Citations

Abstract The liver is organized into tightly regulated zones with distinct metabolic functions but zonation erodes with age. Cellular senescence contributes to aging and liver diseases, however, its impact on aging biology is ill-defined. As part of The Cellular Senescence Network Consortium, we used multiple spatial transcriptomics approaches (GeoMx, Visium, CosMx) with snRNA-seq to profile senescence signatures, zonation markers, and metabolic pathways in livers from wild-type (WT) mice of multiple ages. We observed a loss of canonical zone signatures in aged mouse livers characterized by “expansion” of midlobular (zone 2) marker gene expression, accompanied by diminished expression of zone 3 marker genes by middle-age (18 months), indicative of loss of cell identity. Multiple analytic approaches identified distinct age-, zone- and sex-specific senescence signatures, which were significantly associated with zonation markers changes. This was recapitulated in Ercc1 mutant models of accelerated senescence, supporting a causal role of senescent cells in liver aging. A “no-zone” hepatocyte-like cluster expanded with age and with the strongest Senescence-Associated Secretory Phenotype (SASP) profile. Gene expression profiles from senescent hepatocytes implicate decreased WNT signaling and increased BMP as contributing to age-related loss of zonation. Together, these data elucidate the role of senescent cells in driving aging biology in non-diseased liver through disruption of cell:cell signaling and the loss of metabolic and cell identity gene expression necessary for hepatocyte function.

Background/Objectives: The objective of this study was to evaluate age-specific effects of intraoperative platelet-rich plasma (PRP) administration on postoperative pain, wound healing, and bleeding after tonsillectomy. Methods: PubMed, Embase, Scopus, Google Scholar, and Cochrane databases were searched from inception to October 2025. Randomized controlled trials comparing intraoperative PRP with placebo or no treatment in patients undergoing tonsillectomy were included. Data on postoperative pain, wound healing, and bleeding were extracted and analyzed using standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analyses were performed by age (adults versus children) and by postoperative day. Results: Nine randomized controlled trials comprising 442 participants were included. In adults, PRP significantly reduced postoperative pain (SMD = −1.26 [−1.70 to −0.81]) and improved wound healing (SMD = −1.43 [−2.65 to −0.22]). The analgesic effect was greatest during the early recovery period (postoperative days 0–5) and diminished thereafter. There were no significant differences in primary postoperative bleeding (OR = 0.49 [0.04 to 5.61]) or secondary postoperative bleeding (OR = 0.23 [0.02 to 2.16]) between the PRP and control groups. In children, PRP did not significantly affect pain or bleeding outcomes. Conclusions: Intraoperative PRP may reduce early postoperative pain and may promote mucosal recovery in adults. However, its clinical efficacy in children remains unclear. Further well-designed, age-stratified trials are warranted to clarify the role of PRP in enhancing postoperative recovery.

This guideline has been updated. This ASCO Living Guideline is reviewed on an eight-week cycle. Please see the online dynamic version for the latest updates. Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual . ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines . Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See appendix for disclaimers and other important information ( Appendix 1 and Appendix 2 , online only). Updates are published regularly and can be found on the ASCO Publications website .

BACKGROUND: Accurate assessment of left ventricular outflow tract (LVOT) gradients is critical for hypertrophic cardiomyopathy management, yet Doppler-based measurements are technically demanding and require expertise. The objective of this work was to develop a multi-view deep learning model capable of classifying LVOT obstruction (>20 mm Hg) using routine 2-dimensional echocardiographic windows without reliance on Doppler imaging. METHODS: We trained and externally validated a cross-attention-based video-to-video fusion framework that integrated EchoPrime-derived video representations from 3 standard transthoracic echocardiographic views to classify LVOT gradients. RESULTS: Training was performed on a derivation cohort (N=1833) from a tertiary care system in the United States, with model performance evaluated on an internally held-out test set (N=275) and a Korean external validation cohort (N=46). Single-view baselines showed limited discrimination (external area under the receiver operating curves, 0.47–0.70). Conversely, the domain-specific foundational model (EchoPrime) achieved superior single-view performance (area under the receiver operating curves, 0.75–0.80 internal; 0.79–0.83 external), highlighting the importance of echo-specific pretraining and temporal modeling. The proposed multi-view fusion further enhanced predictive performance, with the late fusion model reaching an area under the receiver operating curve of 0.84 on the external cohort with significant population-shift. CONCLUSIONS: These results suggest LVOT physiology is encoded in routine 2-dimensional imaging and can be leveraged for clinically relevant gradient classification without Doppler input. The proposed artificial intelligence-guided strategy demonstrates substantial cost savings compared with the screen-all approach. By integrating complementary spatial-temporal information across multiple views, our approach generalizes robustly across populations and may enable real-time decision support, extend LVOT assessment to portable or resource-limited settings, and complement Doppler-based evaluation for longitudinal hypertrophic cardiomyopathy management.

