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Keywords = derived neutrophil-to-lymphocyte ratio

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12 pages, 1185 KiB  
Article
Clostridioides difficile Infections: Epidemiological and Laboratory Data from the Internal Medicine Departments of a Tertiary Care Hospital in Athens, Greece, During the Past Decade
by Dimitris Kounatidis, Edison Jahaj, Eleni V. Geladari, Kyriaki Papachristodoulou, Fotis Panagopoulos, Georgios Marakomichelakis, Vasileios Papastamopoulos, Vasilios Sevastianos and Natalia G. Vallianou
Medicina 2025, 61(8), 1416; https://doi.org/10.3390/medicina61081416 - 5 Aug 2025
Abstract
Background and Objectives: Clostridioides difficile infection (CDI) poses a major public health problem worldwide. Materials and Methods: In this retrospective study, we included 274 patients with CDI, who were hospitalized in Internal Medicine Departments in Evangelismos General Hospital in Athens, Greece, [...] Read more.
Background and Objectives: Clostridioides difficile infection (CDI) poses a major public health problem worldwide. Materials and Methods: In this retrospective study, we included 274 patients with CDI, who were hospitalized in Internal Medicine Departments in Evangelismos General Hospital in Athens, Greece, during the past decade. Demographic, clinical and laboratory parameters of the patients were recorded. Statistical analysis revealed an association between older age and mortality as well as heart failure and mortality among patients with CDI. Results: Notably, WBC (white blood count), neutrophils, NLR (neutrophil-to-lymphocyte ratio), dNLR (derived NLR), SII (systemic immune–inflammation index) and hs-CRP (high-sensitivity C-reactive protein) demonstrated a positive association with mortality, whereas serum albumin levels and PNR (platelet-to-neutrophil ratio) exhibited an inverse relationship with mortality. We propose that the aforementioned biomarkers may be used as prognostic parameters regarding mortality from CDI. Conclusions: Large scale studies among patients with CDI with the advent of AI (artificial intelligence) may incorporate demographic, clinical and laboratory features into prognostic scores to further characterize the global CDI threat. Full article
(This article belongs to the Section Infectious Disease)
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19 pages, 4313 KiB  
Article
Integrating Clinical and Imaging Markers for Survival Prediction in Advanced NSCLC Treated with EGFR-TKIs
by Thanika Ketpueak, Phumiphat Losuriya, Thanat Kanthawang, Pakorn Prakaikietikul, Lalita Lumkul, Phichayut Phinyo and Pattraporn Tajarernmuang
Cancers 2025, 17(15), 2565; https://doi.org/10.3390/cancers17152565 - 3 Aug 2025
Viewed by 181
Abstract
Background: Epidermal growth factor receptor (EGFR) mutations are presented in approximately 50% of East Asian populations with advanced non-small cell lung cancer (NSCLC). While EGFR-tyrosine kinase inhibitors (TKIs) are the standard treatment, patient outcomes are also influenced by host-related factors. This study aimed [...] Read more.
Background: Epidermal growth factor receptor (EGFR) mutations are presented in approximately 50% of East Asian populations with advanced non-small cell lung cancer (NSCLC). While EGFR-tyrosine kinase inhibitors (TKIs) are the standard treatment, patient outcomes are also influenced by host-related factors. This study aimed to investigate clinical and radiological factors associated with early mortality and develop a prognostic prediction model in advanced EGFR-mutated NSCLC. Methods: A retrospective cohort was conducted in patients with EGFR-mutated NSCLC treated with first line EGFR-TKIs from January 2012 to October 2022 at Chiang Mai University Hospital. Clinical data and radiologic findings at the initiation of treatment were analyzed. A multivariable flexible parametric survival model was used to determine the predictors of death at 18 months. The predicted survival probabilities at 6, 12, and 18 months were estimated, and the model performance was evaluated. Results: Among 189 patients, 84 (44.4%) died within 18 months. Significant predictors of mortality included body mass index <18.5 or ≥23, bone metastasis, neutrophil-to-lymphocyte ratio ≥ 5, albumin-to-globulin ratio < 1, and mean pulmonary artery diameter ≥ 29 mm. The model demonstrated good performance (Harrell’s C-statistic = 0.72; 95% CI: 0.66–0.78). Based on bootstrap internal validation, the optimism-corrected Harrell’s C-statistic was 0.71 (95% CI: 0.71–0.71), derived from an apparent C-statistic of 0.75 (95% CI: 0.74–0.75) and an estimated optimism of 0.04 (95% CI: 0.03–0.04). Estimated 18-month survival ranged from 87.1% in those without risk factors to 2.1% in those with all predictors. A web-based tool was developed for clinical use. Conclusions: The prognostic model developed from fundamental clinical and radiologic parameters demonstrated promising utility in predicting 18-month mortality in patients with advanced EGFR-mutated NSCLC receiving first-line EGFR-TKI therapy. Full article
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11 pages, 782 KiB  
Article
Exploring the Association Between Platelet Count, the Systemic Immune Inflammation Index, and Fracture Risk in Postmenopausal Women with Osteoporosis: A Cross-Sectional Study
by Cecilia Oliveri, Anastasia Xourafa, Rita Maria Agostino, Valentina Corigliano, Antonino Botindari, Agostino Gaudio, Nunziata Morabito, Alessandro Allegra and Antonino Catalano
J. Clin. Med. 2025, 14(15), 5453; https://doi.org/10.3390/jcm14155453 - 2 Aug 2025
Viewed by 333
Abstract
Background/Objectives: Platelets play a role in bone metabolism and fracture healing. This study aimed to investigate the association between platelet indices and the derived systemic immune inflammation index (SII) with fracture risk in postmenopausal women. Methods: Platelet count, mean platelet volume, platelet distribution [...] Read more.
