Search Results (1,022)

Background/Objectives: The coronavirus disease 2019 (COVID-19) has more severe symptoms and increased mortality among men than women. To address the prognostic impact of vaccination, comorbidities, and inflammatory biomarkers on classified clinical outcomes in hospitalized COVID-19 patients, we compared common and sex differences. Methods: Besides laboratory and clinical parameters at hospital admission, we performed a common and sex-based comparative analysis for the clinical outcomes, RT-qPCR analyses, and measured severe acute respiratory syndrome coronavirus (SARS-CoV-2)-specific IgM and IgG antibody levels of 702 COVID-19 patients in a single center from June 2020 to April 2022. Results: Pro-inflammatory biomarkers (C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, lactate dehydrogenase (LDH), D-dimer, ferritin), and liver enzymes (AST, ALT, GGT) were significantly more increased in COVID-19 male patients and generally elevated with the severity of clinical outcome, regardless of the SARS-CoV-2 variant. Cycle threshold (Ct) values of RT-qPCR testing were in negative correlation with IL-6 in COVID-19 male patients, indicating that higher viral load largely increased IL-6 levels in parallel with the severity of clinical outcome and regardless of vaccination. IgG levels were higher in early post-COVID-19 male patients. Comorbidities were more frequent in COVID-19 female patients and generally more common in the severe clinical outcomes. Vaccination was negatively correlated with the severity of clinical outcome, liver enzymes, LDH, and inflammatory parameters in hospitalized COVID-19 patients, while the risk of pneumonia was reduced. Vaccination reduced the need for corticosteroid and anti-inflammatory therapies, but increased the need for antiviral drug treatment. Conclusions: In addition to confirming inflammatory biomarkers and the importance of anti-inflammatory therapy in vaccinated patients, this study showed that vaccination reduces, but does not prevent, mortality in patients with COVID-19. Full article

Background: Circulating tumor DNA (ctDNA), shed into bodily fluids by cancer cells through apoptosis, necrosis, or active secretion, is currently used in the field of genomic investigation in clinical settings, primarily for advanced stages of non-small-cell lung cancer (NSCLC). However, its potential role in guiding the multi-omic approach to early-stage NSCLC is emerging as a promising area of investigation. Efforts are being made to integrate the genomics not only in surgery, but also in the definition of long-term prognosis after surgical or radiotherapy and for the prediction of recurrence. Methods: An extensive literature search was conducted on PubMed, covering publications from 2000 to 2024. Using the advanced search tool, titles and abstracts were filtered based on the following keywords: ctDNA, early stage, NSCLC. From this search, 20 studies that fulfilled all inclusion criteria were selected for analysis in this review. Results: This review highlights the growing body of evidence supporting the potential clinical use of ctDNA as a genomic biomarker in managing early-stage NSCLC. Baseline ctDNA levels offer valuable information about tumor molecular biology and histological characteristics. Beyond its prognostic value before treatment, liquid biopsy has proven useful for tracking minimal residual disease and forecasting recurrence following curative interventions such as surgery or radiotherapy. Future adjuvant treatment decisions may increasingly rely on predictive models that incorporate liquid biopsy findings alongside other clinical factors. Conclusions: The potential use of this analyte introduces new opportunities for the integration of genomic data in treatment, as well as relapse monitoring with more accurate and innovative than traditional methods, particularly in patients with early-stage NSCLC Full article

