Search Results (6,921)

Background: The presence of left atrial fibrosis is a marker of advanced remodeling and is associated with a worse outcome after pulmonary vein isolation (PVI). Conventional fluoroscopy-only cryoballoon ablation (CBA) lacks this prognostic information. The addition of electroanatomical mapping (EAM) using the inner lumen spiral catheter allows accurate voltage assessment of the left atrial posterior wall. However, the value of the finding of posterior wall low-voltage zones (pwLVZs) is unknown. Purpose: To study the value of left atrial voltage maps during CBA by comparing clinical and procedural characteristics and clinical outcome between patients with and without pwLVZs. Methods: A cohort of 250 consecutive patients who underwent index CBA for atrial fibrillation was analyzed. All patients underwent pre- and post-procedural EAM using the Achieve^TM catheter and EnSite^TM mapping system. The presence of LVZs was evaluated at the postprocedural voltage map of the posterior wall. Clinical success was defined as freedom from documented AF or atrial tachycardia (AT) >30 s after 1 year. Results: PwLVZs were found in 41/250 (16.4%) of patients. Patients with pwLVZs were older (69.3 ± 8.5 vs. 64.2 ± 10.4; p = 0.003), more frequently female (63.4% vs. 32.5%; p < 0.001) and had higher CHA₂DS₂-VASc scores (3.0 ± 1.6 vs. 2.0 ± 1.5; p < 0.001). The incidence of obesity (31.7% vs. 25.8%; p = 0.048), structural heart disease (35.5% vs. 17.4%; p = 0.021) and persistent AF (68.3% vs. 43.8%; p = 0.004) was higher in the pwLVZs group. Kaplan–Meier analysis of clinical outcome showed a higher recurrence rate in the pwLVZs group. The finding of pwLVZs was a predictor of atrial arrhythmia recurrence during follow-up (HR 2.583; 95%CI: 1.334–5.002; p = 0.005). Conclusions: In CBA facilitated by integrated EAM, pwLVZ was associated with older age, female sex, higher CHADS-VASc scores, obesity, structural heart disease and persistent AF. The finding of pwLVZs is predictive of a worse clinical outcome. Full article

Background and Objectives: This study investigated the prognostic value of two simple blood urea nitrogen (BUN)-based ratios, BUN/hemoglobin (Hb) and BUN/Albumin, for predicting in-hospital mortality and prolonged hospitalization in patients with acute upper gastrointestinal bleeding (UGIB). Their performance was compared with established risk scores, including the Glasgow–Blatchford score (GBS), AIMS-65, ABC and Rockall scores. Materials and Methods: This retrospective cohort study included 486 patients evaluated for acute UGIB between March 2023 and February 2026. The diagnostic performance of BUN/Hb and BUN/Albumin ratios was assessed using receiver operating characteristic (ROC) analysis and compared with established risk scores. Associations with clinical outcomes were evaluated using logistic regression analyses. Results: The median age was 67 years, and 292 patients (60.1%) were male. In-hospital mortality occurred in 17 patients (3.5%), while prolonged hospitalization was observed in 207 patients (42.6%). AIMS-65 showed the highest Area Under the Curve (AUC) for mortality prediction (0.799; 95% CI 0.696–0.902), followed by the ABC score (0.731) and the BUN/Albumin ratio (0.711). For prolonged hospitalization, BUN/Hb showed the highest AUC (0.706; 95% CI 0.660–0.752), although differences from established scores were not statistically significant. In multivariable analysis, BUN/Albumin remained associated with mortality, whereas BUN/Hb did not reach statistical significance for prolonged hospitalization. However, mortality-related findings should be interpreted with caution because only 17 in-hospital deaths occurred in the study cohort. Conclusions: Simple BUN-based ratios may provide complementary prognostic information in acute UGIB. BUN/Albumin was associated with in-hospital mortality and showed modest discriminatory ability, but it did not demonstrate statistically significant superiority over established risk scores. BUN/Hb showed the numerically best discrimination for prolonged hospitalization, but without statistically significant superiority or persistent significance in multivariable analysis. Overall, these ratios may serve as supportive tools for early risk assessment rather than replacements for established risk scoring systems. Full article

