Search Results (1,583)

Background: Cardiovascular (CV) risk is increased in psoriatic arthritis (PsA), yet vascular assessment has largely focused on carotid arteries, potentially underestimating systemic atherosclerosis. Objective: The objective of this study was to characterize the distribution and concordance of atherosclerotic plaques across carotid, femoral, and aortic territories in PsA and evaluate their incremental value over SCORE2. Methods: In this cross-sectional study, 250 unselected patients with PsA underwent carotid and femoral ultrasound and abdominal X-ray. Plaque prevalence and multiterritorial involvement (≥2 vascular beds) were assessed. Agreement between territories was evaluated using Cohen’s κ. In patients aged 50–69 years, the incremental value of vascular territories over SCORE2 was evaluated using ROC curves, bootstrap-corrected decision curve analysis (DCA), and reclassification metrics (IDI and continuous NRI). Results: Plaques were detected in carotid (36.0%), femoral (62.8%), and aortic (31.6%) territories, with multiterritorial involvement in 43.2%. Agreement between vascular beds was moderate (κ ≈ 0.35). Notably, 48.1% of patients without carotid plaques had femoral involvement. SCORE2 categories showed a strong gradient with plaque prevalence (p < 0.0001). In patients aged 50–69 years, adding vascular imaging improved discrimination for multiterritorial disease (AUC 0.73 vs. 0.86–0.90). Reclassification analyses demonstrated that carotid plaque substantially improved the identification of multiterritorial atherosclerosis (IDI 0.32, 95% CI 0.18–0.50; continuous NRI 1.33, 95% CI 1.08–1.60), with similar results observed for aortic plaque (IDI 0.33, 95% CI 0.20–0.50; continuous NRI 1.24, 95% CI 0.99–1.48). Femoral plaque provided a more modest improvement (IDI 0.26, 95% CI 0.16–0.37; continuous NRI 1.11, 95% CI 0.80–1.33). Conversely, when the outcome was defined as the presence of any plaque, femoral plaque provided the greatest incremental value over SCORE2 (AUC 0.96, 95% CI 0.93–0.99). Bootstrap-corrected DCA confirmed improved net benefit. Conclusions: The incremental value of vascular imaging over SCORE2 appears to be phenotype-dependent. Femoral plaque provided the greatest improvement for detecting the presence of subclinical atherosclerosis, whereas carotid and aortic plaques offered greater incremental value for identifying multiterritorial vascular involvement. These findings support a tailored, multiterritorial approach to cardiovascular risk assessment in patients with PsA. Full article

Background/Objectives. Automated lateral ventricle volumetry is increasingly used in population-based neuroimaging, but correlation between methods does not establish agreement of absolute volumes. We quantified agreement and calibration between FreeSurfer and a visually quality-controlled FSL/FAST–ALVIN lateral ventricle workflow within the Study of Health in Pomerania (SHIP). Methods. This cross-sectional agreement-and-calibration study included 2988 SHIP participants with visually accepted FSL/FAST–ALVIN total lateral ventricle volumes; paired FreeSurfer data were available for 1913 participants. FSL/FAST–ALVIN was treated as the study reference scale rather than biological ground truth. Agreement was assessed using Pearson and Spearman correlations, Bland–Altman analysis, log-ratio agreement, Lin’s concordance correlation coefficient, and a two-way mixed-effects single-measure absolute agreement intraclass correlation coefficient. Directional calibration models predicted FSL/FAST–ALVIN volume from FreeSurfer volume and were internally validated using 2000 bootstrap resamples. Results. In the paired sample, volumes were almost perfectly associated (Pearson r = 0.9978; Spearman ρ = 0.9974), but FreeSurfer yielded systematically lower values (mean FreeSurfer-minus-FSL bias, −3.02 mL; 95% limits of agreement, −4.52 to −1.53 mL; geometric mean FreeSurfer/FSL ratio, 0.844). Lin’s concordance coefficient and the absolute agreement ICC were both 0.9598. Calibration was strong but workflow-specific: FSL/FAST–ALVIN volume = 2.611 + 1.0210 × FreeSurfer volume (R2 = 0.9955; optimism-corrected RMSE = 0.732 mL). Conclusions. FreeSurfer and visually quality-controlled FSL/FAST–ALVIN preserved participant ranking extremely well but were not directly interchangeable as absolute measurements. Cross-workflow comparisons require explicit method reporting, formal agreement analysis, and calibration to the intended measurement scale; the equation should not be used as a universal conversion formula outside comparable acquisition, segmentation, QC and software settings. Full article

