Search Results (22,113)

Background/Objectives: Knee osteoarthritis (OA) significantly impairs physical function and quality of life, particularly in women. Although muscle strength and postural stability are known to influence functional outcomes, their independent contributions after controlling for age, body mass index (BMI), and pain remain unclear. This study aimed to investigate the differential roles of lower extremity muscle strength and postural stability on functional status, evaluated through both performance-based tests and patient-reported outcomes, in women with bilateral knee OA. Methods: Sixty-four women with bilateral knee OA (mean age: 55.71 ± 5.99 years) were included in this study. Lower extremity muscle strength was assessed using the five-times sit-to-stand test, and postural stability was evaluated with the Biodex Balance System. Performance-based function was measured using the Six-Minute Walk Test (6MWT) and the stair climbing test (SCT), while self-reported function was assessed using the WOMAC function subscale (WOMAC-F). Hierarchical linear regression analyses were conducted, controlling for age, BMI, and pain. Results: Muscle strength emerged as the strongest independent predictor of performance-based outcomes, significantly contributing to both SCT (β = 0.330, p = 0.005) and 6MWT (β = −0.409, p = 0.001). In the 6MWT model, the effects of age and BMI became non-significant after the inclusion of muscle strength, indicating a mediating role. In contrast, self-reported function (WOMAC-F) was primarily associated with pain (β = 0.385, p = 0.001) and postural stability (β = 0.243, p = 0.040), while muscle strength showed no significant contribution. Conclusions: Muscle strength is the primary determinant of objective functional performance, whereas pain and postural stability are more influential in shaping perceived functional limitations. These findings highlight a dissociation between actual performance and patient-reported function. Rehabilitation strategies should prioritize strength training to improve physical performance, while also addressing pain and balance to enhance patients’ perceived function. Full article

Background/Objectives: The aim of this study was to precisely characterize neurological deficits in patients with idiophatic scoliosis (IS) by comparing preoperative clinical and neurophysiological examination results in patients with Lenke 1 and 3 spinal curvatures. Bracing alone (NTP) is commonly applied preoperatively in subjects with IS, but incorporating the concept of prerehabilitation with additional physiotherapy (TP) may further slow the progression of scoliosis. Methods: An interview regarding the development and conservative treatment of IS, clinical neurological assessment, and bilateral neurophysiological tests involving electromyography (sEMG) of motor unit activity in the paraspinal and lower extremity muscles, electroneurography (ENG) of neural impulse transmission in the peroneal nerve motor fibers and entire efferent conduction involving recordings of motor evoked potentials (MEPs) induced with transcranial magnetic field stimulation (TMS) were performed in patients with Lenke 1 (N = 33) and Lenke 3 (N = 27) spine curvatures in two groups (N = 30 each) that were treated (TP) or not treated (NTP) with physiotherapy. Results: Back pain, assessed on the VAS by all Lenke 3 patients, was 3.3 on average. Limited spine mobility (p < 0.001) was not associated with better results following physiotherapeutic treatment in either Lenke patient group. Sensory perception studies within the L3–S1 dermatomes and vibration sensation tests were found to be slightly decreased in Lenke 3 patients (p < 0.001), predominantly on the concave IS side, but less so in the TP group. Achilles tendon and patellar reflexes were detected as pathological (p < 0.001) only in Lenke 3 patients, and less frequently in the TP group. Asymmetry on the concave side of scoliosis in manual muscle testing scores was found (p < 0.001) in Lenke 3 patients, showing moderate muscle weakness in the distal lower extremities, mainly in the NTP group. sEMG recordings from the paraspinal muscles revealed moderate neurogenic abnormality that was more intense on the concave side of scoliosis curvature, both main and second; the pattern of muscle motor unit activity in the proximal and distal muscles of the lower extremities was consistent with the muscle strength deficits observed in manual muscle testing, though less so in the TP group. Deficits in MEP amplitudes recorded from lower extremity muscles and the peroneal nerve were found to be more commonly expressed on the concave side of the main scoliosis curvature and on the concave side of the second scoliosis curvature, particularly in Lenke 3 patients, but the significance of changes was lower in the TP group (p = 0.03–0.009). ENG studies showed moderate abnormalities in peripheral neural conduction of peroneal nerve motor fibers originating at the L5 ventral root, especially in Lenke 3 patients from the NTP group. Conclusions: Neurological diagnostic tests, supported by selected clinical neurophysiological studies, reveal greater motor and sensory abnormalities in IS patients with Lenke 3 than with Lenke 1 curvatures. The study indicates that patients in both groups who received only bracing had poorer outcomes than those who received additional physiotherapy. In the context of prerehabilitation, a combined conservative treatment approach including physiotherapy can provide functional benefits for the IS patient before the necessary surgical treatment. In this study, differences were observed between the groups treated with physiotherapy and those not treated; however, a causal link cannot be established. The results are consistent with a possible benefit of the physiotherapy, but they require further prospective studies to be proven. Full article

