Citations

Abstract Purpose Bevacizumab is an effective treatment for radiation necrosis; dose dependent radiographic and edema response data are lacking. Methods Multicenter, retrospective cohort study of adult patients with primary central nervous system tumors or brain metastases who received bevacizumab for radiation necrosis between June 2021 and July 2024. Patients were grouped by bevacizumab dose (7.5 mg/kg vs 10 mg/kg administered every three weeks). Primary outcome was edema response, assessed by a blinded neuro-oncologist. Secondary outcomes included contrast enhancing disease response, clinical response, adverse events, treatment discontinuation, and re-dosing for recurrent radiation necrosis. Analyses were performed with and without adjustment for tumor type. Results 104 patients were included (7.5 mg/kg, n = 53; 10 mg/kg, n = 51). Edema response differed between dosing groups in unadjusted analyses (p = 0.032), favoring the 7.5 mg/kg cohort; however, this association was attenuated after adjustment for tumor type. Contrast enhancing disease response did not differ between groups in either unadjusted or adjusted analyses (p = 0.43). Clinical response was higher in the 7.5 mg/kg group (65.2% vs 37.8%, p = 0.013). Tumor type differed significantly between cohorts (p < 0.001), with more primary CNS tumors in the 10 mg/kg group. Rates of adverse events, treatment discontinuation, and re-dosing were similar. Conclusions While lower-dose bevacizumab was associated with greater edema reduction in unadjusted analyses, this effect was attenuated after accounting for tumor type. Importantly, 7.5 mg/kg dosing appeared sufficient for achieving edema control and contrast enhancing disease response. These findings support an individualized approach to bevacizumab dosing in radiation necrosis and highlight the need for prospective, tumor-stratified studies.

ABSTRACT Background Few studies have examined pretransplant CD4 count and risk of post‐kidney transplant (KT) infection in persons with HIV (PWH). Methods This multi‐center, retrospective cohort study included adult PWH undergoing KT from 2004 to 2019. The primary outcome was infection in the first year post‐KT in PWH with pretransplant CD4 < 350 cells/µL versus CD4 ≥ 350 cells/µL. Relative risk was assessed using modified Poisson modeling. Restricted mean survival time analysis was used to assess 5‐year posttransplant outcomes. Results Of the 75 patients included, 27% had a pretransplant CD4 < 350 cells/µL. Those with CD4 < 350 versus CD4 ≥ 350 were more likely to be hospitalized for infection in the first year (55% versus 16%, p = 0.001). There were no significant differences in relative risk of infection in the first‐year posttransplant (RR: 1.31, p = 0.053), 5‐year overall survival (87.5% vs. 93%, p = 0.49) or 5‐year graft loss (29.4% vs. 23.1%, p = 0.61) betweengroups. Conclusion These findings suggest that pretransplant CD4 count alone may not reflect the true risk of post‐KT infection in PWH.

Abstract Background Bevacizumab is a treatment for radiation necrosis; the optimal dosing remains inadequately studied. Methods Retrospective review of adult patients with primary central nervous system (CNS) tumors or brain metastasis treated with bevacizumab for radiation necrosis from 6/29/2021 to 7/31/2024. Primary outcome was to compare edema response with two different bevacizumab doses: 7.5 mg/kg and 10 mg/kg. Edema response was classified according to the following groups: (1) increase of edema, &gt;105% of baseline; (2) constant edema, 75%-105% of baseline; (3) slight decrease of edema, 25%-75% of baseline; (4) large decrease of edema, &lt;25% of baseline. Results 104 patients were evaluated (median age 59 years, 56% male); 53 patients in the 7.5 mg/kg group and 51 patients in the 10 mg/kg group. Tumor type varied significantly across dosing groups (p &lt; 0.001). In the 7.5 mg/kg group, tumor type was primary CNS (n = 23, 43%), lung (n = 14, 26%), breast (n = 8, 15%), melanoma (n = 4, 8%) and other (n = 4, 8%). In the 10 mg/kg group, tumor type was primary CNS (n = 43, 84%), lung (n = 2, 4%), melanoma (n = 2, 4%) and other (n = 4, 8%). Median number of bevacizumab doses administered was 4. There was a statistically significant difference in distribution of edema response across all response levels favoring bevacizumab 10 mg/kg (p = 0.032). When edema response was dichotomized (large decrease vs other), the difference remained statistically significant (p = 0.015). Conclusion Bevacizumab 10 mg/kg was more efficacious in terms of edema response; this result is impacted by the significantly higher incidence of primary CNS tumors in the 10 mg/kg dosing group.