Background/Objectives: Platelets play a role in bone metabolism and fracture healing. This study aimed to investigate the association between platelet indices and the derived systemic immune inflammation index (SII) with fracture risk in postmenopausal women. Methods: Platelet count, mean platelet volume, platelet distribution width (PDW), platelet crit, percentage of large platelets (P-LCR), platelet–lymphocyte ratio, and the SII, calculated as (NxP)/L, where N, P, and L represented neutrophils, platelets and lymphocytes counts, respectively, were evaluated. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Results: A total of 124 women (mean age 68.4 ± 9 years) were stratified into two groups based on the median platelet count; the “lower platelet count group” (n = 58) had a count of 200,000 (174,000 to 226,000), while the “higher platelet count group” (n = 66) had a count of 281,500 (256,500 to 308,500). The higher platelet count group showed a higher hip fracture risk (7.4 vs. 4.5%, p = 0.08) and lower lumbar spine BMD (0.773 vs. 0.83 gr/cm2, p = 0.03). By dividing the participants into two groups with higher SSI (950,848.6 ± 746,097.99) (n = 61) and lower SII (355,751.2 ± 88,662.6) (n = 63), the group with the higher SII showed the higher hip fracture risk (7.4 vs. 3.6%, p = 0.01). Univariate regression analysis revealed correlations between chronological age and PDW (r = 0.188, p = 0.047), and P-LCR (r = 0.208, p = 0.03), as well as associations between vitamin D status and P-LCR (r = −0.301, p = 0.034), and between SII and hip fracture risk (r = 0.12, p = 0.007). Conclusions: Platelet count and SII were associated with fracture risk in postmenopausal women undergoing osteoporosis assessment. Given their reproducibility and cost-effectiveness, these markers warrant further investigation in future prospective studies focused on bone fragility. Full article
(This article belongs to the Special Issue Diagnosis, Treatment, Prevention and Rehabilitation in Osteoporosis)
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13 pages, 1017 KiB  
Article
Elevated Serum TNF-α/IL-1β Levels and Under-Nutrition Predict Early Mortality and Hospital Stay Burden in Pulmonary Tuberculosis
by Ionut-Valentin Stanciu, Ariadna-Petronela Fildan, Adrian Cosmin Ilie, Cristian Oancea, Livia Stanga, Emanuela Tudorache, Felix Bratosin, Ovidiu Rosca, Iulia Bogdan, Doina-Ecaterina Tofolean, Ionela Preotesoiu, Viorica Zamfir and Elena Dantes
J. Clin. Med. 2025, 14(15), 5327; https://doi.org/10.3390/jcm14155327 - 28 Jul 2025
Viewed by 291
Abstract
Background/Objectives: Romania remains a tuberculosis (TB) hotspot in the European Union, yet host-derived factors of poor outcomes are poorly characterised. We quantified circulating pro-inflammatory cytokines and examined their interplay with behavioural risk factors, the nutritional status, and the clinical course in adults hospitalised [...] Read more.
Background/Objectives: Romania remains a tuberculosis (TB) hotspot in the European Union, yet host-derived factors of poor outcomes are poorly characterised. We quantified circulating pro-inflammatory cytokines and examined their interplay with behavioural risk factors, the nutritional status, and the clinical course in adults hospitalised with pulmonary TB. We analysed 80 adults with microbiologically confirmed pulmonary TB and 40 respiratory symptom controls; four TB patients (5%) died during hospitalisation, all within 10 days of admission. Methods: A retrospective analytical case–control study was conducted at the Constanța regional TB referral centre (October 2020—October 2023). Patients with smear- or culture-confirmed TB were frequency-matched by sex, 10-year age band, and BMI class to culture-negative respiratory controls at a 2:1 ratio. The patients’ serum interferon-γ (IFN-γ), interleukin-1α (IL-1α), interleukin-1β (IL-1β), and tumour-necrosis-factor-α (TNF-α) were quantified within 24 h of admission; the neutrophil/lymphocyte ratio (NLR) was extracted from full blood counts. Independent predictors of in-hospital mortality were identified by multivariable logistic regression; factors associated with the length of stay (LOS) were modelled with quasi-Poisson regression. Results: The median TNF-α (24.1 pg mL−1 vs. 16.2 pg mL−1; p = 0.009) and IL-1β (5.34 pg mL−1 vs. 3.67 pg mL−1; p = 0.008) were significantly higher in the TB cases than in controls. TNF-α was strongly correlated with IL-1β (ρ = 0.80; p < 