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9 pages, 527 KB  
Article
Association Between the Aggregate Index of Systemic Inflammation (AISI) and Tirofiban Use During Primary Percutaneous Coronary Intervention in Patients with ST-Elevation Myocardial Infarction
by Kemal Emrecan Parsova, Erkan Kahraman, Furkan Durak, Khagani Isgandarov and Yalcin Velibey
Medicina 2026, 62(1), 155; https://doi.org/10.3390/medicina62010155 - 13 Jan 2026
Viewed by 168
Abstract
Background and Objectives: Inflammation contributes to plaque rupture and thrombosis in ST-elevation myocardial infarction (STEMI). The Aggregate Index of Systemic Inflammation (AISI) is a novel biomarker that reflects innate immune and thrombotic activation. Due to the connection between inflammation and thrombosis, higher [...] Read more.
Background and Objectives: Inflammation contributes to plaque rupture and thrombosis in ST-elevation myocardial infarction (STEMI). The Aggregate Index of Systemic Inflammation (AISI) is a novel biomarker that reflects innate immune and thrombotic activation. Due to the connection between inflammation and thrombosis, higher AISI values could indicate a greater thrombus burden and the necessity of glycoprotein IIb/IIIa inhibitors. The aim of this study was to assess the relationship between AISI and tirofiban use during primary percutaneous coronary intervention (PCI) in STEMI patients. Materials and Methods: This retrospective study included 2624 STEMI patients who underwent primary PCI at a tertiary heart center between 2019 and 2024. Patients with pre-hospital fibrinolysis, missing laboratory data, or rescue PCI were excluded. AISI was calculated as (neutrophil × monocyte × platelet)/lymphocyte. The primary outcome was tirofiban use during PCI. Univariate and multivariable logistic regression analyses were performed to identify independent predictors, and receiver operating characteristic (ROC) curve analysis was used to evaluate AISI performance. Statistical significance was defined as p < 0.05. Results: Among the 2624 patients with STEMI undergoing primary PCI, tirofiban was administered in 23.5% of cases. Patients receiving tirofiban had significantly higher AISI values (p < 0.001). ROC analysis demonstrated that AISI predicted tirofiban use with a modest discriminative performance (AUC = 0.566; 95% CI 0.536–0.596; p < 0.001). In multivariable logistic regression, younger age (OR 0.98; p < 0.001), higher AISI (per 100-unit increase; OR 1.01; p = 0.037), and lower LVEF (OR 0.98; p < 0.001) independently predicted tirofiban use, whereas admission glucose showed only borderline significance (p = 0.089). Conclusions: Elevated AISI was independently associated with tirofiban use during primary PCI, indicating that systemic inflammatory status parallels intraprocedural decision-making in STEMI. Although its discriminative performance was modest, AISI reflects systemic inflammatory–thrombotic activation in this clinical setting. Full article
(This article belongs to the Section Cardiology)
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17 pages, 1032 KB  
Article
Colorectal Cancer—One Disease, Two Fires: Distinct Inflammatory Landscapes in Colon and Rectal Cancer
by Catalin Vladut Ionut Feier, Florin Grama, Georgiana Viorica Moise, Razvan Constantin Vonica, Vasile Gaborean, Alaviana Monique Faur, Vladut Iosif Rus and Calin Muntean
Diagnostics 2025, 15(18), 2387; https://doi.org/10.3390/diagnostics15182387 - 19 Sep 2025
Cited by 1 | Viewed by 1028
Abstract
Background: Systemic inflammatory indices are increasingly used to predict prognosis in colorectal cancer (CRC), yet direct comparisons between colon cancer (CC) and rectal cancer (RC) remain limited. Methods: We conducted a retrospective matched-cohort study including 296 patients (148 with CC and 148 with [...] Read more.
