Citations

465 Background: Molecular testing is crucial in advancing precision medicine, enabling oncologists to tailor targeted treatment strategies for cancer patients (pts). The National Comprehensive Cancer Network (NCCN) and ASCO guidelines recommend comprehensive biomarker testing for pts with mPC. However, compliance can vary considerably among institutions. This study aimed to assess current practices of molecular testing in diverse healthcare settings across the state of Florida and identify opportunities for improvement to optimize outcomes for pts diagnosed with mPC. Methods: We conducted a detailed 12-question survey, distributed both electronically and in-person to evaluate the molecular testing practices of healthcare providers throughout the state. The survey assessed multiple parameters including adherence to testing, reviewing test results to guide treatment decisions, and the availability of different supportive resources in biomarker testing. This initiative was executed in partnership with the Florida Society of Clinical Oncology and industry partners. Results: A total of 40 responses were collected from 11 institutions in Florida, including 5 academic centers and 6 community-based hospitals. Notably, 22.5% of respondents reported that their institutions either do not fully comply with NCCN guidelines or lack protocols to identify eligible pts and 67.5% stated they are responsible for their own biomarker education and updates. Only 56.4% consistently review molecular testing results during disease progression to guide treatment decisions. Nearly all institutions lack clinical decision support tools in the electronic medical records (EMR) to support testing, and 82.5% receive biomarker results outside the EMR. Additionally, 38.5% lack a standard process for obtaining prior authorization for testing. Furthermore, 38.5% lack a multidisciplinary review process for genetic test results, and 76.3% reported that their biomarker testing process does not involve geneticists or genetic counselors. Conclusions: Our study identified critical gaps in adherence to biomarker testing guidelines with many practices lacking decision support tools across healthcare institutions in Florida. Potential areas for improvement include better standardization of result integration into EMR, targeted educational initiatives, and stronger multidisciplinary collaborations. The implementation of these measures aims to improve the quality of care and outcomes for pts with mPC.

ABSTRACT Light chain multiple myeloma (LCMM) is a subtype of multiple myeloma (MM) characterized by the exclusive production of immunoglobulin light chains and accounts for 15%–20% of newly diagnosed MM. A comprehensive comparison of LCMM with MM producing intact immunoglobulin (non‐LCMM) remains limited. In this retrospective study, we described distinct clinical and cytogenetic features and assessed long‐term outcomes in 852 LCMM patients diagnosed between 01/01/2004 and 12/31/2022, compared with non‐LCMM controls matched for age, sex, and year of diagnosis. On univariable analysis, LCMM patients were more likely to present with elevated creatinine (> 2 mg/dL), beta‐2‐microglobulin ≥ 5.5 mg/L, elevated LDH, hypercalcemia, t(11;14), del(13q), and t(6;14). Conversely, IMS‐IMWG high‐risk disease, hyperdiploidy, t(4;14), and serum albumin < 3.5 g/dL were less common. On multivariable analysis, elevated creatinine (OR: 5.1, 95% CI: 1.2–27, p = 0.04), t(11;14) (OR: 2.6, 95% CI: 1.3–5.2, p = 0.006), and del(13q) (OR: 4.1, 95% CI: 2.1–8.2, p < 0.001) were independently associated with LCMM, while IMS‐IMWG high‐risk disease (OR: 0.3, 95% CI: 0.1–0.8, p = 0.02) and hyperdiploidy (OR: 0.3, 95% CI: 0.1–0.7, p = 0.002) were less frequent. Despite these differences, progression‐free survival with frontline treatment (HR: 0.97, 95% CI: 0.84–1.11, p = 0.63) and overall survival (HR: 0.99, 95% CI: 0.87–1.13, p = 0.94) were similar between LCMM and non‐LCMM patients. This study highlights the distinct clinical and cytogenetic features of LCMM, marked by higher rates of renal failure, t(11;14), and del(13q), lower prevalence of IMS‐IMWG high‐risk disease, and comparable survival outcomes.

This JAMA Insights explores the management of severe refractory asthma, including medications, access to specialists, and managing environmental triggers.

