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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.

Background: Sexual dimorphism in the facial skeleton is fundamental to aesthetics and gender perception. This study employs AI-assisted three-dimensional (3D) imaging to analyze morphological differences between males and females in the upper, mid, and lower facial regions. Methods: A retrospective analysis was conducted on 280 high-resolution craniofacial CT scans (147 females, 133 males) of adults aged 20 years and older. AI-assisted segmentation and modeling were performed using Materialise Mimics and 3-Matic software. The facial skeleton was divided into upper, mid, and lower regions for detailed morphometric evaluation. Statistical shape modeling (SSM) and heatmaps were used to visualize surface projection differences across age groups. Statistical comparisons were conducted to assess gender-based variation. Results: Significant sexual dimorphism was observed across all facial regions. In the upper face, males had greater interorbital width, frontotemporal brow width, inter-medial canthi distance, and more prominent frontal bossing. In the midface, males exhibited increased width, depth, and vertical height, with the most pronounced differences occurring in middle age. The lower face showed larger mandibular dimensions in males, including bigonial width, ramus height, and a sharper mental angle, while females had a more rounded chin and smoother mandibular contour. Heatmaps confirmed greater surface projection in male skeletons, particularly in the gonial and midfacial regions, with dimorphism decreasing with age. Conclusion: This represents the first large-sample CT study utilizing AI to comprehensively quantify facial skeletal dimorphism. Findings support the importance of gender-specific planning in facial reconstructive and aesthetic procedures.

BACKGROUND: Obstructed defecation syndrome and posterior compartment (rectal) prolapse significantly impact patients’ quality of life. Pelvic floor physical therapy is a critical part of multidisciplinary management for these conditions, yet there is little guidance or standardization to guide providers’ referral practices, diagnostic approaches, or treatment. OBJECTIVE: To develop multidisciplinary consensus-based recommendations for incorporating pelvic floor physical therapy into the treatment of obstructed defecation syndrome and posterior compartment prolapse. DATA SOURCES: MEDLINE, PubMed, Embase, and the Cochrane Database of Systematic Reviews were searched for English-language studies on pelvic floor physical therapy, obstructed defecation, diagnostic criteria, imaging, and pelvic organ prolapse. STUDY SELECTION: Studies identified in the literature search were reviewed by multidisciplinary expert subgroups, who formulated draft statements based on the available evidence. INTERVENTION: Consensus meetings were conducted and included experts from colorectal surgery, urogynecology, physical therapy, gastroenterology, radiology, and urology. Statements were evaluated via structured discussions and voting processes. Those reaching more than 70% consensus were adopted for inclusion. Statements underwent final review and editing by the leadership of the American Society of Colon and Rectal Surgeons and the International Urogynecological Association. MAIN OUTCOME MEASURES: Consensus statements addressed referral criteria, diagnostic evaluations, therapy protocols, timing, coordination with surgery, and management of anatomical abnormalities. RESULTS: Fifteen statements reached consensus. Key recommendations included prompt referral to pelvic floor physical therapy for patients without contraindications, individualized therapy based on appropriate diagnostic evaluation and patient goals, timing of pelvic floor physical therapy relative to surgery, and trauma-informed patient care. LIMITATIONS: Recommendations primarily reflect expert consensus due to limited high-quality evidence. Variability in practitioner expertise and geographic access to trained therapists are barriers to consistent implementation. CONCLUSIONS: These recommendations provide structured guidance for integrating pelvic floor physical therapy into the management of obstructed defecation syndrome and rectal prolapse. Additional research and standardized training are essential to optimize patient outcomes.

INTRODUCTION: Colonoscopies reduce colorectal cancer incidence and mortality, but challenges remain in detecting all precancerous lesions. Operator fatigue, technique variability, and subtle lesions can lead to missed adenomas, highlighting the need for tools that standardize detection quality. Computer-aided detection (CADe) systems use artificial intelligence to enhance lesion detection and improve screening colonoscopy quality. This study evaluates the impact of CADe on key quality and efficiency metrics in a clinical setting. METHODS: A single-center retrospective study at an academic tertiary center analyzed 4,028 colonoscopies from October 2022 to December 2023. The CADe system was used in 4 of 8 endoscopy suites, creating a CADe and control group. Propensity matching accounted for age, sex, indication, and physician. Primary outcomes included adenoma detection rate (ADR) and polyp detection rate (PDR). Adenomas per colonoscopy (APC) and polyps per colonoscopy (PPC) were also measured. Per-polyp analyses were performed as a tertiary outcome. RESULTS: ADR was significantly higher in the CADe group (38.6%) vs control (34.2%) (rate ratio [RR] = 1.127, P < 0.05). PDR was significantly higher in the CADe group (67.2%) vs control (59.4%) (RR = 1.130, P < 0.05). APC was significantly higher in the CADe group (M = 0.406, SD 0.637) vs control (M = 0.359, SD 0.599) (RR = 1.131, P < 0.05). PPC was significantly higher in the CADe group (M = 1.297, SD 1.188) vs control (M = 1.046, SD 1.002) (RR = 1.240, P < 0.05). The increase in polyp resection with CADe was driven predominantly by ≤5 mm lesions, with comparatively smaller differences for larger polyps. DISCUSSION: Implementing CADe in clinical practice significantly improved ADR, PDR, APC, and PPC. However, the increase in ADR seems inflated by the detection of polyps ≤5 mm, whose clinical significance in reducing colorectal cancer remains uncertain.

