Search Results (1,249)

Endoscopic retrograde cholangiopancreatography (ERCP) is the cornerstone in the management of choledocholithiasis. Despite continuous advancements in technique and safety, ERCP carries a risk of significant complications, underscoring the importance of avoiding unnecessary procedures. The principal contributor to potentially avoidable ERCPs in patients with known choledocholithiasis is the spontaneous passage of common bile duct stones. Small stone size and a long interval between diagnosis and the procedure have increasingly been found to favor this event. Moreover, despite the development of well-defined risk stratification scores for patients with suspected choledocholithiasis, the incidence of negative ERCPs within this patient population remains considerable, even when a high suspicion of choledocholithiasis is evident. This review summarizes current evidence on the incidence and predictors of avoidable ERCPs in these contexts, with particular emphasis on spontaneous stone passage. It also discusses the role of endoscopic ultrasound (EUS) as a diagnostic tool to reduce unnecessary procedures when initial imaging fails to confirm the presence of stones despite persistent high clinical suspicion. By integrating and critically appraising recent findings, we provide practical guidance for clinicians on decision-making regarding ERCP, particularly in situations where spontaneous stone passage is likely or imaging results are inconclusive. Full article

Background: Keloid scarring is a fibroproliferative disorder driven by a complex interplay of genetic, epigenetic, and environmental factors, resulting in significant cosmetic and functional impairment. Despite its high prevalence in African, Asian, and Hispanic populations, the molecular mechanisms underlying ancestry-dependent susceptibility remain incompletely understood. Methods: This narrative review synthesizes current genomic, epigenetic, and multi-omic evidence related to keloid scarring. Relevant literature was identified through a targeted, structured, non-systematic search of PubMed, Scopus, Web of Science, SciELO, and Google Scholar up to August 2025, focusing on genetic susceptibility loci, epigenetic regulation, and ancestry-related differences. PRISMA-ScR guidelines were used as a reporting framework to enhance transparency, without implying a formal systematic review methodology. Results: This synthesis identifies recurrent susceptibility loci at 1q41, 3q22.3, and 15q21.3 across multiple populations. Variants in NEDD4 and regulatory regions near BMP2 emerge as key modulators of profibrotic signaling pathways, including TGF-β/SMAD and NF-κB. Additionally, epigenetic reprogramming and long non-coding RNA networks, such as CACNA1G-AS1, appear to sustain fibroblast hyperactivation. A persistent limitation is the marked underrepresentation of Latin American populations in current genomic studies. Conclusions: Integrating ancestry-specific genomic variation with epigenetic markers is essential for advancing precision diagnostic and therapeutic strategies in keloid scarring. Future research should prioritize diverse, multicenter cohorts and integrative multi-omics approaches to improve risk stratification and enable targeted interventions for this disfiguring condition. Full article

Background/Objectives: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide and a systemic condition in which outcomes are influenced by respiratory impairment, multimorbidity, exacerbation burden, and functional status. This study aimed to identify multidimensional determinants of all-cause mortality in a population-based cohort of primary care patients with spirometry-confirmed COPD. Methods: We conducted a retrospective population-based cohort study using electronic health records from primary care in the Lleida health region (Catalonia, Spain). Adult patients with spirometry-confirmed COPD (FEV1/FVC < 0.70) between 2019 and 2023 were included. Baseline demographic, clinical, spirometric, functional, and social variables were extracted. Exacerbations in the year prior to baseline were classified as 0, 1, or ≥2 events (and, where available, as moderate vs. severe) using a prespecified operational definition. The primary outcome was all-cause mortality during follow-up (censoring date: 31 December 2023). Time-to-event analyses were performed using Cox proportional hazards models. Results: A total of 2056 patients were included (median age 71 years; 78.4% male). During follow-up, 558 patients died (27.1%). Independent predictors of mortality included male sex, increasing age, current smoking, and prior exacerbations, whereas sufficient physical activity and better lung function (FEV1 % predicted) were protective. Conclusions: Mortality in spirometry-confirmed COPD managed in primary care is driven by a multidimensional vulnerability profile beyond lung function alone. Integrating respiratory, clinical, and functional determinants may improve risk stratification and management in chronic lung disease. Full article

