Search Results (84)

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare vasculitis. A key bio-logical hallmark is peripheral blood eosinophilia while antineutrophil cytoplasmic an-tibody (ANCA) positivity is not always present. Therefore, an early phase suspicion of EGPA leading to a correct diagnosis can be challenging. We performed an observa-tional cross-sectional study limited to baseline data on 38 patients between December 2019 and December 2025 at the Allergy and Clinical Immunology Unit, Messina, Italy. Data collection included eosinophil, neutrophil, and lymphocyte counts; ANCAs and antinuclear antibodies (ANAs); erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) determination; and the Birmingham vasculitis activity score (BVAS) questionnaire: Median eosinophil counts were 685 cells/µL, the neutro-phil-to-lymphocyte ratio (NLR) was 2.29, ESR median values were 24 mm/h, and CRPs were 1.99 mg/L. ANCAs were positive in five patients, and ANAs in 20. The trend in ANA+ patients was of lower median eosinophil counts and higher ESR and CRP me-dian values and median BVASs. General, nervous system, and ENT BVAS domains had higher scores.: Disease activity in EGPA at diagnosis can be difficult to recognize. We defined it as chameleon-like and could not be captured by specific immunological sig-natures. Therefore, an early diagnosis needs multidimensional assessment, integrating laboratory parameters with clinical scores. In our EGPA cohort, ANAs were detected in just over half the patients, suggesting that rather than acting as bystanders, these could help clinicians, together with eosinophil counts, NLRs, and BVASs, to suspect EGPA at an early stage for referral to specialized medical centers. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease in which identifying simple biomarkers reflecting disease severity remains challenging. This study aimed to evaluate the relationship between systemic inflammatory indices and radiological disease severity assessed by the Lund–Mackay (LM) score. This retrospective study included 90 adult patients with CRSwNP who underwent endoscopic sinus surgery. Preoperative computed tomography findings were scored using the LM system, and systemic inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), eosinophil-to-lymphocyte ratio (ELR), neutrophil-to-monocyte ratio (NMR), systemic immune-inflammatory index (SII), systemic inflammation response index (SIRI), and eosinophil/leukocyte ratio, were calculated from complete blood count parameters. Spearman correlation and univariate logistic regression analyses were performed. ELR (r = 0.49, p < 0.001) and eosinophil/leukocyte ratio (r = 0.46, p < 0.001) showed moderate positive correlations with LM score, whereas other indices were not significantly associated. In logistic regression analysis, both ELR (OR = 5.44 × 10⁴, p < 0.001) and eosinophil/leukocyte ratio (OR = 4.99 × 10¹², p = 0.001) were significantly associated with high disease burden (LM ≥ 15). These findings suggest that eosinophil-based inflammatory indices may better reflect radiological disease severity in CRSwNP compared to traditional systemic inflammatory markers. Full article

Existing diagnostic markers of sepsis indicate already developed inflammatory complications, whereas predictors enable preoperative identification of high-risk patients for preventive measures. This study aimed to evaluate the prognostic value of preoperative inflammatory biomarkers for postoperative complications in cardiac surgery patients. Preoperatively, we assessed age, body mass index, EuroSCORE II (European System for Cardiac Operative Risk Evaluation II), complete blood count with hematological indices including neutrophil-to-lymphocyte ratio (NLR), serum cytokines, HIF1A (hypoxia-inducible factor 1-alpha), and EPAS1 (endothelial PAS domain protein 1) expression in peripheral blood leukocytes. During surgery, cardiopulmonary bypass time, myocardial ischemia time, and blood loss were recorded. Postoperatively, complications, intensive care unit (ICU) stay, and total hospitalization were documented. No differences were found in non-modifiable risk factors or perioperative parameters between groups, except for longer ICU stay in the complications group. Preoperatively, absolute neutrophil count and NLR were higher in patients without complications, while eosinophil count, HIF1A expression, and HIF1A/EPAS1 ratio were higher in those with it. The HIF1A/EPAS1 ratio demonstrated the best diagnostic characteristics. Thus, preoperative predictors of postoperative inflammatory complications include low neutrophil count and NLR, as well as high HIF1A expression and HIF1A/EPAS1 ratio. These markers may facilitate early risk stratification and preventive strategies before surgery. Full article