Background/objectives: Catheter-related bloodstream infection (CRBSI) is a frequent and morbid complication in catheter-dependent maintenance hemodialysis, and rapid risk stratification is needed while awaiting cultures. This study aimed to evaluate admission complete blood count-derived indices—neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and pan-immune-inflammation value (PIV)—for identifying CRBSI. Methods: This single-center retrospective study (1 January 2011–31 October 2024) included adult catheter-dependent hemodialysis patients classified as CRBSI or controls. CRBSI required compatible clinical findings and concordant growth of the same microorganism(s) in paired simultaneous catheter and peripheral blood cultures. Controls were hospitalized for non-infectious reasons without infection during the index admission. Indices were calculated from admission blood counts. Discrimination was assessed using ROC analysis, and adjusted associations were evaluated using multivariable logistic regression. Results: Among 286 patients (147 CRBSI, 139 controls), CRBSI cases had higher NLR, SII, and PIV and lower LMR; PLR did not differ. NLR showed the numerically highest discriminatory performance among the evaluated indices (AUC 0.737; cut-off 5.96; sensitivity 68.7%, specificity 68.3%; p < 0.001). SII (cut-off 1189.21; AUC 0.693) and PIV (cut-off 821.62; AUC 0.686) had moderate discrimination, and LMR was modest (cut-off 1.65; AUC 0.642); PLR was not discriminatory (AUC 0.559; p = 0.086). In models adjusted for age, sex, hypertension, and cardiovascular disease, NLR remained associated with CRBSI (OR 1.159; p < 0.001), together with hypertension (OR 2.441; p = 0.017) and cardiovascular disease (OR 2.626; p < 0.001). Conclusions: Admission hematologic inflammation indices, particularly NLR, showed moderate ability to discriminate CRBSI from non-infectious admissions in catheter-dependent hemodialysis patients and may provide rapid adjunctive information while awaiting microbiological confirmation. Full article

Background: The growing complexity of liquid biopsy in precision oncology demands a structured classification framework that can accommodate its expanding multi-omic scope. As the field has matured from early Tumor Microemboli research—focused on multicellular clusters of circulating tumor cells (CTCs) that drive high-efficiency metastasis—to the broader systemic analysis of the “Tumor Microenvironment” (TME) encompassing malignant and non-malignant components, the need for a hierarchical taxonomy has become evident. Objective: To integrate these diverse data streams into a coherent clinical framework, a multi-tiered classification system is needed. This review proposes a foundational roadmap that formally distinguishes the systemic ecosystem from its physical and functional subsets and highlights their clinical utility in therapeutic decision-making. Proposed Taxonomy: We advocate for the adoption of Circulating Tumor Microenvironment (cTME) as the inclusive term for the systemic environment, encompassing non-cellular factors such as ctDNA, extracellular vesicles, and biophysical attributes. Conversely, physical cellular clusters should be strictly classified as Circulating Tumor Emboli (CTE). Crucially, we define Circulating Tumor-Associated Cells (C-TACs) as the functional cellular subset within the cTME, encompassing single CTCs, CTE, and supporting non-malignant cells like CTECs and CAFs. Clinical Applications: Establishing this distinction allows for the seamless integration of molecular profiling (NGS) and functional assays. We highlight emerging evidence that C-TACs may serve as the primary substrate for Chemo-Response Profiling (CRP), with early proof-of-concept studies reporting high concordance with clinical outcomes that still await independent prospective confirmation. Furthermore, preliminary evidence suggests that identifying these functional units, particularly perioperative CTE, may help predict the efficacy of adjuvant chemotherapy in early-stage malignancies, although this remains to be confirmed in prospective studies. Conclusions: Adopting this unified taxonomy may help advance precision oncology. By recognizing the cTME as the superordinate ecosystem and C-TACs as its functional executors, clinicians may be better positioned to interpret multi-modal liquid biopsy data, providing a conceptual roadmap for integrating these technologies into platforms for personalized cancer management. We emphasize that this framework is intended to be hypothesis-generating and that its clinical applications require prospective validation before routine adoption. Full article