Background: Operating rooms generate substantial visual data that is rarely captured systematically. Image-based AI (IBAI) systems using computer vision offer a new approach to real-time perioperative workflow monitoring, but evidence of their impact on surgical case volume remains limited. The aim of this study was to evaluate the association between deployment of an IBAI system and monthly surgical case volume in a high-acuity cardiothoracic operating suite, using synthetic control with difference-in-differences estimation. Methods: We deployed an IBAI system with wall-mounted cameras and a YOLO-based (You Only Look Once) object detection model coupled with a transformer-based event detector in a 15-room cardiothoracic suite at Houston Methodist Hospital (HMH), the tertiary academic hospital of Houston Methodist health system. The deployment was conducted under an IRB-determined quality improvement framework with patient consent for ambient video capture, defined retention limits, and restricted access to recordings. Over a 16-month period spanning 6 months pre-deployment and 10 months post-deployment, the system monitored 5417 surgical cases and automatically detected additional perioperative events including patient entry, draping, and room turnover. Using a synthetic control methodology, we compared post-deployment outcomes at the intervention site against a weighted combination drawn from a pool of 11 Houston Methodist sites that did not yet implement IBAI (116,098 cases across the comparison sites; 121,515 cases in the full analytic dataset). Results: The synthetic control analysis with difference-in-differences estimation showed a statistically significant increase of approximately 25 cases per month (95% CI 8.3 to 41.0; p < 0.01; Bonferroni-adjusted p < 0.05), corresponding to a 7% increase in monthly case volume relative to baseline. Conclusions: Our findings suggest that IBAI can meaningfully improve OR efficiency and support data-driven perioperative management. Future work should evaluate whether case volume gains generalize across other surgical specialties, assess changes in operational outcomes such as turnover time and first-case on-time starts, and examine clinicians’ perceptions of IBAI. Full article

Background/Objectives: Intermediate vision has become increasingly important after cataract surgery because many daily activities require functional visual performance beyond distance vision alone. Enhanced monofocal intraocular lenses may improve intermediate visual function while maintaining good distance visual acuity. The aim of this study was to compare binocular distance and intermediate visual outcomes after bilateral implantation of Clareon and TECNIS Eyhance intraocular lenses. Methods: This was a single-center, non-randomized comparative observational study with assessment of postoperative visual outcomes. Eighty-six patients who had previously undergone uncomplicated bilateral age-related cataract surgery with implantation of the same IOL model in both eyes were included. Forty-two patients received Clareon IOLs and forty-four patients received TECNIS Eyhance IOLs. Postoperative assessment was performed at least 12 weeks after surgery of the second eye. Binocular corrected distance visual acuity (CDVA) and distance-corrected intermediate visual acuity (DCIVA) were measured using ETDRS charts at 4 m and 66 cm. Results: Baseline biometric and clinical parameters were comparable between groups. Mean postoperative DCIVA was 0.23 ± 0.09 logMAR in the Clareon group and 0.21 ± 0.08 logMAR in the Eyhance group. The mean between-group difference, calculated as Clareon minus Eyhance, was 0.02 logMAR, with a 95% confidence interval from −0.02 to 0.06 logMAR. Mean binocular CDVA was 0.02 ± 0.02 logMAR in the Clareon group and 0.02 ± 0.03 logMAR in the Eyhance group, with a 95% confidence interval for the between-group difference from −0.01 to 0.01 logMAR. Mean postoperative manifest refraction spherical equivalent was −0.27 ± 0.42 D in the Clareon group and −0.29 ± 0.37 D in the Eyhance group. Conclusions: Both Clareon and TECNIS Eyhance IOLs provided good binocular distance and intermediate visual acuity after bilateral implantation. Intermediate visual performance after Clareon implantation was comparable to that achieved with TECNIS Eyhance, while distance visual acuity remained similarly high in both groups. These findings suggest that both IOL models may represent useful options for patients undergoing cataract surgery who expect good distance vision and functional intermediate visual performance. Full article