Abstract Rationale Mechanically ventilated intensive care unit patients receive sedatives based on clinician observations of arousal and motor activity with potential for negative consequences and poor mitigation of symptoms. Objectives To test the preliminary efficacy of patient self-managed sedative therapy compared to usual care of nurse-administered sedation on self-reported anxiety, duration of mechanical ventilation, and delirium incidence (CAM-ICU). Methods A two-group, open-label, randomized, multicenter clinical trial in 5 Midwestern hospitals enrolled 161 patients receiving invasive mechanical ventilation who were willing and able to use a push-button device to self-administer sedation for up to 7 days. Patients were randomized 1:1 using center-stratified blocks to usual care (n = 81) or intervention (n = 80) with self-administered dexmedetomidine. Intervention patients were allowed 3 self-administered dexmedetomidine boluses per hour (0.25 mcg/kg) with 20-minute lock-outs. The initial basal infusion (0.2 mcg/kg/hr) was adjusted by nurses between 0.1-0.7 mcg/kg/hr based on patient-delivered boluses in the prior 2 hours. Analysis consisted of linear mixed-effects model for comparisons of anxiety ratings over time and duration of mechanical ventilation. Incidence of delirium was analyzed using generalized estimating equations. Measurement and Main Results Sample characteristics had a female (54.7%) and Caucasian preponderance (92.5%) with a median age of 62 years on protocol for a median of 88 hours. Nine intervention patients were extubated prior to protocol initiation. Patient self-reported three times daily anxiety ratings with a visual analog scale (VAS) ranged from 0-100 over time but were not significantly different between groups in either an intention-to-treat (ITT) or per protocol (PP) analysis (p = 0.94, p = 0.30 respectively). While intervention patients had shorter duration of MV [(mean 50.8(52.8) vs. usual care 68.7(58.2) hours), p = 0.02 ITT], PP analysis resulted in no difference between groups (mean 56.4 (53.0) vs. 68.7(58.2), p = 0.23). 10.2% of intervention patients developed new incidence of delirium vs. 8.5% of usual care which was not significantly different between groups by either ITT (p = 0.65) or PP analyses (p = 0.58). Conclusions Intervention patients had similar outcomes compared to usual care patients. Self-administration of sedative therapy is a safe, novel patient-centered intervention warranting further rigorous investigation for anxiety self-management.

Urinary urea is a key biomarker for tracking protein oxidation and nitrogen balance. A persistent analytical limitation is that conventional total-nitrogen assays do not deconvolute urinary urea from urinary ammonia, and direct measurement still requires capital-intensive clinical analyzers. Here, we implement and independently validate two cost-effective methods that resolve urinary urea by pairing the presence and absence of urease: Method 1 is a urease-coupled potentiometric assay using an ammonium ion-selective electrode (ISE method); Method 2 is a microplate Berthelot–salicylate colorimetric assay employing a repurposed consumer-grade aquarium ammonia test kit (API®) (API method). Each method was validated against the Roche Cobas C311 clinical analyzer (ISE for urinary ammonia and API for urinary urea) in healthy adult volunteers (n = 10 each), and API–ISE were then compared head-to-head for urinary urea. ISE vs. Cobas yielded R2 = 0.967, slope 95% CI [0.867, 1.173], and Bland–Altman bias of −1.02 mM (95% LoA [−7.40, +5.36] mM). API vs. Cobas yielded R2 = 0.973, slope 95% CI [0.790, 1.039], and bias of −1.55 mM (95% LoA [−11.56, +8.46] mM). API–ISE urinary urea comparison confirmed mutual agreement (R2 = 0.9976, slope 95% CI [0.946, 1.024]; bias of +3.47 mM; 95% LoA [−14.60, +21.53] mM), with mean recoveries near 100% (API: 100.7 ± 2.9%; ISE: 100.6 ± 5.4%; 20–350 mM). Both methods agreed with the clinical analyzer, supporting their potential for decentralized, resource-limited testing; clinical and point-of-care validations are needed.

