Search Results (7,040)

Background/Objectives: Head and neck sarcomas account for 11% of all soft tissue and 9% of all bone sarcomas in the UK. Diagnostic delays are common, with non-specific symptoms and histological misdiagnosis reported in up to 42% of cases. This study aims to evaluate the association between presenting symptoms, symptom duration, and tumour size to inform a tailored HNS diagnostic strategy for early referral to a tertiary centre. Methods: We analysed a retrospective cohort of 425 adult and paediatric patients referred to the London Sarcoma Service between 2002 and 2025. Results: Our cohort analysis identified a median tumour size of 44.00 mm and symptom duration of 3 months. Although symptom duration did not predict tumour size (β = 0.63, p = 0.76), non-specific symptoms (swelling, pain, nasal/oral changes) were significantly associated with larger tumours (OR 1.96–3.66), alongside systemic symptoms (β = 22.90 mm, p = 0.044). Each 1 mm increase in tumour size was also associated with a 2.60% increased chance of a higher-grade sarcoma (OR = 1.03 per mm, p < 0.001). Conclusions: To our knowledge, this is the largest cohort study to characterise diagnostic patterns in HNS. Our findings reveal three critical insights: 1. Current size-based referral thresholds are inadequate. 2. Non-specific symptoms, such as nasal or oral symptoms, are frequently overlooked. 3. The anatomical complexity of the HN region demands early tailored diagnostic strategies. We propose a hypothesis-generating ‘1–2–1’ framework to support earlier clinical suspicion, which requires prospective validation. Full article

Background: The protective effect of physical activity on breast cancer recurrence may be mediated by sex hormone levels. In this study, we examined the association between habitual physical activity and estrogen and androgen plasma levels in postmenopausal women with localised breast cancer. Methods: We conducted a cross-sectional study among 47 postmenopausal women who were breast cancer survivors with estrogen receptor-positive tumours (enrolled at the Medical Oncology Department of University Hospital Dr. Peset, Valencia, Spain). Habitual physical activity was assessed using the International Physical Activity Questionnaire (IPAQ), and a weighted estimate of total physical activity per week (MET∙min∙wk⁻¹) was calculated. Total plasma levels of estrone, 17β-estradiol, progesterone, androstenedione, testosterone, and dehydroepiandrosterone-sulphate (DHEA-sulphate) were measured. Bivariate analyses by the Spearman correlation test were done between physical activity and each hormone concentration. Multivariate analyses (linear regression) using concentration of each hormone as the dependent variable and physical activity, age, marital status, BMI, Charlson Comorbidity Index, tumour stage, previous radiotherapy, or previous chemotherapy as predictor variables. Results: Estrone concentration was positively and significantly correlated with BMI (ρ = 0.332, p = 0.022), but no other correlations were found between BMI and the other hormone concentrations, nor were concentrations of any hormone associated with age or Charlson Comorbidity Index (p > 0.05 in all cases). Physical activity was significantly and inversely correlated with estrone concentration (ρ = −0.308; p = 0.035). Linear regression analysis confirmed a statistically significant association between estrone concentration and BMI and physical activity, after adjusting for all potential confounders (for BMI: standardised β coefficient = 0.407; non-standardised β coefficient = 1.054; t = 2.898; p = 0.006; 95% CI for non-standardised beta: 0.318- to 1.790; for physical activity: standardised β coefficient = −0.300; non-standardised β coefficient = −0.005; t = −2.135; p = 0.039; 95% CI for non-standardised beta: −0.010- to 0.000). Conclusions: The relationship between estrone concentration and physical activity may be further explored as a biomarker for evaluating the protective effect of physical activity against breast cancer recurrence in women receiving anti-estrogen therapies. Full article

