Citations

Background: Normothermic machine perfusion (NMP) may reduce preservation injury in donation-after-circulatory-death (DCD) liver transplantation, but its association with patient-centered recovery and longer-term graft survival remains uncertain. Study Design: We retrospectively analyzed 306 consecutive adult DCD liver transplant recipients at a single center from January 2019 through December 2022, comparing NMP (n=95) with static cold storage (SCS; n=211). The primary endpoint was days alive and out of hospital at 365 days (DAOH365). Quasi-Poisson regression evaluated factors associated with DAOH365, and Cox regression evaluated graft survival. Propensity-matched and calendar-year sensitivity analyses assessed measured confounding. Results: Median DAOH365 was 357.0 (352.0, 360.0) days with NMP versus 353.0 (336.0, 359.0) with SCS (p<0.001), but preservation strategy was not independently associated with DAOH365 (adjusted rate ratio 1.02; p=0.331). NMP recipients had less early allograft dysfunction (35.8% vs 59.7%; p<0.001), ischemic cholangiopathy (4.2% vs 23.7%; p<0.001), and retransplantation within 2 years (0.0% vs 6.6%; p=0.007). Two-year patient survival did not differ significantly. NMP was associated with improved twoF-year graft survival (HR 2.9, 95% CI 1.23–6.87; p=0.015), an association maintained in propensity-matched and calendar-year sensitivity analyses. Adjusted total 1-year costs did not differ (p=0.512). Conclusions: In this single-center DCD cohort, NMP was associated with superior 2-year graft survival but not independently with DAOH365. These hypothesis-generating findings support multicenter prospective evaluation of NMP using both graft survival and patient-centered recovery endpoints.

Background: Reliable access to postoperative guidance between clinic visits remains inconsistent, and the usefulness of large language models depends on how clinical knowledge is structured and retrieved. Knowledge graph-only (KG-only), vector retrieval-augmented generation (RAG-only), and hybrid graph-retrieval (GraphRAG) architectures have not been directly compared under controlled conditions for postoperative care. Objective: It was to compare these three pipelines on a curated postoperative question-answering benchmark using automated grounding metrics and blinded clinician review. Methods: A benchmark of 250 expert-authored questions (200 in-scope, 20 emergency-intent, 30 out-of-scope) was evaluated on an identical knowledge corpus using Gemini 2.5 Flash for generation and Gemini Embedding-001 for retrieval. Three blinded clinicians rated all 750 outputs; the primary outcome was majority-consensus accuracy across all 250 questions. GraphRAG is a multi-component pipeline that also includes query expansion, a second retrieval stage, evidence fusion, and a monotonic RAG fallback, and is therefore evaluated as a complete hybrid system rather than as graph retrieval in isolation. Results: Overall accuracy was 96.8% (95% CI: 93.8–98.4) for GraphRAG, 94.8% (95% CI: 91.3–96.9) for RAG-only, and 56.0% (95% CI: 49.8–62.0) for KG-only. Both retrieval-augmented systems outperformed KG-only (adjusted p < 0.001). The GraphRAG versus RAG-only difference was 2.0 percentage points, arose from five discordant question pairs and did not reach the Bonferroni-adjusted threshold (exact McNemar p = 0.062; adjusted p = 0.188). The monotonic RAG fallback determined 44.8% of GraphRAG outputs (112 of 250 queries). GraphRAG showed higher context recall (0.851 versus 0.796; adjusted p < 0.001), whereas RAG-only showed higher context precision. Estimated hallucination risk, derived from an LLM-as-a-judge procedure using Gemini 2.5 Flash rather than independent clinical adjudication, was 0.108, 0.132, and 0.436, respectively; the GraphRAG versus RAG-only difference was not significant (adjusted p = 0.771). Inter-rater agreement was high (Fleiss’ kappa = 0.854). Conclusions: Retrieval augmentation, rather than the choice of retrieval architecture, accounted for most of the difference observed. The incremental advantage of GraphRAG over a well-implemented RAG-only system was small, was not statistically significant after correction and reflects the complete hybrid system rather than graph augmentation alone. Emergency-intent accuracy was 75.0% for both retrieval-augmented systems; the architecture is therefore suited to supervised clinical workflows with clinician review, not autonomous patient-facing triage. Prospective validation on authentic patient messages and formal component ablations are required.