The prognostic value of post-radiotherapy (RT) lymphocyte recovery remains unclear in locally advanced esophageal squamous cell carcinoma (ESCC), and tools to predict recovery are lacking. This study evaluated lymphocyte recovery as a survival predictor and developed a prediction model. We analyzed 233 patients (2019–2024; training:validation = 7:3). Lymphocyte recovery was assessed at 1 and 3 months post-RT (ΔALC₁ > 0.41 and ΔALC₃ > 0.25 × 10⁹/L, calculated as ALC at each time point minus ALC at the end of RT). Patients were stratified into three groups by recovery status: no recovery (Group 0), recovery at both time points (Group 2), or at only one time point (Group 1). Multivariate logistic regression identified predictors of lymphocyte recovery, and a nomogram was developed and internally validated. Median overall survival (OS) was 26.4 months and median progression-free survival (PFS) was 13.9 months. OS differed significantly among groups: 16.0 months (Group 0), 26.0 months (Group 1), and 50.0 months (Group 2) (p < 0.001). Median PFS was 10.2, 12.0, and 36.6 months, respectively (p < 0.001). Independent predictors included ECOG 0 and thoracic spine V₅ < 57.3%; planning target volume < 210 cm³ showed a trend toward association (p = 0.051). The nomogram demonstrated AUCs of 0.77 and 0.75 in the training and validation cohorts. Superior lymphocyte recovery appears to be associated with improved survival. The model, if externally validated, may facilitate individualized risk stratification. Full article

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is a biologically heterogeneous disease. Beyond VHL inactivation, alterations in chromatin remodeling genes BAP1 and PBRM1 define distinct tumor phenotypes with prognostic implications. We sought to characterize the clinicopathological features and oncological outcomes associated with IHC-defined loss of these markers in a contemporary surgical cohort. Methods: We retrospectively analyzed 214 patients undergoing partial or radical nephrectomy for ccRCC (2010–2021). Loss of BAP1 and PBRM1 expression was assessed by automated immunohistochemistry. Tumors with retained expression were classified as wild-type and compared with those showing loss of at least one marker. Survival outcomes were evaluated using Kaplan–Meier analysis, multivariable Cox models, and Restricted Mean Survival Time (RMST). Results: IHC-defined loss was identified in 19 patients (8.9%): BAP1 in 12 (5.6%) and PBRM1 in 7 (3.3%). Tumors with IHC-defined loss showed more aggressive features, including larger size (7.7 vs. 4.7 cm; p = 0.009), higher necrosis (36.8% vs. 18.5%; p = 0.050), and more advanced stage (pT3–pT4: 47.4% vs. 16.4%; p < 0.001). Kaplan–Meier analysis demonstrated significantly worse survival outcomes in the IHC-loss group across all endpoints (p ≤ 0.011). RMST analysis at 60 months confirmed significantly worse outcomes across all endpoints (p ≤ 0.005). Conclusions: Loss of BAP1 or PBRM1 identifies a biologically aggressive ccRCC subset with worse oncological outcomes. IHC-based molecular profiling is a practical and accessible tool for risk stratification in surgically treated ccRCC. Full article

Background and Objectives: Small lymphocytic lymphoma (SLL) represents the tissue-based manifestation of chronic lymphocytic leukemia (CLL). Despite their shared biological background, patients with SLL have been underrepresented in CLL-focused clinical trials, and data addressing the clinical behavior of pure nodal SLL remain scarce. The present study aimed to identify factors associated with time to first treatment (TTFT) and progression-only survival in patients with pure nodal SLL. Materials and Methods: In this prospective observational study, 46 patients with pure nodal SLL were included and followed for a median duration of approximately 5 years. Clinical, laboratory, histopathological, and TP53-related parameters were evaluated for their prognostic impact on TTFT and progression-only survival. Results: On univariable analysis, advanced-stage disease, hemoglobin < 10 g/dL, elevated serum β2M, elevated lactate dehydrogenase, del(17p), and aberrant p53 immunohistochemical expression were significantly associated with shorter TTFT and progression-only survival. Conclusions: Pure nodal SLL is a heterogeneous entity with a variable clinical course. Easily assessable clinical and biological parameters, including TP53 abnormalities, may help predict treatment requirement and disease progression, thereby contributing to better risk stratification and more individualized management. Kaplan–Meier analysis demonstrated significantly shorter time-to-first-treatment (TTFT) among patients with elevated β2M levels (≥3.5 mg/L), bulky lymphadenopathy (≥5 cm), and advanced-stage disease. Full article

