Search Results (7,694)

Crimean–Congo Hemorrhagic Fever (CCHF) disease, caused by the CCHF virus (CCHFV), poses a significant fatality risk whose underlying pathological mechanisms, including the contribution of coagulation factors, imbalances and platelet abnormalities, remain poorly understood. Here we present a meta-analysis and meta-regression analysis using clinical data from coagulation assays and platelet parameters as predictive disease indices with the goal of uncovering pathognomonic factors and to pave a way for the development of effective therapeutic approaches. Methods: We systematically analyzed published studies reporting coagulation assays and platelet indices in patients with confirmed CCHF. Data from 1779 patients across the published studies were analyzed to assess associations between laboratory parameters and the fatality risk, while evaluating heterogeneity and prognostic significance. Results: Fatal outcomes were strongly associated with elevated liver enzymes (AST: 1116.71 ± 1454.08 IU/mL; ALT: 446.56 ± 457.41 IU/mL) and prolonged clotting times (PT: 19.53 ± 6.57 s; aPTT: 64.02 ± 23.13 s; INR: 1.53 ± 0.56). D-dimer levels did not significantly predict fatality. Thrombocytopenia and coagulopathy emerged as independent risk factors for adverse outcomes. Notably, protein C and protein S levels did not differ between survivors and non-survivors, suggesting that the coagulopathy is not purely consumptive or a result of impaired hepatic synthesis. In contrast, mildly reduced antithrombin levels (83.65 ± 19.90) were weighted toward increased mortality. Full article

Background and Purpose: This study retrospectively evaluates the outcomes of head and neck adenoid cystic carcinomas (ACCs) treated with particle therapy, including carbon ion radiotherapy (CIRT) alone or combined with photon therapy, at a single institution. Methods and Materials: Patients with ACC who underwent CIRT alone or a combination of CIRT and photon therapy at the Marburg Ion Therapy Center between February 2017 and December 2023 were included. Radiation therapy was administered postoperatively in surgically resectable patients and as definitive treatment in unresectable patients. Newly diagnosed patients received CIRT as a boost in combination with photon intensity-modulated radiation therapy (IMRT), while those with recurrent disease received CIRT alone. Prognostic factors were analyzed using Kaplan–Meier analysis and proportional hazards regression for multiple regression. Late toxicities (grade 3 or higher) were recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. Results: A total of 73 patients were included, with a median age of 57 years (range: 16–86 years) and a median follow-up of 20 months (range: 3–70 months). The cohort included 28 males (38%) and 45 females (62%). The median CIRT dose was 24 Gy (relative biological effectiveness (RBE)) (range: 15–60 Gy) in a median of 8 fractions (range: 5–20), and the median photon dose was 50 Gy (range: 45–54 Gy) in 25 fractions (range: 15–30). Locoregional recurrence-free survival rates at 1 and 3 years were 89.6% and 75.4%, respectively, while distant metastasis-free survival rates were 82.1% and 61.4%, respectively. LC was significantly influenced by T stage, with patients with T4 tumors showing worse outcomes. Treatment was generally well tolerated, with acute side effects including mucositis and skin erythema. Severe chronic toxicities were rare, with only 1% of patients experiencing grade 3 dysphagia and grade 3 xerostomia. Conclusions: CIRT, particularly when combined with photon therapy, demonstrates favorable local control and promising efficacy in head and neck ACC, though distant metastasis remains the primary pattern of failure. Tumor stage is a significant negative prognostic factor for local control and overall survival. Full article

Background: In this study, we aimed to explore the relationship between quantitative indices derived from computed tomography (CT) attenuation histograms and disease prognosis in patients with pneumonia and acute respiratory failure. We also sought to assess the effectiveness of these parameters as clinical prognostic markers. Methods: CT images of patients with pneumonia and acute respiratory failure were analyzed using Vitrea^® Advanced Visualization software. The analyzed quantitative CT (qCT) indices included mean lung Hounsfield unit (HU) and density-based volume measurements, specifically low-, medium-, and high-density volume (LDV, MDV, and HDV). Comparative analyses were performed to examine the differences in the volume density between the lungs bilaterally; these were accompanied by regional analyses and density indices. All indices were calculated using previously defined and validated Hounsfield unit (HU) thresholds, which helped to ensure accurate and consistent quantitative measurements and facilitated a more robust evaluation of the prognostic potential of qCT parameters. Results: Quantitative CT indices proved to have significant prognostic value in predicting mortality. In multivariable analysis, Difference for Lung HDV > 193 mL emerged as an independent risk factor (aOR: 4.29, p = 0.041). The prognostic significance was especially evident in patients with unilateral dominant pneumonia, where Difference for Lung MDV >219 mL (aOR: 9.30, p = 0.03) and Difference for Lung HDV > 193 mL (aOR: 10.85, p = 0.02) emerged as strong independent predictors of mortality. In this subgroup, lung volume differences demonstrated the strongest diagnostic performance (AUC: 0.808, 95% CI: 0.667–0.908, p < 0.001). Conclusions: Clinical outcomes are associated with quantitative CT-derived lung volume and density difference indices. Inter-lung differences in Lung MDV and Lung HDV are linked to mortality and may provide additional prognostic information beyond conventional imaging methods. Prospective studies should be conducted to validate these findings, and caution should be exercised during their interpretation. Full article