0.001), while NLR showed weak concordance with multiplex cytokine patterns. Among the patients with TB, four early deaths (5%) exhibited a tripling of TNF-α (71.4 pg mL−1) and a doubling of NLR (7.8) compared with the survivors. Each 10 pg mL−1 rise in TNF-α independently increased the odds of in-hospital death by 1.8-fold (95% CI 1.1–3.0; p = 0.02). The LOS (median 29 days) was unrelated to the smoking, alcohol, or comorbidity load, but varied across BMI strata: underweight, 27 days; normal weight, 30 days; overweight, 23 days (Kruskal–Wallis p = 0.03). In a multivariable analysis, under-nutrition (BMI < 18.5 kg m−2) prolonged the LOS by 19% (IRR 1.19; 95% CI 1.05–1.34; p = 0.004) independently of the disease severity. Conclusions: A hyper-TNF-α/IL-1β systemic signature correlates with early mortality in Romanian pulmonary TB, while under-nutrition is the dominant modifiable determinant of prolonged hospitalisation. Admission algorithms that pair rapid TNF-α testing with systematic nutritional assessment could enable targeted host-directed therapy trials and optimise bed utilisation in high-burden settings. Full article
(This article belongs to the Section Infectious Diseases)
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15 pages, 1321 KiB  
Article
The Role of Inflammatory Biomarkers in Predicting Postoperative Fever Following Flexible Ureteroscopy
by Rasha Ahmed, Omnia Hamdy, Atallah Alatawi, A. Alhowidi, Nael Al-Dahshan, Ahmad Nouraldin Alkadah, Siddique Adnan, Abdullah Mahmoud Alali, Yazeed Hamdan O. Alwabisi, Saleh Alruwaili, Muteb Bandar Binmohaiya, Amany Ahmed Soliman and Mohamed Elbakary
Medicina 2025, 61(8), 1366; https://doi.org/10.3390/medicina61081366 - 28 Jul 2025
Viewed by 259
Abstract
Background and Objectives: Flexible ureteroscopic surgery is a common minimally invasive procedure utilized for the management of various urological conditions. While effective, postoperative complications such as fever can occur, necessitating the identification of reliable biomarkers for early detection and management. In this [...] Read more.
Background and Objectives: Flexible ureteroscopic surgery is a common minimally invasive procedure utilized for the management of various urological conditions. While effective, postoperative complications such as fever can occur, necessitating the identification of reliable biomarkers for early detection and management. In this study, we specifically evaluated the predictive performance of three preoperative hematologic indices: the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune–inflammation index (SII). Materials and Methods: By systematically comparing these biomarkers through receiver operating characteristic (ROC) curve analysis and logistic regression modeling, we aimed to identify the most accurate predictor of postoperative fever development. Our cohort included patients who developed postoperative fever, many of whom exhibited normal WBC counts, allowing us to evaluate the discriminatory power of alternative inflammatory biomarkers. Results: Among the 150 patients, 32 developed postoperative fever. Conventional WBC counts did not predict fever, with 91% of feverish individuals having normal WBC values. In the ROC curve analysis, NLR outperformed SII (AUC 0.847, cutoff 796) and PLR (AUC 0.743, cutoff 106), with an AUC of 0.996 at 2.96. A combined logistic model achieved 100% sensitivity and 91% specificity (AUC = 0.996). Conclusions: This study addresses a critical gap in perioperative monitoring by validating readily available complete blood count-derived ratios as clinically meaningful predictors of postoperative inflammatory responses. Full article
(This article belongs to the Section Urology & Nephrology)
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17 pages, 706 KiB  
Article
Hematological Parameter-Derived Inflammatory Scores in Non-Pancreatic Hyperlipasemia (NPHL)—The Prognosis Lies in the Blood
by Krisztina Eszter Feher, David Tornai and Maria Papp
Biomedicines 2025, 13(7), 1719; https://doi.org/10.3390/biomedicines13071719 - 14 Jul 2025
Viewed by 295
Abstract
Background/Objectives: Non-pancreatic hyperlipasemia (NPHL) is associated with high in-hospital mortality, with sepsis being one of the most common etiologies. The prognostic value of hematological parameter-derived inflammatory scores has not been extensively studied in NPHL to date. Methods: The prognostic value of eight inflammatory [...] Read more.