Objectives: To assess whether outcomes differ in patients with aortic graft and endograft infections (AGEIs) according to therapeutic approach (medical treatment alone versus combined medical and surgical treatment) and to describe in detail the radiological and microbiological features of these infections. Methods: This was a single-centre, observational, retrospective study including patients admitted to Monaldi Hospital, Naples, Italy, with a diagnosis of AGEI between 2005 and 2025. All patients fulfilled MAGIC criteria for definite or suspected AGEI. Results: During the study period, 37 patients were enrolled. According to MAGIC criteria, 25 patients had a definite AGEI, while 12 met criteria for suspected infection. A microbiological diagnosis was obtained in 31 patients (84%), mainly from blood cultures (68%). Medical treatment alone was chosen for 19 patients (51%), whereas 18 patients received combined medical and surgical treatment. Crude 30-day, 90-day and 1-year mortality estimates were similar between treatment groups, whereas crude 3-year mortality was numerically higher in patients receiving medical treatment alone. Kaplan–Meier analysis showed a non-significant difference in survival according to treatment strategy (log-rank p = 0.160). Conclusions: AGEIs remain a severe and often fatal complication. In this small retrospective cohort, no statistically significant survival difference was observed between treatment strategies, although a clinically meaningful benefit of surgery cannot be excluded. Graft location was associated with distinct microbiological patterns and may help guide empirical antimicrobial therapy. Full article

Background/Objectives: Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant malignancies, driven in part by heterogeneous, therapy-resistant glioma stem cells (GSCs). Improving clinical outcomes will require innovative therapeutic approaches that target unique molecular vulnerabilities. The mitogen-activated protein kinase (MAPK) pathway drives tumor progression across multiple cancers, including GBM. MAPK-interacting kinases (MNK1/2) represent MAPK downstream effectors that phosphorylate eukaryotic translation initiation factor 4E (eIF4E), a regulator of oncogenic and anti-apoptotic mRNA translation. We previously identified pharmacological MNK inhibition as a promising therapeutic strategy for GBM, but most available MNK inhibitors lack specificity. Methods: Novel MNK inhibitor compounds were developed using medicinal chemistry optimization and evaluated through molecular docking and kinome profiling analyses. Antineoplastic activity was assessed in established GBM cell lines and patient-derived glioma stem cell models cultured as 3-D neurospheres under stem cell-permissive conditions. Effects on MNK signaling, cell viability, neurosphere growth, migration, invasion, and apoptosis were analyzed using immunoblotting, flow cytometry, viability assays, wound healing assays, and 3-D invasion assays. In addition, a compound screen was performed to identify therapeutic agents that enhance MNK-targeted therapy, followed by validation using pharmacological inhibition and siRNA-mediated knockdown approaches. Results: Our next-generation MNK inhibitor NUCC-201893 exhibited high target specificity and greater potency than the lead compound NU808, effectively suppressing eIF4E phosphorylation, GBM cell viability, neurosphere growth, migration, and invasion. Compound screening identified DNA methyltransferase (DNMT) inhibition as a potent enhancer of MNK blockade. Pharmacological DNMT inhibition enhanced the cytotoxic effects of siRNA-mediated MNK1 knockdown, while concurrent pharmacological inhibition of MNKs and DNMT resulted in greater suppression of neurosphere growth and robust induction of apoptotic responses in GSCs. Conclusions: These findings identify dual MNK and DNMT inhibition as a promising combinatorial strategy that effectively triggers antineoplastic effects in GBM cells and GSCs. Full article