Pancreatic neuroendocrine tumors (pNETs) are rare malignancies, accounting for 1–2% of pancreatic cancers, with an incidence of ≤1 case per 100,000 individuals annually. Originating from pancreatic endocrine cells, pNETs display significant clinical and biological heterogeneity. Traditional classification based on proliferative grading does not fully capture the complex mechanisms involved, such as oxidative stress, mitochondrial dysfunction, and tumor-associated macrophage infiltration. Recent advances in molecular profiling have revealed key oncogenic drivers, including MEN1 (menin 1), DAXX (death domain–associated protein), ATRX (alpha thalassemia/mental retardation syndrome X-linked), CDKN1B (cyclin-dependent kinase inhibitor 1B) mutations, chromatin remodeling defects, and dysregulation of the mTOR pathway. Somatostatin receptors, particularly SSTR2, play a central role in tumor biology and serve as important prognostic markers, enabling the use of advanced diagnostic imaging (e.g., Gallium-68 DOTATATE PET/CT) and targeted therapies like somatostatin analogs and peptide receptor radionuclide therapy (PRRT). Established biomarkers such as Chromogranin A and the Ki-67 proliferation index remain vital for diagnosis and prognosis, while emerging markers, like circulating tumor DNA and microRNAs, show promise for enhancing disease monitoring and diagnostic accuracy. This review summarizes the molecular landscape of pNETs and highlights genomic, transcriptomic, proteomic, and epigenomic factors that support the identification of novel diagnostic, prognostic, and therapeutic biomarkers, ultimately advancing personalized treatment strategies. Full article

Lung cancer (LC), with non-small-cell lung cancer (NSCLC) as its predominant subtype, remains the leading cause of cancer-related mortality worldwide. While immune checkpoint inhibitors (ICIs) have redefined the therapeutic paradigm in advanced NSCLC, durable responses are confined to a limited subset of patients. A major clinical challenge persists: the inability to accurately predict which patients will derive meaningful benefit, which will exhibit primary resistance, and which are at risk for severe immune-related toxicities. The imperative to individualize ICI therapy necessitates robust, dynamic, and accessible biomarkers. Liquid biopsy has emerged as a transformative, minimally invasive tool that enables real-time molecular and immunologic profiling. Through analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and peripheral blood immune components, liquid biopsy offers a window into both tumor intrinsic and host-related determinants of ICI response. These biomarkers not only hold promise for identifying predictive signatures—such as tumor mutational burden, neoantigen landscape, or immune activation states—but also for uncovering mechanisms of acquired resistance and guiding treatment adaptation. Beyond immunotherapy, liquid biopsy plays an increasingly central role in the landscape of targeted therapies, allowing early detection of actionable driver mutations and resistance mechanisms (e.g., EGFR T790M, MET amplification, and ALK fusion variants). Importantly, serial sampling via liquid biopsy facilitates longitudinal disease monitoring and timely therapeutic intervention without the need for repeated tissue biopsies. By guiding therapy selection, monitoring response, and detecting resistance early, liquid biopsy has the potential to significantly improve outcomes in NSCLC. Full article

Background/Objectives: No reliable noninvasive biomarkers are available to predict RT-induced cardiotoxicity. Because the pericardial sac is a fast responder to cardiac injury, we investigated whether RT-induced radiographic pericardial changes might serve as early imaging biomarkers for late cardiotoxicity. Methods: We performed a retrospective study of 476 patients (210 males, 266 females; median age, 69 years; median follow-up, 26.7 months) treated with chemo-RT for small cell and non-small cell lung cancers at one single institution from 2009 to 2020. The heart and its 4 mm outmost layer (representing the pericardial sac) were contoured on standard-of-care baseline CTs. Six-month post-RT follow-up CTs were deformably registered on the baseline CTs. Data were harmonized for the effect of contrast. We labeled voxels as Fat, Fluid, Heme, Fibrous, and Calcification using Hounsfield units (HUs). We studied pericardial HU-change histograms as well as volume change and voxel-based mass change in each tissue composition. Results: Pericardial HU-change histograms had skewed distributions with a mean that was significantly correlated with mean pericardial dose. Voxels within Fluid, Heme, and Fibrous had mass changes consistent with the dose. In Kaplan–Meier curves, Fibrous and Heme volume changes (translating into thickening and effusion), Fat mass change, mean doses to heart and pericardium, history of cardiac disease, and being male were significantly associated with shorter survival, whereas thickening and effusion were significantly associated with shorter time to a post-RT cardiovascular disease diagnosis. Conclusions: Pericardium composition distribution has dose-dependent changes detectable on standard-of-care CTs at around 6 months post-RT and may serve as surrogate markers for clinically relevant cardiotoxicity. The findings should be validated with additional research. Full article