Background: Oesophagogastric cancer is associated with poor survival and major alterations in body composition. This study investigated the relationship between myopenia and myosteatosis in patients with oesophagogastric cancer and evaluated their prognostic significance and association with systemic inflammation. Methods: In this retrospective single-centre study, 161 consecutive patients diagnosed with oesophagogastric cancer between 2019 and 2023 underwent computed tomography-based body-composition analysis at diagnosis. Skeletal muscle index (SMI) and skeletal muscle density (SMD) were measured at the third lumbar vertebra. Myopenia and myosteatosis were defined using Martin’s criteria. Associations with overall survival (OS) and progression-free survival (PFS), and systemic inflammation assessed using C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), were analysed using Kaplan–Meier and Cox regression analyses. Results: Among the 161 patients included (67.1% male; median age 66 years), myopenia and myosteatosis were highly prevalent (62.7% and 87.6%, respectively), despite a median body mass index (BMI) within the normal range. Lowest SMI tertile was significantly associated with poorer OS and PFS, whereas lowest SMD tertile showed markedly reduced OS. On multivariate analyses, lower SMD remained independently associated with OS and with PFS, whereas SMI lost significance after adjustment for clinical and inflammatory factors. The coexistence of myopenia and myosteatosis was associated with significantly worse survival outcomes. An exploratory continuous muscle score integrating muscle quantity and muscle quality was associated with OS (hazard ratio 1.28 per SD increase) and demonstrated moderate prognostic discrimination (concordance-index 0.63). Conclusions: Muscle quantity and quality represent complementary dimensions of cancer-associated muscle impairment in oesophagogastric cancer. Collectively, these results suggest that a continuous measure integrating both muscle quantity and muscle quality provides a more clinically informative assessment of muscle impairment than traditional binary definitions of myopenia and myosteatosis. Full article

Invasive candidiasis caused by drug-resistant Candida species represents a critical global health challenge, with few novel therapeutic scaffolds under development. Here, silver nanoparticles were synthesized using a 21-day fermented Chun Mee kombucha tea extract (K-AgNPs) and characterized by UV-Vis spectroscopy, transmission electron microscopy, nanoparticle tracking analysis, and Fourier-transform infrared spectroscopy. LC-MS/MS profiling of the kombucha substrate documented a phytochemical landscape dominated by epigallocatechin (up to 122,631 µg/mL) and epigallocatechin gallate (up to 415 µg/mL), with a progressive ~80% decline in epicatechin and concomitant increases in gallic acid and chlorogenic acid across the 21-day fermentation. K-AgNPs obtained were spherical, 19.4 nm (±7.9 nm SD) in diameter, with a surface plasmon resonance peak at 415 nm. FTIR confirmed phenolic, carboxylate, and glycosidic surface capping. Antifungal susceptibility testing against eight Candida species, including the WHO critical–priority pathogen Candidozyma auris, showed concordant minimum inhibitory and minimum fungicidal concentrations of 0.80–1.60 µg/mL, confirming fungicidal activity. In vivo evaluation in Galleria mellonella larvae across six infection models demonstrated that K-AgNP treatment at the species-specific MIC significantly improved larval survival versus untreated infected controls (p < 0.01–0.001), while nanoparticle-only groups maintained ≥98% survival, indicating negligible toxicity. Co-treatment amplified total hemocyte mobilization, and K-AgNP-only larvae maintained hemocyte viability above 96% at all time points, indistinguishable from negative controls. Together, these findings demonstrate antifungal activity of K-AgNPs across the genus Candida in standardized in vitro and in vivo settings and provide justification for further investigation, including head-to-head comparison against licensed antifungals and physicochemical validation of nanoparticle stability under assay conditions. Full article

