetts, New York, and Ohio, USA. PARTICIPANTS/METHODS:Simulated community residents with non-prescribed opioid use or OUD. MEASUREMENTS/METHODS:Estimated number of OODs per 100 000 individuals between 2025 and 2030 in each community, averaged across the 26 communities. FINDINGS/RESULTS:Under the status quo, the model projected 158 OODs (range across communities: 39-468) per 100 000 individuals between 2025 and 2030. Increasing medications for the treatment of OUD (MOUD) retention alone reduced OODs by 6% (range: 3-15%), while increasing MOUD initiation alone reduced OODs by 9% (range: 8-12%). Increasing both MOUD initiation and retention had a synergistic effect, reducing OODs by 21% (range: 15-31%). Reduction in OODs in response to increased MOUD initiation and/or retention was similar across urban and rural communities. The effect of increasing naloxone distribution varied substantially across communities due to differing saturation levels; in some communities, additional naloxone kits provided only marginal benefits. Rural communities were further from saturation whereas most urban communities were at or close to saturation. CONCLUSIONS:A tailored, multi-pronged approach that scales up medications for opioid use disorder alongside widespread naloxone distribution, and that addresses community-specific needs and capacities, will be most effective at reducing opioid overdose deaths in the United States.