Citations

Breast biopsy markers have evolved from simple metallic devices to sophisticated multimaterial tools that have become essential for breast cancer care, demonstrating their clinical benefits in surgical planning, radiation targeting, and cost reduction.

Importance Thirty-day hospital readmission is used to guide postdischarge care; however, a single binary 30-day estimate does not distinguish when risk occurs from when intervention is most actionable, with implications for allocation of postdischarge resources. Objective To evaluate time-structured hospital readmission risk within 30 days after discharge and implications for clinical utility. Design, Setting, and Participants Retrospective prognostic study of adults with hospital discharges from 2017 to 2024 (from 19 hospitals within a US health system for the development cohort) and 2008 to 2019 (from Medical Information Mart for Intensive Care IV for the external cohort) with 30-day follow-up. Analyses were conducted from November 2025 through June 2026. Exposure Postdischarge prediction window, including landmark intervals of 0 to 7, 8 to 14, 15 to 21, and 22 to 30 days and cumulative horizons through days 7, 14, 21, and 30 after discharge. Main Outcomes and Measures First all-cause hospital readmission before death during each landmark interval and by each cumulative horizon. Risk estimates were derived using clinical information available at hospital discharge. Performance was assessed using discrimination, calibration, decision curves, and capacity-constrained analyses. Results Among 617 841 discharges in the development cohort, the median (IQR) patient age was 65 (50-76) years, and 315 220 discharges (51.0%) occurred among female patients. The 30-day readmission rate was 16.3% (95% CI, 16.2%-16.5%), with 68 797 readmissions (68.2%) occurring within 14 days. Cumulative-horizon analyses characterized readmission risk through days 7, 14, 21, and 30, whereas landmark interval-specific analyses showed lower positive predictive values (PPVs) beyond day 7. At 5% intervention capacity, landmark PPVs were 58.3% (95% CI, 57.4%-59.1%) for days 0 to 7, 16.0% (95% CI, 15.5%-16.6%) for days 8 to 14, 14.5% (95% CI, 13.9%-15.0%) for days 15 to 21, and 12.9% (95% CI, 12.4% to 13.5%) for days 22 to 30; numbers needed to prevent 1 readmission were 8.6, 31.3, 34.6, and 38.6, respectively. Conclusions and Relevance In this prognostic study of adult hospital discharges, hospital readmission risk varied over time and was not captured by a single binary 30-day estimate. These findings suggest that time-structured readmission modeling can characterize when readmission risk occurs, but additional work is needed before such models can reliably guide interventions during specific postdischarge intervals.

Abstract INTRODUCTION Centiloid (CL) scaling standardizes amyloid positron emission tomography (PET) quantification across tracers and platforms; however, variability across software implementations may affect diagnostic classification. This study evaluated inter‐software variability and diagnostic performance across five platforms using identical 1 8 F‐florbetapir datasets. METHODS Retrospectively, 192 patients undergoing 1 8 F‐florbetapir PET/computed tomography (CT) and magnetic resonance imaging (MRI) were analyzed. CL values were generated using four US Food and Drug Administration (FDA) ‐cleared platforms and an in‐house Centiloid standard pipeline. Agreement was assessed using intraclass correlation coefficient, with bias and limits of agreement evaluated by linear modeling and Bland–Altman analysis. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis and classification against visual interpretation. RESULTS Agreement was excellent (intraclass correlation coefficient [ICC] 0.969; 95%CI 0.961–0.975). Some platforms produced systematically higher CL values versus others slightly lower. LoA reached ± 30 CL. Diagnostic accuracy was high (area under the curve [AUC]: 0.949–0.975), with sensitivity 0.923–0.968 and specificity 0.667–0.806. DISCUSSION Despite excellent agreement, systematic differences persist and may affect classification near thresholds, supporting consistent use of a single processing pipeline.

