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Importance Advances in Alzheimer disease (AD) have shifted research focus to earlier disease stages, necessitating more scalable approaches to identify cognitively unimpaired individuals with amyloid β (Aβ) pathology. Objective To assess the utility of plasma phosphorylated tau 217 (p-tau217) for classifying Aβ status in cognitively unimpaired individuals, both as a stand-alone test and in a 2-step approach where positive plasma results were confirmed using a second modality (Aβ positron emission tomography [PET] or cerebrospinal fluid [CSF]). Design, Setting, and Participants This cross-sectional cohort study used data collected between June 2009 and March 2024. We included 2916 cognitively unimpaired participants from 12 international independent observational cohorts in the US, Europe, Australia, and Canada with available plasma p-tau217 levels and CSF or PET Aβ biomarkers. Performance comparisons between mass spectrometry and immunoassay-based p-tau217 measurements were also performed (n = 964). Exposures Plasma p-tau217 levels measured by immunoassay. Main Outcome and Measures Aβ status, determined by CSF or Aβ PET biomarkers. Results Participants had a mean (SD) age of 66.9 (9.9) years; 971 (33.3%) were Aβ positive by either CSF or PET, 1667 (57.2%) were women, and 1108 (38.1%) carried at least 1 APOE ε4 allele. As a stand-alone test, plasma p-tau217 achieved a positive predictive value (PPV) of 79% (95% CI, 74-84) and an overall accuracy of 81% (95% CI, 80-82). In a 2-step workflow, the PPV and accuracy significantly increased to 91% (95% CI, 86-95). While this approach required screening of 677 individuals with plasma p-tau217 to identify 100 Aβ-positive individuals, compared to 536 participants when using PET alone, it reduced the need for PET testing to 124. Immunoassays demonstrated comparable PPVs to mass spectrometry (80% [95% CI, 74-86] vs 85% [95% CI, 81-90]; P = .12) but significantly lower overall accuracy (82% [95% CI, 79-84]% vs 88 [95% CI, 86-90]; P < .001) and true Aβ-positive detection rate (49% [95% CI, 43-55] vs 69% [95% CI, 64-75]; P < .001). Conclusions and Relevance The findings highlight the potential of plasma p-tau217 as a stand-alone test—or when used in a sequential 2-step approach alongside PET or CSF testing—as a cost-effective, scalable, and minimally burdensome strategy for identifying preclinical AD. Tailored screening workflows that incorporate p-tau217 can improve efficiency in participant selection for preclinical AD trials and, in the future, help guide access to disease-modifying treatments.

Abstract Background and Aims Intestinal ultrasound (IUS) is increasingly used to monitor treatment efficacy in inflammatory bowel disease (IBD) trials. However, standardized definitions for response, remission, and optimal assessment timing remain undefined. An international expert consensus meeting was held to establish IUS endpoints for clinical trials. Methods A panel of 35 international gastroenterologists and radiologists participated in a modified Delphi process, reviewing the literature and developing consensus statements. Agreement was defined as at least 75% consensus. Results Consensus was reached on 150 statements across four domains: general IBD (30 statements), luminal Crohn’s disease (CD) (43), perianal CD (51), and ulcerative colitis (UC) (26). For luminal CD and UC, ultrasound response was defined by: (1) a ≥25% reduction in bowel wall thickness (BWT) from baseline, or (2) multifactorial improvement, combining BWT reduction with ≥1 grade decrease in color Doppler signal (CDS) or another IUS parameter. Assessments were set at weeks 4-8 for the colon and week 12 for the terminal ileum. Ultrasound remission in luminal CD was defined as: (1) BWT normalization (≤3 mm) or (2) normalization of multiple parameters, including BWT, CDS, and all other IUS parameters. Similar remission criteria were proposed for UC, but the sigmoid BWT normal range (3-4 mm) remained uncertain. The bowel ultrasound score (BUSS) for CD and the Milan ultrasound criteria (MUC) for UC were supported as standardized scoring systems for trials. Conclusion This consensus provides standardized IUS definitions to enhance consistency in IBD trials, supporting the integration of IUS in future research.

