Search Results (16,395)

Background. Survival of patients with brain metastases (BMs) is poor. It has become clear that targeted therapy has an effect on BMs and patient’ prognosis. The question remains which patients benefit from additional systemic therapy. This assumption was evaluated in a large single-center cohort. Methods. Patients consecutively planned to undergo local radiotherapy for their BMs in 2006–2017 were selected (n = 200). Prognosis, using CERENAL, disease-specific graded prognostic assessment (DS-GPA), and Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA), was evaluated. Results. Ninety-three (46.5%) patients received at least one additional line of systemic therapy subsequent to the diagnosis of their BMs. The median overall survival (OS) was 6.3 months. Having received subsequent systemic therapy resulted in a more favorable OS (10.4 versus 3.9 months). Interestingly, using dichotomized scores, CERENAL showed prognostic properties in all patients for disease-specific survival on multivariate analysis, whereas RTOG RPA and DS-GPA were not withheld in the model. Lastly, only having a favorable DS-GPA resulted in prolonged progression-free survival for first systemic therapy following BM diagnosis. Conclusions. Receiving subsequent systemic therapy has a profound influence on outcome in patients with BMs, indicating the effect of systemic therapy on BMs. Use of the CERENAL brain prognostic score shows potential for further prognostication of patients with more favorable outcomes. Full article

Background: Cachexia is common in patients with oesophagogastric cancer. The syndrome is characterised by tissue wasting (muscle and fat), anorexia, and reduced physical function, which result from complex interactions between the tumour and its host. Heterogeneity in the diagnostic criteria used for cachexia has hindered their clinical utilisation. This study aimed to compare the two established cachexia definitions (Fearon’s consensus definition and the Global Leadership Initiative on Malnutrition [GLIM] criteria) and their relationships with survival in patients with oesophagogastric cancer. Methods: Consecutive patients newly diagnosed with oesophagogastric cancer (January 2019 to December 2020) were identified from a prospective regional database. Involuntary weight loss, BMI, CT body composition analyses, and neutrophil–lymphocyte ratios were recorded at clinical staging. These data were used to assess patients for cachexia according to Fearon and GLIM diagnostic criteria. The primary outcome of interest was overall survival. Results: Overall, 465 patients (66.9% male, median 71 years) were diagnosed with oesophagogastric cancer during the 2-year study period. Cachectic proportions differed between definitions (Fearon: 59.1% vs. GLIM: 44.1%), and only 49.1% of the 322 patients who met one set of diagnostic criteria were cachectic according to both. Patients who met the GLIM criteria were significantly more comorbid and had a poorer performance status; however, no such difference was evident when using the Fearon definition. Those patients who met either set of diagnostic criteria had shorter survival than those who met neither (p < 0.001). Following adjustment for confounders, GLIM-defined cachexia was more strongly associated with reduced survival (aHR: 1.57 [95% CI: 1.25–1.96], p < 0.001) than Fearon-defined cachexia (aHR: 1.41 [95% CI: 1.13–1.76], p = 0.002). Patients who only met the Fearon diagnostic criteria had prolonged survival (median: 363 days) when compared to those who met only GLIM (median: 158 days) or both definitions (median: 120 days). A secondary analysis of those patients who met the GLIM diagnostic criteria (n = 205) compared the three potential phenotypical criteria used in this definition. Only reduced muscle mass, and not low BMI or weight loss, was associated with poorer survival (aHR: 1.88 [95% CI: 1.15–3.07], p = 0.012) in this group. Conclusions: Cancer cachexia is strongly associated with shortened survival in patients with oesophagogastric cancer. Classification using the GLIM criteria provides more effective prognostication and this definition should be utilised in multidisciplinary patient care. Full article

The liquid biopsy has gained significant attention in cancer diagnostics, with circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) being recognized as key biomarkers for tumor detection and monitoring. However, each biomarker possesses inherent limitations that restrict its standalone clinical utility, such as the rarity and heterogeneity of CTCs and the variable sensitivity and specificity of ctDNA assays. This highlights the necessity of integrating both biomarkers to maximize diagnostic and prognostic potential, offering a more comprehensive understanding of the tumor biology and therapeutic response. In this review, we summarize clinical studies that have explored the combined analysis of CTCs and ctDNA as biomarkers, providing insights into their synergistic value in diverse tumor types. Specifically, this paper examines the individual advantages and limitations of CTCs and ctDNA, details the findings of combined biomarker studies across various cancers, highlights the benefits of dual biomarker approaches over single-biomarker strategies, and discusses future prospects for advancing personalized oncology through liquid biopsies. By offering a comprehensive overview of clinical studies combining CTCs and ctDNA, this review serves as a guideline for researchers and clinicians aiming to enhance biomarker-based strategies in oncology and informs biosensor design for improved biomarker detection. Full article