Background Disruption in rest‐activity rhythm (RAR) is an emerging risk factor for cardiovascular disease (CVD) and mortality, but the strength of evidence is unclear. Therefore, we conducted a systematic review and meta‐analysis to assess associations between RAR characteristics and cardiovascular disease incidence or prevalence, cardiovascular mortality, and all‐cause mortality. Methods A systematic search was conducted in PubMed, Web of Science, Cochrane Library, and Embase for cohort or cross‐sectional studies published up to August 2025. The exposure variables were nonparametric RAR parameters, including interdaily stability (describing day‐to‐day stability of the RAR), intradaily variability (a measure of RAR fragmentation), and relative amplitude (indicating robustness or strength of the RAR). The primary outcomes were cardiovascular mortality and all‐cause mortality. The secondary outcomes included cardiovascular disease prevalence and incidence. Results Seven studies involving 109 365 participants were included. Pooled results showed that higher intradaily variability was associated with a significantly increased risk of all‐cause mortality (hazard ratio [HR], 1.05 [95% CI, 1.02–1.09]) and cardiovascular disease prevalence (odds ratio, 1.73 [95% CI, 1.21–2.47]). Lower relative amplitude was significantly associated with higher cardiovascular mortality (HR, 1.50 [95% CI, 1.13–1.98]) and all‐cause mortality (HR, 1.46 [95% CI, 1.27–1.68]). Interdaily stability showed no significant associations with any outcome. Conclusions Measures of disrupted rest‐activity rhythms were associated with increased cardiovascular mortality, and all‐cause mortality. These findings support using RAR metrics as early, noninvasive risk indicators. Future work should investigate whether appropriately timed physical activity and sleep, as well as other interventions targeting RAR can mitigate cardiovascular risk.

Abstract Background Late preterm (LP) children (34 0/7 – 36 6/7 weeks of gestation) are at risk for neurocognitive challenges, yet the neuroanatomic and functional disruptions underlying these developmental differences remain poorly understood. Purpose or Hypothesis Investigate (1) regional differences in cortical surface area and thalamic nuclei volume and (2) structural variations that may explain heterogeneity in neurocognitive functioning in LP versus full term (FT) school-aged children, using two complementary approaches: a vertex-wise analysis of cortical surface area and a region-of-interest volumetric analysis of thalamic nuclei. Study Type Secondary analysis of a prospective observational cohort study. Population or Subjects 48 LP and 72 FT children aged 6–13 years. Field Strength/Sequence 3T; Sagittal T1-weighted MP-RAGE and axial T2-weighted 3D SPACE. Assessment FreeSurfer 7.4.1 was used to parcellate cortical regions (Destrieux atlas) and segment thalamic nuclei (25 nuclei). Neurocognitive functioning was assessed across four domains: hyperactivity/inattention (Pediatric Behavior Scale), processing speed (WISC-IV), working memory (WISC-III), and visual-spatial perception (Benton JLO). Statistical Tests Independent samples t-tests for group comparisons; vertex-wise GLMs for cortical surface analyses with false discovery rate (FDR) correction; and multiple linear regression for thalamic nuclei analyses with FDR-corrected q < 0.05. Results Vertex-wise analyses revealed regional differences in cortical surface area between LP and FT children in both hemispheres, along with associations between surface area in several cortical regions and hyperactivity/inattention, working memory, and visual-spatial perception. In contrast, using an ROI approach, thalamic nuclei volumes did not differ between groups and were not associated with any neurocognitive domains. Conclusion LP birth may be associated with subtle, region-specific bidirectional left and right hemispheric cortical surface area differences rather than widespread structural alterations in middle childhood, with regional macrostructural measures associated with individual differences in neurocognitive functioning.