Circulating tumor DNA (ctDNA) has emerged as a promising and versatile biomarker in colorectal cancer (CRC), providing real-time insights into the tumor burden, minimal residual disease (MRD), and treatment response across both early and metastatic stages. In patients with resected stage II–III CRC, post-operative ctDNA positivity is a robust predictor of recurrence and may outperform traditional clinicopathologic risk factors. It can facilitate adjuvant therapy discussions; however, treatment escalation or de-escalation based solely on ctDNA results is not yet supported by available interventional data. In the metastatic setting, ctDNA-based techniques could provide non-invasive molecular profiling and a monitoring response to systemic therapies. Peripheral blood-based techniques could also help detect emerging resistance to systemic therapy. Emerging evidence highlights that quantitative assessment of ctDNA dynamics, including the baseline burden and post-treatment clearance, could further refine risk stratification and inform treatment personalization. Collectively, ctDNA represents a promising and evolving biomarker with well-established prognostic and emerging predictive potential and is poised to support precision oncology across the continuum of CRC. Full article

Mitral annular disjunction (MAD) is associated with an increased risk of ventricular arrhythmias and sudden cardiac death, yet its genetic background remains poorly defined. We report the case of a 50-year-old man with MAD who survived cardiac arrest and carries three variants of unknown significance (VUS) in genes involved in cardiomyopathy pathogenesis. To explore the genetic basis of non-syndromic MAD, we performed a systematic review of the literature, identifying five case reports and one retrospective cohort study. The case reports described patients with MAD harboring four pathogenic variants and ten VUS. Two pathogenic variants were linked to cardiomyopathies, involving proteins of the nuclear envelope and cytoskeleton, while two were associated with channelopathies. The retrospective cohort study identified a recurrent variant in a gene involved in intercellular adhesion segregating within a family affected by MAD. Overall, available evidence suggests that genetic factors may hypothetically modulate susceptibility to MAD, not only in connective tissue disorders but also in isolated mitral valve disease. Variants associated with arrhythmogenic cardiomyopathies and channelopathies appear to cluster in families with non-syndromic MAD and arrhythmic phenotypes, suggesting a role in the arrhythmic substrate. However, in absence of definitive functional, segregation, or longitudinal data, the contribution of genetic variants to MAD should be interpreted with caution. Further genomic studies are needed to clarify their genetic contribution and prognostic implications. Full article

Backgrounds: Single-arm studies evaluating reduced intensity (de-escalated) therapy for low-risk Human Papillomavirus-related oropharyngeal cancer (HPV+OPC) patients demonstrated high cure rates and reduced toxicity compared with historical results of standard of care (SOC). However, randomized studies demonstrated that the outcomes of de-escalated therapies were inferior to standard therapy, suggesting that a minority of patients may not benefit from de-escalation. Objectives: to review strategies and prognostic biomarkers before or early during therapy to identify low-risk HPV+OPC patients who may require SOC and who should be excluded from de-escalation trials to avoid compromising outcomes. Methods: A comprehensive narrative literature review between January 2000 and August 2025 was performed to identify prognostic biomarkers in HPV+OPC, as well as studies reporting early-response indicators with prognostic potential in clinically defined good-prognosis HPV+OPC treated with chemo-irradiation. Preclinical studies were excluded unless their findings had implications for clinical outcomes. Data were synthesized qualitatively in this narrative report due to the substantial heterogeneity of the clinical and methodological aspects of the reviewed studies. The risk of bias in non-randomized studies was assessed using the Newcastle–Ottawa Scale (NOS) for cohort studies. Results: Multiple candidate prognostic biomarkers were identified, including molecular, histopathological, imaging, and clinical factors. Almost all studies were retrospective, included small cohorts and lacked internal or external validation, and had poor NOS scores, mostly due to lack of sufficient follow-up and lack of information about loss to follow-up, thereby precluding most biomarkers from current clinical utilization. Response-based selection based on induction chemotherapy is effective but limited by its added toxicity. Early tumor responses assessed by hypoxia, metabolic imaging, and circulating HPV DNA kinetics show encouraging preliminary results that need to be validated. Conclusions: Current evidence indicates major methodological limitations in most studies of prognostic biomarkers in clinically defined good-prognosis HPV+OPC. Early tumor response-based selection strategies are promising and warrant comparison with SOC in multi-center randomized trials. Full article