Background/Objectives: Considering the physiological analogies between the eye and the kidney, this study aimed to investigate the potential relationship between retinal vascular density, assessed using Optical Coherence Tomography Angiography (OCT-A), and the renal resistive index (RRI) in patients with arterial hypertension. Methods: A total of 82 hypertensive patients (mean age 48 ± 13) were enrolled in the study. Participants underwent routine biochemical evaluations, office-based blood pressure measurement, 24 h ambulatory blood pressure monitoring, OCT-A imaging, and renal Doppler ultrasound examinations. Results: The mean RRI in the study population was 0.616 ± 0.06. Participants were divided into two groups based on the 75th percentile threshold of the RRI distribution (0.66, 95% CI 0.64–0.68). The group with RRI > 75th percentile, which appeared to have a higher number of smokers, exhibited significantly higher mean triglyceride and urinary albumin excretion (UAE) levels and a significantly reduced estimated glomerular filtration rate (eGFR) as compared to the group with RRI < 75th percentile. Among the hemodynamic parameters, 24 h pulse pressure (PP), daytime and nighttime PP, and nighttime systolic blood pressure (SBP) were significantly higher in the group with RRI > 75th percentile. Regarding retinal vascular density indices, the only significant difference was observed in the deep foveal vascular plexus, which displayed a reduced density in the group with RRI > 75th percentile. Logistic regression analysis revealed that RRI > 75th percentile was independently associated with increased nighttime mean pulse pressure (OR = 1.13, 95% CI: 1.049–1.221, p = 0.0014) and reduced deep foveal vascular density (OR = −0.5026, 95% CI: 1.0493–1.2211, p = 0.0044). Conclusions: Our findings demonstrate that ocular microvascular alterations are associated with RRI, a marker with a well-established prognostic value for renal disease progression and systemic macrovascular dysfunction. These results further substantiate the close relationship between renal and ocular microcirculation. Full article

Background/Objectives: Soluble αKlotho (sαKlotho) and fibroblast growth factor 23 (FGF-23) are increased in acute heart failure (AHF). This study aimed to assess changes in serum sαKlotho and FGF-23 concentrations during an episode of AHF as well as the usefulness of both biomarkers for predicting long-term prognosis. Methods: The study included 104 consecutive patients hospitalized in t he intensive cardiac care unit due to AHF (mean age, 65.8 ± 14.6 years; mean ejection fraction, 31.4% ± 14). New-onset AHF was reported in 43.3% of the population. Blood samples were measured at entry and on discharge from hospital. The main clinical outcomes assessed in this study were all-cause mortality or rehospitalization due to HF during a 3-year follow-up. Results: At admission sαKlotho, FGF-23, and NT-pro BNP levels, compared with discharge, were significantly higher at p < 0.001, p < 0.001, and p < 0.001 respectively. The 3-year Kaplan–Meier analysis, based on tertiles, revealed, for sαKlotho levels from Tertile 1 on admission and at discharge, a 2-fold higher rate of all-cause mortality or rehospitalization for HF compared with Tertile 3 (p = 0.006 and p = 0.028, respectively). One-third of patients showed an increase in FGF-23 and sαKlotho levels during hospitalization. Patients with the highest percentage increase in the levels of both biomarkers had an elevated risk of all-cause morality or hospitalization for HF (hazard ratio, 2.75; confidence interval, 1.19–6.35; p = 0.02). Conclusions: sαKlotho and FGF-23 levels are elevated during an episode of AHF. Low sαKlotho levels are associated with an increased risk of all-cause mortality or rehospitalization for HF. Increases in sαKlotho and FGF-23 values during hospitalization identify patients with poor prognosis. Full article

