Faculty Bibliography

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable success in treating various B-cell malignancies, redirecting T-cell cytotoxicity toward cancer cells. Despite its efficacy, CAR-T therapy is associated with potential risks, including cytokine release syndrome (CRS) and cytopenia. We present a case of a 69-year-old man with diffuse large B-cell lymphoma treated with axicabtagene-ciloleucel CAR-T therapy, who developed a rare and severe cutaneous toxicity resembling toxic epidermal necrolysis (TEN). The patient exhibited persistent fevers, CRS, and subsequent development of a widespread erythematous macular eruption, progressing to vesiculation with bullae. Notably, allopurinol-induced TEN was considered with the patient's recent exposure to allopurinol, although the onset and minimal mucosal involvement did not align with typical presentations of allopurinol-induced cases. The cutaneous reaction, distinct from typical SJS/TEN, showed minimal mucosal involvement and coincided with the cytokine release storm, differing from allopurinol-induced TEN. Despite the absence of guidelines, the patient was managed with systemic steroids, achieving significant improvement. This case expands the spectrum of CAR-T therapy-related cutaneous toxicities, highlighting the need for early recognition of histopathology and tailored management by dermatologists. Further understanding of these reactions is crucial for optimizing the safety profile of this groundbreaking immunotherapy.

BACKGROUND:Breast cancer (BC) with germline BRCA1/2 mutations and their association with triple-negative BC has been thoroughly investigated. However, some carriers of BRCA1/2 mutations have human epidermal growth factor receptor 2 (HER2/neu)-positive BC, which has a different targeted therapy approach, and data are scarce for this patient population. The authors sought to characterize the clinical characteristics and outcomes of patients with HER2/neu-positive BC who had germline BRCA1/2 mutations. METHODS:This was a retrospective analysis of data from 1099 patients diagnosed with HER2/neu-positive BC who were screened for germline BRCA mutations between 1996 and 2022. Clinicopathologic features and survival rates were analyzed by BRCA mutation status. Univariate and multivariable Cox proportional hazards regression models were used to analyze the association between clinical variables and outcomes. RESULTS:Of 1099 patients with HER2/neu-positive BC, 73 (6.6%) tested positive for BRCA1/2 mutations. Age, race, and tumor characteristics did not differ between BRCA noncarriers and carriers. At a median follow-up of 78.6 months, the 5-year recurrence-free survival rate was 85% in BRCA carriers and 87% in noncarriers (p = .79), and the 5-year overall survival rate was 94% in BRCA carriers and 94% in noncarriers (p = .78). In a multivariable model, BRCA was not associated with recurrence-free survival (hazard ratio, 0.99; 95% confidence interval, 0.51-1.90; p = .96) or overall survival (hazard ratio, 0.83; 95% confidence interval, 0.33-2.07; p = .69). CONCLUSIONS:BRCA1/2 mutations occurred in 6.6% of patients with HER2/neu-positive BC and did not affect survival outcomes. Assessing the potential benefits of new treatment strategies, such as combining anti-HER2/neu therapies with poly(ADP-ribose) polymerase inhibitors, may lead to enhanced outcomes for these patients.

BACKGROUND/UNASSIGNED:Exacerbations of noncystic fibrosis bronchiectasis (bronchiectasis) are associated with reduced health-related quality of life and increased mortality, likelihood of hospitalisation and lung function decline. This study investigated patient clinical characteristics associated with exacerbation frequency. METHODS/UNASSIGNED:A cross-sectional cohort study of patients ≥18 years with bronchiectasis enrolled in the US Bronchiectasis and Nontuberculous Mycobacteria (NTM) Research Registry (BRR) September 2008-March 2020. Patients were stratified by exacerbation frequency in their 2 years before enrolment. Patient demographics, respiratory symptoms, healthcare resource utilisation, microbiology, modified bronchiectasis severity index (mBSI) and select comorbidities were collected at enrolment. Patient characteristics associated with exacerbation frequency were assessed using a negative binomial model. RESULTS/UNASSIGNED:% predicted, asthma, and gastro-oesophageal reflux disease were associated with more exacerbations. CONCLUSIONS/UNASSIGNED:infection in patients with bronchiectasis and multiple exacerbations.