Background: Systemic inflammatory indices are increasingly used to predict prognosis in colorectal cancer (CRC), yet direct comparisons between colon cancer (CC) and rectal cancer (RC) remain limited. Methods: We conducted a retrospective matched-cohort study including 296 patients (148 with CC and 148 with RC) surgically treated between January 2018 and December 2024. Patients were matched by tumor stage, sex, and age (±3 years). Preoperative blood samples were used to calculate several inflammatory markers, including Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Monocyte-to-Lymphocyte Ratio (MLR), Systemic Inflammation Response Index (SIRI), Systemic Immune-Inflammation Index (SII), and Aggregate Index of Systemic Inflammation (AISI). Subgroup analyses were performed based on the Charlson Comorbidity Index (>3 vs. ≤3), surgical context (elective vs. emergency), and tumor stage (T1–T2 vs. T3–T4). Results: Colon cancer patients exhibited significantly higher levels of systemic inflammation compared to those with rectal cancer, with notable differences in NLR (3.99 vs. 2.84, p < 0.001), PLR (219.8 vs. 163.3, p < 0.001), SIRI (3.7 vs. 1.91, p = 0.004), SII (1533.8 vs. 847.8, p < 0.001), and AISI (1714.7 vs. 593.6, p = 0.009). These differences remained statistically significant in key subgroups. In elective surgeries, CC patients had elevated PLR (p < 0.001), SIRI (p = 0.003), SII (p < 0.001), and AISI (p = 0.013). Among patients with advanced tumors (T3–T4), CC was associated with higher SII (p < 0.001), AISI (p = 0.008), PLR (p < 0.001), and SIRI (p = 0.004). For those with a Charlson index > 3, CC patients showed significantly higher PLR (p < 0.001), NLR (p < 0.001) and SIRI (p = 0.001). Conclusions: colon cancer presents with a markedly stronger systemic inflammatory response than rectal cancer, particularly in patients with advanced disease, elective surgical treatment, and higher comorbidity burden. These findings suggest that indices such as SIRI, SII, and PLR may serve as valuable stratification tools beyond tumor location in CRC. Full article
(This article belongs to the Special Issue Diagnosis and Management of Colorectal Lesions)
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23 pages, 2160 KB  
Review
Why Are Internal Mammary (Thoracic) Arteries Less Prone to Developing Atherosclerosis Compared to Coronary Arteries? Do Gut Microbiota Play a Role? A Narrative Review
by Leon M. T. Dicks
Int. J. Mol. Sci. 2025, 26(18), 9052; https://doi.org/10.3390/ijms26189052 - 17 Sep 2025
Cited by 1 | Viewed by 2274
Abstract
Atherosclerosis (AS), the leading cause of cardiovascular disease (CVD), is the thickening and stiffening of arterial walls, mainly of coronary arteries, the aorta, and the internal carotid artery. Blood flow is restricted by the deposit of lipid-rich macrophages (foam cells), calcium, fibrin, and [...] Read more.
Atherosclerosis (AS), the leading cause of cardiovascular disease (CVD), is the thickening and stiffening of arterial walls, mainly of coronary arteries, the aorta, and the internal carotid artery. Blood flow is restricted by the deposit of lipid-rich macrophages (foam cells), calcium, fibrin, and cellular debris into plaques on the inner lining (tunica intima) of arterial walls. Damaged endothelia become inflamed and accumulate macrophages, monocytes, granulocytes, and dendritic cells, which intensifies plaque formation and increases the risk of myocardial infarction (MI) and thrombosis. Many of the anatomical and physiological abnormalities in arterial walls can be linked to colonic bacteria that produce inflammation-inducing metabolites, e.g., succinate, fumarate, fatty acids (FAs), reactive oxygen species (ROS), lipopolysaccharides (LPS), and trimethylamine-N-oxide (TMAO). TMAO triggers platelet formation, inhibits the synthesis of bile acids (BAs), accelerates the formation of aortic lesions, and upregulates the expression of membrane glycoprotein CD36 (also known as platelet glycoprotein 4) on the surface of platelets and epithelial cells. The ability of internal mammary arteries (IMAs) to produce higher levels of apolipoprotein C-III (apo-CIII) and paraoxonase (PON), compared to coronary arteries, prevents plaque buildup. The tunica intima of IMAs is rich in heparin sulfate and endothelial nitric oxide synthase (eNOS). Increased production of NO relaxes VSMCs and suppresses GTP cyclohydrolase (GTPCH), which lowers blood pressure. Higher levels of prostacyclin (PG12) produced by IMAs inhibit platelet aggregation. IMAs are structurally different from coronary arteries by having a thinner, non-fenestrated, tunica intima without a prominent internal elastic lamina. These characteristics render IMAs ideal conduits in coronary artery bypass graft (CABG) surgery. This review provides information that may explain why IMAs are less affected by inflammatory reactions and more resilient to plaque formation. Full article
(This article belongs to the Special Issue Molecular Diagnosis in Cardiovascular Diseases)
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34 pages, 17016 KB  
Article
Investigation of the Expression, Localization, and Acidosis-Associated Conformational Changes in Connexin 43 in Traumatic Brain Injury with the Development of a Neural Network Model for Assessing Systemic Inflammation
by Chizaram Nwosu, Evgeniya Kirichenko, Stanislav Bachurin, Mikhail Petrushan, Alexey Ermakov, Rozaliia Nabiullina, Marya Kaplya, Alexander Logvinov and Stanislav Rodkin
Int. J. Mol. Sci. 2025, 26(18), 8855; https://doi.org/10.3390/ijms26188855 - 11 Sep 2025
Cited by 1 | Viewed by 1181
Abstract
Traumatic brain injury (TBI) is one of the most common forms of neurotrauma, accompanied by significant disruptions in neuronal homeostasis and intercellular communication. A key protein involved in these processes is connexin 43 (Cx43), which facilitates the formation of gap junctions in the [...] Read more.