With the approval of tolvaptan as the first specific medicine for the treatment of rapidly progressive Autosomal Dominant Polycystic Kidney Disease (ADPKD), biomarker discovery has gained renewed interest as it is widely recognized that these will be crucial in clinical decision-making, serving as either prognostic or predictive tools. Since the marketing authorization was first issued in 2015 for ADPKD, tolvaptan has remained the sole pharmacological compound specifically targeting the disease. For ADPKD patients it is an invaluable medicine for retarding disease progression. Although the field of overall biomarker discovery and validation has been detailed in several publications, the role of inflammation remains largely overlooked in ADPKD. The current work aims to provide the reader with an updated review of inflammation biomarkers research in ADPKD, highlighting the role of urinary MCP-1 (monocyte chemoattractant protein-1) as the most promising tool. Full article

Cancer heterogeneity is a major challenge in oncology, complicating diagnosis, prognostication, and treatment. The clinical heterogeneity of cancer, which leads to differential treatment outcomes between patients with histopathologically similar cancers, is attributable to molecular diversity manifesting through genetic, epigenetic, transcriptomic, microenvironmental, and host biology differences. Heterogeneity is observed between patients, individual metastases, and within individual lesions. This review discusses clinical implications of heterogeneity, emphasizing need for personalized approaches to overcome challenges posed by cancer’s diverse presentations. Understanding of emerging molecular diagnostic and analytical techniques can provide a view into the multidimensional complexity of cancer heterogeneity. With over 90% of cancer-related deaths associated with metastasis, we additionally explore the role heterogeneity plays in treatment resistance and recurrence of metastatic lesions. Molecular insights from next-generation sequencing, single-cell transcriptomics, liquid biopsy technology, and artificial intelligence will facilitate the development of combination therapy regimens that can potentially induce lasting and even curative treatment outcomes. Full article

Carotid artery stiffness is associated with aging and atherosclerotic disease, leading to cerebrovascular events. Shear Wave Elastography (SWE) is a novel ultrasound technique offering a direct, quantitative assessment of the arterial wall elasticity. The aim of this study is to validate the technical feasibility of SWE in measuring carotid stiffness (CS). A literature search was performed across the PubMed and Scopus databases, with keywords including “carotid stiffness”, “Shear Wave Elastography”, “atherosclerosis”, and “vascular elasticity”. The findings reveal the potential of SWE in quantifying carotid Intima–Media Complex (IMC) stiffness, with implications for the early diagnosis of vascular disease, aiding in clinical decision making and prognostic assessment. Based on the findings of the literature search, a small pilot study was conducted involving 10 participants, using the Philips EPIQ Elite system for the SWE measurements. The technical analysis revealed optimizing the region of interest (ROI) size, probe positioning, and cine-loop analysis as crucial factors for obtaining accurate results. The results of the literature review and small pilot study demonstrate the potential of SWE as a non-invasive method for assessing carotid stiffness. Certain technical adjustments, such as smaller ROIs and careful probe placement, improved the accuracy and repeatability of carotid SWE measurements. Further studies are needed to assess and standardize carotid SWE across larger patient populations. Full article

Introduction: Prostate cancer, notably prostate adenocarcinoma (PARD), has high incidence and mortality rates. Although typically resistant to immunotherapy, recent studies have found immune targets for prostate cancer. Stratifying patients by molecular subtypes may identify those who could benefit from immunotherapy. Methods: We used single-cell and bulk RNA sequencing data from GEO and TCGA databases. We characterized the tumor microenvironment at the single-cell level, analyzing cell interactions and identifying fibroblasts linked to mitophagy. Target genes were narrowed down at the bulk transcriptome level to construct a PARD prognosis prediction nomogram. Unsupervised consensus clustering classified PARD into subtypes, analyzing differences in clinical features, immune infiltration, and immunotherapy. Furthermore, the cellular functions of the genes of interest were verified in vitro. Results: We identified ten cell types and 160 mitophagy-related single-cell differentially expressed genes (MR-scDEGs). Strong interactions were observed between fibroblasts, endothelial cells, CD8⁺ T cells, and NK cells. Fibroblasts linked to mitophagy were divided into six subtypes. Intersection of DEGs from three bulk datasets with MR-scDEGs identified 26 key genes clustered into two subgroups. COX regression analysis identified seven prognostic key genes, enabling a prognostic nomogram model. High and low-risk groups showed significant differences in clinical features, immune infiltration, immunotherapy, and drug sensitivity. In prostate cancer cell lines, CAV1, PALLD, and ITGB8 are upregulated, while CLDN7 is downregulated. Knockdown of PALLD significantly inhibits the proliferation and colony-forming ability of PC3 and DU145 cells, suggesting the important roles of this gene in prostate cancer progression. Conclusions: This study analyzed mitophagy-related genes in PARD, predicting prognosis and aiding in subtype identification and immunotherapy response analysis. This approach offers new strategies for treating prostate cancer with specific molecular subtypes and helps develop potential biomarkers for personalized medicine strategies. Full article