Background/Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication in osteoporosis patients undergoing tooth extraction. This study aimed to develop and evaluate an interpretable, machine learning–derived triage score for rapid risk stratification at the initial dental visit. Methods: This retrospective study included 850 osteoporosis patients (443 MRONJ, 407 controls) in the derivation cohort and 559 independent multicenter MRONJ cases for external evaluation. A reference random forest model identified a hierarchical feature structure, which was translated into an additive integer-weighted scoring system through systematic hyperparameter optimization. Structural tipping points were identified using isotonic regression and first discrete derivative analysis. Internal performance was further characterized by sensitivity, specificity, PPV, NPV, calibration slope and intercept, the Hosmer–Lemeshow test, decision curve analysis, bootstrap optimism correction, and subgroup analyses. External evaluation assessed three-tier distribution concordance and case capture rates with non-inferiority testing. Results: The reference random forest achieved an AUC of 0.792. The final MRONJ triage score (range 0–17) incorporated six binary predictors with mutually exclusive drug route categories. The triage score preserved discriminative performance (AUC 0.772; ΔAUC = 0.020; p = 0.149). Two tipping points at scores 7 and 14 defined three risk tiers: low (0–6; 20.9%), moderate (7–13; 55.3%), and high (≥14; 83.5%). At the moderate-risk threshold (≥7), the score achieved sensitivity 90.3% (95% CI 87.2–92.7%) and specificity 45.0% (40.2–49.8%); at the high-risk threshold (≥14), specificity rose to 91.4% and PPV to 83.1%. Calibration was adequate (slope 0.994; intercept 0.0006; Hosmer–Lemeshow p = 0.381), and decision curve analysis demonstrated higher net benefit than reference strategies across all clinically relevant threshold probabilities. The bootstrap optimism-corrected AUC was 0.778, and discriminative performance remained stable across age, route, duration, and site subgroups (AUC range 0.70–0.79). In the external cohort, the case capture rate at the ≥7 threshold was non-inferior (83.4% vs. 88.0%; Δ = −4.6%; margin −10%). Conclusions: The MRONJ triage score demonstrated stable discrimination and reproducible case capture in an independent multicenter cohort. By relying on six variables obtainable at the initial dental visit, this framework may have the potential to reduce unnecessary tertiary referrals and support safer clinical decision-making, although this benefit was not directly demonstrated and requires confirmation in prospective implementation studies. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) and osteoporosis (OP) are epidemiologically linked, but shared cell-type-specific molecular features remain unclear. We integrated public single-cell/single-nucleus transcriptomic datasets for OP (GSE147287) and MASLD (GSE289173) with two-sample Mendelian randomization (MR), colocalization, network annotation, macrophage-focused in silico perturbation, and exploratory serum assessment. After quality control, 13,753 OP cells and 42,438 MASLD cells/nuclei were analyzed. Macrophages were consistently identified in both datasets and showed disease-associated expansion. Directionally concordant macrophage differentially expressed genes yielded 147 shared candidate genes, with enrichment mainly involving lipid/sterol metabolism, extracellular matrix and adhesion processes, immune presentation, lysosomal processing, and phagocytic pathways. MR prioritized MUC20 as the only candidate with concordant odds ratios greater than 1 for both OP (OR = 1.044, 95% CI 1.003–1.086) and MASLD (OR = 1.111, 95% CI 1.038–1.189). Colocalization supported shared genetic signals for MUC20 in OP (PP.H4 = 0.855) and MASLD (PP.H4 = 0.816). In silico perturbation suggested a limited but pathway-enriched predicted transcriptional footprint. Serum MUC20 was higher in patients with OP+MASLD than in healthy controls. This integrative analysis identified shared macrophage-associated transcriptional themes and prioritized MUC20 as a candidate molecule for future liver–bone crosstalk studies. Full article