Aims Extensor mechanism disruption is a major complication following total knee arthroplasty, with treatment often consisting of extensor mechanism reconstruction utilizing monofilament polypropylene mesh (Marlex mesh, C. R. Bard, Inc). Infection following this procedure is devastating, often resulting in revision surgery and mesh removal, with permanent limb dysfunction. This study evaluated the in vitro ability of vancomycin-loaded polypropylene mesh to inhibit growth of isolates of three Staphylococcus species from patients with periprosthetic joint infection. Methods The mesh was prepared in two configurations – single-layer and eight-layer – and soaked for ten minutes in either sterile water (control) or vancomycin solution (50 mg/ml), after which the mesh was placed on tryptic soy agar plates inoculated with staphylococci and incubated at 37°C for 18 to 24 hours. Zones of inhibition were measured daily over seven days, with mesh transferred to freshly inoculated plates daily. Testing was performed in triplicate, with experiments repeated three times for each bacterial isolate. A total of 30 clinical isolates were tested (five methicillin-susceptible Staphylococcus epidermidis , five methicillin-resistant S. epidermidis , ten methicillin-resistant Staphylococcus aureus , and ten Staphylococcus lugdunensis ). Results Across all species, the eight-layer vancomycin-loaded mesh produced statistically significantly larger median zones of inhibition than the single-layer mesh. The antibacterial activity of the eight-layer mesh persisted through to day 7, while the single-layer mesh showed reduced activity by days 4 to 5. Conclusion Compared with single-layer vancomycin-loaded mesh, multilayer vancomycin-loaded mesh, which mimics clinical application, provides enhanced and sustained antibacterial activity in vitro. Cite this article: Bone Joint Res 2026;15(8):998–1004.

PURPOSE Age ≥40 years is regarded as a high-risk feature and an indication for adjuvant chemoradiotherapy for patients with lower-grade glioma in clinical practice guidelines. It is unclear whether age remains a relevant prognostic factor for contemporary definitions of lower-grade gliomas in the molecular era. METHODS The Prospective Gliomas Research (PROGRES) database contains individual patient-level data from 11 prospective clinical trials or observational registries of histologically defined lower-grade 2-3 oligodendroglioma or astrocytoma. We determined the association of age (18-39 years v ≥40 years) with progression-free survival (PFS) stratified by isocitrate dehydrogenase 1 or 2 ( IDH1/2 ) status, using log-rank tests and Cox regression models. We validated our findings in a separate multi-institutional retrospective cohort (Retrospective Glioma Research [REGRES] database). RESULTS We identified 1,619 and 1,292 eligible patients in the PROGRES and REGRES cohorts, respectively. IDH -wildtype tumors were more common in patients 40 years and older (38% v 5%, odds ratio: 11.3 [95% CI, 6.5 to 19.7]). Age was associated with PFS in IDH -wildtype (5-year PFS for ≥40 v 18-39 years: 6% v 24%, hazard ratio [HR], 1.74 [95% CI, 1.21 to 2.50]) but not in IDH -mutant glioma (60% v 59%, HR, 0.89 [95% CI, 0.76 to 1.05], P interaction < .001). In IDH -wildtype tumors, older age predicted aggressive molecular features, including TERT promoter mutation (65% v 28%), EGFR amplification (41% v 15%), and chromosome +7/–10 alteration (57% v 25%). In a pooled analysis of four clinical trials, age was not predictive of a benefit from chemoradiotherapy versus radiotherapy alone for IDH -mutant glioma. CONCLUSION In the absence of additional clinical or molecular risk factors, age alone should not be considered an indication for administration or deferral of adjuvant treatment. Practice guidelines should be revised to reflect contemporary prognostic factors in the molecular era.

