Citations

The author feels himself to be an anomaly—both a full professor at age 38 at a nationally ranked medical center and a Black man from Baltimore with dreadlocks. He considered leaving academic medicine given the political changes occurring in the United States. The National Institutes of Health are terminating funded grants focused on health equity, and the Centers for Disease Control and Prevention are rolling back effective public health strategies specifically designed to mitigate health disparities. His main impetus for entering academic medicine—advancing health equity—as well as his identity as a Black male is being threatened. He is running out of positive coping mechanisms to counter these threats to remain in academic medicine. Addressing these challenges will require intentional efforts from faculty implementing health equity interventions, academic centers taking a stance, and foundations financially supporting health disparities research and interventions now abandoned by federal agencies.

Background: Progressive heart failure cardiogenic shock (HFCS) often requires escalation to temporary or durable mechanical circulatory support (MCS) as a bridge to transplant (BTT). Following the 2018 UNOS allocation changes, our center revised its BTT strategy to optimize support and shorten wait times. At our institution, the Impella 5.5 with SmartAssist via the axillary approach was selectively used for patients who remained refractory to guideline-directed medical therapy, failed single-inotrope therapy, and were not considered suitable durable LVAD candidates by our multidisciplinary heart team. We compared transplant-related outcomes of BTT patients supported with Impella 5.5 versus durable LVAD. Methods: We performed a single-center retrospective review of all heart and heart/kidney transplant candidates at Mayo Clinic Florida from October 2018 to February 2021. INTERMACS profile, baseline characteristics, and perioperative data were collected at the time of device implantation and throughout the transplant hospitalization. Results: A total of 87 heart and 4 heart–kidney transplants were completed. Forty-five patients (49%) required MCS as BTT: 27 (60%) with a durable LVAD and 18 (40%) with an Impella 5.5. All eighteen patients with Impella 5.5 as BTT (100%) were transplanted compared to nineteen patients with durable LVAD (70%), p = 0.001. The median time from listing to transplant was substantially shorter with Impella (32 vs. 696 days, p < 0.001), and this difference persisted across INTERMACS profiles. UNOS status at transplant was more urgent for Impella than LVAD (p < 0.001). Transplant surgery following Impella support required shorter cardiopulmonary bypass time (181 vs. 219 min, p < 0.001) and resulted in lower postoperative vasoactive-inotropic requirements (7.9 vs. 13, p = 0.003). No patients in the Impella group died or were delisted while awaiting transplant, whereas 5 LVAD patients (26%) died or were removed due to LVAD complications (p < 0.001). Conclusions: Our data demonstrates that the use of the Impella 5.5 as BTT was associated with significantly shorter waitlist time, higher transplantation rates, reduced perioperative morbidity, and lower postoperative vasoactive support compared with durable LVAD as BTT. These benefits were achieved despite a higher severity of illness at transplantation in the Impella cohort.

Background: Total wrist arthrodesis is a well-established procedure providing pain relief and stability for patients with symptomatic radiocarpal arthritis refractory to nonoperative measures. Little research exists on reimbursement and utilization trends for this procedure. This study aimed to characterize Medicare reimbursement trends for total wrist arthrodesis, along with trends in Medicare utilization and comparison with Medicaid reimbursement. Methods: Medicare reimbursement for Current Procedural Terminology codes 25800, 25805, and 25810 were collected from the Centers for Medicare & Medicaid Services (CMS) Physician Fee Schedule from 2000 to 2025. Rates were inflation-adjusted to 2025 dollars, and percentage changes were calculated. Medicare utilization trends from 2000 to 2022 were analyzed using CMS Part B data. Most recent Medicaid reimbursement was collected from online state fee schedules and compared with 2025 Medicare rates, with additional analyses of variability and adjustment for work Relative Value Units. Results: Inflation-adjusted Medicare reimbursement for total wrist arthrodesis decreased by 49.1% from 2000 to 2025 ( P < .0001), averaging a 1.96% annual decline. Utilization trends remained stable, with wrist arthrodesis with iliac or other autograft (CPT 25810) being the most commonly billed procedure. Medicaid reimbursed 13.6% less than Medicare on average, with substantial state variability, ranging from 44.7% (New Hampshire) to 135.4% (Alaska) of Medicare reimbursement. Conclusion: Reimbursement for total wrist arthrodesis has declined significantly despite stable utilization in the Medicare population. Medicaid reimbursement is consistently lower and highly variable by state, potentially impacting access to care. Given the effectiveness of wrist arthrodesis, policymakers should advocate for equitable reimbursement for this procedure.