Importance Primary hyperparathyroidism (PHPT) is common and contributes to skeletal and kidney end-organ damage. Although parathyroidectomy can mitigate these complications, many patients are managed with observation, and real-world data on the population-based frequency and timing of end-organ damage under usual care are limited. Objective To evaluate the frequency and timing of end-organ damage associated with PHPT. Design, Setting, and Participants This cohort study included a population-based cohort identified from national electronic health record (EHR) and claims data (2010-2023) with follow-up through 2023. Participants were adults with a new biochemical diagnosis of PHPT. Data analysis was performed from August 2025 to April 2026. Exposure A new biochemical diagnosis of PHPT was defined as an elevated PTH (&amp;gt;65 pg/mL) within 1 month after a second elevated calcium level (serum calcium &amp;gt;10.2 mg/dL or ionized calcium &amp;gt;1.3 mmol/L or &amp;gt;5.3 mg/dL). Main Outcomes and Measures PHPT-associated end-organ damage (osteoporosis, atraumatic fractures, kidney stones, stage 3 or worse chronic kidney disease) at or after PHPT diagnosis using EHR or claim codes and laboratory data, in addition to the frequency and timing of parathyroidectomy. Results A total of 43 399 patients with PHPT were identified (mean [SD] age, 67.9 [12.5] years; 33 854 [78%] female and 9545 [22%] male), of whom 22 279 (51.3%) had end-organ damage at diagnosis. Among 21 120 patients without end-organ damage at diagnosis, 6762 (32.0%) progressed to end-organ damage after a median (IQR) 516 (166-1125) days. Only 4442 patients (19.9%) with end-organ damage at diagnosis were treated with parathyroidectomy. Among those who progressed to end-organ damage, 1348 (19.9%) underwent subsequent parathyroidectomy, which occurred a median (IQR) 154 (41-439) days later. Conclusions and Relevance In this national cohort of adults with a biochemical diagnosis of PHPT, 67% had PHPT-associated end-organ damage at diagnosis or on follow-up. Despite this, parathyroidectomy was uncommon. These findings may inform strategies to optimize utilization of parathyroidectomy and mitigate PHPT-associated morbidity.

Background: Shared Decision Making in palliative care encompassing patient-clinician collaboration has shown potential for improved patient outcomes. However, the impact of decision aids intended to support palliative care decision making discussions across clinical care settings remains uncertain. Aim: To assess the impact of shared of decision aids on decision making, clinical outcomes, and quality of life for patients with palliative care needs and their caregivers. Design: Systematic review and meta-analysis of randomized controlled trials, reported according to PRISMA, with overall evidence quality assessed using GRADE. Data sources: Ovid MEDLINE (all segments), EMBASE, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, and Scopus, from inception through September 20, 2024, without restrictions on publication date, sample size, or language. Eligible studies were randomized controlled trials that included adult patients with palliative care needs or their caregivers, using any form of decision aids. Outcomes encompassed decision-related, clinical, and quality of life measures. Results: Sixteen randomized controlled trials were included. Participant ages ranged from 44 to 85 years. Predominant decision aids were videos or printed materials addressing goals of care and treatment options, with aims that included improving understanding of prognosis and supporting values clarification. Decision aids significantly improved decision-related knowledge (SMD: 0.40, 95% CI: 0.14–0.67, p = 0.003) and lowered preference for cardiopulmonary resuscitation (OR: 0.28, 95% CI: 0.20–0.40, p < 0.001). They showed no significant impact on decisional conflict, satisfaction, or regret. Conclusion: Evidence regarding the effectiveness of decision aids in palliative care decision making is limited and of low overall quality, with observed improvements primarily in patient knowledge and changes in stated treatment preferences rather than established improvements in decision quality or values-concordant care. Future research should prioritize integration into comprehensive shared decision making frameworks, cultural adaptations, and larger-scale studies to enhance patient-centered outcomes.

Abstract Black/African American populations, globally, bear the greatest prostate cancer (CaP) burden compared to other racial/ethnic groups. Addressing CaP disparities in Black men is complex, requiring a patient-centered, community-centric and comprehensive approach. This study integrates iCCaRE Consortium findings and broader literature to address unmet needs in survivorship care. The iCCaRE Consortium implemented five complementary pilot studies using mixed-methods designs, including feasibility trials, qualitative research, and observational analyses across the United States and sub-Saharan Africa. Descriptive statistics, subgroup analyses, and qualitative thematic analyses were performed across these studies. Collectively, projects addressed multilevel determinants including social, behavioral, and biological drivers of disparities. Project 1 implemented a Virtual Reality Assistant (ViRA) across clinical and community settings, with ongoing evaluation in pragmatic trials. Project 2 showed strong patient preference for home-based cancer care. Project 3 enrolled demonstrated trends toward improved health-related quality of life. Project 4 identified key themes influencing survivorship experiences. Project 5 identified biological mechanisms linking stress, immune modulation, and symptom burden. The iCCaRE pilot projects demonstrate the feasibility and early impact of a consortium-based, transdisciplinary approach to addressing CaP disparities in Black men. These findings highlight the importance of integrating patient-centered interventions, community engagement, and biological insights to inform scalable strategies aimed at improving survivorship outcomes and advancing health equity. The iCCaRE Consortium demonstrates that a transatlantic, patient-centered, and multidisciplinary approach integrating social, clinical, and biological factors can generate scalable strategies to improve survivorship outcomes and advance equity in CaP care for Black men.

