Citations

Abstract Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for older adults with hematologic malignancies. Concerns on nonrelapse mortality (NRM) in older adults limit allo-HCT utilization. We executed a prospective, observational study BMT-CTN 1704 (Blood and Marrow Transplant Clinical Trials Network) enrolling allo-HCT recipients aged ≥60 years from 49 centers in the United States. We analyzed associations between 13 measurements of older adult health and NRM within 1 year to construct a comprehensive health assessment risk model (primary-CHARM) using multivariate Fine-Gray model and grouped penalized variable selection. Two machine learning (ML) models (Cox and pseudo-value boosting) were also explored. Models’ performances were compared using area under the curve (AUC), with bootstrap and cross-validation sampling to correct for optimism, decision curve analysis (DCA), calibration, and Brier scores. Among 1105 patients with median age of 67 (range, 60-82) years who received allo-HCT, NRM was 14.4% and overall survival (OS) 71.7% at 1 year. Factors statistically selected for inclusion in primary-CHARM were higher comorbidity burden, lower albumin, higher C-reactive protein, older age, higher weight-loss percentage, lower patient-reported performance score, and cognitive impairment. Primary-CHARM scores were independently associated with higher NRM (hazard ratio [HR], 2.72; P < .0001) and worse OS (HR, 2.09; P < .0001). Bootstrap bias–corrected AUC for primary-CHARM was 0.591. Comparing primary-CHARM with HCT-comorbidity index and 2 ML-CHARM models, calibration, Brier score, and DCA analysis favored primary-CHARM. Primary-CHARM, with mostly simple and readily available parameters, risk stratifies older adults for allo-HCT. Adopting primary-CHARM in practice may promote broader use of HCT by quantifying risk and enhance the design of strategies to improve outcomes. This trial was registered at www.ClinicalTrials.gov as #NCT03992352.

Objective Early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) differ in many respects. Here, we address the issue of possible differences in fibrillar amyloid pathology as measured by positron emission tomography (PET), which remains unresolved due to the lack of large‐scale comparative studies. Methods Three hundred ninety‐nine cognitively impaired participants younger than 65 years of age from the multicenter Longitudinal Early‐onset Alzheimer's Disease Study (LEADS) and 450 cognitively impaired participants older than 65 years from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent clinical assessment, brain magnetic resonance imaging (MRI), and amyloid PET and were included in this study. We compared amyloid PET outcomes (positivity rate based on visual read and quantified tracer uptake expressed as Centiloids [CLs]) between the 2 cohorts and studied their association with age, sex, APOE genotype, and cognition. Results The amyloid positivity rate was higher in LEADS (78%, 95% confidence interval [CI] = 74–82) than in ADNI (71%, 95% CI = 67–75, p = 0.02). Lower Mini‐Mental State Examination (MMSE) and APOE4 genotype increased the odds of amyloid positivity in both cohorts. Visually positive scans had higher CLs in LEADS (EOAD, mean = 95.3 ± 26.1) than in ADNI (LOAD, mean = 80.9 ± 36.8, p < 0.0001), predominantly in parietal cortex/precuneus, superior temporal, and frontal cortices. In amyloid‐positive patients, (1) CLs were higher in female patients in both cohorts; (2) APOE4 carriership was associated with lower CLs in EOAD, which was not observed in LOAD; and (3) correlations between CLs and MMSE scores were significantly stronger in EOAD than in LOAD. Interpretation Differences in the burden of amyloid pathology may contribute to differences in clinical and anatomic patterns in sporadic EOAD and LOAD, and have implications for optimizing therapeutic strategies in each group. ANN NEUROL 2025;98:236–248

