Citations

ACCESS is a prospective, multicenter phase II trial evaluating peripheral blood stem cell (PBSC) transplantation using 4-7/8 HLA-mismatched unrelated donors (MMUD) with post-transplant cyclophosphamide (PTCy), tacrolimus, and mycophenolate. Adults undergoing first HCT with myeloablative (MAC) or reduced-intensity/nonmyeloablative (RIC/NMA) conditioning were enrolled, with donors aged 18-35 years and matched at 4/8-7/8 HLA loci by high-resolution typing. This expanded analysis includes all enrolled adult PBSC recipients, including the protocol-specified RIC/NMA cohort expansion, to improve precision of outcome estimates and provide descriptive analyses by HLA match level. Among 268 adults, 183 received 7/8 and 85 received <7/8 MMUD grafts; 82.4% of the <7/8 cohort received 6/8 grafts. Median follow-up among survivors was 11.9 months. At 1-year, overall survival was 78.6% (95% CI, 71.9-83.9) in the 7/8 cohort and 85.6% (95% CI, 76.0-91.5) in the <7/8 cohort. One-year relapse, non-relapse mortality, and GVHD-free relapse-free survival were 17.1%, 13.7%, and 51.1% versus 22.8%, 8.4%, and 54.6%, respectively. The cumulative incidence of grade II-IV and grade III-IV acute GVHD by day 100 was 36.6% and 7.7% in the 7/8 cohort versus 28.3% and 5.9% in the <7/8 cohort. Moderate-to-severe chronic GVHD at 1 year was 11.3% versus 7.7%, respectively. Among adult ACCESS recipients treated on a uniform young-donor PBSC/PTCy platform, short-term outcomes with predominantly 6/8 MMUD transplantation were encouraging. Because donor match level was not prospectively assigned and between-group comparisons were exploratory, these findings are descriptive and should not be interpreted as establishing equivalence with 7/8 MMUD transplantation. (Registered as NCT04904588 at CT.gov)

ABSTRACT Background Radiotherapy is a cornerstone of treatment for pediatric central nervous system (CNS) tumors, but dose selection remains uniform despite interpatient variability in tumor radiosensitivity. This is consequential in children, for whom toxicity can have lifelong effects. Genomic-adjusted radiation dose (GARD) integrates tumor genomics with delivered radiation dose to quantify the biological effect of radiotherapy and has been validated across adult malignancies. Its relevance in pediatric CNS tumors is unknown. Methods We performed a cohort study using gene expression and data from 246 pediatric patients with high-grade glioma, medulloblastoma, or ependymoma from the Children’s Brain Tumor Network. GARD was calculated using a sequencing-adapted radiosensitivity index integrated with radiation dose through the linear–quadratic model. Associations of GARD and physical radiation dose with event-free and overall survival were evaluated using Cox proportional hazards models stratified by tumor type and anatomic location. Patients who did not receive radiotherapy comprised a negative control cohort (sham-GARD). Results Among patients receiving radiotherapy, physical dose was uniform, whereas GARD showed substantial interpatient variability in biological effect. Higher GARD was associated with improved event-free survival (hazard ratio [HR] 0·90, 95% CI 0·83–0·97; p=0·004) and overall survival (HR 0·90, 95% CI 0·83–0·99; p=0·018). Physical dose was not associated with either endpoint. Among patients who did not receive radiotherapy, sham-GARD was not associated with outcomes, supporting GARD as a treatment-specific predictor rather than a prognostic biomarker. Conclusions In pediatric CNS tumors, the biological effect of radiotherapy quantified by GARD was associated with outcomes, whereas physical dose was not. These findings challenge uniform radiotherapy dosing and support genomically informed dose individualization. Prospective evaluation of GARD-guided radiotherapy is warranted to optimize tumor control while minimizing long-term toxicity in children.

