Citations

Abstract Background In the current clinical workflow of radiation oncology, therapists manually summarize the physician‐issued Computed Tomography (CT) simulation orders to prepare patients' CT simulations. This process increases the workload, introduces variability in documentation quality, and is prone to human errors. Purpose This study aims to address these challenges using a large language model (LLM) to automate the generation of summaries from the CT simulation orders and evaluate its performance. Methods A total of 607 CT simulation orders were collected from the Aria database at our institution. A locally hosted LLaMa 3.1 405B model, accessed via the Application Programming Interface (API) service, was used to extract keywords from the CT simulation orders and generate summaries. The downloaded CT simulation orders were categorized into seven groups based on treatment modalities and disease sites. For each group, a customized instruction prompt was developed collaboratively with therapists to guide the LLaMa 3.1 405B model in generating summaries. The ground truth for the corresponding summaries was manually derived by carefully reviewing each CT simulation order and subsequently verified by therapists. The accuracy of the LLM‐generated summaries was evaluated by therapists using the ground truth. Results Over 98% of the LLM‐generated summaries aligned with the ground truth in terms of accuracy. Our evaluations showed an improved consistency in format and enhanced readability from the LLM‐generated summaries compared to the corresponding therapist‐generated summaries. This automated approach demonstrated consistent performance across all groups, regardless of treatment modality or disease site. Conclusions This study demonstrated the high precision and consistency of the LLaMa 3.1 405B model in extracting keywords and summarizing CT simulation orders, suggesting that LLMs have great potential to assist in this task, reduce the workload of CT simulation therapists and improve radiation oncology workflow efficiency.

ABSTRACT Purpose The purpose of this study was to evaluate the incidence and risk factors for developing recurrent clinically significant cytomegalovirus infections (csCMVi) in heart transplant recipients. Methods We conducted a retrospective cohort study involving adult heart transplant recipients at three large transplant centers in the United States between January 2011 and March 2019. All patients with a history of csCMVi, defined as CMV disease or CMV infection requiring preemptive therapy, were followed from the date of treatment completion for the primary csCMVi episode. Outcomes of interest were recurrent csCMVi and all‐cause mortality. Results Among 98 heart transplant recipients with csCMVi, 22 (22.4%) episodes of recurrent csCMVi occurred. Median time‐to‐recurrent csCMVi was 31.5 (IQR 21.3–59.8) days following treatment completion. A preceding episode of CMV disease (versus infection) was associated with a lower risk of recurrent csCMVi (HR 0.29, 95% CI 0.08–0.98; p = 0.047). Patients with lymphopenia had higher rates of recurrent csCMVi without statistical significance (HR 2.13, 95% CI 0.88–5.13; p = 0.093). Seroconversion by the end‐of‐therapy among CMV D+/R− mismatched patients was associated with a reduced risk of csCMVi recurrence (HR 0.07, 95% CI 0.02–0.30; p < 0.001). Overall, 17 (17.3%) patients died during follow‐up, which was not significantly higher among those with recurrent csCMVi (HR 2.13, 95% CI 0.78–5.79; p = 0.141). Conclusions About one in five heart recipients with csCMVi developed post‐treatment recurrence. A preceding episode of CMV disease and seroconversion was protective against recurrence. Lymphopenia may be a practical biomarker to stratify recurrence risk. Overall, recurrent csCMVi was not significantly associated with mortality.

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.