Background/Objectives: Penile squamous cell carcinoma (PSCC) is a rare malignancy with a potential major impact on survival. Prognostic assessment remains challenging, particularly in underrepresented eastern European populations, where region-specific evidence is lacking. This paper aimed to identify independent predictors of overall survival in surgically treated patients with PSCC from a Romanian high-volume tertiary center. Methods: This retrospective cohort study analyzed 60 patients who were surgically treated for PSCC between October 2020 and December 2024. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify independent prognostic factors. Results: The mean patient age was 62 ± 12 years. T-stage distribution showed 30% pT1, 35% pT2, 31.67% pT3, and 3.33% pT4, with 55% of patients presenting with nodal metastases. Univariate analyses demonstrated significant associations between lymphovascular invasion (p < 0.001), perineural invasion (p = 0.022), and positive surgical margins (p = 0.030) and risk of death. Multivariate analysis identified three independent prognostic factors: absence of histologically documented urethral invasion (HR 0.32; p = 0.027), T3–T4 disease (HR 8.26; p = 0.005 vs. T1), and N3 stage (HR 3.53; p = 0.030 vs. N0–N1). Patients without urethral invasion demonstrated significantly longer median overall survival (63 months vs. 11 months). The final three-variable prognostic model demonstrated good discrimination (C-index 0.78), providing a potential practical risk stratification tool. Conclusions: Urethral invasion, advanced T-stage, and N3 disease independently predict poor survival in surgically treated PSCC. The identification of urethral invasion as an independent prognostic factor warrants consideration in clinical practice. This is the first study of a Romanian cohort to provide critical data for risk-adapted treatment strategies in underrepresented eastern European populations. Full article

Background/Objectives: EndoPredict is a second-generation prognostic assay for estrogen-receptor-positive, HER2-negative breast cancer that integrates molecular and clinical parameters for risk stratification. Multiple studies have reported its clinical utility, while differences in the proportion of patients classified as high- or low-risk have been observed across cohorts. This study aimed to characterize clinical, pathological, and demographic factors associated with these differences. Methods: We conducted a descriptive review of 17 published studies and analyzed a single-institution cohort of 140 patients. Associations between clinicopathological variables and high-risk classification were assessed, including tumor size, lymph node status, histological grade, Ki-67 expression, and reproductive and demographic factors. Differences in inclusion criteria and cohort characteristics were also examined. Results: Tumor size and lymph node involvement emerged as primary determinants of high-risk classification. A high histological grade and Ki-67 levels above 25% were significantly associated with high-risk status (p < 0.001). Conversely, age, age at menarche, menopausal status, Body Mass Index, progesterone receptor expression, molecular subtype, and histological type showed no significant association. A higher number of pregnancies correlated with a lower frequency of high-risk classification (p < 0.01). Heterogeneity in risk distribution across studies was largely attributable to differences in tumor size, nodal involvement, and histological grade. Additional variability was associated with inclusion criteria, sample selection, and regional demographic characteristics. Conclusions: Variability in EndoPredict risk classification reflects both tumor biological features and population-specific factors. These findings emphasize the importance of interpreting genomic risk scores within their clinical and demographic context and support the comparison of risk distributions across heterogeneous patient cohorts. Full article

Background/Objectives: Patients with pre-existing heart failure (HF) represent a clinically vulnerable population with increased susceptibility to adverse outcomes during acute systemic illnesses, including coronavirus disease 2019 (COVID-19). Systemic inflammation is increasingly recognized as a central pathophysiological mechanism linking cardiovascular vulnerability with infection-related organ dysfunction. However, the prognostic role of inflammatory biomarkers in hospitalized COVID-19 patients with pre-existing HF remains incompletely defined. This study aimed to evaluate the association between inflammatory biomarkers and clinical outcomes in this high-risk population. Methods: This retrospective single-center cohort study included 395 consecutive adult patients hospitalized with confirmed COVID-19 between March 2020 and December 2024 at a tertiary referral center. Pre-existing HF was documented in 143 patients (36.2%). Inflammatory biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin, and D-dimer, were measured at admission. The primary outcomes were development of sepsis and in-hospital mortality. Multivariable logistic regression models were constructed to identify independent predictors of adverse outcomes after adjustment for demographic characteristics, comorbidities, disease severity, and cardiac biomarkers. Results: Patients with pre-existing HF had significantly higher in-hospital mortality compared with those without HF (11.9% vs. 4.8%, p = 0.016) and showed a trend toward increased intensive care unit admission. HF patients exhibited higher admission IL-6 levels, indicating enhanced inflammatory activation. In univariable analysis, HF was associated with mortality (OR 2.67, 95% CI 1.22–5.83, p = 0.014). After multivariable adjustment, the association between HF and mortality was attenuated, whereas IL-6 remained an independent predictor of mortality (adjusted OR 1.38, 95% CI 1.04–1.82, p = 0.021). Elevated IL-6 and procalcitonin levels were also independently associated with sepsis development. Conclusions: Pre-existing heart failure identifies a population at increased risk of adverse outcomes in hospitalized COVID-19 patients, and this excess risk appears to be partly mediated by systemic inflammatory activation. Interleukin-6 emerged as a key biomarker linking cardiovascular vulnerability, immune dysregulation, and clinical deterioration. These findings support the potential role of inflammation-based risk stratification to improve prognostic assessment and guide personalized management in high-risk patients with underlying cardiovascular disease. Full article