Background/Objectives: Magnetic nanoparticles have emerged as powerful tools for biomedical imaging, targeted drug delivery, and hyperthermia therapy. Magnetic particle imaging (MPI) is among the most promising technologies built around its properties: a radiation-free, quantitative tomographic modality that detects superparamagnetic iron oxide nanoparticles (SPIONs) directly against a biologically silent background. This review synthesizes MPI’s physical principles, nanoparticle design strategies, and preclinical applications within the broader landscape of magnetic material engineering for biomedical use. Methods: A systematic review was conducted covering MPI signal generation and image reconstruction, nanoparticle core synthesis and surface coating approaches, and preclinical applications, spanning cell tracking, oncological imaging, vascular perfusion, neuroimaging, and MPI-guided theranostics. Studies were selected to provide quantitative benchmarks and direct comparisons with competing modalities where available. Results: MPI delivers signal-to-background ratios above 1000:1, iron-mass linearity at R² ≥ 0.99, regardless of tissue depth, and acquisition rates up to 46 volumes per second. Tracer architecture—encompassing single-core particles, multicore nanoflowers, and stimuli-responsive cluster designs—is the primary determinant of sensitivity, environmental robustness, and theranostic capability. Preclinical results include detection of cell populations in the low thousands, earlier ischaemia identification than diffusion-weighted MRI, real-time drug release quantification, and spatially confined tumour hyperthermia. Three translational bottlenecks are identified: the absence of a clinically approved tracer with optimal relaxation dynamics, hardware performance losses when scaling to human-bore systems, and overestimation of passive tumour accumulation in murine models. Conclusions: MPI illustrates how progress in magnetic material design directly expands clinical imaging and theranostic possibilities. Successful translation will require indication-driven, interdisciplinary development that integrates materials science, scanner engineering, and regulatory strategy in parallel. Full article

Organoselenium chemistry has undergone remarkable development over the past five decades, evolving from its initial association with high toxicity into a field with pivotal contributions to materials science, organic synthesis, catalysis, and Medicinal Chemistry. Among the diverse biological activities displayed by organoselenium compounds, their redox behaviour is particularly compelling, as many of these molecules act as efficient mimetics of the antioxidant enzyme glutathione peroxidase (GPx). In this work, we investigated the GPx-like activity of a series of N,N′-diaryl selenoureas toward the depletion of H₂O₂ and cumene hydroperoxide (CumOOH) as model ROS. Their reactivity was correlated with the electronic nature of the aryl substituents using a Hammett-type analysis, revealing a strong dependence of the reaction rate on remote electronic perturbations within the aromatic ring. Combined UV and NMR studies provided mechanistic evidence supporting a catalytic cycle in which selenoureas, operating at sub-stoichiometric loadings (1 mol%) and using a thiol as a cofactor-like molecule, can be used to efficiently scavenge ROS with half-lives of only a few minutes (~10–60 min). Furthermore, these selenoureas exhibited potent antiproliferative activity across several human solid tumour cell lines. Overall, these results offer mechanistic insight into the ROS-eliminating pathways of selenoureas and highlight their potential as chemopreventive or anticancer agents. Full article

Introduction: Upper tract urothelial carcinoma is a rare disease with variable prognosis depending on the stage and grade at diagnosis. Current modalities are far from perfect in diagnosis and risk stratification. In this setting, there is an urgent need for diagnostic and prognostic biomarkers to overcome these limitations. Methods: We carried out a narrative review of the literature searching for research articles on diagnostic and prognostic biomarkers for upper tract urothelial carcinoma (UC) and underlined the limitations of current diagnostic modalities. Results: CT urogram (CTU) is the imaging modality of choice in suspected upper tract UC with sensitivity and specificity exceeding 90% but with limitations in smaller lesions. Urine cytology has an excellent specificity for high-grade UC but is limited by low sensitivity leading to a high number of diagnostic ureteroscopies with significant associated risks. Adjuncts such as Fluorescence In Situ Hybridization (FISH) technology and urine DNA methylation markers have shown promising results but need further validation in large cohorts of upper tract UC. Finally, circulation tumour DNA (ctDNA) is a novel approach with great potential in risk stratification and monitoring of minimal residual disease post radical surgery; however, larger prospective studies are required to validate its role similarly to the recent bladder UC trials. Conclusions: There is an urgent need for non-invasive biomarkers that can reliably replace diagnostic ureteroscopies, identify high-risk/invasive disease and select patients for radical surgery or kidney sparing procedures. Full article