Background: Occupational bronchopulmonary diseases (OBPDs)—including pneumoconiosis, silicosis, and occupational COPD—remain a pressing public health issue, especially in regions with intensive mining, metallurgy, and construction industries. Caused by chronic inhalation of fibrogenic dusts, these conditions are often diagnosed at late stages, resulting in irreversible lung damage and diminished work capacity. Methods: A scoping review was performed using the Arksey and O’Malley framework, with methodological refinements from the Joanna Briggs Institute. Following PRISMA-ScR guidelines, we searched PubMed, Scopus, and gray literature for publications from 2014 to 2024. After screening 1761 records and full-text review, nine studies were included in the final synthesis, comprising two systematic reviews, two narrative literature reviews, and five observational studies. Results: Key risk factors identified included prolonged exposure to silica and coal dust, tobacco use, and genetic susceptibility. Diagnostic delays were attributed to the underuse of high-resolution CT and exhaled nitric oxide analysis. Several studies highlighted the diagnostic value of oxidative stress and inflammatory markers (e.g., IL-6, TNF-α). Nutritional rehabilitation and polyphenol-enriched herbal therapies were associated with improved respiratory function and quality of life. However, these strategies remain underutilized, particularly in low-resource settings. Conclusions: A coordinated, biomarker-driven approach integrating early diagnosis, dust exposure control, and tailored rehabilitation is urgently needed. Multidisciplinary models may reduce the clinical and socioeconomic burden of OBPDs. Full article

We aimed to establish non-invasive diagnostic models comparable to pathology testing and explore reliable digital imaging biomarkers to classify diffuse large B-cell lymphoma (DLBCL) and invasive ductal carcinoma (IDC). Our study enrolled 386 breast nodules from 279 patients with DLBCL and IDC, which were pathologically confirmed and underwent ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) examination. Patients from two centers were separated into internal and external cohorts. Notably, we introduced 2.5D deep learning and machine learning to extract features, develop models, and discover biomarkers. Performances were assessed using the area under curve (AUC) and confusion matrix. Additionally, the Shapley additive explanation (SHAP) and local interpretable model-agnostic explanations (LIME) techniques were employed to interpret the model. On the internal cohort, the optimal model PT_TDC_SVM achieved an accuracy of 0.980 (95% confidence interval (CI): 0.957–0.991) and an AUC of 0.992 (95% CI: 0.946–0.998), surpassing the other models. On the external cohort, the accuracy was 0.975 (95% CI: 0.913–0.993) and the AUC was 0.996 (95% CI: 0.972–0.999). The optimal imaging biomarker PET_LBP-2D_gldm_DependenceEntropy demonstrated an average accuracy of 0.923/0.937 on internal/external testing. Our study presented an innovative automated model for DLBCL and IDC, identifying reliable digital imaging biomarkers with significant potential. Full article

