Faculty Bibliography

BACKGROUND:Black men are underrepresented in hypertension trials, even though this population has higher prevalence and more adverse sequelae from hypertension, compared to other groups. In this article we present recruitment and community engagement strategies for the Community-to-Clinic Linkage Implementation Program (CLIP), a cluster-randomized trial on hypertension prevention among Black men. METHODS:Using a 2-stage recruitment process: 1) we enrolled Black-owned barbershops from zip-codes with high hypertension prevalence; and 2) recruited Black male participants who fulfilled the eligibility criteria and were customers of the barbershops. Barbershop and participant recruitment was conducted by a partner community-based organization. RESULTS:The study met the recruitment goals for barbershop enrollment (N=22) and individual participants. Of eligible individuals (N=461), 430 enrolled in the study (93% consent rate, exceeding the original enrollment goal of N=420 participants). Throughout recruitment, the study team conducted 101 unique engagements (41 prior to recruitment, 60 during recruitment), totaling engagement with180 partners across all events, including individual and group meetings, attendance at community events, and educational presentations. In addition to a primary partner community organization, the study team collaborated with a Community Advisory Council, comprised of residents, and civic and community leaders, and with the local health department and varied other organizations. CONCLUSIONS:In CLIP, a high number of academic-community engagement encounters and close collaboration with community partners contributed to successful recruitment of Black men at risk for hypertension and with adverse social determinants. Our experience may serve as to inform investigators focused on recruiting underserved populations in hypertension research trials.

BACKGROUND:Pituitary neuroendocrine tumors (PitNETs) are the most common intracranial neuroendocrine tumors. PitNETs can be challenging to classify, and current recommendations include a large immunohistochemical panel to differentiate among 14 WHO-recognized categories. METHODS:In this study, we analyzed clinical, immunohistochemical and DNA methylation data of 118 PitNETs to develop a clinico-molecular approach to classifying PitNETs and identify epigenetic classes. RESULTS:CNS DNA methylation classifier has an excellent performance in recognizing PitNETs and distinguishing the three lineages when the calibrated score is ≥0.3. Unsupervised DNA methylation analysis separated PitNETs into two major clusters. The first was composed of silent gonadotrophs, which form a biologically distinct group of PitNETs characterized by clinical silencing, weak hormonal expression on immunohistochemistry, and simple copy number profile. The second major cluster was composed of corticotrophs and Pit1 lineage PitNETs, which could be further classified using DNA methylation into distinct subclusters that corresponded to clinically functioning and silent tumors and are consistent with transcription factor expression. Analysis of promoter methylation patterns correlated with lineage for corticotrophs and Pit1 lineage subtypes. However, the gonadotrophic genes did not show a distinct promoter methylation pattern in gonadotroph tumors compared to other lineages. Promoter of the NR5A1 gene, which encodes SF1, was hypermethylated across all PitNETs clinical and molecular subtypes including gonadotrophs with strong SF1 protein expression indicating alternative epigenetic regulation. CONCLUSION/CONCLUSIONS:Our findings suggest that classification of PitNETs may benefit from DNA methylation for clinicopathological stratification.

PURPOSE/OBJECTIVE:Financial toxicity can negatively affect treatment adherence, quality of life, and survival in patients with cancer. Although screening for financial toxicity is increasingly implemented across oncology practices and cancer centers, less is known about challenges in delivering timely interventions after a positive screen. We evaluated outcomes and barriers in a systematic financial toxicity screening and referral program at a large comprehensive cancer center. METHODS:From March 2023 to December 2024, patients in breast, gynecologic, GI, and thoracic oncology clinics at Memorial Sloan Kettering Cancer Center completed an electronic survey assessing health-related social risks and the 12-item Comprehensive Score for Financial Toxicity (COST). A positive screen was defined as COST <16, unmet essential need, or new loan/borrowing for treatment. Patients screening positive and requesting assistance were referred to Patient Financial Services (PFS) for follow-up. Outcomes included proportions with documented outreach, receipt of any intervention, intervention types, and barriers. RESULTS:A total of 83,978 patients were eligible; of whom 50,949 (61%) completed screening. Of 9,724 positive screens, 8,004 (82%) requested follow-up, and 6,987 referrals were placed. PFS attempted follow-up in 3,383 patients (of the 6,987 = 48%), with documented interventions in 1,510 of 3,383 (45%). Counseling on financial resources (983/3,383 = 29%) was most common, followed by insurance-related counseling (402/3,383 = 12%) and formal program referrals (823/3,383 = 24%). Among patients referred to assistance programs, this was most often to the institutional Financial Assistance Program (438/796 = 55%) or social work (318/796 = 40%). The most frequent barrier was the inability to contact patients (1,464/3,383 = 43%). CONCLUSION/CONCLUSIONS:Routine financial toxicity screening was implemented at scale and connected many patients to meaningful financial support. However, 81% of those who screened positive did not receive an intervention, underscoring the need for expanded infrastructure and policy reforms to address financial toxicity in cancer care.