Study Design: Single-center retrospective analysis. Objective: To establish an empirically derived threshold to define both coronal and sagittal malalignment (CM & SM) based on preoperative patient-reported outcomes (PROs). Summary of Background Data: Currently, no radiographic alignment threshold defines preoperative CM in adult spinal deformity (ASD) patients based on disability. In a cohort of ASD patients undergoing corrective surgery, we sought to establish a threshold to define both CM and SM based on PRO and assess the clinical impact of CM and combined with SM. Methods: ASD patients with ≥6 level fusions were included. CVA and SVA were measured. PROs included preoperative ODI and SRS-22r scores. CVA and SVA thresholds were derived to accurately differentiate patients with ODI >40 and SRS-pain+function <5. Patients were then separated into 4 groups: (1) neutral alignment (NA); (2) CM; (3) SM; and (4) combined coronal and sagittal malalignment (CCSM). Results: Totally, 368 patients were included. Thresholds to distinguish patients with ODI ≥40 and SRS-pain/function <5 were: (1) CVA=3.96 cm (ODI) and 3.17 cm (SRS); (2) SVA=4.97 cm (ODI) and 7.52 cm (SRS). The lower numbers were chosen to define each threshold: CVA=3 cm and SVA=5 cm. Alignment breakdown was: NA=179 (48.6%), CM=66 (17.9%), SM=65 (17.7%), and CCSM=58 (15.8%). Both SM=( P =0.006) and CCSM ( P <0.001) patients had significantly worse ODI scores than NA patients, and CCSM patients were significantly worse than SM alone ( P =0.010). On the basis of preoperative total SRS-22r scores, only CCSM ( P =0.003) patients were significantly worse than the NA group. CVA significantly correlated with 4/7 (57.1%) preoperative PROs (ODI/SRS-total/function/image), while SVA correlated with 5/7 (71.4%) preoperative PROs (ODI/SRS-total/function/image/pain). A linear relationship was seen between increasing CVA and worsening ODI (β=0.92, 95% CI: 0.37–1.48, P =0.001). A significant and slightly stronger relationship was seen between increasing SVA and worsening ODI (β=1.28, 95% CI: 1.00–1.56, P <0.001). Conclusions: CM and SM thresholds that accurately distinguished ASD patients with severe pain and disability preoperatively were 3 cm for CVA and 5 cm for SVA, respectively. Preoperative CM was significantly associated with worse ODI, SRS-22r total/function/image scores. CCSM led to more disability than SM alone.

OBJECTIVES: To develop the first core Critical Care Data Dictionary (C2D2) with common data elements (CDEs) to characterize critical illness and injuries. DESIGN: Group consensus process using modified Delphi approach. SETTING: Electronic surveys and in-person meetings. SUBJECTS: A multidisciplinary workgroup of clinicians and researchers with expertise in the care of the critically ill and injured. INTERVENTIONS: The Delphi process was divided into domain and CDE portions with each composed of two item generation rounds and one item reduction/refinement rounds. Two in-person meetings augmented this process to facilitate review and consideration of the domains and by panel members. The final set of domains and CDEs was then reviewed by the group to meet the competing criteria of utility and feasibility, resulting in the core dataset. MEASUREMENTS AND MAIN RESULTS: The 23-member Delphi panel was provided 1833 candidate variables for potential dataset inclusion. The final dataset includes 226 patient-level CDCs in nine domains, which include anthropometrics and demographics (8), chronic comorbid illnesses (18), advanced directives (1), ICU diagnoses (61), diagnostic tests (42), interventions (27), medications (38), objective assessments (26), and hospital course and outcomes (5). Upon final review, 91% of the panel endorsed the CDCs as meeting criteria for a minimum viable data dictionary. Data elements cross the lifespan of neonate through adult patients. CONCLUSIONS: The resulting C2D2 provides a foundation to facilitate rapid collection, analyses, and dissemination of information necessary for research, quality improvement, and clinical practice to optimize critical care outcomes. Further work is needed to validate the effectiveness of the dataset in a variety of critical care settings.