Background/Objectives: Injury occurrence in physically active young adults is considered a multifactorial phenomenon influenced by body composition and training-related characteristics. This study aimed to investigate the multidimensional relationships between body composition, training context variables, and injury phenotypes in physically active university students using exploratory multivariate approaches. Methods: The study included 418 physically active university students. Participants completed questionnaires regarding injury history, physical activity, and sport participation and underwent standardized anthropometric and body composition assessments. Analyses included Kendall’s Tau correlations, multiple correspondence analysis (MCA), hierarchical clustering, heatmap phenotyping, tanglegram-based clustering analysis, and distance-based redundancy analysis (dbRDA). The tanglegram analyses were intended as exploratory structure-matching procedures designed to evaluate similarities in hierarchical organization between domains rather than direct biological associations, causal relationships, or predictive effects. Results: Weak but significant associations were observed between selected body composition variables and injury outcomes, particularly for skeletal-muscle-related indicators and lower limb injuries. MCA and clustering analyses identified partially differentiated sport-training profiles and exploratory injury-burden phenotypes. Topology-based cross-domain matching analyses suggested partial structural correspondence between body composition, training context, and injury phenotypes; however, the most anatomically coherent patterns were observed for local body composition variables. Nevertheless, overall cross-domain concordance remained weak-to-moderate. dbRDA demonstrated statistically significant but weak associations for body composition (adjusted R² = 0.027, p = 0.001) and the combined explanatory model (adjusted R² = 0.022, p = 0.023), whereas the training context model was not significant (adjusted R² = 0.002, p = 0.304). Conclusions: Injury occurrence was weakly associated with body composition and training context characteristics within a multidimensional exploratory framework. The findings are consistent with the interpretation of injury occurrence as a heterogeneous and predominantly multifactorial phenomenon and highlight the utility of multidimensional exploratory approaches for investigating complex injury-related patterns. Full article

Background: Chatbots are becoming increasingly valuable in clinical settings, offering rapid access to medical information, aiding documentation, and improving perioperative patient education. Their adaptability makes them promising tools for personalized perioperative risk stratification (PRS) and anesthesia planning, but their definitive role remains uncertain. We aimed to evaluate chatbot performance in PRS compared to standard clinical judgment and to assess the certainty of the evidence supporting their use. Methods: This systematic review (PROSPERO ID: CRD42025642357) followed PRISMA extended and PRISMA-S guidelines. The population was defined according to the PICO framework: we included adult surgical patients undergoing anesthesia assessment (P), evaluated with LLM-based chatbots for perioperative risk stratification and anesthesia planning (I), compared with traditional clinician assessment (C), and extracted performance metrics (O). Comprehensive searches of PubMed, MEDLINE, Scopus, Embase, Google Scholar, Open Gray, ClinicalTrials.gov, WHO ICTRP, and Cochrane Library Central were conducted through January 2026. Risk of bias and study quality were assessed using PROBAST-AI, RoB-2, and ROBINS-I. Certainty of the evidence was assessed using GRADE system. A random-effects meta-analysis of pooled chatbot accuracy was performed, with subgroup analyses by ASA status and perioperative risk stratification. A sensitivity analysis was performed with a leave-one-out exclusion test. Results: Eleven studies published between 2023 and January 2026 were included (N = 227,059 patients). Five prospective cohorts, two large retrospective cohorts, one randomized non-inferiority trial, and three non-clinical or mixed-methods studies were found. Meta-analysis showed that the pooled accuracy of LLM-based chatbots for AI–clinician concordance in perioperative risk stratification and ASA classification was 0.90 [95% CI: 0.42–0.99; 95% prediction interval 0.03–1.00]. Subgroup analyses indicated that the ASA status prediction subgroup reached a pooled accuracy of 0.91 (95% CI: 0.46 to 