Background: Muscle-invasive bladder cancer (MIBC) is associated with high recurrence and mortality rates. While cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy remains the standard of care, many patients are ineligible for cisplatin. Recent advances in immunotherapy and biomarker research are reshaping perioperative strategies, aiming to personalize treatment and improve outcomes. Methods: We conducted a comprehensive narrative review of the recent literature and clinical trials on the perioperative treatment of MIBC. We focused on published phase II and III trials assessing neoadjuvant and adjuvant strategies, including immunotherapy, antibody-drug conjugates (ADCs), combination regimens, and circulating tumor DNA (ctDNA)-based approaches. Results: Numerous trials (e.g., PURE-01, ABACUS, NABUCCO, AURA, NIAGARA) have demonstrated the feasibility and efficacy of immune checkpoint inhibitors (ICIs) in both cisplatin-eligible and -ineligible populations. Combination strategies, including ICIs plus chemotherapy or ADCs, have shown promising pathological complete response rates and event-free survival. In the adjuvant setting, nivolumab improved disease-free survival and received regulatory approval. Biomarkers such as PD-L1 and ctDNA are emerging tools for predicting treatment response and recurrence risk, although prospective validation is ongoing. Conclusions: The treatment paradigm for MIBC is shifting toward multimodal and biomarker-driven approaches. Integration of ICIs into perioperative management, especially in combination with chemotherapy or ADCs, may enhance outcomes. ctDNA shows potential as a predictive and prognostic biomarker, guiding therapeutic decisions and surveillance. Future research should focus on refining patient selection, optimizing treatment sequencing, and validating ctDNA-guided strategies to personalize care while minimizing overtreatment. Full article

Medullary thyroid carcinoma (MTC) is a rare (~2–5% of all thyroid cancers) neuroendocrine thyroid malignancy originating from parafollicular C-cells of the thyroid gland with variable biological behavior and potential for early metastasis. Diagnosis, staging, and surveillance are heavily reliant on circulating biomarkers. We aimed to provide a comprehensive overview of circulating biomarkers in the management of MTC and propose an integrated, evidence-based algorithm to guide clinical decision-making using both established and emerging biomarkers. This is a narrative review on the evolving landscape of biomarker-driven management in MTC with emphasis on analytical advancements, clinical applications, and the prognostic implications of individual and combined biomarkers. Calcitonin remains the cornerstone biomarker for MTC, and new generation immunoassays have addressed several pre-analytical and analytical challenges such as pre-analytical degradation, inter-assay variability, and biological confounders. Procalcitonin (ProCT) has emerged as a stable and less interference-prone alternative or adjunct to calcitonin, which is particularly useful in cases with indeterminate calcitonin levels. Carcinoembryonic antigen (CEA) remains a useful complementary biomarker often correlating with aggressive behavior, advanced disease, and distant metastases. Kinetic evaluation (doubling times) of calcitonin and CEA offers independent prognostic information values and those < 6 months are associated with poor survival, whereas those > 2 years suggest favorable outcomes. Newer biomarkers such as pro-gastrin-releasing peptide (ProGRP) and carbohydrate antigen 19-9 (CA19-9) show potential in monitoring advanced disease and response to therapy. Their role is still under investigation but appears promising, particularly when used in conjunction with calcitonin and CEA. Our work advances a comprehensive and clinically pragmatic framework for the management of MTC by integrating established and emerging biomarkers with evidence-based algorithms, offering greater diagnostic precision, more reliable prognostic stratification, and improved personalization of follow-up and treatment strategies. Full article

Background/Objectives: Endometrial cancer (EC) is the most common gynecological tumor in developed countries, and presents a wide variety of histological and molecular characteristics that make its treatment increasingly complex. In recent years, advances in molecular imaging, particularly with [¹⁸F]FDG-PET/CT and PET/MRI, have changed clinicians’ management of diagnosis, treatment planning, and prognosis of EC. Methods: In this narrative review, a search was conducted for current evidence on the role of [¹⁸F]FDG-PET/CT and PET/MRI throughout the treatment of EC, focusing on their diagnostic performance, clinical relevance, and prognostic implications. Their use in areas such as initial staging, treatment monitoring, recurrence detection, and individualized risk assessment was also discussed. Results: [¹⁸F]FDG-PET/CT is effective in detecting lymph node and distant metastases, while [¹⁸F]FDG-PET/MRI offers greater accuracy for T and N staging. In addition, [¹⁸F]FDG-PET/CT provides early metabolic indicators of therapeutic response and facilitates differentiation between viable tumors and post-treatment changes. Radiomics-derived parameters have shown promising associations with tumor aggressiveness and lymphovascular invasion and survival, supporting their role as prognostic imaging biomarkers. In addition, the use of non-FDG radiotracers, as well as predictive models based on machine learning, can further refine preoperative stratification and treatment planning in certain subtypes of EC. Conclusions: Molecular imaging enhances the accuracy of TNM staging in EC. The incorporation of molecular imaging biomarkers into daily clinical practice could significantly improve personalized decision-making in EC. However, large prospective studies are needed to confirm their efficacy. Full article

Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor DNA (ctDNA), has emerged as a transformative tool for non-invasive detection, real-time monitoring, and treatment selection for PC. This review examines the role of ctDNA in both localized and metastatic PCs, focusing on its utility in early detection, risk stratification, therapy selection, and post-treatment monitoring. In localized PC, ctDNA-based biomarkers, including ctDNA fraction, methylation patterns, fragmentation profiles, and mutations, demonstrate promise in improving diagnostic accuracy and predicting disease recurrence. For metastatic PC, ctDNA analysis provides insights into tumor burden, genomic alterations, and resistance mechanisms, enabling immediate assessment of treatment response and guiding therapeutic decisions. Despite challenges such as the low ctDNA abundance in early-stage disease and the need for standardized protocols, advances in sequencing technologies and multimodal approaches enhance the clinical applicability of ctDNA. Integrating ctDNA with imaging and traditional biomarkers offers a pathway to precision oncology, ultimately improving outcomes. This review underscores the potential of ctDNA to redefine PC management while addressing current limitations and future directions for research and clinical implementation. Full article

Liquid biopsy has emerged as a valuable tool for the detection and monitoring of colorectal cancer (CRC), providing minimally invasive insights into tumor biology through circulating biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Additional biomarkers, including tumor-educated platelets (TEPs) and exosomal RNAs, offer further potential for early detection and prognostic role, although ongoing clinical validation is still needed. This review summarizes the current evidence on the diagnostic, prognostic, and predictive capabilities of liquid biopsy in both metastatic and non-metastatic CRC. In the non-metastatic setting, liquid biopsy is gaining traction in early detection through screening and in identifying minimal residual disease (MRD), potentially guiding adjuvant treatment and reducing overtreatment. In contrast, liquid biopsy is more established in metastatic CRC for monitoring treatment responses, clonal evolution, and mechanisms of resistance. The integration of ctDNA-guided treatment algorithms into clinical practice could optimize therapeutic strategies and minimize unnecessary interventions. Despite promising advances, challenges remain in assay standardization, early-stage sensitivity, and the integration of multi-omic data for comprehensive tumor profiling. Future efforts should focus on enhancing the sensitivity of liquid biopsy platforms, validating emerging biomarkers, and expanding multi-omic approaches to support more targeted and personalized treatment strategies across CRC stages. Full article

Background/Objectives: Traumatic brain injury (TBI), especially mild TBI (mTBI), is frequently caused by traffic accidents, falls, or sports injuries. Although computed tomography (CT) is the gold standard for diagnosis, overuse can lead to unnecessary radiation exposure, increased healthcare costs, and emergency department saturation. Blood-based biomarkers have emerged as potential tools to optimize CT scan use. This systematic review aims to evaluate recent evidence on the role of specific blood biomarkers in guiding CT decisions in patients with mTBI. Methods: A systematic search was conducted in the PubMed, Cochrane, and CINAHL databases for studies published between 2020 and 2024. Inclusion criteria focused on adult patients with mTBI evaluated using both CT imaging and at least one of the following biomarkers: glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and S100 calcium-binding protein B (S100B). After screening, six studies were included in the final review. Results: All included studies reported high sensitivity and negative predictive value for the selected biomarkers in detecting clinically relevant intracranial lesions. GFAP and UCH-L1, particularly in combination, consistently identified low-risk patients who could potentially forgo CT scans. While S100B also showed high sensitivity, discrepancies in cutoff values across studies highlighted the need for harmonization. Conclusions: Blood biomarkers such as GFAP, UCH-L1, and S100B demonstrate strong potential to reduce unnecessary CT imaging in mTBI by identifying patients at low risk of significant brain injury. Future research should focus on standardizing biomarker thresholds and validating protocols to support their integration into clinical practice guidelines. Full article