Abstract INTRODUCTION Early‐onset and late‐onset Alzheimer's disease (EOAD and LOAD, respectively) have distinct clinical manifestations, with prior work based on small samples suggesting unique patterns of neurodegeneration. The current study performed a head‐to‐head comparison of cortical atrophy in EOAD and LOAD, using two large and well‐characterized cohorts (LEADS and ADNI). METHODS We analyzed brain structural magnetic resonance imaging (MRI) data acquired from 377 sporadic EOAD patients and 317 sporadicLOAD patients who were amyloid positive and had mild cognitive impairment (MCI) or mild dementia (i.e., early‐stage AD), along with cognitively unimpaired participants. RESULTS After controlling for the level of cognitive impairment, we found a double dissociation between AD clinical phenotype and localization/magnitude of atrophy, characterized by predominant neocortical involvement in EOAD and more focal anterior medial temporal involvement in LOAD. DISCUSSION Our findings point to the clinical utility of MRI‐based biomarkers of atrophy in differentiating between EOAD and LOAD, which may be useful for diagnosis, prognostication, and treatment. Highlights Early‐onset Alzheimer's disease (EOAD) and late‐onset AD (LOAD) patients showed distinct and overlapping cortical atrophy patterns. EOAD patients showed prominent atrophy in widespread neocortical regions. LOAD patients showed prominent atrophy in the anterior medial temporal lobe. Regional atrophy was correlated with the severity of global cognitive impairment. Results were comparable when the sample was stratified for mild cognitive impairment (MCI) and dementia.

Purpose The Sangre Por Salud (SPS) Biobank was established to facilitate biomedical research opportunities for the Latino community by creating an easily accessible prospective cohort for scientists interested in studying health conditions and health disparities in this population. Participants Individuals self-identifying as Latino, aged 18–85 years, were prospectively recruited from the primary care Internal Medicine clinic at Mountain Park Health Center in Phoenix, Arizona. After obtaining informed consent, detailed medical history questionnaires were captured, and blood samples were obtained for common laboratory tests. Participants authorised the research team to access their electronic health records for research purposes. In addition, participants had serum, plasma and DNA samples isolated and stored at the Mayo Clinic Arizona Biorepository Laboratory for long-term storage and future access. As part of the study, participants consented and agreed to be contacted for potential participation in future research studies. Findings to date 3756 participants provided informed consent, of whom 3733 completed all study questionnaires, an oral glucose tolerance test and had blood collected and stored. The SPS cohort is predominantly composed of females (72%), with a median age at time of consent of 42 years. All participants self-identified as Hispanic/Latino, 45% were married, 53% were employed for wages and 60% had less than a high school degree. Around 25% of participants met diagnostic criteria for overweight (BMI 25–29 kg/m 2 ), and 49% met for obesity (BMI≥30 kg/m 2 ). At time of recruitment, hypertension, hyperlipidaemia and depression affected 22%, 20% and 13% of the cohort, respectively. Future plans We plan to regularly update the participants’ electronic health records and self-reported health data to longitudinal research. Additionally, we plan to obtain a more comprehensive genomic analysis on the entire cohort, ensuring greater research interest and investigation into the underlying genetic factors that contribute to disease susceptibility in this cohort.