Respiratory medicine is transitioning from symptom-driven, standardized care to a more precise, patient-specific approach guided by molecular profiling. This evolution is being enabled by advances in liquid biopsy, multiomics, and artificial intelligence (AI) analytics. Fractional exhaled nitric oxide (FeNO) and blood eosinophils, the two commonly used markers in asthma, are now being joined by more precise airway markers such as galectin-10, which could aid clinicians in making more informed decisions for biological treatments. In chronic obstructive pulmonary disease (COPD) similar progress is underway, with treatment now emphasizing inflammation endotypes, especially eosinophilic patterns, to direct therapeutic choices. Alongside these developments, routine blood-based ratios (e.g., platelet-to-lymphocyte and neutrophil-to-lymphocyte) are being explored as predictors of exacerbation risk, and forced oscillation testing (FOT) is proving useful for picking up early disease shifts. In more severe conditions, biomarkers are linked to an early and better prognosis, enabling timely intervention. Markers like Matrix metalloproteinase-7 (MMP-7) and CC chemokine ligand 18 (CCL18) have proven to be reliable indicators of mortality and disease progression in idiopathic pulmonary fibrosis. Meanwhile, in lung cancer, liquid biopsies, especially those measuring circulating tumor DNA and micro-RNA (miRNA) panels, are enhancing screening accuracy while helping to cut down on the high false-positive rates seen with low-dose computerised tomography (CT). Other respiratory conditions such as bronchiectasis, pulmonary embolism, pneumonia, and acute respiratory distress syndrome (ARDS) are also benefiting from biomarker advances. At the same time there is a growing push to standardize how these biomarkers are measured. AI-based clinical decision support systems are also playing an increasingly important role in the translation of all these complicated data into actionable clinical insights. Together these developments pave the way for improved respiratory care that is precise and responsive to individual patient needs. Full article

Kingella kingae is now recognised as the leading cause of osteoarticular infections (OAIs) in young children. Because these infections typically produce mild symptoms and a weak inflammatory response, early diagnosis remains challenging. Complete blood count-derived immune-inflammatory biomarkers (IIBs) have recently gained interest as accessible, low-cost indicators of systemic inflammation, with potential diagnostic value in several fields, including oncology, rheumatology, cardiology, and infectious diseases. This study therefore aimed to assess whether IIBs could support the screening of K. kingae OAIs. We retrospectively reviewed the medical records of 209 children admitted to our hospital between 2007 and 2025 with confirmed or highly suspected K. kingae OAIs. Complete blood counts were analysed for each patient, including leukocyte subtypes such as neutrophils, lymphocytes, monocytes, eosinophils, and basophils. We then calculated biomarkers (NLR, MLR, PLR, SII, SIRI, and PIV) and interpreted them using age-adjusted reference values. As expected, most children were younger than 48 months, and septic arthritis was the predominant clinical presentation. Classical acute-phase reactants (WBC, CRP, and ESR) were frequently normal or only mildly elevated. Likewise, most IIBs remained within or near reference ranges; the platelet-to-lymphocyte ratio was the most commonly abnormal marker, exceeding the threshold in only 59.3% of patients. These results indicate that, like conventional inflammatory markers, CBC-derived IIBs have limited standalone screening utility for K. kingae OAIs. Further studies are needed to determine whether systemic IIBs can help distinguish OAIs caused by K. kingae from those caused by pyogenic bacteria. Full article