Normothermic machine perfusion (NMP) enables preservation and functional assessment of liver allografts, improving outcomes, particularly in marginal organs. However, the TransMedics Organ Care System (OCS) permits only single hepatic artery (HA) cannulation, limiting its use in grafts with variant arterial anatomy. Arterial reconstruction before NMP may overcome this limitation and expand the pool of grafts eligible for perfusion. We conducted a retrospective single-center cohort study of adult liver transplants utilizing OCS from January 2022 to September 2024. Allografts with variant hepatic artery anatomy requiring arterial reconstruction before NMP initiation were identified. Postoperative outcomes, including vascular and biliary complications, were compared between reconstructed and non-reconstructed grafts. Among 541 OCS-preserved grafts, 74 (13.7%) underwent arterial reconstruction. Compared with non-reconstructed grafts, reconstructed grafts had longer cross-clamp to cannulation time (2.8 vs. 2.4 h, p <0.001), but similar rates of early allograft dysfunction (23.0% vs. 20.8%, p =0.65), ischemic cholangiopathy (4.1% vs. 4.1%, p =1.00), and primary nonfunction (0.0% vs. 0.4%, p =1.00). Early (2.7% vs. 0.2%, p =0.05) and late hepatic artery thrombosis (HAT) (4.1% vs. 2.1%, p =0.40) were infrequent and not significantly different between non-reconstructed and reconstructed groups, respectively. Hepatic artery stenosis occurred more often in reconstructed grafts (12.2% vs. 4.1%, p =0.008), though most cases were managed with interventional radiology or surgical revision. Only one reconstructed graft required retransplantation due to vascular complications. Arterial reconstruction before NMP is safe and feasible, enabling successful perfusion and transplantation of liver allografts with variant HA anatomy. These findings support the broader application of NMP in anatomically complex donor livers.

Abstract Introduction: The disproportionate prostate cancer (CaP) burden, which includes high mortality rates, is significantly attributed to the characteristics of the social determinants of the health status of the Black Male population. Designing targeted interventions to address poor health outcomes through a collaborative population-based approach could reduce CaP health disparities. The Community Living Lab (CoLLab) Learning Health System was developed to address ethnically sensitive, targeted approaches that will eliminate CaP health disparities among Black Men. This study assessed demographic factors and Knowledge on prostate cancer screening attitudes and research participation among black men. Method: The collab project employed a social ecological model to design intervention to address barriers to CaP screening and participation in clinical trials. A validated, pretested questionnaire was used to collect information on demographics, CaP knowledge, attitudes, testing, and a history of participation in research and clinical trials. Baseline data were collected from 3 American Legion posts (ALPs). The association between variables was evaluated using the Chi-square test. Results: Participants between 60-69 years were 28.38%, and those aged 40-49 were 12.16%. Most are US-born Black (89.8%), with others identifying as African-born Black (6.76%) and Caribbean-born Black (1.35%). Approximately 43.24% were retired, and 36.49% were working full-time. CaP knowledge was high in 43.9%, moderate in 46.6%, and low in 9.5%. Only 45% of the participants have undergone Prostate-Specific Antigen test, and 24.6% have had a Digital Rectal Examination. Reported past clinical trials and research participation were very low (9.38%). Participants with higher knowledge levels had higher information scores (p &lt; .0001), favored various research settings (p = 0.0008), had favorable attitudes towards CaP testing (p &lt; .0001), and were more likely to participate in research (p = 0.0117). Work status was found to impact CaP Knowledge (p = 0.0117). Participants with stronger beliefs about prostate cancer may have different attitudes toward testing (p = 0.0444). Age did not impact attitudes toward CaP testing (p = 0.4298). Conclusion: The knowledge of CaP was found to impact the attitudes, testing, and disposition of the participants towards research. The baseline data generated from the clinical study will curate insightful evidence that will create innovative approaches to prostate cancer education among males in Black communities. Citation Format: Opeyemi O. Bolajoko, Quincy A. Wimberly, Daniel W. Lee, Collisa Mahin, Michelle Fudge, Shaina E. Flynn, Arnold J. Merriweather, Trevanne R. Matthews Hew, Monica L. Albertie, Dery Greene, Wayne Ford, Toshiko Moultrie, Floyd B. Willis, Folakemi T. Odedina. Influence of demographic factors and knowledge on prostate cancer screening attitude and research participation among Black men [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C138.