Background: Systemic autoimmune rheumatic diseases-associated interstitial lung disease (SARD-ILD) presents with varied disease courses, emphasizing the need for reliable predictors of progression. The prognostic utility of bronchoalveolar lavage (BAL) in SARD-ILD remains underexplored. The objective of this study was to evaluate the role of BAL fluid lymphocyte count in predicting disease progression in patients with SARD-ILD. Methods: This observational study included patients with SARD-ILD undergoing BAL as part of their diagnostic workup. Disease progression was defined as either Forced vital capacity (FVC) decrease >10%, two out of the following three criteria within two years: FVC decrease of 5–10%, worsening symptoms, increased fibrosis on imaging, or any of the following: escalation of treatment, Interstitial lung disease (ILD) exacerbation, lung transplantation, or disease-specific mortality. Logistic regression identified predictors of progression. Time-to-progression was assessed using Kaplan–Meier survival curves. The optimal BAL lymphocyte threshold for predicting progression was identified using the Youden Index and the Wilcoxon method. Results: We identified 89 patients, of whom 30 (33.7%) had progressive disease. Progressors had a significantly higher BAL lymphocyte count compared to non-progressors (31.6 ± 24.8% vs. 14.3 ± 16.5%, p < 0.001). BAL lymphocyte proportion was significantly and independently associated with disease progression (odds ratio, 1.05; 95% confidence interval 1.02–1.07; p < 0.01). A lymphocyte count above 9 percent was associated with a markedly increased risk of disease progression (odds ratio, 13.14; 95% confidence interval, 4.20–51.98; p < 0.01). Conclusions: BAL lymphocyte count was associated with a higher likelihood of progression in SARD-ILD. BAL assessment may help identify patients at increased risk of disease progression. However, these findings should be considered exploratory and require validation in larger prospective studies and across individual SARD-ILD subtypes. Full article

Background: Hyperglycemia after aneurysmal subarachnoid hemorrhage (aSAH) is associated with poor outcome, but admission glucose may not reflect dynamic metabolic stress during neurocritical care. Unlike previous studies focused primarily on admission measurements, we evaluated longitudinal glycemic trajectories and repeated glucose–potassium ratio (GPR) assessment across multiple observation windows in relation to clinical outcomes after aSAH. Methods: This retrospective single-center cohort study included 199 consecutive adults with aSAH treated between 2014 and 2025. Serial glucose and potassium measurements obtained during intensive care unit (ICU) stay were used to calculate admission values, longitudinal means across predefined observation windows, glycemic variability, hyperglycemia burden, and GPR. Primary outcomes were 30-day mortality and poor functional outcome at discharge (modified Rankin Scale ≥ 3). Secondary outcomes included delayed cerebral ischemia (DCI), delayed neurological deterioration (DND), transcranial Doppler (TCD) vasospasm, neurological deficit at ICU discharge, and length of stay. Results: Thirty-day mortality occurred in 35 patients (17.6%). Longitudinal metabolic markers demonstrated stronger associations with outcomes than admission values. Mean 30-day GPR was independently associated with mortality (OR 2.56, 95% CI 1.66–4.16; p < 0.001) and poor functional outcome (OR 2.90, 95% CI 1.80–5.03; p < 0.001). Hyperglycemia burden was associated with mortality (OR 1.10 per additional hyperglycemic day, 95% CI 1.02–1.20; p = 0.020) and poor functional outcome (OR 1.39, 95% CI 1.19–1.71; p < 0.001). Early GPR during the early brain injury period was associated with DCI (OR 1.40, 95% CI 1.01–1.93; p = 0.043), whereas 30-day GPR was associated with DND (OR 1.47, 95% CI 1.08–2.07; p = 0.019). ICU-specific GPR was associated with neurological deficit at ICU discharge (OR 2.06, 95% CI 1.29–3.50; p = 0.004), but not with TCD-defined vasospasm. Addition of GPR improved mortality prediction compared with the clinical model alone (AUC 0.86 vs. 0.77; p = 0.002). Conclusions: Longitudinal metabolic dysregulation after aSAH is strongly associated with mortality and neurological outcomes. Persistent hyperglycemia and repeated GPR assessment provide prognostic information beyond admission glucose, with early abnormalities associated with DCI and sustained disturbances linked to mortality and disability. Full article