Background/Objectives: Metabolic syndrome (MetS) and dry eye disease (DED) share inflammatory mechanisms, yet few studies have examined objective tear function and serum inflammatory markers together in this population. The aim of this study was to compare tear function tests and a panel of systemic inflammatory indices between patients with MetS who did and did not have DED. Methods: This observational comparative study enrolled 104 adults with MetS (52 MetS-DED and 52 MetS-nonDED), with group-level comparability for age and sex. All participants underwent ophthalmologic evaluation, including the Ocular Surface Disease Index (OSDI), the Schirmer I test, and fluorescein tear break-up time (TBUT). DED was defined by a mean Schirmer I value of ≤5 mm/5 min. Routine blood tests were used to derive the neutrophil-, platelet-, monocyte-, and eosinophil-to-lymphocyte ratios (NLR, PLR, MLR, ELR), the neutrophil–lymphocyte–platelet ratio (NLPR), the C-reactive protein (CRP)-to-albumin ratio, and the monocyte-to-high density lipoprotein cholesterol (HDL) ratio. Between-group comparisons, receiver operating characteristic (ROC) analysis with Youden’s index, and age- and sex-adjusted binary logistic regression were performed. Results: TBUT and Schirmer I values were significantly lower in the MetS-DED group, whereas OSDI scores did not differ between the groups. NLR, MLR, NLPR, CRP, and the CRP-to-albumin ratio were significantly higher in MetS-DED patients (all p < 0.05), while classic metabolic parameters were comparable. ROC analysis revealed statistically significant but weak-to-modest discriminatory ability (areas under the curve (AUCs) 0.617–0.652). In age- and sex-adjusted models, MLR (odds ratio (OR) = 1.072 per 0.01 unit, p = 0.046), the CRP-to-albumin ratio (OR = 1.062 per 0.01 unit, p = 0.011), and NLPR (OR = 1.123 per 0.001 unit, p = 0.038) remained significantly associated with MetS-DED. Conclusions: Among individuals with MetS, the presence of DED was accompanied by impaired tear function and a more pronounced systemic inflammatory profile despite similar metabolic parameters. However, the modest discriminatory performance and borderline adjusted associations indicate that these findings should be regarded as preliminary signals rather than evidence supporting the clinical use of these markers for screening or risk identification. Full article

Background: Acute respiratory distress syndrome (ARDS) remains one of the most serious causes of respiratory failure and mortality in critically ill patients. Although the Berlin Definition provides a standardized framework for diagnosis, it offers limited predictive value for clinical outcomes. In this context, there is growing interest in the use of routinely available hematological markers as practical tools for early risk stratification. This study aimed to examine the association between hematological parameters and mortality in patients with ARDS, with particular emphasis on complete blood count-derived inflammatory indices. Methods: This multicenter retrospective cohort study included 404 adult patients with a confirmed diagnosis of ARDS who were admitted to intensive care units in Saudi Arabia. Demographic, clinical, and laboratory data were collected from electronic medical records. In addition to standard hematological parameters, the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and hemoglobin–albumin–lymphocyte–platelet (HALP) score were calculated from admission laboratory findings. Comparisons between survivors and non-survivors were performed using non-parametric statistical tests, and a receiver operating characteristic (ROC) curve analysis was used to evaluate the prognostic performance of these indices for in-hospital mortality. Results: Of the 404 included patients, 295 survived, and 109 died during hospitalization. Non-survivors demonstrated significantly higher white blood cell and neutrophil counts, alongside significantly lower lymphocyte, eosinophil, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and albumin levels. The derived inflammatory indices further demonstrated clear differences between outcome groups, as NLR and SII were significantly higher in non-survivors, whereas HALP scores were significantly lower. In ROC analysis, NLR showed the strongest discriminatory ability for mortality (AUC = 0.80, 95% CI 0.74–0.85), followed by SII (AUC = 0.76, 95% CI 0.71–0.81) and HALP (AUC = 0.76, 95% CI 0.70–0.81). The optimal cutoff values were 4.26 for NLR, 958 for SII, and 2.15 for HALP. No significant correlations were identified between age and any of the three indices. Upon applying multivariable regression analysis, only NLR maintained its prognostic ability for ARDS-related mortality. Conclusions: Routine hematological parameters, together with derived inflammatory and nutritional indices, were significantly associated with mortality in patients with ARDS. Among the evaluated markers, NLR demonstrated the strongest prognostic performance, both in univariate and multivariate analysis, followed by SII and HALP. As these indices are derived from inexpensive, readily available laboratory tests, they may offer practical value for early risk stratification and clinical decision-making, particularly in resource-limited settings. Full article