Abstract Tissue-mimicking phantoms play a crucial role in evaluating new imaging modalities, simulating clinical scenarios, and ensuring the quality and reliability of imaging systems. Styrene–ethylene/butylene–styrene (SEBS) is an extremely stable and versatile material that has been recently used in ultrasound, elastography, and photoacoustic imaging across diverse applications. Despite its extensive use, a systematic viscoelastic characterization of different SEBS-based formulations reported in the literature, particularly using shear wave elastography (SWE), remains limited. To address this gap, this study investigates the viscoelastic properties of tissue-mimicking phantoms composed of SEBS, glycerol dispersions in SEBS gels, and mixtures of SEBS with low-density polyethylene (LDPE) in mineral oil, using gelatin phantoms as a reference for comparison. Viscoelastic parameters were estimated from shear wave velocity and attenuation dispersion curves using a Kelvin–Voigt model, based on SWE measurements with acoustic radiation force (ARF) excitation, shear plane-wave excitation, and complementary mechanical testing. SEBS-based phantoms exhibited broad, composition-dependent viscoelastic tunability. Increasing SEBS or LDPE content led to stiffer and more viscous responses, while glycerol primarily modulated viscosity and, at higher concentrations, also affected stiffness. Consistent and concordant values were obtained using both ARF and plane wave SWE techniques. The resulting stiffness (2–22 kPa) and viscosity (0.01–1.24 Pa⋅s) overlaps with the mechanical properties of several biological soft tissues, supporting use of these phantoms for SWE validation.

Scientific evidence regarding AKI and acute kidney care has advanced in recent years. However, a knowledge gap remains on the implementation of these evidence-based practices (EBPs) into clinical care. Implementation science (IS) is focused on ensuring that this knowledge is translated in an effective, efficient and sustainable fashion. Objectives: 1) Define the current status of IS; 2) Define a roadmap for accelerating IS with a focus on patient/care partner advocacy, digital tool application, social determinants of health, and resource-limited settings; and 3) Develop a robust and broad research agenda incorporating IS methodology into the programs. Evidence Review: ADQI XXXV was conducted through a modified Delphi process with virtual meetings preceding an in-person meeting. Five workgroups were determined a priori to focus on 1) IS definitions and methods applicable to AKI and acute kidney care; 2) IS literature in AKI and acute kidney care; 3) Innovations in IS to accelerate the adoption, adherence to, and sustainment of EBPs in AKI and acute kidney care; 4) IS methods in resource-limited settings; and 5) Recommendations to identify and evaluate EBPs that are ready for implementation or de-implementation. Prior to the in-person meeting, each workgroup met virtually to review the literature and develop framework questions to address their objectives. During the two-day in person meeting, through iterative discussions, questions and supporting statements were finalized. These questions and statements were agreed upon through voting to achieve consensus, defined as agreement of ≥80%. Conclusions and Relevance: We report a structured multidisciplinary consensus for defining the role of IS in AKI and acute kidney care. Future programs should address these consensus questions and apply these statements along with IS methodology in the translation of science into clinical practice and the implementation/de-implementation of EBPs in clinical care.

ABSTRACT Introduction Composite indolent B‐cell lymphomas may remain unrecognized when one component dominates the clinical presentation. Apparent relapse after therapy may, therefore, represent the emergence of a biologically distinct lymphoma rather than the recurrence of the original disease. Case Presentation An 82‐year‐old woman presented with systemic low‐grade B‐cell lymphoma that was most consistent with marginal zone lymphoma (MZL). Staging demonstrated peripheral blood involvement and multifocal FDG‐avid disease. Treatment with the CD20×CD3‐bispecific antibody mosunetuzumab resulted in complete metabolic remission. During surveillance, a new, isolated cervical lymph node developed despite sustained systemic response. Biopsy revealed follicular lymphoma (Grade 1–2) with a germinal center phenotype and a BCL2 rearrangement, findings discordant with recurrence of MZL. Retrospective review of the original specimen identified in situ follicular neoplasia within the initial biopsy. The disease course was, therefore, reinterpreted as a synchronous composite lymphoma in which treatment of the dominant MZL unmasked a previously clinically silent B‐cell neoplasm with follicular lineage. Local radiotherapy achieved remission of the follicular component. Conclusions New disease following treatment of an indolent lymphoma should not automatically be interpreted as relapse. Discordant clinical behavior, particularly focal progression after systemic response, warrants repeat biopsy and integrated pathologic reassessment. This case illustrates how therapy may reveal preexisting clonal heterogeneity and emphasizes the importance of temporality in distinguishing relapse from composite lymphoma. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