Traumatic brain injury (TBI) is one of the most common forms of neurotrauma, accompanied by significant disruptions in neuronal homeostasis and intercellular communication. A key protein involved in these processes is connexin 43 (Cx43), which facilitates the formation of gap junctions in the astrocytic network. In this study, using confocal and immunofluorescence microscopy, ultrastructural analysis, and molecular modeling, we investigated the dynamics of Cx43 expression and structural changes in neuroglia during various post-traumatic periods following TBI. It was shown that in the acute phase, 24 h post-injury, there is a reduction in Cx43 expression, accompanied by apoptotic neuronal degradation, disruption of nuclear NeuN localization, and destruction of cellular ultrastructure. By 7 days post-injury, a significant increase in Cx43 levels was observed, along with the formation of protein aggregates associated with pronounced reactive astrogliosis. Peripheral blood analysis revealed persistent neutrophilia, lymphopenia, and reduced monocyte levels, reflecting a systemic inflammatory response and immunosuppression, which was corroborated by a custom-trained neural network-based computer vision model. Linear regression and correlation analyses further identified a strong positive association between normalized monocyte levels and Cx43 expression, a moderate negative correlation with lymphocytes, and no significant correlation with neutrophils. Using a custom-built computer vision model, we confirmed these hematological trends and detected subtle changes, such as early increases in platelet counts, that were not captured by manual evaluation. The model demonstrated strong performance in classifying common blood cell types and proved to be a valuable tool for monitoring dynamic post-traumatic shifts in blood. Molecular dynamics modeling of Cx43 identified a pH-dependent mechanism of conformational reorganization under post-traumatic acidosis, mediated by the interaction between protonated His142 and Glu103. This mechanism mimics the structural consequences of the pathogenic E103K mutation and may play a critical role in the neurotoxic effects of Cx43 in TBI. These findings highlight the complexity of Cx43 regulation under traumatic conditions and its potential significance as a target for neuroprotective therapy. Full article
(This article belongs to the Special Issue The Function of Glial Cells in the Nervous System: 2nd Edition)
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15 pages, 392 KB  
Article
Systemic Immune-Inflammation Index and Related Hematologic Markers as Prognostic Tools in Type 2 Diabetes
by Raluca Cosma-Lăzuran, Daniel-Corneliu Leucuta and Mihaela-Simona Popoviciu
Medicina 2025, 61(8), 1433; https://doi.org/10.3390/medicina61081433 - 9 Aug 2025
Cited by 4 | Viewed by 2344
Abstract
Background and Objectives: Chronic low-grade inflammation plays a key role in the pathogenesis of type 2 diabetes mellitus (T2DM) and its vascular complications. Hematological indices derived from routine blood counts, such as neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte [...] Read more.