0.99), whereas the exploratory perioperative risk stratification subgroup showed an accuracy of 0.73 (95% CI: 0.10 to 0.98). Performance decreased with increasing patient complexity. Evidence is limited by small sample sizes, extreme sample size skew toward a single center, geographic bias, inconsistent outcome definitions and performance metrics, and incomplete reporting of adverse events. Most studies lacked prospective trial registration or robust control for confounding, and publication bias cannot be excluded. Conclusions: LLM-based chatbots show promising performance in routine perioperative risk stratification but remain unreliable in complex cases, with potential safety concerns. Given the overall very low GRADE certainty of evidence, these tools should be used as clinician-supervised decision support aids for routine ASA assessment, and should not be relied upon for autonomous use in complex cases or for general perioperative risk stratification. Other: This research received no external funding. PROSPERO ID: CRD42025642357. Full article

Background/Objectives: IL23R encodes a pivotal component of the IL-23/Th17 signaling axis and represents a validated genetic susceptibility locus for inflammatory bowel disease (IBD), psoriasis, and ankylosing spondylitis. Despite extensive GWAS data, the functional consequences of the full spectrum of IL23R missense single-nucleotide variants (SNVs) have not been systematically characterized. This study aimed to identify high-risk missense SNVs through a multi-tool in silico pipeline. Methods: A total of 723 missense SNVs from NCBI dbSNP were verified against transcript NM_144701.3/Q5VWK5-1 (629 aa) using Ensembl VEP (GRCh38). Sequential filtering was performed using applied SIFT, PolyPhen-2, PROVEAN, E-SNPs&GO, MutPred2, and ConSurf (grade ≥ 7); AlphaMissense and FATHMM-MKL were used as independent annotation layers. Protein stability was assessed with MuPro and DynaMut2 (AlphaFold2 AF-Q5VWK5-F1-v6; pLDDT = 68.19); structural characterization was performed with Project HOPE, and interaction networks were constructed using STRING and GeneMANIA. Results: Sequential filtering identified 37 high-risk missense variants. MuPro predicted destabilizing effects for 36/37 variants, with concordant DynaMut2 results for 35/37. Project HOPE identified disulfide bond disruption in 11 variants, charge-altering substitutions in 8, and glycine/proline backbone conformational changes in 11. STRING analysis identified IL12RB1 (0.999), IL23A (0.999), JAK2 (0.995), IL12B (0.986), and STAT3 (0.980) as the leading IL23R interactors. The protective variant R381Q was appropriately characterized as neutral by PROVEAN (−1.16) and AlphaMissense (likely_benign), supporting the specificity of the pipeline. Conclusions: Comprehensive in silico analysis identified 37 high-risk IL23R missense candidates with convergent computational evidence of predicted deleteriousness, predominantly involving cysteine bridge disruption, charge alteration, and glycine/proline backbone conformational changes. These variants are presented as prioritized candidates for future functional validation and may inform subsequent investigations of IBD susceptibility and IL-23 pathway pharmacogenomics. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease. Accurate staging of hepatic fibrosis is pivotal for risk stratification; however, ultrasonography (US)-based elastography techniques may yield variable results across various technologies and manufacturers. The present study aimed to assess the concordance of liver stiffness (LS) measurements between two different US elastography technologies and manufacturers in patients with MASLD. Methods: This cross-sectional study included 68 postmenopausal women with MASLD. LS was measured using two-dimensional shear wave elastography (2D-SWE) on a LOGIQ™ E10 device and both 2D-SWE and point SWE (pSWE) on an Acuson Sequoia device. Hepatic steatosis was quantified using the ultrasound-guided attenuation parameter (UGAP). Results: The LS measurements were 5.0 ± 1.3 kPa with 2D-SWE on LOGIQ™ E10, 4.3 ± 1.5 kPa with 2D-SWE on Acuson Sequoia, and 3.8 ± 0.8 kPa with pSWE on Acuson Sequoia. A significant, but low correlation was found between LOGIQ™ E10 2D-SWE and Acuson Sequoia pSWE (rs = 0.25, p = 0.045), and a moderate correlation between Acuson Sequoia 2D-SWE and pSWE (rs = 0.37, p = 0.002). No correlation was shown for 2D-SWE between the two different manufacturers. Bland–Altman analysis showed moderate-to-poor agreement of LS values between the three different US elastography techniques. Conclusions: LS measurements differed across US elastography technologies and manufacturers in postmenopausal women with early-stage MASLD. These findings highlight the need to standardize existing US elastography devices before elastography-derived LS can be applied interchangeably in MASLD diagnostic algorithms. Full article