Immunohistochemical (IHC) detection is crucial in diagnosing lung cancer. Interleukin-24 (IL-24) is a valuable marker in IHC analysis, aiding in tumor characterization and prognostication. However, current manual scoring methods are labor-intensive, imprecise, and subjective, leading to inconsistencies among observers. Automated scoring methods also have limitations, such as poor segmentation and lack of interpretability. In this paper, we introduce RMD-Net, a novel scoring network framework specifically designed for IL-24 scoring in lung cancer. The framework incorporates a regional attention mechanism and a multi-channel scoring network. Initially, diagnostic region identification and segmentation are accomplished by integrating the diagnostic regional spatial attention module into the fully convolutional network. Subsequently, we employ the Adaptive Multi-Thresholding algorithm to derive expert, strong feature description maps. Finally, the attention-guided IHC images and expert feature description maps are fed into a multi-channel scoring network. Its backbone includes feature fusion layers and scoring layers to ensure the accuracy and interpretability of the final result. To the best of our knowledge, this is the first system that directly employs lung cancer IL-24 IHC images as input and combines both expert-derived features and deep-learning abstract features to produce clinical scores. Our dataset is sourced from the Institute of Life Sciences and Bioengineering at Beijing Jiaotong University. The experimental results demonstrate that the proposed method achieves an IL-24 score precision of 89.25%, an F1 score of 89.00, and an accuracy of 95.94%, outperforming other state-of-the-art methods. This contribution has the potential to advance clinical diagnosis and treatment strategies for lung cancer. Full article

Background and Objectives: Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury with high mortality, characterized by hypoxemic respiratory failure and diffuse lung damage. Despite advancements in care, no definitive biomarkers have been established for ARDS diagnosis and prognostic stratification. Soluble receptor for advanced glycation end-products (sRAGE), a marker of alveolar epithelial injury, has shown promise as a prognostic indicator in ARDS. This study evaluates sRAGE’s utility in predicting 28-day mortality. Materials and Methods: A retrospective cohort study was conducted at a tertiary care ICU in Serbia from January 2021 to June 2023. Adult patients meeting the Berlin definition of ARDS were included. Exclusion criteria included pre-existing chronic respiratory diseases and prolonged mechanical ventilation before diagnosis. Serum sRAGE levels were measured within 48 h of ARDS diagnosis using enzyme-linked immunosorbent assay (ELISA). Clinical severity scores, laboratory markers, and ventilatory parameters were recorded. Logistic regression and survival analyses were used to assess the prognostic value of sRAGE for 28-day mortality. Results: A cohort of 121 patients (mean age 55.5 years; 63.6% male) was analyzed. Non-survivors exhibited higher median sRAGE levels than survivors (5852 vs. 4479 pg/mL, p = 0.084). The optimal sRAGE cut-off for predicting mortality was >16,500 pg/mL (sensitivity 30.4%, specificity 86.9%). Elevated sRAGE levels were associated with greater disease severity and an increased risk of 28-day mortality in ARDS patients, highlighting its potential as a prognostic biomarker. The main findings, while indicative of a trend toward higher sRAGE levels in non-survivors, did not reach statistical significance. Conclusions: The main findings, while indicative of a trend toward higher sRAGE levels in non-survivors, did not reach statistical significance (p = 0.084). sRAGE demonstrates potential as a prognostic biomarker in ARDS and has moderate correlation with 28-day mortality. Integrating sRAGE with other biomarkers could enhance risk stratification and guide therapeutic decisions. The retrospective design limits the ability to establish causation, underscoring the need for multicenter prospective studies. Full article