INTRODUCTION: Chronic gastroduodenal disorders are highly prevalent and encompass heterogeneous pathophysiology. Autonomic dysfunction may contribute, but its relative contribution to disease pathophysiology and symptoms is unclear. This study aimed to clarify the contributions of autonomic dysfunction in gastroduodenal disorders and symptom associations using multimodal testing, hypothesizing that distinct disorder subgroups would be revealed. METHODS: This prospective observational cohort study included 80 patients with chronic gastroduodenal symptoms. Participants underwent expert clinician-led autonomic evaluation, body surface gastric mapping (BSGM; Gastric Alimetry, New Zealand), and gastric emptying scintigraphy testing. BSGM phenotyping, gastric emptying cutoffs, and autonomic criteria followed standard criteria. RESULTS: Gastroparesis was diagnosed in 27 (33.8%) patients. Autonomic dysfunction was present in 21 (26.3%) patients, and abnormal BSGM in 20 (25%). Autonomic dysfunction and abnormal BSGM were both more prevalent in gastroparesis (51.9% vs 13.2%, P = 0.001; and 44.4% vs 15.1%, P = 0.005, respectively). However, these diagnoses tended not to overlap, with patients having autonomic dysfunction generally exhibiting normal BSGM tests. Autonomic dysfunction independently predicted delayed gastric emptying (OR 13.8, P < 0.001) and was associated with earlier meal responses (higher meal response ratio, P = 0.04) and worse postprandial distress symptoms ( P < 0.05). DISCUSSION: Autonomic dysfunction independently predicted delayed gastric emptying and revealed a gastroparesis mechanism distinct from gastric myoelectrical impairment. Autonomic dysfunction altered the postprandial gastric motor response and was associated with a greater symptom burden. Multimodal physiological testing including autonomic profiling reveals distinct mechanistic subgroups in patients with chronic gastroduodenal symptoms.

BACKGROUND: The incidence of early-onset colorectal cancer is rising, yet survivorship care guidelines rarely address concerns unique to younger adults. Although treatment for colorectal cancer can have devastating consequences related to sexual function and fertility, these issues remain underrecognized and seldom addressed. OBJECTIVE: To better understand the impact of colorectal cancer diagnosis and treatment on sexual and reproductive health. DESIGN: Qualitative study of patients with early-onset colorectal cancer. SETTINGS: Semi-structured one-to-one Zoom interviews of patients recruited through convenience sampling from 7 academic institutions. PATIENTS: Sixty-three individuals diagnosed with colorectal cancer aged 50 years or younger were interviewed between March 2021 and August 2024. MAIN OUTCOME MEASURES: Patient perspectives regarding the sexual and reproductive health impacts of colorectal cancer diagnosis and treatment. Data were analyzed iteratively using directed and conventional qualitative content analysis. RESULTS: Participants discussed sexual and reproductive health side effects resulting from surgery, chemotherapy, and radiation. These side effects ranged in severity, with some experiencing almost none and others facing significant issues. They identified several domains, including surgical and treatment side effects, psychological impacts, effects on relationships, and unmet needs. Subdomains included sexual health, reproductive health, emotional distress, body image, communication challenges, impacts on dating, informational needs, financial support, and consultations. LIMITATIONS: Participants were recruited from academic medical centers only, and as such, responses may not reflect the experiences of those cared for in nonacademic settings. CONCLUSIONS: Sexual and reproductive health are critical but often overlooked concerns among younger patients with CRC, with significant impacts on physical functioning, partner relationships, and psychological well-being. Current survivorship guidelines fail to adequately address these needs. Our findings highlight the importance of pretreatment counseling and fertility preservation as well as the need for ongoing mental health support during and after cancer treatment. See Video Abstract . «NADIE ME LO DIJO»: ESTUDIO CUALITATIVO SOBRE LAS PREOCUPACIONES SEXUALES Y REPRODUCTIVAS TRAS EL TRATAMIENTO DEL CÁNCER COLORRECTAL DE APARICIÓN TEMPRANA ANTECEDENTES: La incidencia del cáncer colorrectal de aparición temprana está aumentando, pero las directrices sobre cuidados para supervivientes rara vez abordan las preocupaciones específicas de los adultos jóvenes. Aunque el tratamiento del cáncer colorrectal puede tener consecuencias devastadoras para la función sexual y la fertilidad, estas cuestiones siguen sin reconocerse lo suficiente y rara vez se abordan. OBJETIVO: Comprender mejor el impacto del diagnóstico y el tratamiento del cáncer colorrectal en la salud sexual y reproductiva. DISEÑO: Estudio cualitativo de pacientes con cáncer colorrectal de aparición temprana. ENTORNO: Entrevistas individuales semiestructuradas por Zoom a pacientes reclutados mediante muestreo por conveniencia en siete instituciones académicas. PACIENTES: Se entrevistó a 63 personas diagnosticadas con cáncer colorrectal antes de los 50 años entre marzo de 2021 y agosto de 2024. PRINCIPALES MEDIDAS DE RESULTADOS: Perspectivas de los pacientes sobre el impacto del diagnóstico y el tratamiento del cáncer colorrectal en la salud sexual y reproductiva. Los datos se analizaron de forma iterativa mediante un análisis de contenido cualitativo dirigido y convencional. RESULTADOS: Los participantes discutieron los efectos secundarios en la salud sexual y reproductiva derivados de la cirugía, la quimioterapia y la radiación. Estos efectos secundarios variaban en gravedad, ya que algunos no experimentaban casi ninguno y otros se enfrentaban a problemas importantes. Identificaron varios ámbitos, entre ellos los efectos secundarios de la cirugía y el tratamiento, las repercusiones psicológicas, los efectos en las relaciones y las necesidades no satisfechas. Los subámbitos incluían la salud sexual, la salud reproductiva, el malestar emocional, la imagen corporal, los problemas de comunicación, las repercusiones en las relaciones sentimentales, las necesidades de información, el apoyo financiero y las consultas. LIMITACIONES: Los participantes fueron reclutados únicamente en centros médicos académicos, por lo que es posible que las respuestas no reflejen las experiencias de las personas atendidas en entornos no académicos. CONCLUSIONES: La salud sexual y reproductiva son cuestiones fundamentales, pero a menudo se pasan por alto entre los pacientes jóvenes con CCR, con repercusiones significativas en el funcionamiento físico, las relaciones de pareja y el bienestar psicológico. Las directrices actuales para la supervivencia no abordan adecuadamente estas necesidades. Nuestros hallazgos ponen de relieve la importancia del asesoramiento previo al tratamiento y la preservación de la fertilidad, así como la necesidad de un apoyo continuo a la salud mental durante y después del tratamiento del cáncer. (AI-generated translation )

