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Importance Patients with recurrent prostate cancer after previous radiotherapy typically have poor survival. Those with recurrences prostate confined might be suitable for salvage focal therapy (sFT) or salvage radical prostatectomy (sRP). sFT may offer good cancer control with comparatively less toxic effects, but outcomes beyond 5 years have not been reported, and no study has compared sFT to sRP. Objective To compare cancer control and perioperative complications among patients after sFT vs sRP. Design, Setting, and Participants In this international, multicenter cohort study of matched comparison data, patients undergoing sFT were derived from the prospective UK HIFU (high-intensity focused ultrasound) Evaluation and Treatment and International Cryotherapy Evaluation registries (9 centers; 2006-2024) and the prospective UK Focal Recurrent Assessment and Salvage Treatment cohort study (6 centers; 2014-2018). Patients undergoing sRP were derived from an international retrospective registry (12 centers in 8 countries; 2000-2021). Patients with biopsy-confirmed, localized recurrent prostate cancer postradiotherapy, either external beam radiotherapy, brachytherapy, or both, were included. Data were analyzed from March to July 2025. Exposures sFT using HIFU or cryotherapy vs sRP. Main Outcomes and Measures The primary outcome was cancer-specific survival up to 10 years. Secondary outcomes were overall survival, any perioperative complications (Clavien-Dindo grades 1-5), and major perioperative complications (Clavien-Dindo grades 3-5). Comparisons were made on matched patients following 1:1 cardinality matching within individual multiply-imputed datasets. Matching variables used were radiotherapeutic treatment, years between primary and salvage treatments, European Association of Urology recurrence risk group, and presalvage age, prostate-specific antigen, prostate volume, grade group, T stage, and androgen-deprivation therapy use. Results A total of 923 patients were eligible for matching (419 undergoing sFT and 504 undergoing sRP). Of the patients undergoing sFT, 325 (77.6%) underwent HIFU and the remainder cryotherapy, with 241 (57.5%) treated with quadrant ablation. Of patients treated with sRP, 376 (74.6%) underwent open surgery and the remainder robot-assisted surgery. For sFT vs sRP, 10-year cancer-specific survival was 92% (95% CI, 86%-98%) vs 99% (95% CI, 97%-100%), with no statistically significant difference (restricted mean time lost, −0.09 years; 95% CI, −0.22 to 0.03 years; P = .15; subdistribution hazard ratio, 0.45; 95% CI, 0.05-4.00; P = .47). There was no statistically significant difference in 10-year overall survival (restricted mean survival time, −0.13 years; 95% CI, −0.86 to 0.60 years; P = .72). Undergoing sRP was associated with statistically significant higher odds of any complication (adjusted odds ratio, 24.20; 95% CI, 12.94-45.27; P < .001) and major complication (adjusted odds ratio, 9.31; 95% CI, 3.42-25.36; P < .001). Conclusions and Relevance In this cohort study, sFT and sRP were effective for treating localized radiorecurrent prostate cancer, while sFT was associated with fewer perioperative complications. sFT may provide a favorable therapeutic ratio for many patients with localized radiorecurrent prostate cancer.

Abstract Glioblastomas exhibit low immunogenicity and a highly immunosuppressive tumor microenvironment (TME) mediated by both tumor cells and tumor associated microglia/macrophages (TAMs). However, biomarkers that allow for specific detection, monitoring and therapy response assessment of the TAM phenotype in glioblastoma are still lacking. To address this gap, we characterized the dynamics of TAM clusters in the TME of experimental SB28 glioblastoma using single-cell RNA sequencing, immunofluorescence, and molecular imaging and identified Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) as a dynamic TAM-specific target. Consequently, we investigated a novel 64 Cu-labeled TREM2 radiotracer with a blood-brain barrier transport vehicle for translational mapping of TAMs in the TME of glioblastoma. We found strong and highly myeloid cell-specific PET signals that followed the trajectory of TREM2 gene expression from early- towards late-stage tumors. Transient myeloid cell depletion via CSF1R inhibition showed a reduction of TREM2 PET signals compared to placebo and prolonged survival in SB28 glioblastoma mice, while TREM2 stimulation led to increased TREM2 PET signals. Translation into a pilot cohort of patients with glioblastoma revealed strong TREM2 PET signals predominantly at lesion edges and high heterogeneity across individuals, matching with immunohistochemistry. In summary, TREM2 PET imaging has strong potential as an immune cell-specific biomarker for personalized assessment of the TAM phenotype in the TME of patients with glioblastoma.

Convergent framework for future POC cancer diagnostics aligning clinical needs (why), enabling technologies (how), and translational bridges. It integrates lab-on-chip biosensing and analytics for decentralized, early, longitudinal care.