Background: Previous preclinical data have shown that the dynamic cross-talk between abnormal tumor vasculature and immune cell factors in the tumor microenvironment may exert a critical role in the progression and treatment resistance of non-small cell lung cancer (NSCLC). In the clinical setting, a variety of blood-based angiogenesis- and immune-related factors are being increasingly investigated as potential biomarkers of prognosis or treatment response in immunotherapy-treated NSCLC. We herein aimed to evaluate the clinical relevance of the peripheral blood levels of vascular endothelial growth factor-A and -B (VEGF-A and VEGF-B, respectively), soluble programmed cell death-1 (sPD-1), and programmed cell death-ligand 1 (sPD-L1) in patients with advanced NSCLC treated with immune checkpoint inhibitors (ICIs). Methods: Consecutive patients with advanced-stage, non-oncogene-addicted NSCLC, eligible to receive ICIs at the Oncology Unit of Sotiria Athens General Hospital, were prospectively recruited. A group of sex- and age-matched healthy controls was also enrolled for the evaluation of the potential diagnostic significance of the examined biomarkers. Serum levels of all biomarkers were measured using ELISA, both before and after treatment, and were correlated with standard clinicopathological features of patients, treatment response, progression-free survival (PFS), and overall survival (OS). Results: A total of 55 patients and 16 healthy controls were included in the final analysis. The mean age of patients and controls was 66.5 years (SD = 8.0 years) and 65.4 years (SD = 9.1 years), respectively. The majority of patients (65.5%) received pembrolizumab in combination with chemotherapy, while the remaining patients received pembrolizumab monotherapy. ROC curve analysis showed that VEGFB and sPD-1 were the only markers with a significant diagnostic value. Higher pre-treatment values of sPD-L1 (HR = 1.68; p = 0.040) and sPD-1 (HR = 10.96; p = 0.037) as well as higher post-treatment values of VEGF-B (HR = 2.99; p = 0.049) were all significantly associated with a reduced OS in univariate Cox regression analysis. The adverse prognostic significance of higher pre-treatment values of sPD-L1 (HR = 2.10; p = 0.014) and higher post-treatment values of VEGFB (HR = 3.37; p = 0.032) was further confirmed in multivariate analysis. Conclusions: Our study results suggest that serum levels of sPD-L1 and VEGF-B may independently predict prognosis in ICI-treated advanced-stage NSCLC. Full article

About 5% of annual access to emergency departments (EDs) and up to 25–30% of hospital admissions involve patients with symptoms suggestive of acute coronary syndrome (ACS). The process of evaluating and treating these patients is highly challenging for clinicians because failing to correctly identify an ACS can result in fatal or life-threatening consequences. However, about 50–60% of these patients who are admitted to the hospital because of chest pain are found to have no ACS. Coronary computed tomographic angiography (CCTA) has emerged as a proposed new frontline test for managing acute chest pain in the ED, particularly for patients with low-to-intermediate risk. This narrative review explores the potential of adopting an early CCTA-based approach in the ED, its significance in the era of high-sensitivity troponins, its application to high-risk patients and its prognostic value concerning atherosclerotic burden and high-risk plaque features. Additionally, we address clinical and technical issues related to CCTA use for triaging acute chest pain in the ED, as well as the role of functional testing. Finally, we aim to provide insight into future perspectives for the clinical application of CCTA in the ED. Full article

Background: Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) are the most prevalent subgroup among NETs and include heterogeneous tumors characterized by different clinical behavior and prognosis. The NETest is a tool based on real-time PCR combined with deep learning strategies to specifically identify tumors with a neuroendocrine genotype. Despite the promising results achieved regarding its utility in the field of GEP-NETs, the NETest has not yet entered into routine clinical practice. Methods: We performed a systematic review aimed at summarizing available evidence on the application of the NETest in both the diagnosis and the prognostic stratification of GEP-NETs. Results: We identified five studies evaluating the diagnostic role of the NETest and nine studies evaluating its prognostic value. The NETest emerged as a reliable biomarker for GEP-NET diagnosis with an accuracy higher than 90%, regardless of tumor stage and grade. However, according to some studies, the NETest showed a low specificity, mainly attributed to interferences with other gastro-intestinal malignancies. In terms of prognostic value, the NETest correlated with the detection of residual disease after surgery in six studies. The NETest was also associated with patients’ survival outcomes, namely progression-free survival (PFS) and overall survival (OS) in three studies. Conclusions: According to current systematic review, the value of the NETest both for diagnosis and for prognosis of GEP-NET emerged as robust across different studies. Further prospective analysis on larger GEP-NET series is encouraged to validate this tool, improving patients’ diagnosis, management, and follow-up. Full article