Background The management of osteochondral lesions of the talus (OLT) is challenging, with 2 main options being conservative and surgical management. Orthobiologic therapies come to bridge the gap between these 2 options; however, inconsistencies in indication, composition, and heterogeneous evidence limit clinical decision-making. To address these challenges, 3 International Congress Meetings on Cartilage Repair of the Ankle were convened in Pittsburgh, USA (2017), Dublin, Ireland (2019), and New York, USA (2025) to establish agreement on the role of conservative management and injectable orthobiologic strategies in the treatment of OLT. Methods Seventy-five multidisciplinary experts from over 25 countries and 1 territory participated in a structured Delphi-based consensus process. Blinded surveys, structured questionnaires, and in-person discussions were used to develop and refine statements, supported by literature review and graded evidence (A1–E). Consensus strength was defined as consensus (51%-74%), strong consensus (75%-99%), or unanimous (100%) Results In total, 29 consensus statements were achieved across the 3 meetings. Strong agreement was reached regarding indications and expected outcomes of conservative management, including the role of immobilization and appropriate timing for surgical intervention. Orthobiologic injections, including platelet-rich plasma, concentrated bone marrow aspirate, and hyaluronic acid, were considered appropriate in select patients with persistent symptoms, although no superiority was demonstrated among formulations, preparation methods, or injection strategies. When used as adjuncts to surgical procedures, orthobiologics may improve radiological outcomes, with limited evidence for improvement in clinical outcomes. Technical considerations, including preferred harvest sites and a lack of standardized preparation protocols, were identified, along with key principles for patient counseling Conclusion These international consensus statements establish a standardized framework for the conservative management and use of injectable orthobiologic therapies in OLT. By clarifying indications, technical considerations, and current limitations, this work aims to improve consistency in clinical practice, guide treatment decision-making, and inform future research.

At a time when there was no unifying hypothesis and no broadly effective treatments for heart failure with a preserved ejection fraction (HFpEF), it was proposed that HFpEF represented a multitude of different disorders. Accordingly, characterization of phenotypic heterogeneity was envisioned as a means of identifying novel causal pathways that could lead to new treatments while simultaneously discerning patients who would selectively benefit from a specific therapy. However, efforts over the past decade to characterize phenotypic diversity in diverse and complex ways have not achieved these goals. Subgroup analyses of neutral HFpEF trials have failed to reliably identify responders to treatments. Neither proteomics nor unsupervised cluster analysis across multiple phenotypic domains has yielded reproducible results (even in the same dataset), elucidated novel mechanistic pathways for new drug development, or identified patients most likely to benefit from treatment. In marked contrast to these efforts to characterize phenotypic heterogeneity, large-scale trials in HFpEF enrolled patients using broad eligibility criteria, and they established the benefits of sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists without evidence for subgroup effects. However, it is noteworthy that patients enrolled in recent large-scale HFpEF trials were characterized by general uniformity with respect to the presence of excess adiposity, with central obesity being a feature of the vast majority of enrolled participants. Of note, patients with obesity showed particularly large benefits when treated with effective drugs for HFpEF. These observations raise the possibility that, if these trials had permitted the participation of patients with class III obesity or with lower natriuretic peptide levels, the magnitude of the observed treatment effects might have been greater than originally reported. These findings are consistent with a central role for visceral adiposity (and the secretion of an altered suite of adipokines) in the pathogenesis of HFpEF. Therefore, because the field of HFpEF has a unifying hypothesis (applicable to the large majority of patients), enrolled a broad population of patients in large-scale trials without subgroup interactions, and has several broadly applicable effective treatments (as is true for heart failure with a reduced ejection fraction), the motivation to characterize phenotypic heterogeneity in HFpEF in complex ways may no longer be supported or needed.

Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTL) analyses in six tissues and cell types, including whole blood ( n = 6454) and lung ( n = 1291). We detected tens of thousands of secondary cis-e/sQTLs, showing that secondary cis-e/sQTL discovery remains unsaturated. We fine-mapped UK Biobank–derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs. Our results suggest that even larger e/sQTL analyses will uncover additional secondary e/sQTLs, further benefiting GWAS interpretation.