Background: Treatment response to neoadjuvant therapy in rectal cancer exhibits a considerable degree of interpatient heterogeneity. Select components of the tumour immune microenvironment have been identified as predictive biomarkers of therapeutic response, for which more evidence is required for future clinical prediction models. Aim: The research aimed to identify key tumour immune microenvironment biomarkers predictive of the response to neoadjuvant therapy through the systematic appraisal of existing literature. Methods: A structured search was performed across PubMed, Ovid Embase, and Cochrane databases to retrieve primary studies investigating the association between the tumour immune microenvironment and pathological complete response (pCR) or tumour regression grade (TRG) in patients with rectal cancer. Studies were screened against predefined inclusion and exclusion criteria. Results: Fifteen studies satisfied the inclusion criteria, with cohorts ranging between 24 and 298 participants with predominantly stage II–III disease. Considerable heterogeneity was observed in both types and methods of quantification of biomarkers. Biomarkers assessed in pretreatment biopsies included tumour-infiltrating lymphocytes (TILs), investigated by subtype (cluster of differentiation (CD)8+, CD4+, forkhead box protein 3+ (FOXP3)) or as a composite measure, as well as programmed death-ligand 1 (PD-L1), PD-1+, natural killer (NK) cells, CD163+, and CD68+. Findings showed that high densities of TILs—particularly the CD8+ subtype—consistently correlated with improved tumour regression. FOXP3+ and CD163+ were inconsistently associated with reduced treatment response. NK cells and CD68+ cells were less frequently investigated and yielded non-significant findings. Conclusions: CD8+ TILs have the potential to serve as predictive biomarkers of therapeutic response to neoadjuvant treatment in patients with rectal cancer. Inconsistent findings with FOXP3+ Tregs and CD163+ macrophages reinforce the need for their further investigation. Full article

Background/Objectives: Protein kinases play a crucial role in cancer initiation, progression, and therapeutic resistance by regulating signalling pathways involved in tumour growth and survival. Consequently, they represent major targets in anticancer drug discovery. Among heterocyclic scaffolds explored in kinase inhibitor design, benzimidazole has emerged as a privileged structure due to its strong hydrogen-bonding capability and structural resemblance to purine moieties. Triazole motifs are also widely incorporated into bioactive molecules because of their metabolic stability, favourable electronic properties, and ability to establish key interactions within kinase active sites. This review aims to summarise and critically discuss benzimidazole- and triazole-based kinase inhibitors, both as individual scaffolds and as hybrid systems, with emphasis on their kinase targets and multitarget potential. Methods: The relevant literature was surveyed from major scientific databases focusing on studies describing the synthesis, biological evaluation, and molecular modelling of benzimidazole- and triazole-containing kinase inhibitors. Results: Numerous studies demonstrate that both benzimidazole and triazole scaffolds exhibit significant kinase inhibitory activity against oncogenic targets, including EGFR, cyclin-dependent kinases (CDKs), and components of the PI3K/Akt/mTOR signalling pathway. Hybrid molecules combining these pharmacophores frequently enhance binding interactions and facilitate the development of multitarget kinase inhibitors. Structure–activity relationship trends indicate that pharmacophore accessibility, substitution patterns, and linker architecture influence inhibitory potency and selectivity. Conclusions: Overall, benzimidazole- and triazole-based scaffolds represent promising platforms for developing next-generation multitarget anticancer agents and provide valuable insights for the rational design of improved kinase inhibitors. Full article

Background: The plantaris muscle (PM) shows substantial variability in its proximal belly attachments. Although often deemed vestigial, specific variants may narrow or reshape the popliteal corridor and contribute to vascular (popliteal artery entrapment syndromes, PAES) and neural conflict (TN, CPN, sural nerves). Despite abundant anatomical descriptions of the plantaris, its contribution to neurovascular compression has not been organised into a classification-linked, imaging-integrated framework. Objective: To synthesise adult and foetal anatomical data with clinical–radiological evidence into a classification-linked framework that stratifies vascular and neural compression risk by proximal PM variants, and to propose an integrated risk matrix and variant-directed diagnostic/operative pathway. Methods: Narrative, classification-centred review centred on the Olewnik schema (Types I–VI) and multi-headed/accessory variants. We mapped variant geometry to (1) physiological compromise on provoked Doppler US and (2) anatomical correlates on MRI/MR angiography (MRA) (axial “band sign”), deriving graded risk for vascular and neural axes and an integrated, action-oriented grade per limb. Results: Baseline risk is low for canonical/compact footprints (Type I–IA, Type V), moderate for capsular-junction patterns (Types II/III), and potentially higher-risk for lateral linkage (Type IV; iliotibial band (ITB)/Kaplan fibres continuity) and multi-headed configurations (duplication, bifurcation, ≥3–4 heads; accessory proximal slips). The integrated matrix upgrades risk for a clear band sign, reproducible compromise on provoked Doppler US, or multi-headed/Type IV anatomy and downgrades when rigorous provocation is negative and muscle volume is small. We provide a variant-indexed imaging checklist, common pitfalls (e.g., Type IV misread as ITB thickening; multi-headed variants misread as cyst/tumour), and operative checkpoints to target capsular clefts, lateral bands, tunnels, and accessory slips. Conclusions: A classification-linked, imaging-integrated approach clarifies which proximal PM variants are plausibly associated with neurovascular entrapment (based on case-level evidence) and aligns work-up with targeted decompression and may improve diagnostic precision and inform surgical planning. Clinical relevance: The framework operationalises variant naming in reports, standardises dynamic provocation and axial mapping, and prioritises variants considered higher risk (Type IV; multi-headed) for early multidisciplinary review. Given that most clinical signals derive from case reports/series (Level IV), these recommendations are inferential and should be applied with clinical judgement. Full article