Abstract Background Meningiomas lack effective therapies for recurrent or aggressive disease. NF2 inactivation, commonly in meningioma, may sensitize tumors to FAK inhibition and interact with MAPK signaling. This study investigated the therapeutic activity of defactinib (FAK inhibitor) and avutometinib (RAF/MEK inhibitor) alone and in combination in preclinical meningioma models. Methods MAPK-altered meningioma cell lines, IOMM-Lee (NF2 wild-type, BRAF p.V600E) and CH157-MN (NF2 mutant, NRAS p.Q61K), BenMen-1 (NF2 mutant, MAPK wild-type), and three patient-derived NF2 mutant cell lines were cultured in matrigel and treated with defactinib and avutometinib in 3D cell viability assays. In vivo, flank and intracranial xenograft models of IOMM-Lee and CH157-MN were treated with VS-4718 (FAK inhibitor, superior pharmokinetics in mice), avutometinib, or combination. Tumor growth, survival, and pharmacokinetic/pharmacodynamic properties were assessed. Results In vitro, combination therapy showed synergistic or additive effects in CH157-MN and IOMM-Lee cells, respectively. Defactinib alone demonstrated activity in NF2-mutant patient-derived and BenMen-1 cells, while avutometinib did not. In vivo, avutometinib monotherapy suppressed tumor growth and extended survival in both flank and intracranial xenograft models, with evidence of favorable pharmacokinetic properties and target pathway inhibition in intracranial tumors. Combination therapy provided enhanced and sustained control of flank CH157-MN meningioma compared to avutometinib alone but did not significantly improve survival over avutometinib alone in intracranial models. Conclusions Avutometinib demonstrated robust anti-tumor effects in flank and intracranial models of MAPK-altered meningioma. Combination benefits were context dependent. Defactinib activity in NF2-mutant patient-derived cells without targetable MAPK-kinase alterations highlights the importance of genomic biomarkers to guide personalized strategies.

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.

Abstract SV40 Large T antigen (LT) is essential for viral replication and a key determinant of host range. This host-range function is mediated by the C-terminal domain (LT-C) through binding to the host serine protease FAM111A, but the underlying mechanism has remained unclear. Here, we report the X-ray crystal structure of the FAM111A serine protease domain in complex with LT-C, revealing the structural basis for direct inhibition of FAM111A. LT-C uses a previously unrecognized zinc-binding motif and a P1-like phenylalanine residue to engage the FAM111A active site through a substrate-mimicking mechanism while avoiding proteolytic cleavage and covalent complex formation. Mutations disrupting either feature abolish FAM111A inhibition and impair SV40 propagation in cells. Consistent with this mechanism, SV40 host restriction requires FAM111A protease activity, which must be antagonized by LT-C for productive infection. Together, these findings define a zinc-dependent, cleavage-avoiding mechanism of protease inhibition that highlights an evolutionary arms race between SV40 and host antiviral proteases.

Background Poor financial literacy and financial behaviors negatively affect the wellness and professional duties of residents and fellow physicians. Major financial missteps can create significant personal stress, leading to worsening wellness and burnout. There are currently no available comprehensive financial literacy curricula for residents and fellows for educators to use to address this gap. Methods We created and assessed the educational impact of a comprehensive 4-module curriculum that covers fundamental personal finance topics which are universally applicable to all physicians regardless of their medical and surgical specialty. We delivered the entire curriculum 6 times between November 2023 and December 2024 to anesthesia residents, internal medicine residents, and critical care fellows. We assessed their self-reported baseline financial behaviors and their knowledge and self-efficacy with core financial topics using pretest and posttest surveys. Results For the 4 modules respectively, 66 (25%), 39 (15%), 44 (17%), and 35 (13%) of 260 possible trainees completed surveys. Self-efficacy significantly increased for creating a financial plan (p<0.001), investing (p<0.001), designing a debt payoff strategy (p=0.005), selecting an asset allocation (p<0.001), selecting optimal asset locations (p<0.001), and selecting appropriate health (p<0.001)/life (p<0.001)/disability (p<0.001) insurance plans. Resident knowledge significantly increased from pretest to posttest for all 4 modules: Financial Plan & Basics of Investing (p<0.001), Budgeting & Debt Management (p=0.010), Retirement Accounts & Asset Allocation (p<0.001), and Insurance (p<0.001). Mean trainee satisfaction with the overall curriculum on a 5-point scale (1-low, 5-high) was 4.2 (standard deviation 0.8). Conclusions We identified poor baseline financial literacy and behaviors in our resident and fellow physicians. This prioritized curriculum effectively adapted to the needs of multiple different training programs and was highly desired by trainees. This curriculum increased their knowledge and self-efficacy with several key topics in personal finance.