Citations

Importance Allogeneic hematopoietic cell transplant (HCT) is curative for hematologic cancers, yet access remains inequitable for racially and ethnically underrepresented and socioeconomically disadvantaged populations, making the goal of having a suitable donor for every patient who needs a transplant challenging. The ACCESS trial broadened access by enrolling patients without matched donors, who instead received an HCT from a mismatched unrelated donor. Objective To compare baseline characteristics of ACCESS trial participants with participants enrolled in a similar clinical trial and a patient-reported outcome (PRO) protocol cohort. Design, Setting, and Participants This cross-sectional study included adult participants (aged ≥18 years) from 3 cohorts—the ACCESS trial (2021-2024), BMT CTN 1703 trial (2019-2021), and Center for International Blood and Marrow Transplant Research (CIBMTR) PRO Protocol observational study (2020-2025)—who completed a baseline PRO survey. The ACCESS and PRO Protocol cohorts were stratified by conditioning intensity (myeloablative [MAC] vs reduced-intensity and nonmyeloablative [RIC/NMA]); all BMT CTN 1703 participants received RIC/NMA. Exposure Hematopoietic cell transplant. Main Outcomes and Measures Racial and ethnic diversity, insurance type, education, and income were compared among cohorts using counts and percentages, and socioeconomic and structural disadvantage were measured using the Social Vulnerability Index and Comprehensive Score for Financial Toxicity–Functional Assessment of Chronic Illness Therapy. Results Baseline surveys were completed by 208 participants in the ACCESS trial (median [range] age at transplant, 62.3 [20.4-78.9] years; 108 male [51.9%]), 122 participants in the PRO Protocol study (median [range] age at transplant, 63.9 [21.1-78.0] years; 67 male [54.9%]), and 342 participants in the BMT CTN 1703 trial (median [range] age at transplant, 66.9 [20.7-78.6] years; 218 male [63.7%]). Participants in ACCESS were more racially and ethnically diverse, with 15 (7.2%), 25 (12.1%), 46 (22.2%), 110 (53.1%), and 11 (5.3%) of Asian, Black or African American, Hispanic or Latino, White, and other race and ethnicity, respectively, compared with 4 (3.3%), 2 (1.6%), 8 (6.6%) 104 (85.2%), and 4 (3.3%), respectively, in the PRO Protocol and 10 (3.0%), 0, 16 (4.8%), 302 (91.0%), and 4 (1.2%), respectively, in the BMT CTN 1703 trial. Participants in ACCESS were more likely to have Medicaid (36 [18.1%]) vs PRO Protocol (8 [6.7%]) and BMT CTN 1703 (16 [5.1%]) participants and reported lower education (some college or an associate’s degree: 103 [49.5%] vs 73 [59.8%] in the PRO Protocol; postcollege education: 34 [17.3%] vs 35 [29.2%] in the PRO Protocol) and household income (<$40 000 annually: 25 [24.0%] vs 8 [11.6%] in the PRO Protocol and 7 [38.9%] in the BMT CTN 1703 trial). Median Social Vulnerability Index scores were highest among participants in the ACCESS MAC group (median [range], 0.72 [0.01-0.97] vs 0.61 [0.16-0.78] in the PRO Protocol MAC group), and 16 participants [27.6%] in the ACCESS MAC group reported moderate to severe financial toxicity. The ACCESS participants lived closer to transplant centers, especially in the RIC/NMA group (median [IQR], 28 [14-75] miles vs 47 [16-96] miles for BMT CTN 1703 participants and 49 [21-104] miles for PRO Protocol participants). Conclusions and Relevance This cross-sectional study of clinical trial participants and a clinical cohort found that the ACCESS trial enrolled a more racially and ethnically diverse and socioeconomically disadvantaged population. Trial designs that broaden eligibility could expand access to HCT, highlighting the need for systemic interventions to ensure equity.

Compared with two-dimensional MR elastography (MRE), three-dimensional MRE demonstrated better test-retest repeatability, between–field-strength reproducibility, and between-day reproducibility at 3 T for measurement of liver stiffness in adults with severe obesity but failed more frequently.

Among patients with treatment-naive hepatocellular carcinoma, glass microsphere radiation segmentectomy before liver transplant achieved high rates of complete pathologic necrosis, which was positively associated with the number of optimized treatment parameter thresholds.

Abstract INTRODUCTION : Despite expanding use of plasma biomarkers for Alzheimer's disease (AD), minimal examination has been undertaken in early‐onset AD (EOAD). Prior analyses assessed criterion and convergent validity of common plasma biomarkers in a well‐characterized sample with sporadic EOAD. METHODS : Plasma amyloid beta (Aβ) 42/40, tau phosphorylated at threonine 231 (p‐tau231), glial fibrillary acidic protein (GFAP), and neurofilament light change (NfL) levels were obtained for 189 EOAD, 52 early‐onset non‐AD (EOnonAD), and 83 cognitively normal (CN) participants. Diagnostic group differences, convergence with imaging biomarkers, and the capacity to predict specific cognitive domains were investigated. RESULTS : After controlling for cognitive status, EOAD participants exhibited more pathologic levels of Aβ42/40, p‐tau231, and GFAP relative to EOnonAD participants. However, NfL displayed the greatest sensitivity to non‐amnestic cognitive impairment across the sample. DISCUSSION : These results establish criterion and convergent validity of plasma biomarkers in sporadic EOAD and highlight complementary roles that AD‐specific and non‐specific plasma markers may play across the course of AD care.