Background/Objectives: Non-pancreatic hyperlipasemia (NPHL) is associated with high in-hospital mortality, with sepsis being one of the most common etiologies. The prognostic value of hematological parameter-derived inflammatory scores has not been extensively studied in NPHL to date. Methods: The prognostic value of eight inflammatory scores for in-hospital mortality was assessed in a total of 545 NPHL patients from two hospitalized patient cohorts (COVID-19 [n = 144] and non-COVID-19 [n = 401], the latter stratified as bacterial sepsis [n = 111] and absence of systemic infection [n = 290]). We assessed the neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), neutrophil-to-lymphocyte and platelet ratio (N/(LP)), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), aggregate index of systemic inflammation (AISI), systemic inflammation index (SII), and systemic inflammation response index (SIRI), comparing their prognostic value among etiological groups. Results: Patients with bacterial sepsis were older, had more comorbidities, and experienced worse outcomes, including longer hospitalization (median: 15, 7, and 11 days; p < 0.001), higher ICU admission rates (75.7%, 33.8%, and 47.9%, p < 0.001), and increased mortality (45.0%, 13.8%, and 38.2%, p < 0.001), compared to those without systemic infection or with COVID-19-induced NPHL. Overall, NLR, dNLR, and N/(LP) were the most accurate predictors of in-hospital mortality at admission (AUROC: non-infection: 0.747; 0.737; 0.772; COVID-19: 0.810; 0.789; 0.773, respectively). The accuracy of NLR decreased in bacterial sepsis, and only N/(LP) and PLR remained associated with in-hospital mortality (AUROC: 0.653 and 0.616, respectively). Conclusions: The prognostic performance of hematological parameter-derived inflammatory scores in NPHL is etiology-dependent. NLR is the most accurate prognostic tool for mortality in the absence of bacterial sepsis, while N/(LP) is the best score in sepsis-induced NPHL. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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12 pages, 617 KiB  
Article
The Role of Neutrophil-to-Lymphocyte Ratio as a Predictor of Orchiectomy or Testicular Atrophy After Torsion in Children: A Multicentric Study
by Carlos Delgado-Miguel, Javier Arredondo-Montero, Julio César Moreno-Alfonso, Isabella Garavis Montagut, María San Basilio, Irene Hernández, Noela Carrera, Leopoldo Martínez, Estíbalitz Iraola, Inmaculada Ruiz Jiménez, Pablo Aguado Roncero, Ennio Fuentes, Ricardo Díez and Francisco Hernández-Oliveros
J. Pers. Med. 2025, 15(7), 310; https://doi.org/10.3390/jpm15070310 - 13 Jul 2025
Viewed by 728
Abstract
Introduction: Neutrophil-to-lymphocyte ratio (NLR) is an inflammatory biomarker (hemogram-derived-ratio) related to ischemic-inflammatory diseases. Its usefulness in the diagnosis of pediatric testicular torsion (TT) has recently been reported, although its prognostic implication has not been evaluated. Our aim is to analyze the role [...] Read more.
Introduction: Neutrophil-to-lymphocyte ratio (NLR) is an inflammatory biomarker (hemogram-derived-ratio) related to ischemic-inflammatory diseases. Its usefulness in the diagnosis of pediatric testicular torsion (TT) has recently been reported, although its prognostic implication has not been evaluated. Our aim is to analyze the role of NLR in the evolution of TT in children, determining its potential for predicting the risk of adverse outcomes such as orchiectomy or testicular atrophy. Methods: We performed a retrospective multicentric case-control study in patients with clinical and ultrasound suspicion of TT, in whom surgical testicular examination was performed between 2016–2022 in seven pediatric hospitals. Patients’ outcomes were analyzed according to the intraoperative and postoperative evolution (orchiectomy/testicular atrophy or not). Demographics and clinical, ultrasound and laboratory features at admission were analyzed. Sensitivity and specificity were determined by the area under the curve (AUC) represented on the receiver operating characteristic (ROC) curves. Results: A total of 455 patients (median age 13.2 years; interquartile range 10.6–14.4 years) were included, in whom 87 orchiectomies (19.1%) were performed and 34 cases of testicular atrophy (7.5%) were observed during follow-up (median follow-up: 10 months). When comparing clinical, ultrasound and laboratory predictors of both events on ROC curves, NLR was the most sensitive and specific parameter for predicting orchiectomy (AUC = 0.834; p < 0.001), as well as testicular atrophy (AUC = 0.849; p < 0.001). Compared with other parameters, the designed cut-off point of NLR = 5.2 had maximum sensitivity and specificity (82.2% and 77.0%, respectively) for predicting orchiectomy or atrophy after testicular torsion. Conclusions: NLR may be considered the best predictor for the risk of orchiectomy or testicular atrophy following torsion in pediatric patients, helping the identification of high-risk cases. It can be useful both for obtaining more accurate preoperative information on patient prognosis and for closer follow-up of high-risk testicular atrophy patients. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Urological Diseases)
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13 pages, 840 KiB  
Article
Full-Blood Inflammatory Ratios Predict Length of Stay but Not Early Death in Romanian Pulmonary Tuberculosis
by Ionut-Valentin Stanciu, Ariadna-Petronela Fildan, Barkha Rani Thakur, Adrian Cosmin Ilie, Livia Stanga, Cristian Oancea, Emanuela Tudorache, Felix Bratosin, Ovidiu Rosca, Iulia Bogdan, Anca Chisoi, Ionela Preotesoiu, Viorica Zamfir and Elena Dantes
Medicina 2025, 61(7), 1238; https://doi.org/10.3390/medicina61071238 - 9 Jul 2025
Viewed by 317
Abstract
Background and Objectives: Blood-borne inflammatory ratios have been proposed as inexpensive prognostic tools across a range of diseases, but their role in pulmonary tuberculosis (TB) remains uncertain. In this retrospective case–control analysis, we explored whether composite indices derived from routine haematology—namely the [...] Read more.