Background: Noninvasive tests are well validated in metabolic dysfunction–associated steatotic liver disease, but evidence in metabolic dysfunction and alcohol-associated liver disease (MetALD) and alcohol-associated liver disease (ALD) is limited. We evaluated noninvasive test–based clinical care pathways for fibrosis risk stratification in MetALD and ALD. Methods: This is a multinational, multicenter, cross-sectional study across 35 centers in 16 countries (2013–2025), including adults with MetALD or ALD. Fibrosis was assessed by liver biopsy and/or vibration-controlled transient elastography (VCTE). In biopsy-proven participants, we analyzed the sequential pathway (Fibrosis-4 [FIB-4] first, followed by VCTE for indeterminate FIB-4) to identify advanced fibrosis (≥F3). Diagnostic accuracy was assessed using the AUC. Results: Among 893 participants (41.3% MetALD and 58.7% ALD), the median age was 52 [43.0–61.0] years, and 79.4% were male. The estimated prevalence of advanced fibrosis was 45% (32.2% in MetALD and 54.0% in ALD). Participants with MetALD had a more dysmetabolic profile but lower fibrosis stages than ALD. Among biopsy-proven participants, FIB-4 AUC was 0.720, and VCTE AUC was 0.833. FIB-4 performed better in MetALD than ALD (AUC 0.773 vs. 0.540), while VCTE accuracy was similar across groups. In the sequential pathways, the false-negative rate for advanced fibrosis (misclassified as low risk) was 6.8% (4.9% MetALD and 11.3% ALD). Conclusions: In biopsy-proven patients, FIB-4 performance was acceptable in MetALD but substantially weaker in ALD. The standard 2-step pathway performed adequately in MetALD but missed a clinically meaningful proportion of advanced fibrosis in ALD.

Abstract Background There is limited data on immune checkpoint inhibitor (ICI) use in patients with non-small cell lung cancer (NSCLC) and known pericardial effusions. Methods This international multi-center observational retrospective study included patients with advanced NSCLC with or without pericardial effusions receiving ICIs. Immune-related adverse events (irAEs) were graded per CTCAE v5.0. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Cox proportional hazards multivariable models assessed the association between survival outcomes and clinicopathologic variables, and an inverse probability of treatment weighting (IPTW) model compared outcomes between the two groups. Results A total of 1248 patients with advanced NSCLC treated with ICIs across 13 institutions were included. Of these, 85 patients (6.8%) had pre-existing pericardial effusions. Compared to controls, patients with pericardial effusions were younger (median age 63 vs 67 years, P = .007), diagnosed more frequently with PD-L1 positive tumors (96% vs 76%, P < .001), and had a higher median number of baseline metastatic sites (3 vs 1, P < .001). IrAEs were similar between both groups (42% vs 38%), and no cardiac irAEs occurred in patients with pericardial effusions. PFS (median 5.6 vs 4.6 months, P = .3) and OS (median 10.2 vs 14.7 months, P = .50) were not statistically different between patients with pericardial effusions and the controls, respectively. In both multivariable and IPTW models, pericardial effusions were not associated with PFS or OS. Conclusions Among patients with NSCLC and pre-existing pericardial effusions, ICIs demonstrate meaningful clinical benefit similar to those without effusions, with no new cardiac or severe toxicities.