Background Large vessel occlusion (LVO) stroke is associated with a high risk of permanent disability. There are no reliable tools providing periprocedural information on clot characteristics, such as composition and length, that may impact first pass effect, which has been shown to improve functional outcomes. In the first study of a novel technology, we evaluated whether the Clotild Smart Guidewire System (Clotild), an impedance-based device, can provide in situ information on clot characteristics during a mechanical thrombectomy procedure. Methods This is the first-in-human, international, multicentric, single-arm trial involving LVO stroke patients. Of 45 enrolled subjects, 41 constituted the safety population; 39 was the per protocol population, of which 26 subjects with complete impedance data comprised the performance population. The latter was divided into development (11 subjects) and validation (15 subjects) populations for prediction model development and assessment. The safety endpoint assessed Clotild-related intracranial vessel perforation/dissection. Performance endpoints evaluated Clotild’s ability to perform classification of impedance measurements distinguishing substantial versus negligible local content in red blood cells (RBCs) and platelets, to detect the arterial wall and the distal end of the clot. Results The safety endpoint was met in all subjects. Performance analysis comparing the agreement between Clotild’s output and impedance experts’ readings showed an area under the receiver operating characteristic curve (AUC) of 0.97 (95% CI 0.93 to 0.99) for RBC, and 0.94 (95% CI 0.89 to 0.98) for platelet clot composition. Regarding detection, Clotild’s performance showed an AUC of 0.69 (95% CI 0.59 to 0.77) for the arterial wall, and 0.83 (95% CI 0.59 to 1.00) for the distal end of the clot. Conclusions Clotild was proven safe to acquire impedance data and to provide information on in situ clot characteristics in large vessel occlusions.

Abstract Background Osteoarthritis is a leading cause of disability worldwide, and cell‐based treatments including adipose‐derived and bone marrow aspirate have been sought by the lay and medical community as treatment options. Objective To perform a scoping review of published literature on cell‐based injections allowed by the U.S. Food and Drug Administration for the treatment of osteoarthritis to synthesize existing evidence and identify research gaps for future evaluation. Methods A comprehensive search of five databases was executed from inception through January 2, 2025. Studies that met the inclusion criteria were original research studies written in English on Food and Drug Administration‐allowed cell‐based treatments in adults with osteoarthritis of any joint. Results The database search yielded 4257 unique records. After screening, 84 studies met the inclusion criteria, encompassing 9996 patients and a total of 10,508 procedures. The primary research study designs were cohort studies ( n = 62), focused on treatment of knee osteoarthritis ( n = 63), and described bone marrow aspirate ( n = 42) and adipose‐derived ( n = 42) treatments. Postprocedure monitoring ranged from 6 weeks to 5 years, with most studies ≤1 year ( n = 59). Patient‐reported outcomes were reported in 83 of 84 studies; few provided imaging outcomes including magnetic resonance imaging ( n = 9) or radiographs ( n = 2). Conclusion This review identified limited randomized controlled trials, limited studies outside the knee, limited description of cell‐based treatments, and treatment protocols, along with inconsistent patient‐reported outcomes limited to 1 year in most studies. We propose establishing reporting guidelines in research on cell‐based therapies.

ABSTRACT Background Platelet factor 4‐polyanion enzyme‐linked immunosorbent assays (ELISAs) are considered highly sensitive for diagnosing heparin‐induced thrombocytopenia (HIT), such that current practice guidelines recommend use of ELISA‐negative results to exclude HIT. Once HIT is ruled out, alternative, non‐heparin‐based anticoagulant treatments are ceased, and heparin reintroduction frequently occurs. Methods Antigen‐based and PF4‐dependent functional testing were used to study PF4/polyvinylsulfonate ELISA‐negative platelet‐activating antibodies in HIT‐suspected patients. Results Three patients with clinical presentations consistent with HIT tested negative in an ELISA using PF4‐polyvinylsulfonate (PF4/PVS), an antigenic target very commonly used for HIT antibody screening. All three patients demonstrated PF4‐dependent platelet activation in functional testing that was sensitive to blockade of platelet FcγRIIa receptors and inhibited by high concentrations of heparin, consistent with pathogenic HIT antibodies. Functional testing‐based screening of 500 ELISA‐negative patients identified three additional patients whose sera activated platelets in a PF4‐ and FcγRIIa‐dependent manner and had clinical histories consistent with HIT. Five of the six ELISA‐negative HIT patients were re‐exposed to heparin, which precipitated a decrease in platelet counts in all re‐exposed patients, and one patient developed a new thrombus. Conclusions Recognition of ELISA‐negative HIT is critical to avoid harm due to the cessation of alternative anticoagulation therapy and re‐exposure of these patients to heparin.