Abstract BCMA-directed CAR T-cell and T-cell engager (TCE) therapies produce high response rates in relapsed multiple myeloma, yet most patients progress. Prior work identified TNFRSF17 alterations mediating antigen escape in up to 43% of TCE progressions. To evaluate the generalizability of these findings and examine antigen-loss-independent resistance, we performed whole-exome sequencing on 32 paired pre- and post-treatment progression bone marrow samples from 15 patients (5 CAR T, 10 TCE); two patients received both agents. TNFRSF17 alterations were infrequent and restricted to TCE recipients (one concurrent frameshift and missense mutation; two heterozygous copy-number losses); no biallelic loss or CAR T-associated events were observed. In contrast, deleterious/loss-of-function variants in NF-κB, PI3K-AKT-mTOR, and MAPK/ERK pathways were universal in pre-treatment samples and acquired or clonally enriched in 80% of patients at progression. Acquired events included loss-of-function alterations in CYLD , activating mutations in KRAS , NRAS and BRAF , and acquired TP53 mutations. In this series, antigen escape via TNFRSF17 /BCMA alteration was uncommon. Instead, pre-existing, acquired and clonally enriched pathogenic variants in NF-κB, PI3K-AKT-mTOR and MAPK cascades, together with TP53 mutation, emerged as a frequent finding. These alterations suggest that deregulation of BCMA-downstream survival signaling, enhanced proliferative fitness, and elevation of apoptotic threshold constitute antigen-loss-independent mechanisms of resistance.

ABSTRACT Aim To systematically review and meta‐analyze cohort studies evaluating associations of gingival inflammation, periodontitis, and tooth loss with cognitive decline and incident mild cognitive impairment or dementia. Methods PROSPERO‐registered searches of MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library identified cohort studies from inception through October 10, 2025, with a PubMed update on June 24, 2026. Random‐effects meta‐analyses pooled adjusted hazard ratios (HRs) for dementia/MCI; cognitive function outcomes were summarized qualitatively. Risk of bias (RoB) was assessed using the Newcastle–Ottawa Scale. Results Fifty‐nine studies met inclusion criteria; 28 contributed to dementia/MCI meta‐analyses. Severe periodontitis (HR: 1.16; 95% CI: 1.06–1.27; I 2 = 0%; Q ‐test p = 0.49), periodontitis of unspecified severity (HR: 1.45; 95% CI: 1.21–1.73; I 2 = 98%; Q ‐test p < 0.001), edentulism (HR: 1.26; 95% CI: 1.19–1.33), and low tooth count (HR: 1.27; 95% CI: 1.14–1.42; I 2 = 94%; Q ‐test p < 0.001) were associated with elevated dementia/MCI risk. RoB was low in 31 studies (53%), moderate in 25 (42%), and high in 3 (5%); inadequate confounder adjustment was common. Meta‐regression showed stronger estimates for ICD‐code periodontitis definitions (fold change (FC) = 1.44 95% CI: 1.04–2.01), older cohorts (FC per year = 1.02 95% CI: 1.00, 1.05), and weaker estimates with lower RoB (FC per NOS star = 0.81 95% CI: 0.73–0.92). Follow‐up duration, cohort age, and RoB were not associated with tooth‐count estimates. Conclusion Periodontitis and tooth loss are associated with modestly higher dementia/MCI risk and poorer cognitive function, but heterogeneity, residual confounding, and bias temper causal interpretation. Longitudinal studies with rigorous baseline cognition assessment and intervention studies are needed.