Background Immune checkpoint therapies targeting programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) have been met with limited clinical responses in the treatment of patients of varying cancer types. Current US Food and Drug Administration (FDA)-approved therapies function to prevent PD-1 binding to PD-L1, thereby preventing T-cell suppression. However, these therapies fail to prevent PD-L1 intrinsic signaling and recycling, which can render these treatments ineffective. Moreover, most research primarily focuses on how these antibodies affect tumor cells and their interactions with T cells. Myeloid cells, which also express PD-L1 and influence T-cell responses, are integral to the efficacy of these therapies. However, strategies that can target these cells to boost antitumor responses have not been effective. Methods Our group has developed a new anti-PD-L1 antibody (H1A), which disrupts PD-L1 recycling and redirects it towards degradation. Due to the loss of available PD-L1 protein, H1A effectively prevents PD-L1 intrinsic signaling. Using in vivo humanized PD-1/PD-L1 mouse tumor models, we evaluated the therapeutic efficacy of H1A against current FDA-approved PD-L1 blocking antibodies. Using human-derived immune cell in vitro assays, we pinpoint the biological consequences of H1A-induced PD-L1 degradation in myeloid cells. Results H1A demonstrated improved tumor control and established immunological memory responses in vivo in the treatment of tumors with moderate immunogenicity that are less responsive to current immunotherapies. This was supported by enhanced activation of myeloid cells (major histocompatibility complex (MHC)-II and CD80) and frequencies of effector T-cell populations found intratumorally. Human myeloid cells treated with H1A were also observed to have increased activation (MHC-II and CD80) and cytokine secretion. Similar to our in vivo findings, human peripheral blood lymphocyte cultures demonstrated increased frequencies of effector T-cell populations and greater tumor cell killing. Conclusions This work highlights the importance of targeting PD-L1 recycling and intrinsic signaling, specifically in myeloid cells, to boost antitumor responses. Our studies suggest that H1A can provide a solution to the lack of responses seen with current therapeutics, while also revealing previously unknown intrinsic functions of PD-L1 in myeloid cells.

Background Immune-related adverse events (irAEs) remain largely unpredictable, potentially affecting multiple organ systems and occurring at almost any point during and even occasionally after immune checkpoint inhibitor (ICI) treatment. To identify populations at risk for these immune-mediated toxicities, we analyzed genetic characteristics and immune markers associated with clinically significant irAEs. Methods We carried out a genome-wide association study on 373 white patients receiving ICI treatment. We identified single nucleotide polymorphisms associated with irAEs. Blood cytokine profiling and peripheral blood mononuclear cell RNA sequencing were performed at pretreatment baseline and 6–8 weeks after ICI initiation. Findings were validated in two external cohorts. Results We identified genetic haplotypes in VWA8 (Von Willebrand Factor A Domain Containing 8) , OSBPL6 (Oxysterol Binding Protein Like 6), and ADAMTS9-AS2 (ADAM Metallopeptidase With Thrombospondin Type 1 Motif 9 Antisense RNA 2) associated with grade ≥2 irAEs. Patients carrying risk haplotypes for one or more genes exhibited significantly greater rates of grade ≥2 (OR 3.02; 95% CI 1.83 to 5.02; p<0.001), grade ≥3 (OR 3.59; 95% CI 1.93 to 6.64; p<0.001), and multiple type irAE (OR 2.60; 95% CI 1.53 to 4.39; p<0.001). Serum CCL3 levels were significantly elevated in individuals carrying risk haplotypes (p=0.03). Gene expression analysis demonstrated activated autoimmune and inflammatory pathways in the genetic risk group. Conclusions Novel polymorphisms in VWA8, OSBPL6, and ADAMTS9-AS2 may impact immune pathways, promote inflammation, potentiate autoimmune phenotypes, and convey risk of irAE in ICI-treated patients.