Background and Objectives: High-risk resected cutaneous melanoma carries a substantial risk of recurrence, and additional host-related prognostic biomarkers are needed beyond conventional tumor-centered factors. Red blood cell distribution width (RDW) reflects systemic inflammation and physiological stress and may provide incremental prognostic information. Materials and Methods: In this retrospective cohort study, 164 patients with stage II–III cutaneous melanoma who underwent curative-intent surgical resection were analyzed. A receiver operating characteristic (ROC) curve analysis determined the optimal RDW cut-off for relapse-free survival (RFS), which was 14.2%. Patients were categorized into low and high RDW groups accordingly. Survival probabilities were estimated using the Kaplan–Meier method and compared with the log-rank test. Univariate and multivariate Cox proportional hazards regression models were used to evaluate associations between RDW status, clinicopathological variables, and RFS. Results: During a median follow-up of 58.3 months, patients with high RDW had significantly shorter RFS compared with those with low RDW. In univariate analysis, elevated RDW was associated with an increased risk of recurrence (HR 2.79, 95% CI 1.39–5.58; p = 0.004). After adjustment for key prognostic factors (e.g., stage, Breslow, age, adjuvant therapy), high RDW remained an independent predictor of inferior RFS (HR 2.74, 95% CI 1.37–5.47; p = 0.004). Stage III disease also independently predicted worse RFS (HR 4.67, 95% CI 2.04–10.68; p < 0.001). Conclusions: Baseline RDW independently predicts RFS in high-risk resected stage II–III cutaneous melanoma and may enhance prognostic stratification using a simple, widely available biomarker. Full article

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with limited targeted treatment options, heterogeneous treatment response, and high risk of early recurrence. Artificial intelligence (AI) has rapidly emerged as a powerful tool to address key clinical challenges in TNBC across diagnosis, treatment response assessment, and prognosis. Diagnostic and staging challenges persist due to variable imaging features in TNBC and limitations in conventional modalities, increasing the risk of delayed detection. Predicting response to neoadjuvant systemic therapy remains difficult, as patient responses are heterogeneous, and existing clinical markers provide limited early predictive value. Prognostication in TNBC is similarly constrained by the absence of widely used genomic tools and reliance on clinicopathologic factors that incompletely reflect tumor biology. This review summarizes recent advances in AI applications for TNBC across diagnosis, tumor characterization and staging, treatment response prediction, and prognosis, highlighting both emerging opportunities and current limitations in clinical translation. Full article

Lymphovascular invasion is an adverse pathologic feature in prostate cancer, but its independent molecular drivers remain unclear due to strong confounding by tumor grade and stage. We performed a confounder-adjusted transcriptomic analysis of 403 TCGA-PRAD samples. Differential expression was adjusted for Gleason score and pathological T stage. A transcriptional profile associated with LVI was derived and tested in multivariable logistic and Cox proportional hazards models for biochemical recurrence-free survival, with bootstrap internal validation. After multivariable adjustment, 129 genes were independently associated with LVI. This gene set was overwhelmingly enriched for interferon-alpha/beta signaling and antiviral response pathways. A continuous composite score derived from this profile predicted a reduced risk of biochemical recurrence independently of standard clinicopathological factors (adjusted HR per unit = 0.911, 95% CI: 0.835–0.993, p = 0.033). Multi-omics integration revealed subtle promoter hypomethylation and strong correlations between methylation and expression for key interferon genes, supporting transcriptional regulation. We identify a robust, interferon-response transcriptional profile that specifically defines LVI in prostate cancer after accounting for major clinical confounders. This transcriptional signature provides independent prognostic information, refines the biological understanding of LVI, and presents a novel targetable pathway for further investigation. Full article