Background and Objectives: Blood-borne inflammatory ratios have been proposed as inexpensive prognostic tools across a range of diseases, but their role in pulmonary tuberculosis (TB) remains uncertain. In this retrospective case–control analysis, we explored whether composite indices derived from routine haematology—namely the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic immune–inflammation index (SII) and a novel CRP–Fibrinogen Index (CFI)—could enhance risk stratification beyond established cytokine measurements among Romanian adults with culture-confirmed pulmonary T. Materials and Methods: Data were drawn from 80 consecutive TB in-patients and 50 community controls. Full blood counts, C-reactive protein, fibrinogen, and four multiplex cytokines were extracted from electronic records, and composite indices were calculated according to standard formulas. The primary outcomes were in-hospital mortality within 90 days and length of stay (LOS). Results: Among TB patients, the median NLR was 3.70 (IQR 2.54–6.14), PLR was 200 (140–277) and SII was 1.36 × 106 µL−1 (0.74–2.34 × 106), compared with 1.8 (1.4–2.3), 117 (95–140) and 0.46 × 106 µL−1 (0.30–0.60 × 106) in controls. Those with SII above the cohort median exhibited more pronounced acute-phase responses (median CRP 96 vs. 12 mg L−1; fibrinogen 578 vs. 458 mg dL−1), yet median LOS remained virtually identical (29 vs. 28 days) and early mortality was low in both groups (8% vs. 2%). The CFI showed no clear gradient in hospital stay across its quartiles, and composite ratios—while tightly inter-correlated—demonstrated only minimal association with cytokine levels and LOS. Conclusions: Composite cell-count indices were markedly elevated but did not predict early death or prolonged admission. In low-event European cohorts, their chief value may lie in serving as cost-free gatekeepers, flagging those who should proceed to more advanced cytokine or genomic testing. Although routine reporting of NLR and SII may support low-cost surveillance, validation in larger, multicentre cohorts with serial sampling is needed before these indices can be integrated into clinical decision-making. Full article
(This article belongs to the Section Pulmonology)
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12 pages, 719 KiB  
Article
Differential Analysis of Hemogram Parameters and Cellular Ratios in Severe Asthma Exacerbations: A Comparative Study of Eosinophilic and Non-Eosinophilic Phenotypes
by Nicolae Demenciuc, Corina Eugenia Budin, Corina Ureche, Mircea Stoian, Teodora Nicola-Varo, Dragos-Florin Baba, Dariana-Elena Pătrîntașu and Diana Deleanu
Life 2025, 15(6), 970; https://doi.org/10.3390/life15060970 - 18 Jun 2025
Cited by 2 | Viewed by 640
Abstract
Asthma exacerbations are acute worsening episodes in individuals with bronchial asthma, frequently necessitating emergency hospital care. Early differentiation between eosinophilic (≥150 eosinophils/mm3) and non-eosinophilic (<150 eosinophils/mm3) subtypes plays a crucial role in treatment decisions and identifying patients eligible for [...] Read more.
Asthma exacerbations are acute worsening episodes in individuals with bronchial asthma, frequently necessitating emergency hospital care. Early differentiation between eosinophilic (≥150 eosinophils/mm3) and non-eosinophilic (<150 eosinophils/mm3) subtypes plays a crucial role in treatment decisions and identifying patients eligible for biologic therapies. The ExBA Study explored variations in complete blood count (CBC) parameters and derived cellular ratios—namely the neutrophil-to-lymphocyte (NLR), thrombocyte-to-lymphocyte (TLR), and eosinophil-to-leukocyte ratios (ELR)—in adults hospitalized with severe asthma exacerbations. Ninety patients were enrolled and categorized into eosinophilic (n = 38) and non-eosinophilic (n = 52) groups. Significant statistical differences were observed in the neutrophil and lymphocyte levels, as well as in all three ratios. ROC analysis highlighted the ELR as the most specific indicator of the eosinophilic phenotype (specificity 100%, AUC 0.938, cut-off 0.003), whereas the NLR and TLR showed stronger associations with the non-eosinophilic group (AUC 0.733 and 0.676). No meaningful differences emerged regarding arterial blood gas levels, length of hospital stay, treatment costs, or mortality. A notable association was found between a personal or family history of atopy and the eosinophilic subtype (p = 0.0181). This study underscores the relevance of CBC-based ratios in asthma phenotyping during exacerbation events. Full article
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35 pages, 1619 KiB  
Review
Blood-Based Biomarkers as Predictive and Prognostic Factors in Immunotherapy-Treated Patients with Solid Tumors—Currents and Perspectives
by Franciszek Kaczmarek, Anna Marcinkowska-Gapińska, Joanna Bartkowiak-Wieczorek, Michał Nowak, Michał Kmiecik, Kinga Brzezińska, Mariusz Dotka, Paweł Brosz, Wojciech Firlej and Paulina Wojtyła-Buciora
Cancers 2025, 17(12), 2001; https://doi.org/10.3390/cancers17122001 - 16 Jun 2025
Viewed by 1059
Abstract
Immunotherapy has revolutionized cancer treatment; however, the availability of cost-effective blood-based biomarkers for prognostic and predictive factors of immune treatment in patients with solid tumors remains limited. Due to low cost and easy accessibility, blood-based biomarkers should constitute an essential component of studies [...] Read more.