Abstract Objective The objective of this study is to characterize contemporary surgical management practices and factors influencing surgical decision‐making in the management of Lennox–Gastaut Syndrome (LGS) across pediatric epilepsy centers in the United States. Methods A 45‐item cross‐sectional survey was developed and distributed to Pediatric Epilepsy Research Consortium centers. Domains included institutional demographics, surgical evaluation timing and goals, presurgical workup, procedural utilization and outcomes, and barriers to surgery. Descriptive statistics and thematic analysis were performed. Results Thirty‐two pediatric epilepsy centers participated (38% response), the majority comprising pediatric epileptologists at Level 4 National Association of Epilepsy Centers. Most centers (66%) considered surgery after failure of 3–4 antiseizure medications. Presurgical workup typically included brain magnetic resonance imaging (MRI), long‐term electroencephalography (EEG) monitoring, and neuropsychological assessment, while use of functional imaging, magnetoencephalography, and intracranial EEG varied considerably. All centers offered vagus nerve stimulation and corpus callosotomy; 80%–90% offered resection, hemispherectomy, responsive neurostimulation (RNS); 60%–65% offered deep brain stimulation (DBS) and laser ablation. Among centers offering RNS, half targeted thalamic structures exclusively, and the remainder targeted cortical or combined cortical‐thalamic structures; the centromedian nucleus was the preferred thalamic target for RNS and DBS. Surgical decision‐making was influenced by patient characteristics, procedural considerations, and systemic factors. Seizure frequency, family preference, and multidisciplinary input were highly rated across all interventions. Etiology was critical for resection and hemispherectomy, while financial constraints, insurance barriers, and the need for future neuroimaging impacted neuromodulation selection. Scenario‐specific trends included less frequent consideration of DBS and RNS in children under five years, less use of hemispherectomy in older children, preference for corpus callosotomy in children with predominantly drop seizures, and procedural selection based on MRI findings. Significance Substantial variability exists in the surgical management of LGS. These findings highlight critical opportunities to harmonize practices, reduce disparities, and guide comparative effectiveness research to optimize outcomes. Plain Language Summary Lennox–Gastaut Syndrome (LGS) is a severe form of epilepsy that may require surgery when medications are not effective. This study found that surgical care for LGS varies widely across pediatric epilepsy centers in the United States, including when surgery is recommended, how patients are evaluated, and which procedures are available. Newer approaches such as brain stimulation are being used more often, although access remains inconsistent. These findings highlight the need for clearer treatment pathways to ensure that children with LGS have equitable access to the best possible care.

ImportanceStudies suggest that everolimus may reduce the risk of rejection, cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), and cytomegalovirus (CMV) after heart transplant. Everolimus use is controversial because of data demonstrating higher infection deaths when everolimus is introduced de novo after transplant. It is unclear whether everolimus is safe and effective when initiated at 6 months posttransplant in children, a population in which median graft survival is limited to 15 years and randomized clinical trials are lacking.ObjectiveTo evaluate the safety and efficacy of everolimus combined with low-dose tacrolimus to prevent major adverse transplant events (MATEs) in children after heart transplant.Design, Setting, and ParticipantsMulticenter, randomized, open-label, clinical trial enrolling 211 patients who were alive 6 months after pediatric heart transplant at 25 US sites from February 2018 to August 2020. The last date of follow-up was April 17, 2023.InterventionsParticipants were randomized to receive everolimus and low-dose tacrolimus (n = 107) or standard-dose tacrolimus and mycophenolate mofetil (n = 104) for 30 months.Main Outcomes and MeasuresThe primary efficacy end point was the MATE-3 score at 30 months, a validated composite ordinal end point including acute cellular rejection, CAV, and CKD. The primary safety end point was the MATE-6 score, encompassing the MATE-3 score plus antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder.ResultsAmong 211 children randomized, the mean age was 8.2 (SD, 6.3) years, 97 (46%) underwent transplant for congenital heart disease, and 49 (23%) were treated for rejection before 6 months. At 30 months, the mean MATE-3 score did not differ between the 2 treatment groups (mean difference, −0.32; 95% CI, −0.90 to 0.20; P = .16). The mean MATE-6 score was no higher in the everolimus group than in the mycophenolate group (baseline-adjusted mean difference, −0.40; 95% CI, −1.81 to 0.93), meeting the success criterion for safety (noninferiority margin &amp;lt;3). There were no differences in graft survival, MATE-free survival, or freedom from any individual MATE. Everolimus was associated with greater improvement in estimated glomerular filtration rate at 12 months (mean difference, 10.5 mL/min/1.73 m2; 95% CI, 1.09-19.91 mL/min/1.73 m2) and a lower incidence of CMV infection (hazard ratio, 0.50; 95% CI, 0.26-0.93).Conclusions and RelevanceAmong 6-month pediatric heart transplant survivors, everolimus and low-dose tacrolimus did not differ from tacrolimus and mycophenolate in preventing the composite of cellular rejection, CAV, and CKD at 30 months. However, everolimus and low-dose tacrolimus appear to be safe based on the total burden of 6 MATEs and may be associated with improved kidney function and less CMV infection.Trial RegistrationClinicalTrials.gov Identifier: NCT03386539