Objective: The objectives of this study were to characterise induction-phase regional cerebral oxygen saturation (rSO₂)–mean arterial pressure (MAP) dynamics during near-infrared spectroscopy (NIRS)-guided selective carotid endarterectomy (CEA) and to examine whether the Awake→Intubated pressure–oxygenation pattern may represent an early adjunctive physiological signal of subsequent cross-clamp-related ipsilateral cerebral desaturation. Methods: In this retrospective observational cohort study, 322 consecutive elective CEAs managed with an NIRS-guided selective shunting protocol between October 2019 and February 2025 were analysed, after excluding patients considered for routine pre-emptive shunting because of contralateral internal carotid artery occlusion or ≥70% stenosis. Standardised MAP and bilateral rSO₂ values were extracted at the Awake, Intubated, and Clamp stages, defined as 3 min after carotid cross-clamping. Awake→Intubated ipsilateral ΔrSO₂/ΔMAP was evaluated as a continuous, exploratory pressure–oxygenation index, with MAP–rSO₂ directional change classified as concordant or discordant. Clamp-related desaturation was defined as a ≥20% ipsilateral rSO₂ decrease from Awake to Clamp. Discrimination and adjusted associations were evaluated using receiver operating characteristic analysis and multivariable logistic regression, respectively. Results: Clamp-related ≥20% ipsilateral rSO₂ desaturation occurred in 43 patients (13.4%). The Awake→Intubated ipsilateral ΔrSO₂/ΔMAP ratio differed significantly between patients with and without ≥20% desaturation and showed significant discrimination on receiver operating characteristic analysis, with an area under the curve (AUC) of 0.799 (95% confidence interval [CI] 0.723–0.876; p < 0.001). Concordant pressure–oxygenation change was more frequent among patients with ≥20% desaturation (31/43, 72.1%), whereas discordant change predominated among those without desaturation (228/279, 81.7%; p < 0.001). In multivariable analysis, Awake→Intubated ipsilateral ΔrSO₂/ΔMAP remained associated with clamp-related ≥20% desaturation after adjustment (adjusted odds ratio [OR] 1.63, 95% CI 1.15–2.33; p = 0.006), along with symptomatic presentation and 50–69% contralateral stenosis. Postoperative stroke occurred in 4/322 patients (1.2%), and no 30-day mortality occurred. Conclusions: During NIRS-guided selective CEA, induction-phase rSO₂–MAP dynamics were associated with subsequent cross-clamp-related ipsilateral cerebral desaturation. As the outcome was a NIRS-defined desaturation rather than an independent clinical, neurological, or imaging endpoint, these findings indicate association with a surrogate marker rather than prediction of clinically relevant cerebral ischaemia. The Awake→Intubated ΔrSO₂/ΔMAP ratio and directional pressure–oxygenation pattern may represent early adjunctive physiological signals associated with clamp-related desaturation. These findings are hypothesis-generating and require prospective validation with systematic multimodal monitoring. Full article

Background/Objectives: San-Huang-Xie-Xin-Tang (SHXXT) is a classical traditional Chinese herbal formula composed of Coptis chinensis, Scutellaria baicalensis, and Rheum palmatum, with documented anti-inflammatory and anticancer properties. Despite growing interest in its pharmacological potential, systematic evaluation of its gene regulatory effects across multiple cancer types remains limited. This study aimed to assess the prognostic relevance of SHXXT-regulated genes across pan-cancer contexts using publicly available transcriptomic and clinical datasets. Methods: Fifteen active compounds of SHXXT were identified from traditional Chinese medicine databases (Encyclopaedia of Traditional Chinese Medicine (ETCM) 2.0, Chinese Compound Medicine Database (ccTCM), and Integrated Traditional Chinese Medicine Database (ITCM)). Compound-induced gene expression profiles were obtained from MCF7-based transcriptomic perturbation data in the ITCM database and integrated with The Cancer