Objective: Glutamic acid decarboxylase 65 (GAD65) antibody-associated epilepsy often presents as chronic focal epilepsy, usually with temporal lobe predominance, marked drug resistance, and inconsistent response to first-line immunotherapy. We assembled a large, harmonized, and literature-derived patient-level cohort to examine whether immunotherapy timing and regimen composition were associated with seizure outcome and to identify clinically meaningful prognostic signals. Methods: We performed a literature-derived patient-level analysis of 375 unique published cases linked to 132 contributory source publications from an audited full-text register of 166 reviewed studies. Descriptive analyses used the whole cohort. Treatment-response analyses assessed seizure outcome at the first evaluable post-immunotherapy assessment and at the last follow-up. Good seizure outcome was defined as seizure freedom and/or ≥50% seizure reduction. The primary timing comparison contrasted early treatment, defined as immunotherapy within 6 months of symptom onset, with late treatment, defined as immunotherapy after more than 12 months; four cases treated in the intermediate >6 to ≤12 month window were retained for descriptive timing summaries but excluded from the primary comparison. Statistical testing used the Fisher exact, Chi-square, Mann–Whitney U, and prespecified clustered logistic sensitivity analyses where appropriate. Results: The pooled phenotype was predominantly female, usually temporal-lobe-based, and frequently drug-resistant, with common autoimmune comorbidity and heterogeneous MRI abnormalities. Among timing-evaluable treated cases, earlier immunotherapy showed a class-specific, exploratory signal rather than a uniform regimen-independent effect. In rituximab/CD20-directed regimens, early treatment was associated with a higher rate of good seizure outcome than late treatment at both the first post-immunotherapy assessment and last follow-up (93.8% vs. 50.0%; risk difference [RD]: 43.8 percentage points; 95% CI: 7.7 to 72.7). A similar pattern was observed in the broader escalation group (94.4% vs. 55.6%; RD: 38.9 percentage points; 95% CI: 6.3 to 68.1). By contrast, steroid-containing regimens showed no clear early-versus-late advantage (84.6% vs. 88.2%; RD: −3.6 percentage points; 95% CI: −18.4 to 20.1). Shorter epilepsy duration before immunotherapy and absence of established drug resistance were the most clinically meaningful favorable baseline features. Significance: In GAD65 antibody-associated epilepsy, the therapeutic window may be most relevant for escalation strategies rather than for steroid-containing first-line regimens. However, these class-specific findings are exploratory and hypothesis-generating. They derive from non-randomized, literature-derived data and may reflect treatment intensity, center practice, publication era, and confounding by indication rather than isolated regimen superiority. Prospective collaborative registries with standardized longitudinal seizure outcome measures are needed to validate these observations. Full article