Background: Post-COVID-19 cognitive impairment, commonly referred to as “brain fog,” represents a significant clinical problem, yet its underlying mechanisms remain incompletely understood. New research indicates that long-term cognitive consequences of SARS-CoV-2 infection may result from chronic immunological dysregulation and neurometabolic changes. Objective: We aimed to assess the associations between cognitive performance, cerebral glucose metabolism, and inflammatory markers in patients with COVID-19 brain fog symptoms. Methods: This study included 47 patients with post-COVID-19 cognitive complaints enrolled in the COVMENT trial. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA). Brain glucose metabolism was evaluated with FDG PET-CT, and inflammatory markers, including C-reactive protein (CRP), monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, eosinophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were measured. Correlation analyses, logistic regression, and ROC analysis were performed to explore relationships between these factors. Results: A lower score of the MoCA abstraction domain correlated significantly with lower FDG uptake in multiple brain regions, including inferior parietal lobules and precuneus. Among inflammatory markers, only PLR demonstrated significant associations with both brain metabolism and abstraction performance. Lower PLR values were associated with greater neurometabolic impairment, and PLR < 130.1 was associated with abnormal abstraction performance. Conclusions: Post-COVID-19 cognitive dysfunction can be associated with selective neurometabolic alterations in brain regions supporting abstract reasoning. PLR seems to be associated with both cognitive performance and regional brain metabolism, suggesting a potential link between chronic immune dysregulation and neurocognitive impairment in post-COVID-19. Full article

Background: Immune-mediated cholangitis (IMC) is a rare complication of immune checkpoint inhibitor (ICI) therapy, and its clinical characteristics and prognostic implications remain unclear. This study aimed to clarify the characteristics, risk factors, and outcomes of IMC compared with non-cholangitis cases of immune-mediated hepatotoxicity (IMH). Methods: In this single-center retrospective study, 1332 patients who received ICIs between 2014 and 2023 were analyzed. IMH was diagnosed based on liver enzyme elevation and exclusion of other liver diseases, while IMC was identified through characteristic imaging findings. Baseline factors, clinical presentations, treatment responses, and overall survival (OS) were evaluated. Multivariate analysis identified IMC risk and IMH prognostic factors. Results: Among the cohort, 81 (6.1%) patients had IMH, including 10 (0.8%) with IMC. Baseline eosinophil count > 270/μL (odds ratio [OR] 10.33, p = 0.004) and C-reactive protein (CRP) levels > 0.8 mg/dL (OR 6.260, p = 0.027) were independent predictors of IMC. IMC was associated with delayed onset, cholestatic liver injury, abdominal pain, and neutrophil-predominant inflammation. In prognostic analysis, IMC was not associated with OS. However, cholestatic liver injury (hazard ratio [HR] 2.318, p = 0.023) and neutrophil-to-lymphocyte ratio (NLR) ≥ 4.0 (HR 3.622, p = 0.001) were independent predictors of poor OS. Bile duct imaging abnormalities before or after onset were common in patients with treatment-resistant IMC. Conclusions: Baseline eosinophil count and CRP may help predict IMC. While IMC was not a prognostic factor, cholestatic injury and high NLR were associated with worse outcomes. IMC exhibits distinct clinical features, and radiologic findings may support earlier diagnosis and management. Full article

Objective: This study aimed to investigate the relationship between bronchoalveolar lavage (BAL) cellular profiles, microbiological status, and clinical outcomes such as hospital admission in adult patients with non-cystic fibrosis bronchiectasis. Methods: A retrospective cross-sectional study was conducted on thirty adult bronchiectasis patients. Demographic, clinical, and laboratory data were collected. The cellular components of BAL fluid (macrophages, neutrophils, lymphocytes, and eosinophils) were analyzed. Patients were grouped according to the presence of microbial culture growth and history of hospitalization in the past year. Statistical analyses were performed to determine significant relationships. Results: The median age was 57 years, and the gender distribution was equal. There was no significant difference in BAL cellular profiles between groups with and without culture growth. However, in the group with a hospital admission in the past year, BAL showed a significantly lower percentage of alveolar macrophages (20% vs. 47%, p = 0.011) and a higher percentage of eosinophils (5% vs. 1%, p = 0.036). The hospitalized group also showed a trend toward a higher neutrophil percentage and a lower lymphocyte/neutrophil ratio. Furthermore, surprising associations were noted, such as a higher BAL macrophage count in married individuals and higher BAL eosinophilia in patients with diabetes. Conclusions: BAL cellular analysis provides valuable information beyond routine microbiological investigations in bronchiectasis. The low-alveolar-macrophage and high-eosinophil profile was found to be significantly associated with hospitalization, and this profile has the potential to serve as a prognostic biomarker in defining the “high-risk” phenotype. These findings highlight the complexity of the local inflammatory response and reveal the potential role of BAL in developing personalized treatment strategies for patients with bronchiectasis. Full article