INTRODUCTION: The American College of Gastroenterology assembled a multidisciplinary task force to evaluate the current state and future direction of artificial intelligence (AI) in gastroenterology, hepatology, and endoscopy leading to the development of consensus-based recommendations for responsible AI integration in clinical practice. METHODS: A total of 32 subject-matter experts and 12 industry partners, representing diverse practice settings and expertise, conducted subgroup literature reviews across 5 key areas (endoscopy, practice management clinical applications, training and education, inflammatory bowel disease and liver disease, ethics and equity). Draft statements were developed and rated on a 5-point Likert scale using a modified Delphi process. A consensus was set at ≥70% combined agreement. Nonconsensus items were revised and revoted electronically. RESULTS: A total of 43 statements, 40 (93%) reached consensus in round 1 and the remaining 3 achieved consensus after round 2. Evidence supports computer-aided detection improving adenoma detection rate and miss rate in controlled studies, with mixed real-world impact and insufficient long-term outcomes (e.g., interval colon cancer rate). Recommendations emphasize thorough validation and reduction of bias by heterogeneous Data sets. Outside endoscopy, ambient AI scribes, natural language processing (NLP)-enabled coding, workflow optimization, and previous authorization support show potential. Training recommendations endorse a structured AI curriculum while preserving independent procedural competence to avoid deskilling. In inflammatory bowel disease and hepatology, AI could help improve diagnostic accuracy, help predict risk of disease progression, and help guide therapy. Equity, governance, and reimbursement statements call for chain-of-custody data protections, specialty-society oversight, and payment models that reward quality and cost reduction. DISCUSSION: This consensus outlines how AI can augment rather than replace clinical expertise while promoting safety, transparency, interoperability, and equity. Priorities include pragmatic and prospective trials, multi-institutional data-sharing consortia, bias mitigation, and workforce training to enable trustworthy and clinically impactful AI adoption in gastroenterology, liver, and endoscopy care.

BACKGROUND AND OBJECTIVES: En bloc spondylectomies are essential for controlling malignant spinal tumors, but existing classification systems are often complex and impractical. This study introduces the Column, Line-of-Sight, Margins, Ring (CLiMR) framework, a novel system simplifying and standardizing en bloc spondylectomy planning and classification. METHODS: A retrospective review of patients who underwent single- or multistage en bloc spinal tumor resections was conducted at a single academic center (October 2019-December 2024). The CLiMR framework assigns scores to 4 components: Column (osteotomies/diskectomies for tumor release), Line-of-Sight (approach for circumferential access), Margin (adjacent structures sacrificed), and Ring (size of the vertebral ring window for safe delivery of neural tissue). Scores were applied using operative notes and imaging. RESULTS: Column scores ranged from 0.5 to 4.5. Of the patients included, 40.9% underwent sagittal split osteotomies, 22.7% radical diskectomies, 18.2% horizontal osteotomies, and the remaining 18.2% combinations of previous osteotomies . A posterior-only approach (Line-of-Sight score = 1) was used in 45.4% of cases, whereas 45.4% required a multistage approach (score = 2). Margin scores reflected increasing morbidity: 31.8% (n = 7) involving chest wall/pleura resection (grade 3), 40.9% (n = 9) requiring eloquent nerve sacrifice (grade 6), and 9.1% (n = 2) necessitating limb sacrifice (grade 7). The majority (86.4%, n = 19) of ring scores were grade 1, requiring laminectomies/facetectomies. The mean CLiMR score was 9.36 ± 2.43, with higher scores correlating with longer hospital stays (R = 0.64, P = .0012), longer case durations (R = 0.61, P = .0023), and increased blood loss (R = 0.40, P = .067). Patients with local recurrence, positive margins, or complications trended toward greater CLiMR scores. CONCLUSION: The CLiMR framework provides a novel, user-friendly method for planning and communicating en bloc spondylectomies. By addressing technical complexities and morbidity, CLiMR enables standardized assessment, facilitates surgical decision-making, and supports future research. This study demonstrates feasibility and lays the foundation for future validation studies.

Abstract Recurrence scores based on a 21-gene assay are clinically useful for predicting prognosis and chemotherapy benefit in postmenopausal node-positive breast cancer patients, but its performance in premenopausal patients is inconsistent. Here, we evaluated Ataraxis Breast RISK (ATX), an AI test that predicts recurrence risk, and compared it with the genomic assay. ATX identified high risk patients misclassified as low risk by the genomic assay and therefore may refine selection of patients for adjuvant chemotherapy.