BMT CTN 1506 ("MORPHO") was a phase 3 study of post-hematopoietic cell transplantation (HCT) maintenance with gilteritinib versus placebo for patients with FLT3-ITD-mutated acute myeloid leukemia (AML) in first remission. Subgroup analysis indicated a significant benefit of post-HCT gilteritinib for participants in North America, but no benefit for those in Europe or Asia. We conducted a post-hoc analysis of the data focusing on days from AML diagnosis to HCT, pre-HCT FLT3 inhibitor use, and FLT3-ITD measurable residual disease (MRD). Participants transplanted < 120 days from AML diagnosis and/or those treated with FLT3 inhibition pre-HCT were more likely to have improved survival from post-HCT gilteritinib. Pre-HCT MRD levels were higher (P = 0.001) in participants transplanted within 120 days from diagnosis and in those treated with a FLT3 inhibitor pre-HCT and transplanted within 120 days (P = 0.008). Pre-HCT MRD was dependent on both FLT3 inhibitor use and time to HCT, as participants treated with successive courses of chemotherapy + FLT3 inhibition had successively lower MRD by the time of HCT. Time from AML diagnosis to HCT and pre-HCT FLT3 inhibitor use both appeared to impact MRD levels immediately prior to HCT, and geographic differences in these two practice patterns likely accounted for the observed regional differences in benefit from post-HCT gilteritinib. Increasing the number of courses of treatment pre-HCT may lower MRD sufficiently to eliminate the need for post-HCT inhibition, but with a presumed risk of some patients experiencing early progression. This trial was registered at www.clinicaltrials.gov as #NCT02997202.

ABSTRACT Background Mycobacterium genavense is a rare opportunistic non-tuberculous mycobacterium primarily reported in advanced human immunodeficiency virus infection. Case Summary A 70-year-old woman with systemic lupus erythematosus developed progressive abdominal pain, weight loss, and mesenteric lymphadenitis repeatedly responsive to corticosteroids. Endoscopic biopsies revealed abundant acid-fast bacilli, and molecular testing confirmed the presence of M. genavense . Treatment with azithromycin, ethambutol, and rifabutin led to gradual recovery. Conclusion Steroid-responsive mesenteric inflammation in immunocompromised patients should prompt evaluation for infection, including mycobacteria and other culture-negative microorganisms using molecular diagnostics. This case report highlights the importance of plasma microbial cell-free DNA assays in the identification of fastidious organisms, like M. genavense , and, in some cases, serial testing may be useful to monitor treatment response.

Bachmann's bundle (BB) pacing is an emerging physiological atrial pacing strategy designed to preserve interatrial conduction and coordinated atrial activation. Conventional right atrial appendage pacing may produce non-physiological activation, contributing to atrial dyssynchrony, impaired left atrial function, and increased risk of atrial fibrillation. Because BB is the predominant pathway for right-to-left atrial conduction, targeted BB pacing can shorten the P-wave duration and improve atrial synchrony. Recent fluoroscopic, electrogram-guided, and P-wave morphology criteria have improved confirmation of BB capture. Available studies suggest that BB pacing is feasible and generally safe, with potential benefits in reducing the burden of atrial arrhythmias. However, the long-term clinical outcomes remain uncertain. Larger prospective studies are needed to standardize BB capture criteria, define optimal patient selection, and assess long-term outcomes.

Hospital medicine offers diverse career opportunities, yet formal guidance for residents pursuing hospitalist careers is often lacking. To address this gap, the Hospital Internal Medicine Interest Group (HIMIG) was launched at an academic institution in the Southeastern United States to provide structured mentorship and professional development. Residents expressing interest completed an entry survey to identify career goals and areas of focus, informing a longitudinal curriculum that included education, leadership, research, quality improvement, and networking. Seventeen residents (≈25% of the IM residency program) joined HIMIG, and 88% completed the initial survey. Education, leadership, and quality improvement were top interests, while mentorship and career guidance were primary motivators. A post-implementation survey revealed all participants met mentors and felt HIMIG supported their career goals. HIMIG demonstrates a flexible, personalized approach to hospitalist career development that may serve as a model for other programs.