Abstract Motivation Illumina DNA methylation arrays have evolved rapidly, expanding genomic coverage while introducing backward incompatibilities by removing many CpG sites present in earlier versions. These changes result in systematic missing values when integrating data across array generations and substantially limiting the reuse of legacy datasets. Results We developed a two-stage framework for imputing missing DNA methylation values. The procedure first imputes randomly missing values using standard imputation techniques and then addresses systematic missingness using multi-output machine learning models, including support vector regression, nearest-neighbor methods, random forest models, and deep neural networks. When evaluated on real datasets with up to fifty percent induced missingness, the proposed framework consistently outperformed conventional imputation approaches. It also accurately imputes the missing CpG sites between methylation arrays and reduced representation bisulfite sequencing data, enabling robust cross-platform data integration. Analyses of large brain tumor methylation datasets demonstrate that the method restores array-specific methylation patterns while preserving biological complexity. Importantly, imputing missing methylation sites significantly improves the performance of epigenetic age prediction models. Availability and implementation This tool is implemented in the Python package “ultra-impute,” freely available at https://github.com/liguowang/ultra-impute. A code snippet demonstrating the usage of the ultra-impute package is provided in a Jupyter Notebook (https://github.com/liguowang/ultra-impute/blob/master/doc/Tutorial.ipynb).

ABSTRACT Background Factor XI/XIa inhibitors are emerging anticoagulants with potential to reduce bleeding complications in atrial fibrillation (AF) patients. This meta‐analysis evaluated their efficacy and safety compared to direct oral anticoagulants (DOACs) and explored dose optimization. Methods A systematic search of PubMed, Cochrane, and Embase was conducted through March 2025 following PRISMA guidelines. Randomized controlled trials (RCTs) comparing Factor XI/XIa inhibitors with DOACs in AF patients were included. Outcomes assessed were major bleeding, stroke, systemic embolism, all‐cause and cardiovascular mortality and serious adverse events. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a Mantel‐Haenszel random‐effects model. Heterogeneity was evaluated with the I² statistic, and evidence certainty assessed by the GRADE approach. Trial Sequential Analysis (TSA) was performed. Results Three RCTs including 16,772 patients (mean age 73 years, CHA₂DS₂‐VASc 3.9–5) were analyzed. Factor XI/XIa inhibitors significantly reduced major bleeding (RR: 0.41, 95% CI: 0.36–0.46, I² = 0%) compared to DOACs. However, stroke risk was increased (RR: 3.42, 95% CI: 2.62–4.46), particularly with asundexian 50 mg (RR: 4.02). No significant differences were observed in all‐cause mortality (RR: 0.82) or cardiovascular death (RR: 1.05). Systemic embolism risk was higher (RR: 4.26), while serious adverse events were comparable (RR: 0.95). TSA indicated encouraging safety outcomes but highlighted the need for further large‐scale studies. Conclusion Factor XI/XIa inhibitors lower major bleeding risk in AF patients but increase stroke and systemic embolism rates without impacting mortality.