Disparities in maternal health outcomes are striking. Historical and biased clinical support tools have potential to exacerbate inequities. In 2022, NewYork-Presbyterian, with ∼25,000 annual births, and our academic partners, Columbia and Weill Cornell, launched a program to better understand practice patterns and clinician attitudes toward a vaginal birth after cesarean (VBAC) calculator, which predicts VBAC success. This article summarizes the program, focusing on the VBAC calculator utilization survey, which measured provider awareness of the revised calculator and key factors considered in patient counseling. Our preliminary findings warrant future research and education on the calculator's implications for counseling and outcomes.

IMPORTANCE/UNASSIGNED:Stroke is a leading cause of death and disability in the US. Accurate and updated measures of stroke burden are needed to guide public health policies. OBJECTIVE/UNASSIGNED:To present burden estimates of ischemic and hemorrhagic stroke in the US in 2019 and describe trends from 1990 to 2019 by age, sex, and geographic location. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:An in-depth cross-sectional analysis of the 2019 Global Burden of Disease study was conducted. The setting included the time period of 1990 to 2019 in the US. The study encompassed estimates for various types of strokes, including all strokes, ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs). The 2019 Global Burden of Disease results were released on October 20, 2020. EXPOSURES/UNASSIGNED:In this study, no particular exposure was specifically targeted. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary focus of this analysis centered on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100 000 individuals. RESULTS/UNASSIGNED:In 2019, the US recorded 7.09 million prevalent strokes (4.07 million women [57.4%]; 3.02 million men [42.6%]), with 5.87 million being ischemic strokes (82.7%). Prevalence also included 0.66 million ICHs and 0.85 million SAHs. Although the absolute numbers of stroke cases, mortality, and DALYs surged from 1990 to 2019, the age-standardized rates either declined or remained steady. Notably, hemorrhagic strokes manifested a substantial increase, especially in mortality, compared with ischemic strokes (incidence of ischemic stroke increased by 13% [95% uncertainty interval (UI), 14.2%-11.9%]; incidence of ICH increased by 39.8% [95% UI, 38.9%-39.7%]; incidence of SAH increased by 50.9% [95% UI, 49.2%-52.6%]). The downturn in stroke mortality plateaued in the recent decade. There was a discernible heterogeneity in stroke burden trends, with older adults (50-74 years) experiencing a decrease in incidence in coastal areas (decreases up to 3.9% in Vermont), in contrast to an uptick observed in younger demographics (15-49 years) in the South and Midwest US (with increases up to 8.4% in Minnesota). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cross-sectional study, the declining age-standardized stroke rates over the past 3 decades suggest progress in managing stroke-related outcomes. However, the increasing absolute burden of stroke, coupled with a notable rise in hemorrhagic stroke, suggests an evolving and substantial public health challenge in the US. Moreover, the significant disparities in stroke burden trends across different age groups and geographic locations underscore the necessity for region- and demography-specific interventions and policies to effectively mitigate the multifaceted and escalating burden of stroke in the country.

BACKGROUND:associated with exacerbation frequency (objective 2). METHODS:% predicted over 24 months stratified by baseline exacerbation frequency. RESULTS:% predicted was significantly lower at baseline (P < 0.0001) and at 12 (P = 0.0002) and 24 month follow-ups (P < 0.0001). CONCLUSIONS:decline may not differ by baseline exacerbation frequency.

Interfaces in perovskite solar cells (PSCs) play a pivotal role in determining device performance by influencing charge transport and recombination. Understanding the physical processes at these interfaces is essential for achieving high-power conversion efficiency in PSCs. Particularly, the interfaces involving oxide-based transport layers are susceptible to defects like dangling bonds, excess oxygen, or oxygen deficiency. To address this issue, the surface of NiO_x is passivated using octadecylphosphonic acid (ODPA), resulting in improved charge transport across the perovskite hole transport layer (HTL) interface. This surface treatment has led to the development of hysteresis-free devices with an impressive ≈13% increase in power conversion efficiency. Computational studies have explored the halide perovskite architecture of ODPA-treated HTL/Perovskite, aiming to unlock superior photovoltaic performance. The ODPA surface functionalization has demonstrated enhanced device performance, characterized by superior charge exchange capacity. Moreover, higher band-to-band recombination in photoluminescence and electroluminescence indicates presence of lower mid-gap energy states, thereby increasing the effective photogenerated carrier density. These findings are expected to promote the utilization of various phosphonic acid-based self-assembly monolayers for surface passivation of oxide-based transport layers in perovskite solar cells. Ultimately, this research contributes to the realization of efficient halide PSCs by harnessing the favorable architecture of NiO_x interfaces.