Abstract Background Real-time endoscopic optical diagnosis involves detailed visualization of the digestive mucosal and microvascular pattern, allowing for prediction of histology. This is advantageous as it can guide endoscopic resection decisions, surgical referrals and provide cost savings to histopathology. There is, however, no standardized or widely implemented curriculum for endoscopists or trainees to learn optical diagnosis skills. Aims To evaluate the impact of a course for the optical diagnosis of esophageal squamous cell carcinoma (ESCC), early gastric cancer (EGC), Barrett’s esophagus (BE), and colorectal polyps Methods 19 gastroenterology trainees were invited to the 2-day course in Kingston, Canada. Number of procedures previously performed was recorded. The impact of the course on lesion diagnosis accuracy was evaluated using a pre-test, immediate post-test, and delayed post-test administered 6 weeks after the course. A repeated measures ANOVA was performed to compare the mean score (%) between the three tests. Results 13 trainees completed all the tests (Table 1). Mean score % values for the overall tests and test scores for esophageal, gastric, and colon lesions were summarized on Table 1. The repeated measures ANOVA determined that the mean score % had a statistically significant difference between the three tests (F (2,24)=5.63, P=0.01). Pairwise comparisons revealed that there was a statistically significant increase in mean scores between pre- and post-tests (13.86 (95% confidence interval (CI) of 4.36 to 23.33), p&lt;0.01) with no significant difference between post and delayed post-tests (8.46 (95% CI of -0.12 to 17.04), p&gt;0.05) (Figure 1). The mean correct % from the delayed post-test was higher than the pre-test but there was no statistical significance (5.39 (95% CI of -3.72 to 14.49), p&gt;0.05). Conclusions This novel optical diagnosis course improved trainee accuracy in diagnosing ESCC, EGC, BE and colorectal polyps. Learning retention was evident, with no significant score difference between immediate and delayed post-tests. This study was limited by the low sample size and low number of test items. Further investigation is required to validate the course for international trainees and explore its clinical transferability. Demography and Mean Score % Figure 1. Mean score %. (*) denotes p&lt;0.05. Funding Agencies None

Importance Obesity is a risk factor associated with multiple myeloma (MM) and its precursor, monoclonal gammopathy of unknown significance (MGUS). However, it is unclear how cumulative exposure to obesity affects the risk of MGUS progression to MM. Objective To determine the association of cumulative exposure to excess body mass index (EBMI), defined as BMI (calculated as weight in kilograms divided by height in meters squared) greater than 25, with risk of MGUS progression to MM. Design, Setting, and Participants This cohort study included patients with MGUS, including immunoglobin G, immunoglobin A, or light chain MGUS, from the nationwide US Veterans Health Administration database from October 1, 1999, to December 31, 2021. A published natural language processing–assisted model was used to confirm diagnoses of MGUS and progression to MM. Data were analyzed from February 12 to November 4, 2024. Exposures Cumulative EBMI was calculated by area under the curve of measured BMI subtracting the reference BMI at 25 during the first 3 years after MGUS diagnosis. Main Outcomes and Measures The main outcome was progression from MGUS to MM. Multivariable Fine-Gray time-to-competing-event analyses, with death as the competing event, were used to determine associations. Results The cohort included 22 429 patients with MGUS (median [IQR] age, 70.5 [63.5-77.9] years; 21 613 [96.4%] male), with 8329 Black patients (37.1%) and 14 100 White patients (62.9%). There were 4862 patients (21.7%) with reference range BMI (18.5 to &amp;lt;25), 7619 patients (34.0%) with BMI 25 to less than 30, and 8513 patients (38.0%) with BMI 30 or greater at the time of MGUS diagnosis. Compared with reference range BMI at MGUS diagnosis, patients with BMI 25 to less than 30 (adjusted hazard ratio [aHR], 1.17; 95% CI, 1.03-1.34) or 30 or greater (aHR, 1.27; 95% CI, 1.09-1.47) at MGUS diagnosis had higher risk of progression to MM. In patients with reference range BMI at MGUS diagnosis, each 1-unit increase of EBMI per year was associated with a 21% increase in progression risk (aHR, 1.21; 95% CI, 1.04-1.40). However, for patients with BMI 25 or greater at MGUS diagnosis, the incremental risk associated with cumulative EBMI exposure was not statistically significant. Conclusions and Relevance This cohort study found that, for patients with BMI 18.5 to less than 25 at the time of MGUS diagnosis, cumulative exposure to BMI 25 or greater was associated with an increased risk of progression. These findings suggest that for these patients, maintaining a healthy and stable weight following MGUS diagnosis may prevent progression to MM.