Background: Small-cell lung cancer (SCLC) is an aggressive type of lung cancer, and several factors are currently used to predict poor outcomes, including performance status (PS), extensive-stage disease, male sex, advanced age, and elevated lactate dehydrogenase (LDH) levels. In this study, we aimed to explore the role of Tegs and inflammatory indices, such as CRP and NLR, in predicting response to immunotherapy. Methods: Fifty-one therapy-naïve ES-SCLC patients and ten healthy donors were enrolled. Peripheral blood mononuclear cells (PBMCs) were isolated and stained with fluorochrome-conjugated monoclonal antibodies. Multicolor flow cytometry was performed to determine the levels of CD8⁺ T cells and CD4⁺ Tregs, as well as their correlation with inflammatory indices and clinical outcomes. Results: ES-SCLC patients harbored higher percentages of CD8⁺ Teffs (p = 0.005) and FOXP3⁺ Tregs (p < 0.0001) in circulation before therapy compared with healthy donors. In addition, high levels of CD3⁺CD8⁺ T effectors were associated with longer PFS (p = 0.018) and longer OS (p = 0.012) compared with patients bearing low levels, while Tregs were not found to be predictive. More importantly, a survival benefit was observed in ES-SCLC patients with a low Treg/Teff ratio, as longer OS was observed in those with high percentages of CD8⁺ Teffs and low FOXP3⁺CTLA-4⁺ Tregs (p = 0.014) compared with those bearing low CD8⁺ Teffs and high FOXP3⁺CTLA-4⁺ Tregs. A low Treg/Teff ratio was further associated with low eosinophil levels and a low NLR before treatment initiation. Conclusions: These findings suggest a novel, easily obtainable blood-based signature that may help predict response to ICIs in ES-SCLC patients. Full article

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease. In recent decades, an increasing incidence of BP has been reported. The rationale for this study arises from the limited availability of advanced immunopathological and serological assays for assessing disease activity in bullous pemphigoid across many clinical centers. This systematic review evaluates evidence regarding hematological markers derived from complete blood count (CBC), such as eosinophil count and neutrophil-to-lymphocyte ratio (NLR), in BP patients. The Ovid MEDLINE and EMBASE databases were searched for English-language peer-reviewed papers published until 2 May 2025. Sixteen studies involving 1775 patients were included. Eosinophil count consistently correlated with disease severity, clinical phenotype, treatment response, and relapse risk, while NLR showed potential as a prognostic and therapeutic marker. Given their accessibility and cost-effectiveness, these parameters may have practical value in the routine clinical management of BP. Full article

Background: Acute Kidney Injury (AKI) is characterized by rising morbidity and mortality rates, along with significant financial costs associated with its treatment, positioning it as a priority health challenge. Difficult access to accurate biomarkers for renal dysfunction poses challenges in identifying high-risk patients prone to progression to severe AKI. Therefore, this study aimed to identify clinical and laboratory variables that could contribute to future risk stratification approaches in AKI. Methods: This observational retrospective study included 106 patients diagnosed with AKI who were admitted to the emergency department of the HGZ05-IMSS Hospital between January 2020 and July 2023. Multivariate logistic regression was used to identify clinical and laboratory factors associated with in-hospital mortality. Results: Patients with AKI exhibited elevated inflammatory indices (NLR, MLR, and PLR), increased levels of glucose, urea, and C-reactive protein (CRP), and reduced lymphocyte counts, serum albumin, FiO₂, and BUN/creatinine (BCR) ratio. The hematological profile showed myeloid predominance, characterized by neutrophilia and lower eosinophil, erythrocyte, and monocyte counts, consistent with systemic inflammation. Multivariable analysis identified COVID-19 infection, thrombocytopenia, low eosinophil levels, and polypharmacy as independent predictors of mortality in AKI patients. Conclusions: These findings underscore the interplay between inflammatory, metabolic, and hematological alterations in AKI and highlight key prognostic factors that may contribute to future risk stratification. Full article