Immunotherapy has revolutionized cancer treatment; however, the availability of cost-effective blood-based biomarkers for prognostic and predictive factors of immune treatment in patients with solid tumors remains limited. Due to low cost and easy accessibility, blood-based biomarkers should constitute an essential component of studies to optimize and monitor immunotherapy. Currently available markers that can be measured in peripheral blood include total monocyte count, myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), relative eosinophil count, cytokine levels (such as IL-6, IL-8, and IL-10), lactate dehydrogenase (LDH), C-reactive protein (CRP), soluble forms of CTLA-4 and PD-1 or PD-L1, as well as circulating tumor DNA (ctDNA). In our mini-review, we discuss the latest evidence indicating that routinely accessible peripheral blood parameters—such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and rheological parameters, which so far have been rarely considered for such an application, may be used as non-invasive biomarkers in cancer immunotherapy. Rheological parameters such as whole blood viscosity are influenced by several factors, such as hematocrit, aggregability and deformability of erythrocytes, and plasma viscosity, which is largely dependent on plasma proteins. Especially in cases where the set of symptoms indicates a high probability of hyperviscosity syndrome, blood rheological tests can lead to early diagnosis and treatment. Both biochemical and rheological parameters are prone to become novel and future standards for assessing immunotherapy among patients with solid tumors. Full article
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19 pages, 2179 KiB  
Article
Variation in CBC-Derived Inflammatory Biomarkers Across Histologic Subtypes of Lung Cancer: Can Histology Guide Clinical Management?
by Claudia Raluca Mariean, Oana Mirela Tiuca, Alexandru Mariean and Ovidiu Simion Cotoi
Diagnostics 2025, 15(11), 1437; https://doi.org/10.3390/diagnostics15111437 - 5 Jun 2025
Viewed by 701
Abstract
Background/Objectives: The early detection of high levels of CBC-derived inflammatory biomarkers and cellular lines, as well as their variations across different histological subtypes of lung cancer, may aid in the early identification of high-risk lung cancer patients and further guide their clinical [...] Read more.
Background/Objectives: The early detection of high levels of CBC-derived inflammatory biomarkers and cellular lines, as well as their variations across different histological subtypes of lung cancer, may aid in the early identification of high-risk lung cancer patients and further guide their clinical approach. Methods: A retrospective descriptive study was conducted and included 202 patients diagnosed with lung carcinoma at the Clinical County Hospital Mureș. The main analyzed parameters were the histological subtype and the stage of the tumor at diagnosis, white blood cell counts, and platelet counts, as well as nine CBC-derived inflammatory indexes like neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), eosinophil-to-neutrophil ratio (ENR), eosinophil-to-monocyte ratio (EMR), systemic inflammatory index (SII), systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI). The statistical analysis was performed using the MedCalc software, version 23.0.2. Logarithmic ANOVA was used to compare groups. Normality was tested using the Shapiro–Wilk test. The Chi-square test compared categorical variables, while the independent Mann-Whitney test was used for continuous variables. Results: The inflammatory response increased as disease severity progressed, with NSCLC-NOS being the histological subtype with the most numerous patients outside the normal ranges. Eosinophil count differed significantly across the histologic subtypes of NSCLC, with adenocarcinoma and adenosquamous patients exhibiting the highest values. In adenocarcinoma patients, we observed that NLR and MLR levels increased progressively as the tumor stage advanced. Based on severity, differences were observed across the histological subtypes of lung cancer in stage III patients for ENR, EMR, AISI, eosinophil count, and platelet count, as well as in stage IV patients for AISI, SIRI, and SII. Disease severity impacts the associated inflammatory response in all histologic subtypes of lung cancer to varying degrees. Conclusions: Histological subtype might have a decisive role in shaping the systemic inflammatory profile of lung cancer patients. CBC-derived indices serve as accessible, cost-effective biomarkers for early risk assessment, aiding in the prognosis evaluation and monitoring of therapeutic response. Future studies are needed to further evaluate the histology-specific inflammatory profiles as adjunctive tools in precision oncology. Full article
(This article belongs to the Special Issue Prognostic and Predictive Biomarkers of Lung Cancer)
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10 pages, 549 KiB  
Article
Complete Blood Count-Derived Biomarkers’ Association with Risk of PD-1 or PD-1/CTLA-4 Inhibitor-Induced Hypothyroidism in Patients with Solid Tumors
by Ketevan Lomidze, Nino Kikodze, Marine Gordeladze, Nino Charkviani and Tinatin Chikovani
Immuno 2025, 5(2), 21; https://doi.org/10.3390/immuno5020021 - 4 Jun 2025
Viewed by 561
Abstract
Background: A novel and highly effective strategy for tumor immunotherapy involves enhancing host immune responses against tumors through the blockade of checkpoint molecules. The most common toxicities associated with checkpoint blockade therapies include autoimmune damage to various organs. Purpose: This study aims to [...] Read more.