Genome Atlas (TCGA) across 24 cancer types. Survival-associated genes were evaluated using Cox proportional hazards regression and Kaplan–Meier analysis. A weighted prognostic scoring framework, supported by normalization and sensitivity analyses, was developed to prioritize cancer types according to the concordance between SHXXT-induced gene regulation and favorable prognostic patterns. Functional enrichment analysis was performed using Annotation, Visualization, and Integrated Discovery (DAVID), and cancer-related genes were annotated using the OncoKB database. Complementary in vitro studies, including Annexin V/propidium iodide (PI) and MT-1 staining assays, were conducted in Hep3B cells using a Good Manufacturing Practice (GMP)-certified commercial SHXXT preparation. Results: SHXXT-regulated genes were significantly enriched in cancer-related pathways, particularly the PI3K–Akt and MAPK signaling pathways. Pan-cancer analysis revealed substantial heterogeneity in prognostic alignment across cancer types. Among the 24 cancer cohorts analyzed, kidney renal clear cell carcinoma (KIRC) achieved the highest prognostic alignment score within the proposed framework. In KIRC, several genes, including PIK3CA, PIK3CB, KRAS, and RAF1, remained significantly associated with favorable prognostic alignment after multivariable adjustment. Pathway enrichment analysis further identified PI3K–Akt and MAPK signaling as the most significantly represented pathways among favorably aligned genes. In contrast, hepatocellular carcinoma exhibited a relatively low prognostic alignment score, consistent with in vitro observations indicating predominantly non-selective cytotoxic stress rather than cancer-specific therapeutic activity. Conclusions: SHXXT-regulated genes exhibited marked heterogeneity across cancer types, with KIRC was consistently prioritized as the top-ranked cancer type across multiple analytical scenarios, suggesting a strong concordance between SHXXT-associated gene regulation and favorable prognostic signatures. These findings represent computational predictions derived from transcriptomic and survival associations rather than direct evidence of therapeutic efficacy. The study provides a reproducible pan-cancer strategy for prioritizing candidate cancer types for future mechanistic and experimental validation of traditional Chinese medicine formulations. Full article

Transepithelial photorefractive keratectomy (Trans-PRK) offers superior re-epithelialization and visual recovery. This study evaluates the impact of preoperative refractive status on clinical outcomes and identifies prognostic factors across varying myopic severities. This retrospective observational study included 125 eyes [64 patients; age > 20 years; best-corrected visual acuity (BCVA) ≥ 20/25] that underwent Trans-PRK between March and December 2022. Patients were stratified into low myopia (LM: > −5.0 D), moderate-to-high myopia (MHM: −5.0 D to −8.0 D), and extremely high myopia (EHM: ≤ −8.0 D) groups. Analysis focused on preoperative refraction, intraoperative parameters, postoperative uncorrected visual acuity (UCVA), and corneal conditions of superficial punctate keratitis (SPKs) and haze. The mean age was 30.20 ± 6.34 years, with a mean initial manifest sphere (MS) of −6.42 ± 2.27 diopter (D) overall and −3.73 ± 0.15 D, −6.28 ± 0.13 D, and −9.17 ± 0.15 D in the LM, MHM, and EHM groups, respectively. At a mean follow-up of 6.69 ± 3.73 months, the overall mean final manifest spherical equivalent (MSE) was −0.12 ± 0.73 D, and the mean final UCVA was 0.01 [Snellen equivalent (SE), 205/200] ± 0.08 logMAR. Predictability was 94.4%, 88.88%, and 94.3% for the final MS ≤ −1.0 D, final MSE ≤ −1.0 D, and UCVA 0.8, respectively. In the LM and MHM groups, cycloplegic and subjective refractions showed the highest concordance with emmetropia, whereas initial manifest refractions were most accurate for the EHM group. Corneal SPK incidence declined from 32.2% (1 month) to 1.6% (6 months), primarily localized to EHM eyes. Corneal haze peaked at 28.2% at three months before receding to 9.4% by 6 months. Refractive and visual stability were achieved by the third month for the LM and MHM groups, whereas the EHM group (mean MSE: −9.59 ± 0.15 D) required six months to reach both refractive and visual plateaus. Despite transiently higher rates of corneal SPKs and haze in EHM eyes, final visual outcomes remained excellent, achieving a mean UCVA of 18/20. Full article