Early risk stratification of COVID-19 severity in oncology patients is critical for improving clinical outcomes and optimizing hospital resource allocation. This study proposes a rule-based clinical decision support system (CDSS) designed for integration into digital triage workflows. In practical terms, the score is intended to be applied at hospital admission or triage, where demographic and comorbidity information is routinely available. The computed score can automatically flag high-risk oncology patients for intensified monitoring or early ICU evaluation, supporting rapid resource allocation while preserving clinician decision-making. Using retrospective clinical data from hospitalized oncological patients with confirmed SARS-CoV-2 infection, we developed a scoring algorithm based on four common comorbidities: age ≥ 70, obesity, diabetes mellitus, and hypertension. Each factor was assigned a weighted contribution to a cumulative score ranging from 0 to 7. Patients were classified into three risk levels (low, moderate, high), correlating with observed rates of ICU admission and mortality. The system is built for low-complexity implementation in electronic health records (EHRs) or web-based triage dashboards and includes a software logic model with pseudocode. Results indicate that the score effectively distinguishes patient risk levels with statistical significance (p < 0.01), and can function as an early triage mechanism. The proposed model does not require laboratory data or imaging, making it particularly suitable for rapid deployment in both hospital and remote settings. This work demonstrates a pragmatic, interpretable, and scalable approach to clinical decision support in pandemic contexts involving vulnerable populations such as cancer patients. Full article

Background/Objectives: HBeAg-positive chronic hepatitis B (CHB) patients with very high viral replication are often clinically considered a homogeneous, low-risk population. However, substantial biochemical, virological, and fibrosis-related heterogeneity may exist. This study aimed to characterize this heterogeneity in treatment-naive, HBeAg-positive CHB patients with ultra-high viral loads (HBV DNA ≥ 7.0 log₁₀ IU/mL). Furthermore, we sought to identify predictors of significant fibrosis and detect clinically relevant discordant phenotypes, such as silent disease progression despite normal alanine aminotransferase (ALT) levels. Methods: This single-center, retrospective, cross-sectional study analyzed consecutively screened eligible patients. A liver stiffness measurement (LSM, kPa) and controlled attenuation parameter (CAP, dB/m) were obtained via transient elastography. Significant fibrosis was defined as an LSM ≥ 7.0 kPa. Statistical evaluations included Spearman’s correlation, multivariable regression, ALT-LSM stratification, and K-means clustering. Results: Among 413 included patients, age and aspartate aminotransferase (AST) emerged as independent risk factors for significant fibrosis, whereas log10 HBV DNA and log10 HBsAg were independent negative predictors. Patients with HBsAg ≥ 25,000 IU/mL exhibited significantly lower LSM values than those with lower HBsAg levels. Notably, 18.4% of patients with strictly normal ALT (≤40 U/L) presented with an LSM ≥ 7.0 kPa, indicating silent progression. Cluster analysis further identified two distinct patient phenotypes characterized by differing age, ALT, viral load, and fibrosis profiles. Conclusions: An ultra-high viral load in HBeAg-positive CHB does not guarantee a uniformly benign clinical state. By quantifying biochemical, virological, and fibrotic heterogeneity, this study highlights a critical subgroup with silent fibrosis progression that risks being overlooked by ALT-based assessments alone. Full article

Background/Objectives: Acute heart failure (AHF) is a leading cause of hospitalization and mortality among very old patients, yet this group is underrepresented in prognostic studies. Carbohydrate antigen 125 (CA125) has emerged as a potential biomarker of congestion and inflammation, but its value in patients aged 80 years and over remains unclear. We aimed to evaluate the prognostic value of plasma CA125 measured at admission for 12-month all-cause mortality and the composite outcome of mortality or heart failure (HF) readmission in very elderly patients hospitalized for AHF. Methods: We conducted a prospective observational study of patients aged ≥80 years admitted to an acute geriatric unit for AHF. CA125 and NT-proBNP were measured within 24 h of admission. Outcomes were assessed at 12 months. Survival analyses were performed using Kaplan–Meier curves, Cox regression models, and restricted cubic splines. Results: A total of 210 patients (mean age 89.8 ± 5.3 years; 75.3% females; 88.1% frail) were recruited. During the one-year follow-up, 70 deaths (37.2%) and 68 HF hospital readmissions (36.1%) were recorded. Patients in the highest CA125 tertile had an increased cumulative mortality risk (log-rank p = 0.061). A CA125 value ≥ 100 U/mL independently predicted both mortality (HR 1.88, 95% CI 1.15–3.09; p = 0.012) and the composite endpoint (HR 1.54, 95% CI 1.04–2.29; p = 0.031). Measures of functional dependence and frailty demonstrated greater discriminative ability than biomarkers. Conclusions: In very elderly patients hospitalized for AHF, elevated CA125 at admission independently predicted 12-month mortality and HF readmission. CA125 provides complementary prognostic information to geriatric assessment and may support risk stratification in this vulnerable population. Full article