Abstract Circumscribed meningeal melanocytic neoplasms (CMMNs) represent a spectrum of rare central nervous system (CNS) tumors. Knowledge of their clinical behavior and molecular correlates remains limited. In this single‐institution retrospective study, we analyzed 31 patients (14 male, 17 female; median age, 59 years) diagnosed with CMMN between 2004 and 2025. In this patient cohort, based on the current World Health Organization Central Nervous System Tumor Classification (WHO CNS5) criteria, the majority of cases (18, 58.1%) fell into the intermediate‐grade melanocytic tumor (IMT) category based on histology, with either increased mitotic activity, CNS invasion, or both; 7 (22.6%) were melanocytomas, 5 (16.1%) melanomas, and 1 (3.2%) indeterminate case because of limited tissue. By next‐generation sequencing, mutations were identified in GNAQ/GNA11 in 21/24 cases, BAP1 in 5/23 (2 IMT, 3 melanoma), EIF1AX in 9/21 (1 melanocytoma, 8 IMT), and SF3B1 in 3/23 (2 IMT, 1 melanoma). Primary sites were spinal (20), posterior fossa (6), and supratentorial (5). During follow‐up, progression was observed in 5/6 melanocytomas, 9/13 IMTs, and 4/5 melanomas, suggesting a high frequency of progression across all groups. Two‐year progression‐free survival was 83.3% (95% confidence interval [CI], 53.5%–100.0%) for melanocytoma, 55.9% (95% CI, 26.7%–85.2%) for IMT, and 25.0% (95% CI, 0.0%–67.4%) for melanoma. Five‐year overall survival (OS) was 80.0% (95% CI, 44.9%–100.0%) for melanocytoma, 65.3% (95% CI, 37.0%–93.6%) for IMT, and 0.0% for melanoma. OS was significantly worse in melanoma compared with melanocytoma ( p = 0.002). BAP1 mutation correlated with worse OS (hazard ratio 8.73, p = 0.006). Upfront maximal safe resection appeared to be associated with improved outcomes in selected patients, whereas radiotherapy and systemic therapy did not demonstrate clear additional benefit in this cohort. In summary, our study shows that all CMMNs, irrespective of grade, have a high propensity to recur and melanoma histology and BAP1 mutation are associated with significantly worse OS.

ABSTRACT Background Pulsed field ablation (PFA) is an emerging non‐thermal ablation modality with proven safety in atrial arrhythmia ablation. However, data on its performance for ventricular arrhythmias (VA) remain limited. Objective To evaluate the feasibility, safety, and efficacy of PFA for complex VA in a multicenter real‐world US registry. Methods This retrospective study included consecutive patients undergoing PFA for ventricular tachycardia (VT) or premature ventricular contractions (PVCs) at three Mayo Clinic centers (April 2024 to July 2025). The primary feasibility outcome was the successful delivery of PFA lesions to the intended target substrate. Primary efficacy outcomes included acute procedural success; sustained VT recurrence requiring implantable cardioverter‐defibrillator (ICD) shocks or multiple antitachycardia pacing therapies; and ≥ 80% reduction in PVC burden. Safety outcomes included procedural complications, valvular function, thromboembolic events, renal function, and conduction disturbances. Results Twenty‐six patients were included (13 PVC, 13 VT). Acute success was achieved in all VT ablations (69.2% complete; 30.8% partial) and in 92.3% of PVC ablations. Complications occurred in 11.5% of patients (transient LBBB [ n = 1] and vascular complications [ n = 2]). No thromboembolic events, intracardiac thrombus, or acute kidney injury were observed. Lesions near the mitral valve apparatus did not worsen mitral regurgitation, including in patients with pre‐existing valve disease. After a median follow‐up of 365 days, one patient experienced VT recurrence requiring ICD shocks. Estimated recurrence‐free survival after VT ablation was 61.5% at 12 months; 58.3% of PVC patients achieved ≥ 80% burden reduction. Conclusion PFA for VA appears feasible and acutely effective, with a low rate of procedure‐related complications. While acute success was high, long‐term outcomes were acceptable for VT ablation and relatively modest for PVC ablation, highlighting the need for continued refinement of technology and energy‐delivery strategies. Larger prospective studies are warranted.