Immunotherapy has transformed cancer treatment; however, clinical benefit remains limited to a subset of patients, underscoring the need for robust biomarkers that capture tumor-immune interactions across cancer types. In this study, we performed a comprehensive pan-cancer, multi-omics characterization of the immune checkpoint–related molecules CD70, CD80, and TIGIT to evaluate their diagnostic, prognostic, and immunological relevance. Using integrative analyses of transcriptomic, epigenomic, genomic, pharmacogenomic, and single-cell RNA-sequencing data from The Cancer Genome Atlas and complementary resources, we assessed expression patterns, DNA methylation, somatic mutations, copy number alterations, immune infiltration, tumor stemness, and drug sensitivity. CD70, CD80, and TIGIT were broadly dysregulated across multiple malignancies, with coordinated overexpression particularly evident in kidney renal clear-cell carcinoma. Elevated expression of these immune checkpoints was associated with advanced tumor stage, aggressive molecular subtypes, and unfavorable survival outcomes in selected cancers, including uveal melanoma and renal malignancies. Functional analyses revealed significant associations between checkpoint expression and key oncogenic pathways, including epithelial–mesenchymal transition, apoptosis, and hormone receptor signaling, suggesting links with tumor progression and immune activation states. Immune deconvolution analyses indicated that TIGIT expression is associated with a T-cell–inflamed microenvironment and reduced neutrophil infiltration, while CD80 exhibited methylation-dependent associations with immune cell composition. Genomic and epigenetic alterations were found to correlate with checkpoint expression patterns and immune phenotypes across tumor types. Pharmacogenomic profiling identified associations between checkpoint expression and sensitivity to multiple anticancer agents; however, these findings are based on cell line datasets and should be considered predictive. Single-cell transcriptomic analyses further resolved cell-type–specific expression patterns, distinguishing tumor-intrinsic from immune-restricted expression profiles. Collectively, our findings establish CD70, CD80, and TIGIT as integrative biomarkers of tumor progression, immune contexture, and therapeutic response, providing a rationale for their clinical exploitation in precision immuno-oncology. Full article

Background/Objectives: Enzalutamide and abiraterone acetate are commonly used androgen receptor pathway inhibitors in metastatic castration-resistant prostate cancer (mCRPC), including after docetaxel. However, real-world outcomes remain heterogeneous, and simple prognostic markers may help describe this variability. This study aimed to describe survival outcomes with enzalutamide and abiraterone acetate after docetaxel and to explore the prognostic value of a routine clinical-inflammatory risk classification. Methods: This retrospective single-center study included 136 patients with mCRPC treated with enzalutamide or abiraterone acetate after docetaxel. A composite risk classification was defined using four routinely available variables: pan-immune-inflammation value (PIV) > 457.99, time to castration resistance < 12 months, baseline hemoglobin ≤ 12 g/dL, and Gleason score ≥ 8. One point was assigned for each adverse factor, and patients were classified as low, moderate, or high risk. Overall survival (OS) was assessed using Kaplan–Meier estimates and Cox regression. The prognostic score and Cox regression-based nomogram were evaluated as exploratory tools. Results: Of the 136 patients, 8 (5.9%) were classified as low risk, 67 (49.3%) as moderate risk, and 61 (44.9%) as high risk. Median OS was not reached in the low-risk group, compared with 33.84 months in the moderate-risk group and 9.66 months in the high-risk group. In multivariable analysis, high-risk status was independently associated with worse OS (HR = 9.87; 95% CI: 2.38–40.92; p = 0.002). No statistically significant OS difference was observed between enzalutamide and abiraterone acetate in this non-randomized cohort (HR = 1.36; 95% CI: 0.90–2.06; p = 0.142). Conclusions: In this real-world post-docetaxel mCRPC cohort, no statistically significant OS difference was observed between enzalutamide and abiraterone acetate; however, the study was not designed to establish comparative effectiveness or therapeutic equivalence. The exploratory risk classification based on routine clinical and inflammatory variables was associated with distinct survival outcomes. External validation is required before clinical application. Full article