Objectives: Type-D personality, characterized by negative affectivity (NA) and social inhibition (SI), has been associated with adverse outcomes in chronic pain and cardiovascular populations. Evidence in spine outpatient settings remains limited. We aimed to assess the prevalence of Type-D personality and its association with pain, disability, and psychological distress in patients presenting to a university spine outpatient clinic. Methods: This exploratory cross-sectional study included 300 consecutive patients (18–85 years) presenting to a university spine outpatient clinic between 2023 and 2025. Patients completed the Type-D Scale-14 (DS14; Type-D defined as NA ≥10 and SI ≥10), the Hospital Anxiety and Depression Scale (HADS), the Visual Analog Scale for pain (VAS, 0–10), and the Oswestry Disability Index (ODI, 0–100). Demographic and clinical characteristics were recorded. Comparisons between Type-D and non-Type-D patients were performed. Results: The prevalence of Type-D personality was 32.3% (95% CI: 27.0–37.6%). Compared with non-Type-D patients, Type-D patients reported higher pain intensity (VAS: 5.23 vs. 3.88), disability (ODI: 38.6 vs. 31.3), anxiety (HADS-A: 10.0 vs. 6.5), and depression (HADS-D: 8.4 vs. 6.4); all p < 0.01. Between-group differences were clinically relevant, with large effect sizes for pain intensity (VAS; Cohen’s d ≈ 1.10) and moderate-to-large effect sizes for functional disability (ODI; Cohen’s d ≈ 0.75). Correlation analyses showed moderate to strong associations between Type-D personality traits (negative affectivity and social inhibition) and psychological distress. In stratified analyses, longer pain duration was descriptively associated with greater disability, particularly among patients with Type-D personality. Conclusions: Type-D personality is common in spine outpatient populations and is associated with greater pain, disability, and psychological distress. These findings underscore the relevance of psychosocial factors in spine outpatient care and highlight the need for further longitudinal research to clarify prognostic implications and potential targets for intervention. Full article

Background: Acute kidney injury (AKI) is a serious complication in vasculitis patients and may adversely affect prognosis. However, the role of blood urea nitrogen (BUN) as a predictor of AKI and mortality in vasculitis has not been fully elucidated. Methods: We retrospectively analyzed 701 patients with large-, medium-, and small-vessel vasculitis from the MIMIC-III/IV databases to evaluate the relationship between BUN, AKI occurrence, and mortality. AKI was defined according to the KDIGO serum creatinine criteria. Logistic and Cox regression models, restricted cubic spline (RCS) analyses, and multiple machine learning models were employed to identify risk factors and assess predictive performance. Results: AKI occurred in 25.1% (176/701) of vasculitis patients and was associated with significantly higher 30- and 365-day mortality rates (p < 0.05). Multivariable logistic regression identified BUN as an independent predictor of AKI (OR: 1.03; 95% CI: 1.02–1.05; p < 0.0001). Patients in the highest BUN tertile had a 5.67-fold greater risk of AKI compared to the lowest tertile (p < 0.0001). The Cox regression confirmed BUN as an independent predictor of 30- and 365-day mortality among patients with AKI (p < 0.05). The RCS analysis identified a critical BUN threshold of 32 mg/dL, above which the mortality risk markedly increased. Machine learning models further validated the prognostic significance of BUN and age, with the logistic regression model achieving the highest predictive accuracy (area under the curve: 0.904). Conclusions: BUN is a practical predictor of AKI and mortality in vasculitis and may assist early risk stratification in this population. Full article

Older patients with unresectable locally advanced non-small-cell lung cancer (NSCLC) frequently receive concurrent chemoradiotherapy (CCRT) with daily low-dose carboplatin; however, real-world data on its efficacy, safety, and prognostic factors remain limited. We aimed to retrospectively evaluate the clinical outcomes of this regimen and examined whether systemic inflammation-based indices predict prognosis in this setting. We reviewed 52 consecutive patients with locally advanced NSCLC treated with first-line CCRT using daily low-dose carboplatin at three Japanese institutions between April 2007 and December 2019. The median progression-free survival (PFS) and overall survival (OS) were 11.5 and 40.1 months, respectively. Twenty patients received durvalumab as consolidation therapy. In the overall cohort, multivariate analysis identified the Glasgow Prognostic Score (GPS) as an independent predictor of PFS. A GPS of 0–1 was also associated with a significantly longer OS in univariate analysis. CCRT with daily low-dose carboplatin provided durable disease control with acceptable toxicity in older patients with unresectable stage II/III NSCLC. The GPS appears to be a simple marker for PFS in this population and may aid in pretreatment risk stratification alongside histology and consolidation strategies. Full article