Background and Objectives: Chronic low-grade inflammation plays a key role in the pathogenesis of type 2 diabetes mellitus (T2DM) and its vascular complications. Hematological indices derived from routine blood counts, such as neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), have been proposed as surrogate markers for systemic inflammation and predictors of cardiovascular risk. This study aimed to evaluate the predictive value of these inflammatory indices concerning the presence of micro- and macrovascular complications and cardiovascular mortality in patients with type 2 diabetes mellitus. Materials and Methods: We conducted a retrospective cohort study including 237 patients with T2DM. We assessed the association between hematological indices and cardiovascular mortality, followed by a ROC curve analysis to evaluate their predictive performance, and a multiple logistic regression. Results: Thirty patients (12.66%) died during the study period. ROC analysis showed that SIRI (AUC = 0.680 [95% CI 0.576–0.779]), LMR (AUC = 0.667 [95% CI 0.564–0.763]), AISI (AUC = 0.662 [95% CI 0.553–0.768]), and NLR (AUC = 0.657 [95% CI 0.545–0.764]) had the best discriminative capacity, all with specificity >70%. The relation remained significant even after adjustments for confounding variables in multiple logistic regression. For microvascular complications, Monocyte count (AUC = 0.611 [95% CI 0.532–0.69]) and LMR (AUC = 0.608 [95% CI 0.521–0.695]) showed minimal but notable predictive value. Conclusions: SIRI, LMR, AISI, and NLR were significantly associated with mortality and demonstrated modest discriminative ability. These markers, accessible and cost-effective, may be useful tools for risk stratification in T2DM patients. Further validation in prospective cohorts is warranted. Full article
(This article belongs to the Section Endocrinology)
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17 pages, 706 KB  
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 1122
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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17 pages, 1391 KB  
Article
The Role of the Inflammatory Prognostic Index in Patients with Non-ST Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention
by Ersan Oflar, Muhsin Kalyoncuoğlu, Atilla Koyuncu, Cennet Yıldız Erbaş, Hasan Ali Sinoplu, Fahrettin Katkat and Gündüz Durmuş
J. Clin. Med. 2025, 14(13), 4491; https://doi.org/10.3390/jcm14134491 - 25 Jun 2025
Cited by 2 | Viewed by 1165
Abstract
Background/Objectives: To evaluate the prognostic role of the inflammatory prognostic index (IPI) value at admission in major adverse cardiovascular and cerebrovascular events (MACCEs) in individuals with non-ST elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI). Methods: A total of 1142 NSTEMI patients [...] Read more.
Background/Objectives: To evaluate the prognostic role of the inflammatory prognostic index (IPI) value at admission in major adverse cardiovascular and cerebrovascular events (MACCEs) in individuals with non-ST elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI). Methods: A total of 1142 NSTEMI patients with a mean age of 61.9 ± 12.5 years were included. Admission C-reactive protein level, serum albumin level, and complete blood counts of participants were collected from hospital records. The IPI was calculated based on the following formula: C-reactive protein/albumin ratio (CAR) x neutrophil-to-lymphocyte ratio (NLR). An aggregate index of systemic inflammation (AISI) value was calculated using the ‘‘neutrophil count x monocyte count x platelet/lymphocyte count’’ formula. The study cohort was divided into two groups according to the median IPI value. Results: Patients with higher IPI values were statistically more likely to suffer from MACCEs within one year (p < 0.001), thus the admission IPI value was found to be associated with future development of MACCEs. Furthermore, it had sufficient discrimination power (AUC = 0.70) and predictive accuracy in identifying MACCEs compared to other inflammatory parameters such as the CAR (AUC = 0.64), the NLR (AUC = 0.64), and the AISI (AUC = 0.59). Adding the IPI to the baseline multivariable logistic regression model significantly improved the model’s discrimination and net clinical benefit effect for identifying patients who would suffer from MACCEs, with a C-index of 0.84 (95% CI: 0.82–0.86) and explanatory power of 23.2% (R2 = 0.232, DeLong test p = 0.001). High-risk patients with an IPI value greater than 2.43 had significantly more adverse events (p < 0.001). Conclusions: The IPI may be a promising inflammatory index for use in clinical practice to determine the risk prediction of MACCEs in NSTEMI patients undergoing PCI. Full article
(This article belongs to the Section Cardiology)
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35 pages, 1619 KB  
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
Cited by 5 | Viewed by 3591
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 KB  
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
Cited by 3 | Viewed by 1488
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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12 pages, 1038 KB  
Article
The Role of Preoperative Immunonutritional Scores in Predicting Complications After Subthalamic Nucleus Deep Brain Stimulation in Parkinson’s Disease
by Marina Raguž, Marko Tarle, Petar Marčinković, Hana Chudy, Darko Orešković, Vladimira Vuletić, Tonko Marinović and Darko Chudy
J. Clin. Med. 2025, 14(11), 3811; https://doi.org/10.3390/jcm14113811 - 29 May 2025
Cited by 2 | Viewed by 1039
Abstract
Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with systemic inflammation, immune dysregulation, and malnutrition, all of which may influence surgical outcomes. Subthalamic nucleus deep brain stimulation (STN DBS) is a widely used treatment for advanced PD, yet postoperative complications [...] Read more.
Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with systemic inflammation, immune dysregulation, and malnutrition, all of which may influence surgical outcomes. Subthalamic nucleus deep brain stimulation (STN DBS) is a widely used treatment for advanced PD, yet postoperative complications remain a concern. This study evaluates the predictive value of preoperative immunonutritional markers—including the Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) score, Aggregate Index of Systemic Inflammation (AISI), Lymphocyte-to-Monocyte Ratio (LMR), and systemic inflammatory response syndrome (SIRS)—for the risk of extracranial complications following STN DBS. Methods: A retrospective cohort study was conducted on 138 PD patients who underwent STN DBS. Clinical and laboratory data were analyzed to assess the association between preoperative immunonutritional markers and postoperative complications, including infections, wound healing disturbances, and surgical revisions. Logistic regression and receiver operating characteristic (ROC) analysis were performed to evaluate the predictive power of these markers. Results: SIRS emerged as the strongest predictor of complications (aOR = 6.99, 95% CI = 1.844–26.509), emphasizing the critical role of systemic inflammation in surgical outcomes. HALP, AISI, and LMR also demonstrated significant predictive potential, with HALP (AUC = 0.69) and LMR (AUC = 0.73) being the most robust predictors of complications. While albumin alone was not a significant predictor, it correlated with inflammatory markers and comorbidities, underscoring its role in broader risk assessments. Conclusions: This study underscores the value of preoperative immunonutritional markers in predicting complications following STN DBS in PD patients. Incorporating these markers into clinical risk stratification may enhance preoperative planning and personalized postoperative care, ultimately improving surgical outcomes. These findings, while promising, warrant validation through prospective, multicenter studies to refine predictive models and enhance patient outcomes. Full article
(This article belongs to the Section Clinical Neurology)
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21 pages, 1398 KB  
Article
The Impact of the Histologic Types of Lung Cancer on CBC-Derived Inflammatory Markers—Current Knowledge and Future Perspectives
by Claudia Raluca Mariean, Oana Mirela Tiucă, Alexandru Mariean, Tiberiu-Bogdan Szekely, Raluca Niculescu, Adrian Horatiu Sabau, Cristina Flavia Al-Akel and Ovidiu Simion Cotoi
J. Clin. Med. 2025, 14(9), 3038; https://doi.org/10.3390/jcm14093038 - 28 Apr 2025
Cited by 2 | Viewed by 2206
Abstract
Background/Objectives: The analysis of the complete blood count (CBC)-derived inflammatory indexes across different histological subtypes of lung cancer supports the early detection of tumor-induced inflammation and has a good predictive value for severity in cancer patients. The main objective of this article [...] Read more.
Background/Objectives: The analysis of the complete blood count (CBC)-derived inflammatory indexes across different histological subtypes of lung cancer supports the early detection of tumor-induced inflammation and has a good predictive value for severity in cancer patients. The main objective of this article was to assess the variations in CBC-derived inflammatory markers across different histologic subtypes of lung cancer, with the final goal of identifying specific predictors of severity for each histologic subtype of lung cancer. Methods: We conducted a retrospective descriptive study that included 202 patients diagnosed with lung carcinoma at the Clinical County Hospital Mureș. The analyzed parameters were as follows: the histological type, the stage of the tumor, patients’ general data, and associated comorbidities. In addition, nine CBC-derived inflammatory indexes, like the 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), were analyzed as predictors of severity and correlated with histologic findings. Results: The predictors of severity differed across the histologic subtypes. SIRI, d-NLR, and age were predictors of severity in adenocarcinoma patients, while the d-NLR, ENR, leukocyte, and neutrophil count predicted severity in squamous cell carcinoma. For SCLC patients, AISI, SIRI, SII, d-NLR, EMR, ENR, MLR, leukocyte count, lymphocyte count, neutrophil count, platelets count, COPD, smoking, and male gender were predictors for severity. Conclusions: Understanding the complexity and variations in the inflammatory response across different histologic types of lung cancer can personalize treatment regimens and target specific abnormal cellular lines, thus improving the outcome of this highly deadly condition. Full article
(This article belongs to the Special Issue Biomarkers and Lung Cancer: Clinical Application)
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14 pages, 2415 KB  
Article
Prostate Tissue-Induced Platelet Activation and Platelet–Neutrophil Aggregation Following Transurethral Resection of the Prostate Surgery: An In Vitro Study
by Po-An Lin, Hsiang-Han Huang, Mei-Hua Hu, Go-Shine Huang, En Meng, Yi-Lin Chiu, Yung-Chi Hsu and Wei-Hung Chan
Biomedicines 2025, 13(4), 1006; https://doi.org/10.3390/biomedicines13041006 - 21 Apr 2025
Cited by 1 | Viewed by 889
Abstract
Background: This study aimed to investigate the effects of prostate tissue on platelet activation markers, primarily assessed through P-selectin expression, and to assess the formation of platelet–leukocyte aggregations in response to prostate tissue exposure. Furthermore, we compared platelet activation induced by prostate [...] Read more.