Background and Objectives: In recent years, frailty has emerged as a prognostic factor in inflammatory bowel diseases (IBD), particularly among patients with active disease. However, evidence regarding its reversibility after treatment optimization remains limited. This study aimed to assess frailty in active IBD and determine whether frailty status improved after 6 months of clinical management and the achievement of clinical remission. Materials and Methods: This prospective, single-center, observational cohort study included adults with active IBD requiring escalation to advanced therapy who achieved clinical remission at the 6-month follow-up. Patients were evaluated at baseline and after 6 months using a modified Fried frailty phenotype. Quality of life was assessed using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Univariate and multivariate logistic regressions were utilized to identify independent factors associated with frailty improvement. Results: The analysis included 54 patients (61.1% male; 42.6% with Crohn’s disease). At baseline, 20.4% were classified as frail, 72.2% as pre-frail, and 7.4% as robust. Following 6 months of clinical management and the achievement of clinical remission, a 100% resolution of frailty was observed, with the robust cohort expanding to 42.6%. Significant improvements occurred across clinical parameters, including handgrip strength, 400 m walk times, and median SIBDQ scores (increasing from 4.4 to 5.9, p < 0.001) alongside a substantial decline in CES-D scores (p = 0.017). Multivariate logistic regression revealed that severe disease at baseline (aOR = 4.51, 95%CI: 1.26–16.18, p = 0.020), anti-TNF therapy initiation (aOR = 3.69, 95%CI: 1.04–13.18, p = 0.044), and higher baseline CES-D scores (aOR = 1.06, 95%CI: 1.00–1.13, p = 0.038) were independently associated with higher odds of frailty improvement. Conclusions: Among patients who achieved clinical remission, frailty and pre-frailty demonstrate substantial short-term improvement following advanced therapy. Functional and psychological recoveries are associated with successful control of baseline disease severity and systemic inflammation. Full article

Background/Objectives: A macular hole represents a significant surgical condition in an increasingly aging population. Advances in surgical techniques, particularly pars plana vitrectomy with inverted internal limiting membrane (ILM) flap, have established high anatomical closure rates exceeding 90%. The prognostic factors influencing visual recovery remain incompletely understood, and it is unclear which patients can be expected to achieve optimal functional outcomes. Methods: This retrospective longitudinal study included 35 eyes of 32 patients followed for 3–12 months. Preoperative OCT parameters (minimum linear diameter, basal diameter, and hole height) and derived indices were correlated with functional outcomes, including best-corrected visual acuity (BCVA) and microperimetry, stratified as central macular sensitivity (CMS) and sensitivity at 4° and 20°. Postoperative ellipsoid zone (EZ) and external limiting membrane (ELM) integrity were also analyzed. Predictive performance was assessed using root mean square error (RMSE) and coefficient of determination (R²). A linear regression model based on BCVA served as baseline, while Extreme Gradient Boosting (XGBoost) models incorporating OCT features were developed. Feature importance was evaluated using Shapley Additive Explanations (SHAP). Results: Overall closure rate was 100%, including 91.4% Type 1 and 8.6% Type 2 closure. Models incorporating OCT parameters outperformed BCVA-based models (lower RMSE, and higher R²). Minimum linear diameter and hole height were the strongest predictors of postoperative outcomes. Microperimetry detected functional improvement beyond BCVA and correlated with EZ and ELM restoration. Conclusions: Preoperative macular hole morphology represents a key determinant of postoperative functional recovery. These structural parameters provide meaningful prognostic value beyond visual acuity alone, supporting the role of combined OCT and microperimetric assessment in predicting surgical outcomes. Full article

Background. Hematological inflammatory indices from the complete blood count have been proposed as inexpensive prognostic markers in sepsis. The systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) are the most studied, but the performance of monocyte-containing alternatives (SIRI, AISI) in the elderly, in whom immunosenescence may alter the leukocyte phenotype, remains poorly characterized. Methods. In a single-center retrospective cohort of patients aged ≥65 years admitted to a tertiary ICU with Sepsis-3-defined sepsis (n = 127, 33 deaths), we compared the discrimination of six indices (NLR, PLR, MLR, SII, SIRI, AISI) for 30-day all-cause mortality using AUROC with bootstrap confidence intervals and pairwise DeLong tests. Independent associations were assessed by logistic regression adjusted for APACHE II and age; incremental value over APACHE II was explored using IDI, cNRI, calibration and decision curve analysis, with bootstrap optimism correction. Results. Thirty-day mortality was 26.0%. The monocyte-containing indices (AISI, SIRI, MLR) discriminated better than SII and NLR, and AISI was significantly superior to SII, NLR and PLR on DeLong testing, though not to SIRI, MLR or APACHE II. After adjustment for APACHE II and age, AISI, SIRI and MLR remained independently associated with mortality, whereas SII and PLR did not. Adding AISI to APACHE II improved reclassification and calibration and yielded higher net clinical benefit across clinically relevant thresholds. Conclusions. In this exploratory, single-center analysis, monocyte-containing indices, particularly AISI, were more strongly associated with 30-day mortality in elderly ICU sepsis than SII or NLR. AISI, SIRI and MLR were strongly intercorrelated and near-equivalent, and AISI did not significantly exceed APACHE II in discrimination. These hypothesis-generating findings require prospective external validation before clinical use. Full article