Background: A novel and highly effective strategy for tumor immunotherapy involves enhancing host immune responses against tumors through the blockade of checkpoint molecules. The most common toxicities associated with checkpoint blockade therapies include autoimmune damage to various organs. Purpose: This study aims to investigate hematological markers derived from complete blood counts (CBCs)—including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), derived neutrophil-to-lymphocyte ratio (dNLR), white blood cell-to-hemoglobin ratio (WHR), neutrophils, lymphocytes, platelets, hemoglobin, red blood cell (RBC) count, neutrophil-to-RBC ratio (NRR), and neutrophil-to-hemoglobin ratio (NHR)—as potential prognostic biomarkers for the early identification of hypothyroidism in patients receiving PD-1 or PD-1/CTLA-4 immune checkpoint inhibitors. Materials and Methods: A prospective observational study was conducted on 44 patients with stage III-IV solid tumors treated with immune checkpoint (PD-1 or PD-1/CTLA-4) inhibitors. Thyroid function tests and CBC-derived biomarkers were collected at baseline, before immunotherapy. In the immunotherapy cohort, 15 of the 44 patients developed immune-related hypothyroidism, defined as overt autoimmune thyroiditis (TSH > 4.0, FT4 < 12, and anti-TPO antibodies > 30 IU/mL and/or anti-TG antibodies > 95 IU/mL) (Group 1). In comparison, 29 patients maintained normal thyroid function (Group 2). The control group comprised 14 age- and sex-matched healthy volunteers (Group 3). Statistical analyses were performed using analysis of variance (ANOVA) to compare blood parameters among the three groups (Group 1, Group 2, and Group 3) before treatment, with statistical significance set at a p-value < 0.05. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic power of the potential prognostic biomarkers areas. The area under the curve (AUC), sensitivity, and specificity were calculated for the 44 immunotherapy patients. Results: The PLR was significantly higher (262.25 ± 162.95), while WBCs-neutrophils, the WHR, the NRR, the NHR, WBCs, neutrophils, and lymphocytes were lower (2.07 ± 0.66, 0.54 ± 0.19, 0.96 ± 0.28, 0.36 ± 0.14, 6.36 ± 2.07, 4.29 ± 1.55, and 1.23 ± 0.41, respectively) at baseline in Group 1 in comparison to Group 2. ROC curve analysis revealed that the areas under the curve (AUC) for WBCs, neutrophils, lymphocytes, WBCs-neutrophils, the PLR, the WHR, the NRR, and the NHR were 0.9, 0.87, 0.83, 0.85, 0.84, 0.92, 0.89, and 0.87, respectively. These values exceeded the threshold, indicating the high prognostic potential of each marker. Conclusions: Lower baseline levels of WBCs-neutrophils, the WHR, the NRR, the NHR, WBCs, neutrophils, and lymphocytes, along with a higher PLR, were associated with an increased risk of hypothyroidism in patients receiving PD-1 or PD-1/CTLA-4 inhibitors. These CBC-derived biomarkers represent simple, accessible, and potentially useful tools for predicting hypothyroidism in cancer patients undergoing immunotherapy. Further studies in bigger cohorts are needed to validate our findings. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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17 pages, 1439 KiB  
Article
Monocyte-to-Neutrophil Ratio as an Immunological Marker of Left Ventricular Hypertrophy in Children with Primary Hypertension
by Katarzyna Dziedzic-Jankowska, Radosław Pietrzak, Michał Szyszka, Adam Bujanowicz, Anna Stelmaszczyk-Emmel, Bożena Werner and Piotr Skrzypczyk
J. Clin. Med. 2025, 14(11), 3896; https://doi.org/10.3390/jcm14113896 - 1 Jun 2025
Viewed by 548
Abstract
Background/Objectives: Activation of the immune system and subclinical inflammation participate in the pathogenesis of primary hypertension (PH) and the formation of hypertension-mediated organ damage. Our study aimed to investigate the relationship between subclinical inflammation and left ventricular hypertrophy (LVH) in pediatric patients [...] Read more.
Background/Objectives: Activation of the immune system and subclinical inflammation participate in the pathogenesis of primary hypertension (PH) and the formation of hypertension-mediated organ damage. Our study aimed to investigate the relationship between subclinical inflammation and left ventricular hypertrophy (LVH) in pediatric patients with PH. Methods: In 34 untreated children with PH (15.1 ± 2.1 years, 28 boys, 6 girls), we investigated markers of subclinical inflammation (high-sensitivity CRP, interleukin 18, and complete blood count-derived indices), parameters of the left ventricle from 2D-echocardiography, office and ambulatory blood pressure, and selected clinical and biochemical parameters. Results: LVH was revealed in 12 (35.3%) patients, and abnormal relative wall thickness (RWT) was found in 6 (17.6%) children. Left ventricular inner dimension at end diastole (LVEDd) Z-score correlated negatively with neutrophils (r = −0.583, p = 0.001), neutrophil-to-lymphocyte ratio (NLR) (r = −0.562, p = 0.002), and positively with monocyte-to-neutrophil ratio (MNR) (r = 0.605, p = 0.001) and left ventricular mass (LVM) for lean body mass Z-score, while LVMI [g/m2] correlated positively with MNR (r = 0.495, p = 0.005 and r = 0.433, p = 0.011). RWT correlated positively with neutrophil count (r = 0.356, p = 0.039 and r = 0.347 p = 0.044) and with monocyte count (r = 0.378, p = 0.027 and r = 0.365, p = 0.034). Patients with LVH had significantly lower NLR (1.430 ± 0.409 vs. 1.797 ± 0.521, p = 0.043) and higher MNR ratios (0.171 ± 0.031 vs. 0.144 ± 0.037, p = 0.042). The receiver operating characteristic analysis demonstrated good diagnostic profiles for mean platelet volume (MPV), NLR, and MNR as predictors of LVH. In multivariate analysis, MNR was the only significant predictor of LVH (OR: 1.329, 95CI: 1.007–1.756). Conclusions: Monocyte-to-neutrophil ratio may be an easily accessible marker of left ventricular hypertrophy in children with primary hypertension. Full article
(This article belongs to the Special Issue Pathophysiology of Hypertension and Related Diseases)
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17 pages, 1042 KiB  
Review
Neutrophil-to-Lymphocyte Ratio in the Alzheimer’s Disease Continuum
by Davide Aprile, Fabiola De Marchi, Federico Menegon, Cristoforo Comi and Giacomo Tondo
Int. J. Mol. Sci. 2025, 26(11), 5157; https://doi.org/10.3390/ijms26115157 - 28 May 2025
Viewed by 789
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder defined clinically by progressive cognitive decline and memory impairment and pathologically by the accumulation of amyloid-beta plaques, tau neurofibrillary tangles, neuroinflammation, and immune system dysregulation. Peripheral biomarkers are gaining attention as valuable tools for elucidating neuroinflammatory [...] Read more.