Pathogens infecting humans continue to emerge or reemerge to cause outbreaks and widespread disease. The National Institute of Allergy and Infectious Diseases has funded Vaccine Treatment and Evaluation Units (VTEUs) for more than 50 years. VTEUs perform clinical studies to assess the safety and immunogenicity of candidate vaccines and other interventions to mitigate the impact of emerging and ongoing infectious diseases. Here, we review clinical studies conducted in the VTEUs since 2000 that have addressed emerging pathogens and other infectious agents with pandemic potential or of bioterrorism concern. The studies conducted range from phase 1 to phase 3 clinical trials, and they have included vaccines, therapeutics, and epidemiological studies. The results of the trials have guided national and often international recommendations for treatment and prevention of many of the evaluated pathogens, culminating in coronavirus disease 2019 studies that began within three months of severe acute respiratory syndrome coronavirus 2 identification. The VTEU network continues to be a critical public health resource for addressing emerging pathogens and expediting the development of safe and effective vaccines and treatments to protect at-risk populations.

PURPOSE/OBJECTIVE:The purpose of this study was to evaluate the effect that associated glenohumeral dislocations have on outcomes following surgical treatment of proximal humerus fractures. METHODS:This IRB-approved study reports on 301 patients, who underwent operative treatment for proximal humerus fractures at an academic medical center from January 2006 to January 2023. Fractures were classified according to the Neer system. Patients were separated into two cohorts based on whether a glenohumeral dislocation was present at the time of initial injury. Outcomes measured included the Disabilities of the Arm, Shoulder, and Hand (DASH) score, shoulder range of motion (forward elevation, external rotation, internal rotation), readmission rates, complications, hardware removal, and need for revision surgery. Independent samples t-tests and chi-squared analysis were used for continuous and categorical variables, respectively. A binary logistic regression was performed to analyze the influence of these factors on complication rate. RESULTS:230 patients sustained an isolated fracture (PHF) and 71 sustained a fracture-dislocation (FD). Significant differences were observed between the FD and PHF groups in all measured outcomes. The FD group had a poorer DASH score (24.38 ± 19.09 vs 10.54 ± 13.67; P < 0.001) and reduced range of shoulder motion in forward elevation (114° ± 40° vs 162° ± 19°; P < 0.001), external rotation (40° ± 19° vs 66° ± 19°; P < 0.001), and internal rotation (57° ± 26° vs 82° ± 21°; P < 0.001). Readmission rates were higher in the FD group (0.28 ± 0.85 vs 0.05 ± 0.28; P < 0.001). The FD cohort also had a higher rate of complications (25.35% vs 6.52%; P < 0.001), need for removal of hardware (14.08% vs 3.04%; P = 0.002), and overall revision surgery (11.27% vs 1.30%; P < 0.001). The FD cohort demonstrated a greater incidence of AVN (12.68% vs 4.35%; P = 0.012). No significant difference was observed regarding rates of fracture healing and recurrent dislocation. Multivariate analysis in the form of binary logistic regression indicated that fracture-dislocation significantly increased the complication risk (OR = 3.310, 95% CI = 1.42-7.70; P = 0.005). CONCLUSION/CONCLUSIONS:Proximal humerus fracture-dislocations are associated with worse functional outcomes and higher complication rates compared to those without dislocations. These findings highlight the potential need for specialized treatment strategies to mitigate the impact of dislocation on recovery.

BACKGROUND:The "July Effect" refers to the potential increase in adverse outcomes associated with the annual turnover of medical trainees, though its impact on surgical fields remains uncertain. Additionally, few studies have examined whether the operative day of the week and subsequent flap monitoring during the weekend affect time to reoperation or flap salvage. This study investigated whether academic quarter and operative day influence reoperation rates, flap salvage, or flap failure in microvascular free flap procedures. METHODS:A retrospective review was conducted on 769 free flaps performed between June 2011 and November 2023. Multivariate analyses adjusted for patient demographics, comorbidities, flap type, and recipient region. Flaps were categorized by academic quarter and operative day, excluding weekends due to limited sample size. Primary outcomes included reoperation rates for vascular compromise, time to reoperation, and flap salvage. RESULTS:No significant differences in reoperation rates for vascular compromise were observed across academic quarters. While procedure duration trended longer in the first three quarters compared to the fourth, these differences were not statistically significant. Additionally, operative day did not impact reoperation rates, flap salvage, or time to reoperation. Flaps were predominantly indicated for head and neck reconstruction (74.4%) and had an overall flap loss rate of 3.0%. CONCLUSION/CONCLUSIONS:We found no evidence of a "July Effect" in microvascular surgery or that operative day affects free flap outcomes. Institutional factors, such as structured flap monitoring, attending oversight, and advanced practice provider support, likely mitigate risks associated with trainee turnover and shift-based staffing fluctuations.