Early detection of hepatocellular carcinoma (HCC) is crucial for curative treatment, yet current screening strategies for high-risk liver cirrhosis (LC) patients lack sufficient sensitivity. This study evaluates plasma cell-free DNA(cfDNA) concentration and fragmentomics as biomarkers to improve HCC diagnosis and prognosis. Plasma samples from 39 HCC and 46 LC patients were analyzed for cfDNA concentration and fragment patterns. A multivariate logistic regression model (CMAC), integrating cfDNA concentration, mononucleosome proportion (%MN), alpha-fetoprotein (AFP), and c-reactive protein (CRP), was developed and validated using Leave-One-Out Cross-Validation and bootstrapping. HCC patients exhibited significantly higher cfDNA concentrations (p < 0.0001) and longer fragment lengths (p < 0.05) compared to LC patients. The CMAC model demonstrated superior diagnostic performance (AUROC = 0.946) compared to AFP alone (AUROC = 0.777, p < 0.001). Notably, in early-stage HCC, the CMAC model remained highly accurate (AUROC = 0.941), whereas AFP failed to reach statistical significance. Higher CMAC scores were significantly associated with advanced BCLC stages (p = 0.009), lymphovascular invasion (p = 0.0063) and reduced overall survival (p = 0.0037). Integration of cfDNA analysis with established clinical markers in the CMAC model shows promise as a complementary tool for the early detection of HCC in LC patients. Validation in larger, multicenter cohorts will be necessary to confirm these findings and their clinical applicability. Full article

Background: Coronary anatomical complexity is commonly used for perioperative risk assessment in patients undergoing coronary artery bypass grafting (CABG), although it may not fully reflect systemic biological vulnerability. This study aimed to evaluate the association between the Prognostic Nutritional Index (PNI), a nutritional–immune marker derived from serum albumin and lymphocyte counts, and in-hospital mortality after CABG in relation to coronary anatomical complexity and established surgical risk scores. Methods: In this single-center retrospective cohort study, 324 consecutive patients who underwent isolated CABG between April 2024 and April 2025 were analyzed. The PNI was calculated according to the standard Onodera formula using preoperative serum albumin and total lymphocyte count. Associations with in-hospital mortality were evaluated using univariable and multivariable logistic regression analyses. Discriminative performance was assessed using receiver operating characteristic curve analysis, while exploratory analyses evaluating the additional prognostic contribution of the PNI beyond surgical risk scores were performed using nested model comparison and reclassification analyses. Internal validation and calibration analyses were also performed. Results: In-hospital mortality occurred in 26 patients. Preoperative and postoperative PNI values were significantly lower in patients who experienced in-hospital mortality. In multivariable analysis, the postoperative PNI remained independently associated with in-hospital mortality, whereas the preoperative PNI lost statistical significance after adjustment for clinical, renal, and surgical risk parameters. Receiver operating characteristic analysis demonstrated modest discriminative ability for the preoperative PNI (AUC: 0.742, 95% CI: 0.661–0.823). Exploratory analyses suggested a modest improvement in model discrimination and risk classification after the addition of the PNI to STS-based models; however, the overall incremental prognostic contribution remained limited. Calibration and internal validation analyses demonstrated acceptable agreement between predicted and observed mortality risk. Conclusions: The postoperative PNI demonstrated a stronger and independent association with in-hospital mortality than the preoperative PNI, suggesting that early postoperative nutritional–immune deterioration may reflect the magnitude of perioperative physiological stress and evolving clinical deterioration after CABG. Although lower preoperative PNI values were associated with mortality in univariable analyses, this association was no longer statistically significant after adjustment for clinical, renal, and surgical risk parameters. These findings indicate that postoperative nutritional–immune status may provide complementary biological information beyond conventional risk models; however, its clinical utility requires confirmation in larger prospective multicenter studies. Full article