Alzheimer’s disease (AD) is a neurodegenerative disorder defined clinically by progressive cognitive decline and memory impairment and pathologically by the accumulation of amyloid-beta plaques, tau neurofibrillary tangles, neuroinflammation, and immune system dysregulation. Peripheral biomarkers are gaining attention as valuable tools for elucidating neuroinflammatory mechanisms in the AD continuum, with potential implications for diagnosis and prognosis. Among these, the neutrophil-to-lymphocyte ratio (NLR) has emerged as a promising systemic inflammatory marker. NLR, a readily available and cost-effective parameter derived from routine blood tests, reflects the balance between innate and adaptive immune responses. Elevated NLR has been associated with AD and mild cognitive impairment (MCI), showing correlations with disease severity, amyloid burden, and neuroinflammation. Increased neutrophil counts may contribute to neurodegeneration through oxidative stress and pro-inflammatory cytokine release, while decreased lymphocyte levels suggest impaired adaptive immunity. However, despite growing evidence, the clinical utility of NLR in AD remains debated due to heterogeneity in study populations and confounding factors, such as comorbidities and medication effects. This review provides a comprehensive analysis of the association between NLR and AD throughout the disease continuum. Future research should prioritize longitudinal studies and integrative approaches that combine NLR with other inflammatory and neurodegenerative markers to enhance early diagnosis and personalized therapeutic strategies. Full article
(This article belongs to the Special Issue Latest Review Papers in Molecular Neurobiology 2025)
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18 pages, 3200 KiB  
Article
Predictive Role of Complete Blood Count-Derived Inflammation Indices and Optical Coherence Tomography Biomarkers for Early Response to Intravitreal Anti-VEGF in Diabetic Macular Edema
by Ece Ergin, Ana Maria Dascalu, Daniela Stana, Laura Carina Tribus, Andreea Letitia Arsene, Marina Ionela Nedea, Dragos Serban, Claudiu Eduard Nistor, Corneliu Tudor, Dan Dumitrescu, Paul Lorin Stoica and Bogdan Mihai Cristea
Biomedicines 2025, 13(6), 1308; https://doi.org/10.3390/biomedicines13061308 - 27 May 2025
Viewed by 743
Abstract
Background: Diabetic macular edema (DME) is the leading cause of vision impairment in diabetic patients, with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections being the first-line therapy. However, one-third of patients exhibit persistent DME despite treatment, suggesting additional pathogenic factors. This study aimed [...] Read more.
Background: Diabetic macular edema (DME) is the leading cause of vision impairment in diabetic patients, with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections being the first-line therapy. However, one-third of patients exhibit persistent DME despite treatment, suggesting additional pathogenic factors. This study aimed to evaluate the predictive value of complete blood count (CBC)-based inflammation indexes and optical coherence tomography (OCT) parameters in determining early anti-VEGF treatment effectiveness in DME. Methods: One hundred and four naïve patients with DME, treated with 0.05 mL of intravitreal aflibercept were retrospectively analyzed. Blood parameters analyzed included neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Baseline OCT biomarkers included subretinal fluid (SRF), intraretinal cysts (IRC), hyperreflective retinal spots (HRS), and disorganization of retinal inner layers (DRIL). Treatment response was defined as a minimum 10% reduction in central macular thickness (CMT) at one month post-injection. Results: NLR, MLR, PLR, and SII were significantly higher in non-responders (p < 0.001), but their predictive value was fair, with an area under the ROC curve ranging between 0.704 (MLR) and 0.788 (SII). A multivariate model including SII, initial CMT, and the presence of IRC showed an excellent prediction value for early anatomical response (AUC ROC of 0.911). At the same time, lower PLR, DRIL, SRF, and the absence of HRF were correlated with early gain in BCVA. Conclusions: CBC-derived inflammation indices and OCT biomarkers have prognostic value in predicting early response to anti-VEGF therapy in DME in terms of functional and anatomical outcomes. These findings could help identify poor responders and guide personalized treatment strategies. Full article
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