Clear-cell renal cell carcinoma (ccRCC) is characterised by constitutive activation of hypoxia-inducible factors (HIFs) following VHL loss, which contributes to tumour progression and therapeutic resistance. Given the limitations of VEGFR-targeted therapies, we investigated the biological and potential therapeutic relevance of the HIF axis in ccRCC. Nuclear and cytoplasmic HIF1A and EPAS1/HIF2A expression were assessed by immunohistochemistry in tumours from 40 patients and correlated with clinicopathological parameters and cancer-specific survival. The functional effects of HIF pathway inhibitors (GN44028, KC7F2, and FM19G11) and sunitinib were analysed in VHL-mutant 786-O and VHL-wild-type Caki-1 cell lines using SRB viability assay, cell cycle analysis, wound closure assay, and RT-qPCR of HIF-related genes, with comparison to non-malignant HK-2 cells. TCGA-ccRCC data from advanced-stage patients (III–IV, n = 185) were analysed as a complementary transcriptomic context. Nuclear, but not cytoplasmic, HIF1A and EPAS1/HIF2A expression was associated with advanced stage and shorter survival in univariable analyses. GN44028 showed the most pronounced antiproliferative effect under tested conditions and was associated with broad suppression of HIF-related transcription, whereas sunitinib was associated with increased expression of selected HIF-related genes. GN44028 did not demonstrate clear selectivity over non-malignant HK-2 cells. Overall, nuclear HIF activation is associated with aggressive ccRCC biology, and broader HIF pathway modulation warrants further experimental investigation; however, the clinical findings remain exploratory, and therapeutic selectivity and translational relevance are not yet established. Full article

Background: The landscape of paediatric oncology has undergone a remarkable transformation over recent decades. Advances in both oncological and supportive therapies have dramatically improved survival in children with haematological malignancies and solid tumours, with current survival rates exceeding 80% for many childhood cancers. However, this therapeutic success has brought with it an unexpected consequence: the intensification of treatment protocols has led to a parallel increase in life-threatening complications requiring intensive care support. Current evidence indicates that up to 40% of paediatric oncology patients will require admission to a Paediatric Intensive Care Unit (PICU) at some point during their disease trajectory. Objectives: This comprehensive review synthesises current evidence to provide an updated framework for PICU admission decision-making in oncology haematology patients. We have integrated the most recently published international guidelines, including the groundbreaking Phoenix 2024 sepsis criteria and the updated PALICC-2 2023 recommendations for paediatric acute respiratory distress syndrome. Beyond establishing admission criteria, we critically analyse the efficacy of advanced support strategies and examine emerging therapeutic approaches in this uniquely vulnerable population. Methods: Our methodology encompassed a systematic review of the literature published between 2011 and 2024, complemented by a detailed analysis of current international guidelines and expert consensus statements. We included randomised controlled trials, observational studies, meta-analyses, and consensus conference proceedings specifically addressing the intensive care management of paediatric patients with oncological or haematological conditions. Main Results: Several key findings emerge from our analysis. The Phoenix 2024 criteria represent a fundamental reconceptualisation of paediatric sepsis diagnosis, validated through an unprecedented dataset encompassing more than 3 million paediatric encounters. In the realm of respiratory support, early implementation of non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP) has demonstrated remarkable efficacy, reducing the need for invasive mechanical ventilation by 45% (RR 0.45, 95% CI 0.26–0.78) when applied to appropriately selected patients. Extracorporeal membrane oxygenation (ECMO), whilst increasingly utilised, shows survival to decannulation ranging from 52% to 64%, though survival to hospital discharge remains less encouraging at 36–42%. Continuous renal replacement therapy (CRRT) has proven highly effective for tumour lysis syndrome, achieving metabolic correction in 90% of severe cases. Perhaps most promisingly, emerging biomarkers—particularly interleukin-6, interleukin-10, and procalcitonin—have substantially enhanced our ability to stratify infection risk, demonstrating sensitivity exceeding 85% for bacteraemia detection. Conclusions: The evidence unequivocally supports several core principles for optimising outcomes in this population. Early identification of deterioration through validated scoring systems enables timely intervention before irreversible organ failure develops. Prompt implementation of non-invasive respiratory support, when appropriately applied, can obviate the need for mechanical ventilation with its attendant complications. Perhaps most critically, centralisation of care in centres with dedicated expertise and comprehensive support capabilities fundamentally improves survival. These findings argue compellingly for the establishment of a formal national network of reference centres, implementing standardised protocols and structured care pathways specifically designed for critically ill paediatric oncology haematology patients. Full article