ABSTRACT Background The available risk prediction models are inadequate to identify a true low‐risk patient for developing new‐onset atrial fibrillation (AF) after typical atrial flutter (AFL) ablation. We aimed to determine whether adding markers of atrial myopathy to HATCH score ( h ypertension, a ge ≥75 years, t ransient ischemic attack/stroke, c hronic obstructive pulmonary disease, and h eart failure) can improve prediction of new‐onset AF after ablation of typical AFL. Methods The study included 208 consecutive patients who underwent successful ablation of typical AFL at Minneapolis VA Medical Center and University of Minnesota Medical Center. Patients with history of AF prior to ablation were excluded. Results Among the 208 patients, 76 (36.5%) developed new‐onset AF post AFL ablation. Mean follow‐up duration was 62 ± 31.8 months. HATCH score was not associated with new‐onset AF. When adding atrial myopathy (presence of at least one of the following: PTFV 1 > 5000 µV*ms, interatrial block determined by biphasic inferior p wave with duration >120 ms, left atrium (LA) diameter ≥44 mm, or LA index ≥3 cm/m 2 ) to HATCH score (HATCH‐A 2 ), the combination was independently associated with new‐onset AF. The AF incidence between HATCH‐A 2 score of 0–1 and ≥2 were 6.7% and 40.5%, respectively (Odds ratio 9.04, 95% confidence interval: 2.05–39.81, p = 0.004). Particularly, when HATCH‐A 2 score was 0, none of the patients developed AF. Conclusions Adding atrial myopathy to HATCH score improved predictability and could be used to delineate a true low‐risk patient of new‐onset AF after typical AFL ablation.

Abstract Obesity has been associated with non‐Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B‐cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome‐wide association studies of European ancestry ( N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist‐to‐hip ratio (WHR), and waist‐to‐hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.18, 95% confidence interval (95% CI): 1.05–1.33, p = .005]. This finding was consistent with Mendelian randomization analyses, which demonstrated a similar increased risk of DLBCL with higher genetically determined BMI (OR per SD = 1.12, 95% CI: 1.02–1.23, p = .03). No significant associations were observed with other NHL subtypes. Our study demonstrates a positive link between a genetically determined BMI and an increased risk of DLBCL, providing additional support for increased adiposity as a risk factor for DLBCL.

ABSTRACT Introduction Children with hepatoblastoma (HB) and other solid tumors frequently undergo intraoperative blood transfusion (IBT) with unknown impact on oncologic outcomes and scant data to guide transfusion in this population. This study tested the hypothesis that IBT is associated with poorer survival in children with HB. Methods A multicenter retrospective observational study of patients aged <18 years with HB who underwent primary tumor resection, including liver transplantation, from 2010 to 2019 was performed at 19 institutions. The association of IBT with risk of recurrence and death were determined using propensity score reweighted (PSR) Cox proportional hazards regression analyses. Results There were 338 patients identified who met inclusion criteria and had sufficient data for inclusion. Of those, 257 (76%) received IBT, including 253 (98%) who received packed red blood cells (pRBC), 84 (33%) who received plasma, and 28 (11%) who received platelets. IBT was associated with higher pretreatment extent of disease ( p < 0.001), presence of annotation factors (+VPEFR: 50%, n = 129 vs. 37%, n = 30, p = 0.035), and complex resections (extended, meso‐, or total hepatectomy: 54%, n = 139 vs. 27%, n = 22, p < 0.001); these differences were mitigated after applying propensity score weighting. Patients who received IBT had greater postoperative hemoglobin (g/dL) (median 10 (I8–11) vs. 9 (8–10), p = 0.013) and required more postoperative plasma and platelet transfusions ( p < 0.05). Median follow‐up was 4.4 (2.0–8.3) years. Compared with non‐IBT patients, those with IBT had higher incidence of death (PSR HR 2.35, 95% CI 1.10–5.02). Recurrence did not significantly differ across groups (PSR HR = 0.82, 95% CI 0.45–1.48). Conclusion IBT was associated with greater hazard of death. Postoperative hemoglobin levels suggested that unnecessary transfusions occurred and a pRBC‐focused approach to IBT led to coagulopathy. Development of optimal transfusion strategies for HB are needed to minimize unnecessary transfusions.

Abstract Background Physical activity (PA) is an established protective factor for colorectal cancer (CRC), but it is unclear if genetic variants modify this effect. To investigate this possibility, we conducted a genome-wide gene–PA interaction analysis. Methods Using logistic regression and two-step and joint tests, we analyzed interactions between common genetic variants across the genome and PA in relation to CRC risk. Self-reported PA levels were categorized as active (≥ 8.75 MET-h/wk) vs. inactive (< 8.75 MET-h/wk) and as study- and sex-specific quartiles of activity. Results PA had an overall protective effect on CRC (OR [active vs. inactive] = 0.85; 95%CI = 0.81–0.90). The two-step GxE method identified an interaction between rs4779584, an intergenic variant near the GREM1 and SCG5 genes, and PA for CRC risk (p-interaction = 2.6×10 − 8 ). Stratification by genotype at this locus showed a significant reduction in CRC risk by 20% in active vs. inactive participants with the CC genotype (OR = 0.80; 95%CI = 0.75–0.85), but no significant PA–CRC association among CT or TT carriers. When PA was modeled as quartiles, the 1-d.f. GxE test identified that rs56906466, an intergenic variant near the KCNG1 gene, modified the association between PA and CRC (p-interaction = 3.5×10 − 8 ). Stratification at this locus showed that increase in PA (highest vs. lowest quartile) was associated with a lower CRC risk solely among TT carriers (OR = 0.77; 95%CI = 0.72–0.82). Conclusions In summary, we identified two genetic variants that modified the association between PA and CRC risk. One of them, related to GREM1 and SCG5 , suggests that the bone morphogenetic protein (BMP)-related, inflammatory, and/or insulin signaling pathways may be associated with the protective influence of PA on colorectal carcinogenesis.