Background/Objectives: Omalizumab is a monoclonal anti-IgE antibody approved for the treatment of chronic urticaria. There are no established or validated prognostic markers currently available to identify likely responders. The aim of this study was to retrospectively analyze a cohort of chronic urticaria patients treated with omalizumab, in order to determine the clinical and laboratory characteristics associated with complete response to therapy. Methods: Medical records of chronic urticaria patients receiving omalizumab were reviewed. The following parameters were collected: age, sex, disease duration, Urticaria Activity Score over 7 days (UAS7), time to response, total serum IgE levels, presence or absence of atopy, neutrophil-to-lymphocyte ratio, eosinophil and basophil counts, presence or absence of autoimmune conditions, and treatment duration. Complete response was classified as dependent on continued drug administration or drug-free (sustained remission after discontinuation). Adverse events were also recorded. Results: Omalizumab was well tolerated by all patients, with no serious adverse events reported. Complete response was achieved in 81.3% of patients; partial and no responses were observed in 8.3% and 10.1%, respectively. The majority of responders (~79.5%) maintained complete control of hives with low-dose omalizumab; subsequently, most of these patients eventually achieved sustained, drug-free remission. Total serum IgE levels appeared to predict complete response, with 164.7 IU/mL identified as the cut-off value potentially distinguishing responders from nonresponders. Conclusions: Omalizumab is a safe and effective treatment for chronic urticaria. Total serum IgE levels may help identify complete responders. Long-term low-dose regimens could be considered to reduce the economic burden on healthcare systems, although this is currently an off-label approach. Full article

Postimplantation syndrome (PIS) is an early inflammatory response following endovascular stent-graft implantation (EVAR and TEVAR), defined by culture-negative fever and leukocytosis. The patient’s preoperative inflammatory status is thought to play a central role in its development. This study aimed to evaluate whether the systemic inflammatory response index (SIRI) and the eosinophil-to-lymphocyte ratio (ELR) can serve as preoperative predictors of PIS. Clinical data from 300 patients who underwent aortic endograft implantation and laboratory results obtained 24 h before the procedure, and at 24 h, 72 h, and 1 week postoperatively, were prospectively recorded. PIS was defined as culture-negative fever ≥ 37.8 °C accompanied by leukocytosis ≥ 12,000/µL. Inflammation-based indices derived from complete blood count (SIRI and ELR), along with serum C-reactive protein (CRP) and albumin levels, were compared between patients with and without PIS. Logistic regression and receiver operating characteristic (ROC) analyses were performed to identify independent predictors. PIS developed in 55 patients (18.3%). Patients with PIS were younger (70.1 ± 8.6 vs. 72.7 ± 7.3 years; p = 0.042) and had larger aneurysm diameters and greater mural thrombus thickness. Preoperatively, leukocyte count, SIRI, and CRP levels were significantly higher in patients who developed PIS, whereas ELR and albumin levels were lower. Multivariable analysis showed that a larger aneurysm diameter (OR: 1.2; 95% CI: 1.0–1.3; p = 0.003), greater mural thrombus thickness (OR: 1.3; 95% CI: 1.0–1.6; p = 0.012), EVAR procedure (OR: 3.7; 95% CI: 1.2–6.3; p = 0.033), elevated SIRI (OR: 1.9; 95% CI: 1.2–3.1; p = 0.005), and higher CRP (OR: 1.4; 95% CI: 1.1–3.2; p = 0.003) were significantly associated with PIS. In contrast, increasing age, higher ELR, and higher albumin levels were associated with a reduced risk of PIS. Simple biomarkers routinely obtained from standard laboratory tests can contribute meaningfully to the preoperative prediction and postoperative identification of PIS. Their integration into risk stratification models and confirmation against definitive diagnostic criteria will require validation in larger, multicenter studies. Full article