Background/Objectives: Early-phase clinical trials (EPCTs) focus on safety and preliminary efficacy, often assessed by RECIST (Response Evaluation Criteria in Solid Tumours) tumour response. Health-related quality of life (HRQoL) is rarely evaluated in EPCTs and may not align with radiological outcomes. Methods: The PEARLER (Patient Experience in Early-Phase Cancer Clinical Trials) study evaluated the demographics, tumour response, HRQoL, and therapy type in two early-phase trial units in Australia between August 2023 and 2024. Patients completed the EORTC QLQ-C30 at baseline and follow-ups. The Global Health Status (GHS) score was selected as the primary HRQoL measure. Tumour response was assessed using RECIST 1.1. Spearman correlation and Kruskal–Wallis testing assessed the associations between RECIST, cross-sectional GHS change (ΔGHS; follow-up minus baseline), and therapy types. Multilevel models were used to evaluate longitudinal GHS values per RECIST category. Results: Of 122 patients recruited to the PEARLER study, 74 patients had paired RECIST and HRQoL data (complete response (CR) n = 0; partial response (PR) n = 15; stable disease (SD) n = 39; progressive disease (PD) n = 20). The median change in GHS was zero across RECIST groups, with broad individual variability. Notably, 18 of 54 patients (33.3%) with stable or responding disease experienced HRQoL decline. Meanwhile, 10 of 20 (50%) patients with PD experienced stable or improving HRQoL. The best RECIST response and ΔGHS showed a weak but statistically significant negative relationship (Spearman ρ = −0.28, p = 0.017), with the Kruskal–Wallis test demonstrating χ² = 6.20 (p = 0.045), indicating modest group differences driven by the deterioration in PD patients. The multilevel model demonstrated a lower GHS in patients with PD, with no statistically significant interaction of GHS change over time with the RECIST response (p = 0.226). Conclusions: HRQoL change is largely independent of radiologic tumour response and therapy type in EPCT participants. Patients experienced a HRQoL decline despite tumour response. Incorporating patient-reported outcomes alongside RECIST and safety outcomes is important to fully capture the impact of investigational therapies and guide patient-centred trial designs. Full article

RCC remains a therapeutically challenging malignancy, particularly in its metastatic stage, in which treatment resistance and limited response durability persist despite recent advances in immunotherapy and targeted therapies. Although immune checkpoint inhibitors (ICIs) have significantly improved outcomes for a subset of patients, reliable prognostic and predictive biomarkers to guide therapy selection are still lacking. Current clinical models, such as the International Metastatic RCC Database Consortium (IMDC) risk score, offer only limited insight into the molecular and immunologic complexity of RCC. Emerging molecular biomarkers implicated in resistance mechanisms reflect the underlying heterogeneity of RCC and may inform future therapeutic strategies. Kidney Injury Molecule-1 (KIM-1), a transmembrane protein that is up-regulated in RCC and detectable in circulation, has demonstrated potential as a non-invasive biomarker for diagnosis, prognosis, and treatment monitoring. Liquid-biopsy approaches, including the analysis of circulating tumour DNA (ctDNA), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs), are also gaining traction due to their minimally invasive nature and potential for real-time disease monitoring. This review aims to provide a structured overview of emerging biomarkers in metastatic RCC, critically evaluate their current clinical applicability, and propose a biologically informed framework for their integration into clinical decision-making. In addition, we propose a conceptual IMDC-Plus framework that integrates clinical, biological, and early dynamic markers to improve risk stratification in the era of immunotherapy (IO). Full article