Background: Endothelial dysfunction is a central pathophysiological hallmark of preeclampsia. Laboratory and clinical features of preeclampsia can rapidly deteriorate and evidence on appropriate surveillance strategies is scarce. We aimed to evaluate the prognostic value of longitudinal changes in the “Endothelial Activation and Stress Index” (EASIX) for adverse outcomes in patients with preeclampsia. Methods: Patients with preeclampsia who delivered at Heidelberg University Hospital between 2017 and 2022 were included in this retrospective analysis. We assessed EASIX, derived from lactate dehydrogenase, creatinine and platelets, longitudinally between first admission and diagnosis of an adverse outcome. Composite adverse outcomes included pulmonary edema, HELLP syndrome, kidney injury, eclampsia, postpartum hemorrhage and death. We applied logistic and mixed linear regression modeling adjusted for age, gestational age and body mass index. Results: In total, 1733 EASIX measurements of 443 patients were included in the analysis, of which 81 patients experienced an adverse outcome. Both the first EASIX (aOR 2.81 [1.86;4.37]) and the absolute change per day (aOR 4.35 [1.77; 12.05]) were independently associated with adverse outcomes. Addition of the absolute change in EASIX to the model including the first EASIX (AUC 0.74 [0.68–0.81]) did not substantially improve the discriminatory performance (AUC 0.76 [0.70; 0.82]). Linear mixed regression modeling demonstrated that patients with adverse outcomes had a steeper rise in EASIX compared to patients without adverse outcomes (β = 0.024 [0.013, 0.034]). Conclusions: In patients with preeclampsia, EASIX diverged over time with steeper slopes in patients who developed adverse maternal outcomes. Our findings suggest that longitudinal EASIX monitoring may correlate with endothelial dysfunction and capture individual disease dynamics that are not apparent from a single measurement. Full article

Sarcopenia is highly prevalent among stroke patients and is associated with poor functional outcomes; however, differences across stroke stages and age groups remain unclear. This cross-sectional study enrolled 80 stroke patients from a regional teaching hospital in Taiwan, categorized into chronic (n = 40) and post-acute care (PAC) groups (n = 40), and further stratified into younger (40–64 years, n = 44) and older (≥65 years, n = 36) groups. Assessments included body composition, muscle strength, ultrasound-measured muscle thickness, gait speed, calf circumference, sarcopenia screening (SARC-F), nutritional status, and health-related quality of life. No significant differences were observed in muscle mass, muscle strength, or ultrasound-derived muscle thickness between the chronic and PAC groups. However, the PAC group demonstrated poorer functional outcomes and health-related quality of life, including lower gait speed (p = 0.018), and lower EQ-5D index and visual analogue scale scores (p = 0.006 and p = 0.002, respectively). In contrast, the chronic group showed a higher prevalence of sarcopenia (p < 0.001), a higher mean SARC-F scores (p = 0.004), a greater proportion of low appendicular skeletal muscle mass index (ASMMI, p = 0.025), and reduced calf circumference (p < 0.001). Age-stratified analysis revealed that older patients had lower muscle mass and structural parameters, including ASMMI (p < 0.001), fat-free mass (p < 0.001), quadriceps thickness (p < 0.001), and calf circumference (p = 0.002), along with a higher prevalence of sarcopenia (p < 0.001). These findings indicate that stroke stage is more closely associated with functional impairment, whereas aging predominantly affects muscle mass and sarcopenia severity. Full article

Background/Objectives: Novel vision-language models (VLMs) can integrate patient textual data with image data to support medical diagnosis. Recent studies reported conflicting results regarding the performance of multimodal VLMs compared to other models and physician performance. This systematic review aims to assess the diagnostic performance of multimodal VLMs integrating both patient textual and image data across diverse real-world hospital settings. Methods: We performed comprehensive searches of eight resources, including Embase, MEDLINE, and SCOPUS, on 17 December 2025. Eligible studies reporting diagnostic performance of VLMs integrating both image and patient history textual data from real-world adult patients compared to that of other models and physicians were included. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Prediction model study Risk Of Bias Assessment Tool + AI (PROBAST + AI) was used to assess the quality and risk of bias. The study protocol was registered in the PROSPERO database (CRD420251244054). This review received no external funding. Results: We screened 11,026 records, of which 18 studies met the inclusion criteria. Six studies comparing multimodal and unimodal models demonstrated the consistent superiority of the multimodal models. Four studies evaluating VLM accuracy as standalone agents compared with physician performance reported conflicting evidence. One study assessing VLMs as a clinical copilot demonstrated higher accuracy from the group of physicians using VLM assistance. A meta-analysis could not be performed due to the heterogeneity across study populations and outcomes. The majority of the studies were assessed as having a high risk of bias due to dataset quality. Primary limitations identified across studies include small sample size, a lack of external validation, and the need for prospective clinical deployment studies. No study provided documented considerations regarding model safety or data security. Conclusions: This systematic review suggests that multimodal VLMs consistently outperform unimodal models with access to only image or text. While model performance as standalone agents compared to humans remains inconclusive, a copilot model has demonstrated high diagnostic accuracy. Given substantial methodological concerns across studies, cautious interpretation is required, No firm clinical recommendation can be made regarding the use of standalone VLMs. Further research employing high-quality datasets is needed to ensure the reliability and clinical applicability of future VLMs. Full article