(1) Background: Pelvic osteosarcoma accounts for a small proportion of osteosarcoma cases but is associated with significantly poorer outcomes than extremity tumors. This study evaluates contemporary survival outcomes and prognostic factors in a single-center cohort. (2) Methods: We retrospectively analyzed 56 patients with primary pelvic osteosarcoma treated between 2006 and 2019. Demographic characteristics, surgical margins, adjuvant therapies, local recurrence, metastasis, survival outcomes and the Musculoskeletal Tumor Society (MSTS) Score were assessed. Kaplan–Meier analysis was performed for overall survival (OS), including subgroup analyses by age and Enneking classification. (3) Results: Median age at surgery was 24 years. R0 margins were achieved in 96.4% of cases. OS at 1, 3, and 5 years was 69%, 54%, and 48%, respectively. Younger patients (≤25 years) showed significantly improved 5-year OS (68%) compared with older groups. Enneking classification showed limited prognostic discrimination. Metastatic disease at any time strongly predicted inferior survival (5-year OS 30% vs. 66%). The mean MSTS score one year after operation was 14.1 points. Functional outcome showed marked variability and was strongly influenced by patient age, extent of resection, reconstruction strategy, and postoperative complications. Younger patients and those undergoing limited or non-acetabular reconstructions achieved superior functional results, whereas complex endoprosthetic reconstructions and revision-requiring complications were associated with reduced MSTS scores. (4) Conclusions: Pelvic osteosarcoma continues to be associated with substantial morbidity and mortality. Younger age and absence of metastatic disease are strong predictors of improved survival. Functional outcomes are typically moderate; further advances are needed to improve results. Full article

Background/Objectives: Acute myeloid leukemia is a genetically diverse hematological malignancy where patient outcomes vary significantly. Long non-coding RNA (lncRNA) GAS5 acts as a tumor suppressor and is frequently downregulated in various cancers, as well as in AML. In the current study, we aimed to explore the effects of GAS5 promoter variants on its expression levels in AML patients, their prognostic significance, and to investigate their functional effects. Methods: The GAS5 promoter region containing rs55829688 and rs145204276 was sequenced in 75 AML patients. Statistical analyses were performed to assess their associations with GAS5 expression and outcomes. An in vitro functional study in K562 cells evaluated the effects of these variants on the transcriptional activity of constructs containing each variant. In silico analysis was used to predict changes to transcription factor binding sites. Results: Patients carrying the rs55829688 TC/CC genotype exhibited lower GAS5 expression and were more frequently categorized into the adverse risk group. In intermediate-risk patients, this genotype trended toward lower overall survival and higher bone marrow blast percentages. In vitro, the construct harboring the rs55829688 C allele showed a two-fold decrease in reporter gene activity compared to the construct bearing both wild type alleles. In silico analysis identified RUNX3 as the most likely transcription factor affected by this variant. The variant rs145204276 was considered for the first time in AML; however, no significant clinical associations or transcriptional effects were found. Conclusions: Taken together, our findings provide evidence that the rs55829688 promoter variant reduces GAS5 expression in AML and could potentially be a prognostic marker. Full article

The integration of artificial intelligence (AI) into medicine, oncology, and radiology represents a marked shift in the diagnosis, prognostication, and management of hepatocellular carcinoma (HCC), a malignancy with high global incidence and poor prognosis. This review examines the application of AI, including machine learning (ML) and deep learning (DL), across the spectrum of HCC care. As AI advances, new convolutional neural networks (CNNs) and other models are enhancing diagnostic accuracy, reducing interpretation times, and improving the characterization of liver lesions across major imaging modalities including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). Beyond diagnosis, the transformative role of AI in prognostication is also improving, where AI can now noninvasively predict critical factors such as microvascular invasion, genetic mutation status, tumor recurrence, and treatment response. Furthermore, AI has shown promise in facilitating patient-specific treatment planning by stratifying patients for interventions such as transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT). The review also addresses the emerging fields of pathomics and the use of AI in positron emission tomography (PET), while critically evaluating the cost-effectiveness of these technologies. Despite its promise, the widespread clinical adoption of AI faces challenges, including limited generalizability, maintaining patient privacy, ethical considerations, and the need for robust prospective validation. Ultimately, this review illustrates that the future of HCC management lies in a collaborative, hybrid-intelligence model, where AI-driven insights augment clinical expertise to optimize diagnostic pathways, personalize therapy, and improve patient outcomes. Full article