Surgical outcomes and perioperative factors associated with pediatric cranioplasty remain incompletely understood. The authors queried the National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database to evaluate outcomes and intraoperative/postoperative blood transfusions in patients undergoing cranioplasty between 2019 and 2023. A total of 249 patients (mean age 9.1 ± 5.4 y) were included. Most cranioplasties (70.7%) utilized alloplastic materials compared with autologous. Blood transfusion was required in 24.1% of cases, predominantly on the day of surgery (86.7%). Multivariable analysis identified age (OR: 0.86 per year, 95% CI: 0.80–0.93, P < 0.001) and cranioplasty size >5 cm (versus ≤5 cm) (OR: 2.10, 95% CI: 1.01–4.50, P = 0.049) as predictors of transfusion. The 30-day unplanned readmission rate was 5.3% at a mean of 14.6 ± 7.9 days from surgery, most commonly for a surgical site infection (33.0%). The 30-day unplanned reoperation rate was 2.9%, at a mean of 10.2 ± 5.6 days. Autologous cranioplasty was not associated with higher odds of readmission (OR: 0.79, 95% CI: 0.25–2.13, P = 0.66) or reoperation (OR: 5.04, 95% CI: 0.96–36.99, P = 0.07) compared with alloplastic cranioplasty. Rates of readmission and reoperation following pediatric cranioplasty are comparable to other complex craniofacial procedures. Younger age and larger cranioplasty size are associated with higher rates of blood transfusion. Our results show that autologous reconstruction is not associated with higher short-term complication rates compared with alloplastic reconstruction, although future studies are still needed to further the understanding of the optimal cranioplasty material.

PURPOSE Patients with cancer take different types of medications with varying schedules and settings. They are also sometimes instructed to stop medications due to toxicity. To measure self-reported nonadherence in this heterogeneous population, we modified and evaluated a measure originally developed to assess nonadherence to daily oral antihypertensives, the Domains of Subjective Extent of Nonadherence (DOSE-Nonadherence). METHODS The measure was refined in an iterative process incorporating feedback from patient investigators and participant interviews in English and Spanish. Branching logic was added for participant selection of medication administration setting: (1) only home, (2) only clinic, or (3) partly home/partly clinic. Participants reported their adherence to medications taken over a setting-specific reference period (1 week for home, 1 month for clinic medications). Participants who missed medications then reported on reasons for nonadherence. Adherence was dichotomized for analysis (complete adherence v any nonadherence). For participants who received clinic-administered medications, concordance between chart-abstracted and self-reported adherence was evaluated. RESULTS Seventy-three participants completed the measure (68% English; 32% Spanish; 86% female; 44% age ≥60 years). The majority had breast cancer; 64% had metastatic disease. Twenty-six percent (15/58) of participants who received medication in clinic and 24% (11/46) of those who took medication at home reported nonadherence. Participants felt able to respond accurately to both reference periods and perceived all reasons for nonadherence to be relevant. Among participants who completed the final version of the measure for clinic-administered medication, 96% (26/27) accurately reported their adherence compared with chart-abstracted data. CONCLUSION Our results support the validity of the DOSE-Nonadherence-Cancer for assessing cancer treatment nonadherence. This measure can be used to assess nonadherence in patients with cancer receiving a broad array of systemic therapies.

Despite improvements in kidney transplantation rates, the shortage of donor kidneys remains a critical issue, exacerbated by non-utilization of recovered kidneys due to quality concerns, necessitating advancements in perfusion methods to enhance graft outcomes and usage. Although static cold storage remains the default standard for kidney preservation, newer methods like hypothermic machine perfusion have shown improved outcomes, including reduced delayed graft function and better survival rates. Hypothermic oxygenated machine perfusion and normothermic machine perfusion offer some potential clinical benefits but studies to date have demonstrated mixed results. In the United States, LifePort and the XVIVO’s Kidney Assist Transport are the most popular hypothermic perfusion devices, with NMP devices mostly in trials. Combining perfusion with biomarkers such as mitochondrial flavin mononucleotide, neutrophil gelatinase-associated lipocalin, and osteopontin shows promise in assessing kidney viability and predicting post-transplant outcomes, though further research is also needed. Emphasis on repair biomarkers, such as uromodulin and osteopontin, aims to better predict graft outcomes and develop new therapies. While notable advancements have been made in the use of machine perfusion and viability testing for liver transplantation, additional research with larger sample sizes is essential to substantiate these results and enhance kidney transplantation outcomes.