Venothromboembolic (VTE) events are considered rare complications following foot and ankle surgery. Most instances of VTE following surgical procedures occur in particularly high-risk patient populations; therefore, VTE prophylactic anticoagulation is initiated based on risk/benefit stratification for each individual patient undergoing foot and ankle surgery. We present a case report on a 40-year-old male who underwent isolated Lisfranc ligament repair and subsequently developed an acute saddle pulmonary embolism and deep vein thrombosis 1 month postoperatively. The patient was on prophylactic Lovenox, yet still developed a life-threatening complication. The patient was found to be on a selective estrogen receptor modulator for the off-label treatment of male infertility. This medication, surgical intervention, and a period of non-weight bearing are believed to be contributory to the patient’s relatively increased hypercoagulable state. This case depicts a rare complication of foot and ankle surgery and highlights the importance of VTE prophylaxis during the postoperative period. Full article

Medulloblastoma is the most common malignant brain tumor in children, but it presents distinct challenges when occurring in adolescents and young adults (AYAs, aged 15–39 years). Recent molecular profiling has identified four principal medulloblastoma subgroups—WNT-activated, SHH-activated, Group 3, and Group 4—each demonstrating unique biological characteristics and clinical outcomes. AYA patients exhibit age-specific molecular patterns and therapeutic responses substantially different from those of younger children. This review synthesizes current evidence regarding epidemiology, diagnostic challenges, molecular characterization, risk stratification, treatment modalities, and outcomes specific to AYA medulloblastoma patients, highlighting the critical need for age-adapted therapeutic strategies and dedicated clinical research in this underserved population. Full article

Background: Malnutrition is highly prevalent in older adults and is associated with functional decline, systemic inflammation, and increased mortality. However, its prognostic role in relation to major adverse cardiovascular events (MACE), particularly when considered alongside established cardiovascular risk scores, remains insufficiently defined in geriatric populations. Methods: This retrospective cohort study included 291 adults aged ≥65 years who underwent a comprehensive geriatric assessment at a geriatric outpatient clinic. Nutritional status was evaluated using the Mini Nutritional Assessment—Short Form (MNA-sf). Cardiovascular risk was estimated using the Framingham Risk Score, SCORE2, SCORE2—Older Persons (SCORE2-OP), and LIFE-CVD (version 1). The primary outcome was the occurrence of MACE, and the secondary outcome was all-cause mortality. Multivariable logistic regression and Cox proportional hazards models were used to identify independent predictors of outcomes. Results: During a mean follow-up of 16.9 ± 4.7 months, 43 participants (14.8%) experienced MACE, and 11 (3.8%) died. Malnutrition or risk of malnutrition (MNA-sf < 12), present in 24.1% of participants, was significantly more frequent among those with MACE and those who died. In multivariable analyses, nutritional status remained a consistent independent predictor of both MACE and mortality, whereas commonly used cardiovascular risk scores showed limited or inconsistent associations with outcomes. Conclusions: In older adults, malnutrition assessed by the MNA-sf is a strong and independent predictor of both major adverse cardiovascular events and all-cause mortality, beyond traditional cardiovascular risk scores. These findings underscore the importance of incorporating nutritional status, together with frailty-related parameters, into cardiovascular risk assessment to improve risk stratification in geriatric care. Full article