Background/Objectives: Cardiovascular involvement is among the most consequential sequelae of SARS-CoV-2 infection. Myocardial injury, arrhythmia, and thromboembolic disease have been characterized in depth, yet the relationship between COVID-19 and valvular heart disease (VHD), and its interplay with heart failure (HF), has received comparatively limited synthesis. This narrative review consolidates current evidence on the mechanisms, diagnosis, differential assessment, and clinical outcomes linking acute and post-acute COVID-19 to valvular dysfunction and to incident or worsening heart failure, with emphasis on practical implications for cardiologists and internists. Methods: We searched PubMed, Scopus, and Web of Science (January 2020–January 2026) for studies on valvular dysfunction, heart failure, myocardial injury, and endothelial pathology in SARS-CoV-2 infection, and synthesized findings narratively. Results: Convergent pathways—endothelial injury, systemic hyperinflammation, micro- and macrovascular thrombosis, and pressure–volume overload—contribute to functional and, less frequently, structural valvular changes. Available evidence suggests that clinically relevant post-COVID valvular abnormalities are more often secondary/functional (mitral and tricuspid regurgitation) than primary structural lesions, although dedicated prospective valvular studies remain scarce. Pre-existing severe VHD markedly worsens acute COVID-19 prognosis. Elevated NT-proBNP, troponin, and interleukin-6 consistently predict decompensation and mortality, and a substantial minority of survivors show persistent fibrotic pulmonary changes and restrictive ventilatory defects on follow-up (pulmonary rather than cardiac findings). Conclusions: Post-COVID valvular dysfunction appears, on currently available but largely indirect evidence, predominantly functional and inflammation-related, and may overlap with HFpEF phenotypes in selected patients when objective diagnostic criteria are fulfilled. Biomarker-guided, multimodality follow-up is reasonable in high-risk survivors, and prospective longitudinal studies with standardized valvular endpoints remain a priority. Dedicated longitudinal evidence on valvular outcomes specifically remains very limited. Full article

Background/Objectives: Adductor canal blocks (ACBs) are widely used for postoperative analgesia following total knee arthroplasty (TKA). However, the duration of analgesia with a single-shot ACB is limited. Pharmacological adjuncts may enhance and prolong the duration of single-injection blocks, but their efficacy in this setting remains unclear. The aim of this study was to assess the analgesic effectiveness of adjuncts added to local anaesthetic for single-shot ACBs following TKA. Methods: An extensive systematic literature review was performed on Medline, Embase, CINAHL, Cochrane CENTRAL, and Web of Science. Adult patients undergoing primary TKA who received a single-shot ACB with an adjunct added to LA were eligible, with a single-shot ACB with LA alone as the comparator. The primary outcome was postoperative analgesic efficacy, assessed by pain scores (VAS/NRS), time to first rescue analgesia, total postoperative opioid consumption, or sensory block duration. Secondary outcomes included functional recovery measures and adverse events. Risk of bias was evaluated using the Cochrane RoB 2 tool, and the certainty of evidence for each adjunct–outcome combination was assessed using GRADE. Due to clinical heterogeneity, a meta-analysis was not feasible and findings were synthesised narratively. Results: Nine randomised controlled trials (RCTs) assessing the analgesic efficacy of adjuncts added to local anaesthetic in ACB following TKA were included in this review. Adjuncts included dexmedetomidine, dexamethasone, butorphanol, buprenorphine, and magnesium sulphate. Three RCTs demonstrated improvements in early postoperative analgesia with dexmedetomidine at doses of 0.5 µg/kg, while lower doses (0.25 µg/kg) did not. Dexamethasone also decreased early postoperative pain across two RCTs and showed the most evidence for significant prolongation in sensory blockade, with a dose of 4 mg needed to produce significant effects. Butorphanol and buprenorphine demonstrated a significant reduction in postoperative opioid consumption and improved pain, but evidence was limited to single trials. Findings for magnesium were inconsistent. No adjunct was associated with any serious side effect or adverse event. Conclusions: Pharmacological adjuncts added to single-shot ACBs following TKA generally improved early postoperative pain and reduced opioid consumption compared with LA alone, with the most consistent benefits observed for dexmedetomidine (0.5 µg/kg) and dexamethasone (≥4 mg). However, these effects appeared dose-dependent, were largely confined to the first 24 h after surgery, and were supported by moderate-to-low certainty evidence with limited functional outcome data. Further high-quality, adequately powered RCTs with standardised functional endpoints and longer follow-up are required to define optimal dosing, clarify safety, and determine whether improved analgesia translates into meaningful gains in rehabilitation and recovery. Full article