Labetalol and nifedipine are first-line antihypertensives for hypertensive disorders of pregnancy. However, there is limited research comparing their effectiveness based on hemodynamic profiles seen in preeclampsia, such as high cardiac output (CO) and high systemic vascular resistance (SVR). This study assesses whether concordance of antihypertensive treatment with the hemodynamic status on echocardiogram reduces time to achieve target postpartum blood pressure (BP) before discharge.This retrospective cohort study included patients with preeclampsia with severe features who received a postpartum echocardiography, excluding patients with cardiac etiology. Antihypertensive choices were provider-dependent. The CO and SVR were calculated retrospectively from the echocardiogram in collaboration with cardiology. Concordance was defined as patients with high CO (>6 L/min) started on labetalol and high SVR (>1,200 dynes·sec·cm⁵) started on nifedipine; opposite pairings were discordant. The primary outcome was time to achieve target BP, defined as the period from the start of antihypertensive therapy to when no titration was needed to sustain BPs of less than 140/90 mm Hg. Chi-square and Fisher's tests were used for categorical variables, and Mann-Whitney U test for continuous variables.Of 298 patients, 155 (52%) received concordant therapy and 143 (48%) discordant. Of the cohort, 229 (76.8%) had high SVR and 69 (23.2%) had high CO. Median time to target BP was not significantly different (concordant: 32 hours [interquartile range, IQR: 0-61], discordant: 41 hours [IQR: 4-75], p = 0.13). The concordant group needed fewer titrations to achieve target BP (1 [IQR: 0-2] vs. 2 [IQR: 1-3]; p = 0.008) and were less likely to be discharged home on multiple antihypertensive medications compared with the discordant group (28.9 vs. 42.7%, p = 0.014). Maternal demographics were similar between groups.While time to target BP did not differ, concordance of antihypertensive therapy to postpartum hemodynamics in patients with severe preeclampsia reduced medication adjustments and increased the likelihood of discharge on a single-agent regimen. · Echocardiography can be used to assess maternal hemodynamics.. · Aligning BP meds to hemodynamics cuts the need for a second agent.. · Aligning BP meds to hemodynamics reduces dose adjustments..

BACKGROUND:Porcine genome editing has revolutionized xenotransplantation, recently enabling the first pig-to-human heart xenotransplants. However, the xeno-immune response in heart xenografts remains largely unexplored. This study aimed to precisely characterize the xeno-immune response and injury in two heart xenografts, transplanted from 10-gene-edited pigs into brain-dead human recipients. METHODS:We analyzed xenograft biopsies at 66-hour post-reperfusion using a multimodal phenotyping approach combining: morphological evaluation, immunophenotyping, ultrastructural assessment, automated quantification of multiplex immunofluorescence staining and gene expression profiling. Xenografts before implantation and wild-type pig hearts with and without ischemia reperfusion injury and brain death were used as controls. RESULTS:Both xenografts showed evidence of endothelial activation and mild microvascular inflammation without capillary C4d deposition. Immune infiltrates were mainly composed of CD15+ and CD68+ innate immune cells. Ultrastructural assessment showed endothelial swelling with occasional intravascular leucocytes. Deep-learning based automated multiplex immunofluorescence analysis confirmed that microvascular inflammation was primarily associated with CD15+ and CD68+ innate immune cells. Both xenografts showed increased expression of genes and pathways associated with monocyte/macrophage activation, neutrophil activation, interferon-gamma response, natural killer cell burden, endothelial activation, apoptosis and injury repair. This phenotype was absent in all control pig hearts, independently from ischemia reperfusion injury and brain death. CONCLUSIONS:Multimodal phenotyping of pig-to-human heart xenografts revealed early signs of xeno-immune response, characterized by mild innate microvascular inflammation, endothelial activation, and molecular signature characteristic of antibody-mediated rejection. Developing such precision diagnostic system could improve graft monitoring in future clinical settings.

Transformed follicular lymphoma (tFL) is typically associated with chemotherapy resistance and a poor prognosis. There are limited data regarding outcomes after CD19-directed chimeric antigen receptor T-cell (CAR T) therapy in relapsed/refractory (R/R) tFL. A total of 923 adult patients with R/R tFL who received commercial CD19 CAR T therapy between 2017 and 2023 were identified in the Center for International Blood and Marrow Transplant Research registry. Median age was 64 years (range: 30-86) and median prior lines of therapy was 4 (range: 1-18). Most patients (78%) received axicabtagene ciloleucel, with 67% of patients having resistant disease at the time of CAR T infusion. At a median follow-up of 25 months (range: 1-72) from CAR T infusion, the 2-year overall survival (OS) was 57% (95% CI: 53-60) and progression-free survival (PFS) was 43% (95% CI: 40-47). The 2-year cumulative incidences of relapse or progression (rel/prog) and non-relapse mortality (NRM) were 47% (95% CI: 44-51) and 9% (95% CI: 7-11), respectively. The overall response rate to CAR T was 76%, with a complete response rate of 63%. Grade ≥ 3 cytokine release syndrome (CRS) was observed in 7.1% and grade ≥ 3 immune effector cell-associated neurologic syndrome (ICANS) in 21.6% of patients. Multivariable analysis suggested that resistant disease status at the time of CAR T, use of bridging therapy, and high comorbidity index ≥ 3 were associated with inferior PFS and OS. Older age ≥ 60 significantly increased the risk of NRM. Our study suggests that CD19 CAR T is effective and safe for tFL.