Background/Objectives: Antisocial personality disorder (ASPD) is strongly associated with violence, substance use, criminal behavior, and elevated suicide risk. Although inflammatory and metabolic dysregulation have been implicated in severe psychiatric disorders, the biological correlates of impulsivity, aggression, and suicide risk in forensic ASPD populations remain unclear. This study aimed to investigate whether routine hematological, inflammatory, and metabolic parameters are associated with these clinical features. Methods: This cross-sectional study included 57 male individuals diagnosed with antisocial personality disorder (ASPD) who had committed crimes and were referred to the Forensic Psychiatry Department of Elazığ Fethi Sekin City Hospital in Turkey by the court, and 56 age-matched healthy controls. Participants completed standardized assessments of impulsivity (BIS-11), aggression (BPAQ), and suicide probability (SPS). Hematological indices, inflammatory markers, and routine biochemical parameters were analyzed. Group comparisons, correlation analyses, and multivariable logistic regression were performed. Results: Compared with age-matched controls, individuals with ASPD showed markedly higher impulsivity, aggression, and suicide probability, alongside substantially higher rates of substance use, imprisonment history, and suicide attempts (all p < 0.001). Hematological and inflammatory analyses revealed lower red blood cell (RBC) counts and elevated mean corpuscular volume (MCV), red cell distribution width (RDW), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and CRP–albumin ratio (CAR) in the ASPD group (all p < 0.05). Biochemical profiling showed reduced glucose, total protein, albumin, HDL, ALT, and vitamin B12 levels, with increased uric acid levels in ASPD (p < 0.05). Multivariable analysis indicated that being married and having higher education were protective against ASPD, whereas higher uric acid and CAR levels were associated with increased risk. Conclusions: The findings indicate that criminal offenders with ASPD show increased inflammatory markers and altered hematological and biochemical profiles. Routine blood parameters, combined with psychometric assessments, may help identify individuals at higher behavioral risk and support early risk stratification in forensic psychiatric settings, although causal relationships cannot be inferred from this cross-sectional study. Full article

Patients with lower limb paralysis following acute ischemic stroke (AIS) are at a markedly increased risk of deep vein thrombosis (DVT), which may lead to pulmonary embolism and substantially higher mortality and disability. This review comprehensively reviews studies from the past decade on the epidemiology, pathophysiology, and prevention of DVT in AIS patients with lower limb paralysis. The pathogenesis of DVT in this population is multifactorial, involving venous stasis due to immobility, stroke-induced hypercoagulability, endothelial dysfunction, neutrophil extracellular trap-mediated immunothrombosis, and autonomic dysregulation. Effective prevention requires individualized risk stratification, integrating clinical assessment, biomarkers, and imaging tools. Current prophylactic strategies include pharmacological anticoagulation (primarily low-molecular-weight heparin), mechanical interventions (such as intermittent pneumatic compression), and early mobilization and rehabilitation. While combined approaches have demonstrated significant benefits, challenges remain regarding the timing of anticoagulation, balancing bleeding risks, extended thromboprophylaxis, and novel immunothrombosis targets. Future research should focus on personalized prevention protocols, the application of artificial intelligence-based predictive models, and innovative therapies targeting endothelial injury and immune-mediated thrombosis, aiming to improve thromboprophylaxis and overall outcomes in this high-risk population. Full article

Background/Objectives: Hepatoblastoma, the most common pediatric primary liver cancer, is no longer regarded as a conventional malignancy but rather as a tumor emerging from disrupted hepatic developmental processes. Although improvements in chemotherapy, surgical techniques, and liver transplantation have markedly enhanced survival, therapeutic decision-making is still primarily guided by anatomical criteria and insufficiently reflects the biological heterogeneity that contributes to variable treatment response and disease recurrence. This narrative review integrates recent advances in molecular biology, tumor stemness, microenvironmental interactions, and translational research models in pediatric hepatoblastoma. We critically examine how developmental signaling pathways, cellular plasticity, and immune–vascular context shape tumor behavior and therapeutic vulnerability, with a focus on emerging targeted, anti-angiogenic, immune, and epigenetic strategies. Results: Hepatoblastoma is characterized by aberrant activation of key developmental pathways, including Wnt/β-catenin, Hippo–YAP, IGF, and mTOR signaling, which cooperate to sustain proliferation, stem-like phenotypes, and treatment resistance. Tumor heterogeneity is further reinforced by cancer stem cell populations and a predominantly immune-cold microenvironment. While innovative therapeutic approaches show promise, their clinical impact has been limited by biological complexity and insufficient integration into current treatment algorithms. Liquid biopsy biomarkers, advanced translational models, and multi-omics approaches offer new opportunities for biologically informed risk stratification and therapy adaptation. Conclusions: Future progress in pediatric hepatoblastoma will require a paradigm shift from purely clinicopathological management toward an integrated molecular and surgical framework. Incorporating biological stratification into therapeutic decision-making may enable personalized treatment, rational therapy de-escalation, and improved outcomes for high-risk disease. This review highlights the foundations and future directions for precision medicine in hepatoblastoma. Full article