Abstract Purpose The female waist and torso remain fundamental aesthetic elements in body contouring, yet empirical data describing public preferences for waist-to-hip ratio (WHR) and abdominal muscle definition are limited. Misalignment between patient perceptions and actual aesthetic preferences may influence body dissatisfaction, drive unnecessary procedures, and shape unrealistic surgical goals. This study aimed to (1) evaluate how females perceive their own waist shape and ideal appearance using standardized manipulated images, (2) quantify male preferences for female WHR and abdominal definition, and (3) assess the discrepancy between what women believe men find attractive and men’s actual preferences. Methods An anonymous online survey was distributed internationally and collected 900 responses from adult participants. Two digitally manipulated, standardized female torso images were created: one varying waist-to-hip ratio across five levels (WHR 0.60 to 0.80) and one varying abdominal muscle definition. Male participants rated which WHR and abdominal definition they found most attractive. Female participants reported (1) which WHR and definition most resembled their current appearance, (2) which represented their ideal, and (3) which they believed men found most attractive. Additional demographic and body image variables were collected. Descriptive statistics were generated, and comparative analyses (chi-square tests) were conducted to evaluate differences in preference distributions and female perception versus male reality. Results A total of 900 respondents participated, including 41% men and 59% women. Male respondents showed a clear preference for smaller waist-to-hip ratios (WHR). The lowest WHR (0.60) was the most frequently selected option (38%), with steadily decreasing selections as WHR increased. Men also most preferred mild abdominal definition (Option B). Female responses revealed notable perception gaps: women most often perceived themselves as having midrange WHRs (0.70) but selected lower WHRs (0.65) as ideal, and they substantially overestimated men’s preference for the smallest WHR. Subgroup analyses showed that male WHR preferences varied significantly by continent (p < 0.05), with Europe, North and South America favoring smaller WHRs, while Africa, Australia, and Asia preferred larger ones. Higher male physical activity was associated with selecting smaller WHRs (r = –0.220, p < 0.05) and slightly greater abdominal definition (r = 0.169, p < 0.05). Social media use did not influence male preferences. Among women, physical activity strongly predicted desired abdominal muscularity (r = 0.236, p < 0.05) but not ideal WHR. Perceived social media influence significantly shaped ideal WHR (r = 0.202, p < 0.05), such that women who reported more negative influence selected smaller, more exaggerated WHRs. Time spent on social media did not significantly affect female aesthetic preferences. Conclusion This study provides quantitative evidence describing public preferences for female waist and torso aesthetics, revealing important divergences between perception and reality. Men strongly prefer smaller waist-to-hip ratios and mild abdominal definition, but not to the extreme levels that women commonly assume. Women’s own ideal waist shape aligns directionally with male preferences, yet women significantly overestimate the degree to which men favor the smallest possible WHR. This misperception may contribute to body dissatisfaction, drive interest in unnecessary procedures, or set unrealistic surgical expectations. For aesthetic surgeons, these findings highlight the need for patient-centered counseling that addresses perception gaps, corrects inaccurate beliefs about male preferences, and reinforces natural, proportionate outcomes rather than extreme contouring. The data support a trend toward moderate enhancement rather than highly exaggerated WHR reduction or aggressive abdominal definition in female body contouring. Incorporating these insights may improve patient satisfaction, promote psychological well-being, and guide surgical planning grounded in evidence-based aesthetics.

The role of human albumin therapy in the management of advanced liver disease is not yet fully established across all settings and remains a topic of debate. The significant and complicated burden of the disease, coupled with limited therapeutic options, presents ongoing challenges. At the European Association for the Study of the Liver (EASL) Congress 2026, studies in patient populations worldwide delivered new insights to add to the debate on the use of human albumin therapy at the most severe end of the liver disease spectrum. This article reviews a selection of the latest data, evaluating long-term albumin therapy for decompensated cirrhosis, as well as Phase III study evidence on the use of therapeutic plasma exchange (TPE) for acute-on-chronic liver failure (ACLF).