Abstract Background In randomized clinical trials (RCTs), anticipating control arm outcomes is important for power calculations and enrollment goals. Unexpected overperformance of the control arm can underpower RCTs. The objective of this study was to estimate the prevalence of control arm overperformance in phase 3 oncology RCTs. Methods The authors conducted a meta‐epidemiological study of two‐arm, superiority‐design, phase 3 oncology RCTs. They reviewed articles/publications and protocols for power calculations, justification, and outcomes. Control arm performance was measured as the ratio of observed control arm outcomes relative to pretrial estimates, and overperformance was defined as a 10% improvement. Results In total, 385 RCTs met inclusion criteria. The primary end point was overall survival (OS) in 134 RCTs (35%). Of 311 RCTs (81%) that provided a pretrial estimate for control arm performance, 138 RCTs (44%) cited a justification for the estimate. Greater than expected control arm performance was associated with lower odds of meeting the primary end point (adjusted odds ratio, 0.989; 95% confidence interval, 0.981–0.998; p = 0.015). Of 244 RCTs that were evaluable for control arm performance, 104 (43%) exhibited overperformance. RCTs that used OS as a primary end point were more likely to exhibit control arm overperformance compared with RCTs that used other primary end points (56% vs. 33%; adjusted odds ratio, 2.43; 95% confidence interval, 1.42–4.15; p = .001). Conclusions Control arm overperformance is common in phase 3 oncology RCTs and is associated with trial outcomes, suggesting an effect on study power. Because overperformance appears to be especially prevalent when OS is the primary end point, the effects of postprogression therapies on OS may be underappreciated. Alternative strategies for designing trials should be considered for reliable estimation of treatment effects.

NF-κB activating protein (NKAP) plays important roles in various cancers, including breast cancer. However, its expression and prognosis value in breast cancer remains uncertain. Gene expression profiling interactive analysis, Human protein atlas database, and University of Alabama at Birmingham Cancer data analysis portal database were used to predict the expression and prognostic value of NKAP in breast cancer. Immunohistochemistry, quantitative real time polymerase chain reaction (qRT-PCR) and western blot were performed to detect NKAP expression. The effects of NKAP on cell proliferation, migration and drug sensitivity were investigated in MDA-MB-231 and SK-BR-3 cells. NKAP protein expression differed in breast cancer tissues and paraneoplastic tissues based on the cancer genome atlas data. The high NKAP expression was significantly correlated with a poor prognosis in breast cancer patients. The results of immunohistochemistry, western blot assay, and qRT-PCR proved that NKAP was highly expressed in breast cancer tissues compared with paraneoplastic tissues. In addition, qRT-PCR results showed that high expression of NKAP was significantly correlated with the larger tumor size and higher TNM stage. Moreover, knockdown of NKAP significantly inhibited the proliferation, migration, and enhanced drug sensitivity of MDA-MB-231 and SK-BR-3 cells. NKAP is highly expressed in breast cancer tissues, and its high expression is closely associated with poor prognosis. NKAP also promotes proliferation, migration, and inhibits drug sensitivity of breast cancer cells.

Background: A critical component of conducting systematic reviews or meta-analyses is assessing the methodological quality and bias of included studies. Several methodological quality assessment tools have been developed; however, these tools may not be relevant to observational sports medicine research, which carries numerous unique nuances and biases. Purpose: To develop the Sport Publication Observational Research Tool (SPORT), which evaluates and scores the methodological quality of observational sports medicine research. Study Design: Consensus statement. Methods: SPORT was developed through a modified Delphi approach involving members from the Herodicus Society and The FORUM. All active members were invited to participate in the process aimed at building consensus on SPORT content and scoring. After finalizing SPORT, a power analysis led to the independent selection of 55 observational clinical sports medicine studies, which were scored twice by 4 reviewers of varying training levels. Interrater and intrarater reliability for SPORT was assessed using intraclass correlation coefficients (ICCs). The distribution and percentiles for total SPORT score across the 55 studies were calculated. SPORT was also compared with the methodological index for non-randomized studies (MINORS), a commonly utilized quality assessment tool. Results: A total of 51 members participated and achieved 100%, 100%, 98.0%, and 98.0% completion rates for rounds 1 through 4, respectively. The final SPORT included 19 subscores related to methodological quality and bias and achieved 94% consensus approval. Mean SPORT completion time was 6 minutes and 19 seconds per study, which varied significantly by reviewer training level. The subscore "peer review" demonstrated unacceptable reliability and was removed. The remaining 18 subscores exhibited ICC ranges of 0.599 to 0.955 for interrater reliability and 0.530 to 0.936 for intrarater reliability. Total SPORT score demonstrated excellent agreement, for interrater (ICC, 0.967) and intrarater reliability (ICC, 0.966). Median SPORT score across the 55 studies was 20.0 and skewed toward lower scores. There was a moderate significant correlation between SPORT and MINORS ( r [53] = 0.575; P < .001). Conclusion: An objective tool to assess the methodologic quality of observational sports medicine research (SPORT) was successfully developed through a modified Delphi approach with numerous content experts in the field. This tool may be useful in assessing the methodological quality of primary observational sports medicine studies included in systematic reviews and meta-analyses.