Background/Objectives: Severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) frequently coexist and are associated with type 2 inflammation, leading to poor symptom control and high healthcare burden. Biologic therapies targeting IL-4Rα and IL-5/IL-5R have shown efficacy in type 2 inflammatory asthma and CRSwNP, but comprehensive evidence on their efficacy, safety, and research trends is limited. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating dupilumab, mepolizumab, benralizumab, or reslizumab in patients with type 2 inflammatory asthma and/or CRSwNP. Primary outcomes included lung function (FEV1), symptom control (ACQ, SNOT-22, nasal polyp score), and serious adverse events (SAEs). Risk of bias was assessed using the Cochrane RoB 2.0 tool. Publication bias was evaluated with funnel plots and Trim-and-Fill analysis. Bibliometric analysis was performed to identify publication trends and emerging research directions. Results: A total of 23 RCTs involving 8758 participants were included. Biologic therapy was not associated with a significant increase in serious adverse events (RR = 1.15, 95% CI: 0.89–1.50). Compared with control treatment, biologics significantly improved FEV1 (MD = 100.67 mL, 95% CI: 65.94–135.40) and ACQ scores (MD = −0.40, 95% CI: −0.54 to −0.25). In patients with CRSwNP and comorbid asthma, biologics also improved SNOT-22 scores (MD = −13.16, 95% CI: −24.85 to −1.47) and nasal polyp scores (MD = −1.31, 95% CI: −1.95 to −0.68). Dupilumab trials showed larger reductions in nasal polyp score than IL-5/IL-5R-targeted trials, although this indirect comparison should be interpreted cautiously. Bibliometric analysis indicated increasing research attention to upstream epithelial targets such as TSLP. Conclusions: Both IL-4Rα and IL-5/IL-5R-targeted biologics are effective and well-tolerated in type 2 inflammatory airway diseases. IL-4Rα inhibition shows favorable upper-airway outcomes in CRSwNP with asthma, but head-to-head trials are needed to clarify its comparative efficacy relative to IL-5/IL-5R-targeted therapies. Emerging research directions are shifting toward upstream epithelial alarmin antibodies. Full article

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide. While established molecular biomarkers such as microsatellite instability (MSI), KRAS, and BRAF are routinely used in clinical practice, the prognostic relevance of tumor suppressor proteins p53 and PTEN remains incompletely defined, particularly when assessed using immunohistochemistry. Objective: The primary aim of this study was to evaluate the prognostic significance of p53 expression and PTEN deficiency in colorectal adenocarcinoma. Secondary aims included assessment of their association with clinicopathological characteristics. Methods: This retrospective cohort study included 103 consecutive patients who underwent surgical resection for colorectal adenocarcinoma. Immunohistochemical analysis of formalin-fixed paraffin-embedded (FFPE) tumor samples was performed to assess aberrant p53 expression and PTEN deficiency. Associations with clinicopathological variables were evaluated, and overall survival was analyzed using Kaplan–Meier curves and Cox proportional hazards regression models. Results: Aberrant p53 expression and PTEN deficiency were both associated with shorter overall survival in univariate analyses. Patients with concurrent aberrant p53 expression and PTEN deficiency demonstrated the poorest survival outcomes. However, in multivariate Cox regression analysis, only nodal status and age remained independent predictors of overall survival, while p53 and PTEN did not retain independent prognostic significance after adjustment for clinicopathological variables. Conclusions: Aberrant p53 expression and PTEN deficiency are associated with reduced overall survival in colorectal cancer; however, their prognostic impact appears secondary to established clinicopathological factors. The combined presence of these alterations may identify a biologically aggressive subgroup of patients with particularly unfavorable outcomes, although this observation should be considered exploratory. Further validation in larger, independent cohorts is required. Full article