The urea cycle (UC) is usually described as the hepatic metabolic pathway responsible for ammonia detoxification, but its role extends far beyond nitrogen (N) elimination to include cellular biosynthesis and metabolic signalling. In cancer cells, the UC is reconfigured/reorchestrated to support high anabolic demand, often involving the dysregulation of key enzymes such as ASS1, ASL, OTC and CPS1. While these changes support biomass production and stress resistance, they also generate measurable biochemical signatures through kinetic and thermodynamic isotope effects (¹⁴N/¹⁵N). In this review, we summarise UC biochemistry and recall key enzymatic mechanisms. Together, these elements provide a mechanistic framework to interpret changes in ¹⁵N abundance observed in tumour tissues and cells. We discuss how the redirection of N flux toward nucleotide and polyamine synthesis, coupled with partial excretion of ¹⁵N-depleted urea, may shape the isotopic composition of cancer cells. By integrating molecular oncology with stable isotope analysis, this review highlights the potential of natural isotope abundance as a functional readout of tumour metabolism and supports further investigation of its translational relevance in cancer phenotyping and monitoring. Full article

Bovine ocular squamous cell carcinoma (BOSCC) is the most common ocular tumour in cattle, with a multifactorial aetiology involving ultraviolet (UV) radiation, genetic factors, pigmentation, and management practices. A detailed epidemiological characterisation of BOSCC in the Azores, Portugal, is provided, with particular emphasis on its spatial distribution and potential risk determinants. Data were obtained through an epidemiological questionnaire completed by field veterinarians between August 2023 and March 2025. A total of 85 BOSCC cases were recorded across 62 farms—45 on Terceira Island and 17 on São Miguel Island. All affected animals were adult Holstein Friesian dairy cows, managed under extensive pasture-based systems. The nictitating membrane was the most frequently affected structure (69.5%), and multiple lesions occurred in 20% of the cases. Farms located at 200–400 m of altitude presented the highest number of cases. Continuous exposure to UV under pasture-based management represents the main environmental risk factor. Although periocular pigmentation may provide partial protection, other environmental and genetic factors can also contribute to tumour development. Artificial insemination is considered a promising preventive tool, enabling genetic selection for protective traits such as periocular pigmentation. This research provides the first regional epidemiological characterization of BOSCC in the Azores, highlighting the interplay among environmental, genetic, and management-related factors in disease occurrence. Full article

Background/Objectives: The purpose of this study was to (i) determine the levels of interleukins in patients with COVID-19 admitted to the Intensive Care Unit (ICU) and (ii) evaluate their early dynamics, as well as (iii) assess their relationships with morbidity and mortality. Methods: This was a prospective analytical study of critically ill patients with COVID-19 who were monitored from admission to three days of stay in the ICU. Circulating levels of IL-1β, IL-2, IL-6, IL-7, IL-8, IL-10, and tumour necrosis factor-alpha (TNF-α) were measured. Cytokine levels were analysed in relation to clinical severity parameters and 28-day mortality. Results: A dynamic cytokine response was observed during the first 72 h, with a significant increase in TNF-α levels and a decrease in IL-10 and IL-1β. Non-survivors showed higher TNF-α levels than survivors. In the multivariable analysis adjusted for clinical severity, TNF-α remained independently associated with 28-day mortality, whereas other cytokines did not retain statistical significance. The overall predictive performance of cytokines was moderate. Conclusions: Early cytokine dynamics reflect the evolving inflammatory response in critically ill COVID-19 patients. TNF-α emerges as an independent predictor of mortality, supporting its role as a relevant biomarker of adverse outcomes. Although its predictive capacity is moderate, TNF-α may provide clinically meaningful information for risk stratification when integrated with established clinical and laboratory parameters. Full article