Abstract Repetitive head impacts are associated with structural brain changes and an increased risk for chronic traumatic encephalopathy, a progressive neurodegenerative disease that can only be diagnosed after death. Chronic traumatic encephalopathy is defined by the abnormal accumulation of phosphorylated tau protein, particularly at the depths of the superior frontal sulci, suggesting that sulcal morphology may serve as a relevant structural biomarker. Contact sport athletes, such as former football players, are at elevated risk due to their prolonged exposure to repetitive head impacts. Cortical atrophy linked to underlying tau accumulation may result in shallower and wider sulci, potentially making sulcal morphology an imaging marker for identifying individuals at risk for this disease. This study investigated sulcal morphological differences in former football players and examined associations with age, football-related exposure, clinical diagnosis of traumatic encephalopathy syndrome, levels of certainty for chronic traumatic encephalopathy pathology, neuropsychological performance, and positron emission tomography imaging using flortaucipir. We analysed structural magnetic resonance imaging data from 169 male former football players (mean age 57.2 (8.2) years, range 45–74) and 54 age-matched, unexposed asymptomatic male controls (mean age 59.4 (8.5) years, range 45–74). Sulcal depth and width were quantified using the CalcSulc, focusing on two regions in each hemisphere commonly affected by chronic traumatic encephalopathy pathology: the superior frontal and occipitotemporal sulci. Generalized least squares models were used to assess group differences and interactions with age and football exposure variables, including age of first exposure, total years played, and cumulative head impact exposure. An analysis of covariance evaluated relationships between sulcal morphology, clinical measures, and flortaucipir uptake, adjusting for age, race, body mass index, education, imaging site, apolipoprotein E4 status, and total intracranial volume. Former football players demonstrated significantly shallower sulcal depth in the left superior frontal sulcus compared to unexposed controls. Earlier age of first exposure and longer football careers were associated with greater widening of the left occipitotemporal sulcus. Higher cumulative head impact exposure was linked to reduced sulcal depth in the left superior frontal region. However, sulcal morphology was not associated with clinical diagnosis, levels of certainty, neuropsychological test performance, or flortaucipir imaging. These findings suggest that sulcal morphology may reflect cumulative exposure to repetitive head impacts, particularly in brain regions vulnerable to chronic traumatic encephalopathy pathology. Future ante- and post-mortem validation studies are needed to determine whether sulcal morphology can serve as a reliable in vivo biomarker of risk.

Abstract The 2022 Supreme Court of the United States' decision in Dobbs v. Jackson Women's Health Organization eliminated federal abortion protections, returning abortion regulation to the states. However, in many states, abortion was already heavily restricted prior to this decision. This study aimed to assess the impact of dynamic restrictive legislation passed from 2020 to 2024 on the prenatal genetic counseling process and to describe similarities and differences between state policy environments by focusing on a group of neighboring states with different legislation. Twenty‐two genetic counselors practicing in Ohio, Kentucky, and Indiana participated in focus groups ( n = 6) and one individual interview. The research team conducted reflexive thematic analysis of qualitative data. We found that participants' perspectives on the effects of legislation varied depending on state abortion policy, patient population served, and institutional resources and directives under which they worked. Most participants expressed changes to the way they document patient visits, approach counseling appointments with patients, and provide patients with resources in lieu of referrals to abortion care. Additionally, many participants expressed feeling more motivation and less burnout in the wake of restrictive legislation—a change from previous study findings. This study provides insights into the ways in which federal case law and state regulations on abortion have impacted genetic counselors' approaches to healthcare practices, documentation, and referrals to abortion care in three states that have experienced dynamic abortion regulatory environments since 2020. Findings may be useful for guiding additional support from professional societies, healthcare institutions, and training programs.