Background: Metastasis and poor chemotherapy response have stagnated therapeutic progress in osteosarcoma (OS) for the past three decades. Defining the transition from localized to metastatic OS before overt dissemination is fundamental for improving survival. However, effective early diagnostic tools remain scarce, largely due to limited exploitation of the metastasis-associated tumor microenvironment’s own record of prior environmental and stress exposures encoded in cell-intrinsic transcriptional states. Here, we employed a supervised machine learning framework with iterative resampling and multi-stage model selection to identify molecular markers associated with metastasis in osteosarcoma and to develop a computational signature, Auto-RS. Methods: Transcriptomic and clinical data from 139 OS patients with ≥5 years of follow-up were analyzed. A LASSO–Cox framework was applied to derive a gene expression-based risk score, Auto-RS, from which a nomogram integrating age and sex was generated for individualized prognosis. Model interpretability was assessed across six independent single-cell OS patient datasets, and drug sensitivity predictions were inferred by integrating Auto-RS with the Precily algorithm to uncover actionable therapeutic vulnerabilities. Results: Auto-RS, constructed from the expression of four autophagy genes (BNIP3, MYC, PEA15, and SAR1A), served as an independent prognostic factor for overall survival (HR = 1.091; 95% CI, 1.047–1.136; p < 0.001). Time-dependent ROC analysis showed that Auto-RS was the most accurate single predictor (AUC = 0.88), exceeding metastasis (0.83), sex (0.45), and age (0.39). A basic prognostic model (BpM) incorporating metastasis status yielded a C-index of 0.741 (95% CI, 0.679–0.803). The addition of Auto-RS (CpM) improved discrimination (C-index = 0.788; 95% CI, 0.731–0.845), whereas a model without metastasis information (ApM) retained predictive ability (C-index = 0.709; 95% CI, 0.640–0.778). Single-cell analysis confirmed that Auto-RS features aligned with known metastatic trajectories, reflecting the transition from proliferative to invasive tumor states and highlighting coordinated programs among cancer-associated fibroblasts and immune cells. Drug sensitivity integration through Precily identified gemcitabine and cytarabine as FDA-approved agents predicted in silico to show greater sensitivity in the high-risk subgroup. Conclusions: We identified autophagy-mediated transcriptional ‘stress fingerprints’ that are tightly associated with OS metastasis. The Auto-RS signature, composed of BNIP3, MYC, PEA15, and SAR1A, enables early therapeutic stratification of patients independent of overt metastatic status. Moreover, Auto-RS delineates key molecular underpinnings of OS metastasis at single-cell resolution. As a practical laboratory tool, Auto-RS may represent a step toward improved risk stratification, where advances in metastasis prediction and therapeutic guidance converge to improve outcomes in OS. Full article

Background/Objectives: Cranioplasty is a common reconstructive procedure following decompressive craniectomy, yet postoperative complications requiring reoperation remain frequent. Sarcopenia has been associated with adverse surgical outcomes. Temporalis muscle thickness (TMT), readily assessed on routine cranial CT, has been proposed as a surrogate marker of sarcopenia; however, its role in predicting cranioplasty outcomes remains to be established. This study aimed to evaluate the association between TMT and postoperative complications requiring reoperation after cranioplasty. Methods: In this retrospective single-center cohort study, 71 patients undergoing cranioplasty after decompressive craniectomy were included. Patients were stratified according to the occurrence of postoperative complications requiring reoperation into a complication group (n = 28) and an uneventful postoperative course group (n = 43). TMT was measured on preoperative CT scans obtained prior to craniectomy and prior to cranioplasty. Reduced TMT was defined as ≤5 mm. Results: Postoperative complications requiring surgical revision occurred in 39.4% of patients. Reduced TMT (≤5 mm) was significantly associated with greater reoperation risk in univariate analysis (p = 0.003). Patients undergoing surgical revision had significantly lower TMT prior to craniectomy (4.6 mm vs. 5.3 mm; p = 0.03) and TMT remained an independent predictor in multivariate analysis. Conclusions: Reduced TMT is independently associated with an increased risk of postoperative complications after cranioplasty requiring surgical revision and may serve as a simple imaging-based marker for preoperative risk stratification. Full article