Hydrogen-rich water (HRW) has shown neuroprotective effects in acute brain injury, but its role in chronic radiation-induced brain injury (RIBI) remains unclear. This study investigated the long-term efficacy of HRW in mitigating cognitive impairment and neuronal damage caused by chronic RIBI. Fifty male Sprague Dawley rats were randomly divided into five groups: control, irradiation (IR), IR with memantine, IR with HRW, and IR with combined treatment. All but the control group received 20 Gy whole-brain X-ray irradiation, followed by daily interventions for 60 days. Behavioral assessments, histopathological analyses, oxidative stress measurements, ¹⁸F-FDG PET/CT imaging, transcriptomic sequencing, RT-qPCR, Western blot, and serum ELISA were performed. HRW significantly improved anxiety-like behavior, memory, and learning performance compared to the IR group. Histological results revealed that HRW reduced neuronal swelling, degeneration, and loss and enhanced dendritic spine density and neurogenesis. PET/CT imaging showed increased hippocampal glucose uptake in the IR group, which was alleviated by HRW treatment. Transcriptomic and molecular analyses indicated that HRW modulated key genes and proteins, including CD44, CD74, SPP1, and Wnt1, potentially through the MIF, Wnt, and SPP1 signaling pathways. Serum CD44 levels were also lower in treated rats, suggesting its potential as a biomarker for chronic RIBI. These findings demonstrate that HRW can alleviate chronic RIBI by preserving neuronal structure, reducing inflammation, and enhancing neuroplasticity, supporting its potential as a therapeutic strategy for radiation-induced cognitive impairment. Full article

Background and Purpose: Stratification based on specific image biomarkers applicable in clinical settings could help optimize treatment outcomes for recurrent non-small cell lung cancer patients. For this purpose, we aimed to determine the clinical impact of positive delta changes (any difference above zero > 0) between baseline [¹⁸F]FDG PET/CT metrics before the first treatment course and reirradiation. Material/Methods: Forty-seven patients who underwent thoracic reirradiation with curative intent at our institute between 2013 and 2021 met the inclusion criteria. All patients had histologically verified NSCLC, ECOG (Eastern Cooperative Oncology Group) ≤ 2, and underwent [¹⁸F]FDG PET/CT for initial staging and re-staging before primary radiotherapy and reirradiation, respectively. The time interval between radiation treatments was at least nine months. Quantitative metabolic volume and intensity parameters were measured before first irradiation and before reirradiation, and the difference above zero (>0; delta change) between them was statistically correlated to locoregional control (LRC), progression-free survival (PFS), and overall survival (OS). Results: Patients were followed for a median time of 33 months after reirradiation. The median OS was 21.8 months (95%-CI: 16.3–27.3), the median PFS was 12 months (95%-CI: 6.7–17.3), and the median LRC was 13 months (95%-CI: 9.0–17.0). Multivariate analysis revealed that the delta changes in SULpeak, SUVmax, and SULmax of the lymph nodes significantly impacted OS (SULpeak p = 0.017; SUVmax p = 0.006; SULmax p = 0.006), PFS (SULpeak p = 0.010; SUVmax p = 0.009; SULmax p = 0.009), and LRC (SULpeak p < 0.001; SUVmax p = 0.003; SULmax p = 0.003). Conclusions: Delta changes in SULpeak, SUVmax, and SULmax of the metastatic lymph nodes significantly impacted all clinical endpoints (OS, PFS and LRC) in recurrent NSCLC patients treated with reirradiation. Hence, these imaging biomarkers could be helpful with regard to patient selection in this challenging clinical situation. Full article