Treatment-induced ovarian function loss is a significant concern for many young patients with breast cancer. Accurately predicting this risk is crucial for counselling young patients and informing their fertility-related decision-making. However, current risk prediction models for treatment-related ovarian function loss have limitations. To provide a broader representation of patient cohorts and improve feature selection, we combined retrospective data from six datasets within the FoRECAsT (Infertility after Cancer Predictor) databank, including 2679 pre-menopausal women diagnosed with breast cancer. This combined dataset presented notable missingness, prompting us to employ cross imputation using the k-nearest neighbours (KNN) machine learning (ML) algorithm. Employing Lasso regression, we developed an ML model to forecast the risk of treatment-related amenorrhea as a surrogate marker of ovarian function loss at 12 months after starting chemotherapy. Our model identified 20 variables significantly associated with risk of developing amenorrhea. Internal validation resulted in an area under the receiver operating characteristic curve (AUC) of 0.820 (95% CI: 0.817–0.823), while external validation with another dataset demonstrated an AUC of 0.743 (95% CI: 0.666–0.818). A cutoff of 0.20 was chosen to achieve higher sensitivity in validation, as false negatives—patients incorrectly classified as likely to regain menses—could miss timely opportunities for fertility preservation if desired. At this threshold, internal validation yielded sensitivity and precision rates of 91.3% and 61.7%, respectively, while external validation showed 92.9% and 60.0%. Leveraging ML methodologies, we not only devised a model for personalised risk prediction of amenorrhea, demonstrating substantial enhancements over existing models but also showcased a robust framework for maximally harnessing available data sources.

Abstract Introduction: While evaluation approaches for community-academic research groups are established, few tools exist for academic institutional advisory groups across multi-core centers and research, education, and clinical care missions. Institutional advisory group evaluation should consider group processes and their impact on community-centered outcomes. This study describes the community-engaged development of a mixed-method evaluation approach to address this gap and presents pilot outcomes across an NIH-funded center. Methods: We utilized a Community of Practice model to co-develop a survey with 14 community and academic representatives of four advisory groups. The final survey included five categories of group process and four categories of outcomes. Storytelling sessions with community partners explored areas where the survey identified discrepancies in perspectives between community and academic team members, as well as areas with lower scores. Results: Nine community and 14 academic (staff and faculty) partners completed the survey. Respondents positively assessed group process outcomes (shared values, leadership, community-centeredness, and decision-making), and slightly less positive assessments of institutional outcomes. Storytelling sessions confirmed the overall satisfaction of community partners but highlighted actionable concerns within power-sharing, decision-making, funding equity, and trust-building. Conclusions: The results of this equity-centered evaluation suggest the utility and importance of participatory, mixed-methods approaches to evaluating community-academic institutional advisory groups.

ABSTRACT Objectives This portion of the Geriatric Emergency Department (GED) Guidelines 2.0 focuses on delirium in the emergency department (ED). Methods A multidisciplinary group applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and develop recommendations related to older ED patients with possible delirium. Results The GED Guidelines 2.0 Delirium Work Group derived six evidence‐based recommendations for risk stratification, diagnosis, and brain imaging. To reduce universal screening, the Delirium Risk Score may be used to identify older adults at low risk for delirium, though the evidence certainty is very low. In adults over 65 admitted to ED observation units, Zucchelli's risk assessment tool (threshold ≥ 4) may stratify delirium risk, also with very low certainty. For adults over 75, the REDEEM Score may be used to identify low‐ or high‐risk individuals, again with very low certainty. For diagnosis, 4AT, bCAM, CAM‐ICU, mCAM, AMT‐4, or RASS may be used to rule delirium in or out, based on very low certainty. The Delirium Triage Screen (DTS) may be used to rule out, but not to rule in, delirium, also with very low certainty. For diagnostic imaging, there is very low certainty of evidence to recommend for or against obtaining a head CT as part of the evaluation for older ED patients with delirium. All recommendations are conditional, reflecting very low certainty of evidence due to the lack of high‐quality ED‐based studies and comparative effectiveness research. Conclusion Rigorous ED‐based research is needed to strengthen evidence and guide delirium care for older adults in geriatric emergency medicine.