Background: This study aimed to investigate the effects of prostate tissue on platelet activation markers, primarily assessed through P-selectin expression, and to assess the formation of platelet–leukocyte aggregations in response to prostate tissue exposure. Furthermore, we compared platelet activation induced by prostate tissue homogenates with that induced by thrombin stimulation. These processes may play a role in the development of disseminated intravascular coagulation (DIC) following transurethral resection of the prostate (TURP). Methods: We collected prostate tissue samples from 12 patients undergoing TURP. The samples were homogenized and used to stimulate platelet-rich plasma in vitro. Flow cytometry was used to measure platelet P-selectin expression and platelet–leukocyte aggregation. Additionally, four experimental groups were established: (A) saline control, (B) thrombin stimulation, (C) phosphate-buffered saline (PBS) control, and (D) prostate tissue homogenate. Data were analyzed to assess the impact of prostate tissue and thrombin on platelet activation and platelet–leukocyte interactions. Results: Prostate tissue homogenates significantly increased platelet P-selectin expression and platelet–neutrophil aggregation compared with the control groups (p < 0.05). Overall, platelet–leukocyte aggregation was not significantly different between the thrombin and prostate tissue groups. However, prostate tissue exposure did not significantly affect platelet–monocyte and platelet–lymphocyte aggregations. Conclusions: Prostate tissue exposure during TURP induces platelet activation, particularly platelet P-selectin expression and platelet–neutrophil aggregation, suggesting a potential mechanism for DIC development. These findings highlight the importance of monitoring platelet activity in patients undergoing TURP and indicate that interventions targeting platelet P-selectin expression and platelet–neutrophil interactions may help mitigate DIC risk. Full article
(This article belongs to the Section Cell Biology and Pathology)
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24 pages, 2050 KB  
Article
The Diagnostic and Prognostic Role of Inflammatory Markers, Including the New Cumulative Inflammatory Index (IIC) and Mean Corpuscular Volume/Lymphocyte (MCVL), in Colorectal Adenocarcinoma
by Robert-Emmanuel Șerban, Dragoș-Marian Popescu, Mihail-Virgil Boldeanu, Dan Nicolae Florescu, Mircea-Sebastian Șerbănescu, Vasile Șandru, Afrodita Panaitescu-Damian, Dragoș Forțofoiu, Rebecca-Cristiana Șerban, Florin-Liviu Gherghina and Cristin-Constantin Vere
Cancers 2025, 17(6), 990; https://doi.org/10.3390/cancers17060990 - 15 Mar 2025
Cited by 12 | Viewed by 2250
Abstract
Background: Colorectal cancer affects a large number of patients worldwide, with numerous factors being involved in its etiopathogenesis and chronic inflammation playing an essential role in tumor development. In this study, we analyzed and compared several markers of inflammation that are relatively [...] Read more.
Background: Colorectal cancer affects a large number of patients worldwide, with numerous factors being involved in its etiopathogenesis and chronic inflammation playing an essential role in tumor development. In this study, we analyzed and compared several markers of inflammation that are relatively easy to obtain for a rapid and accurate diagnosis and prognosis. Methods: This study included 219 patients diagnosed with colorectal cancer, analyzing the inflammation scores derived from their blood cells and inflammatory circulating proteins. These inflammatory markers are neutrophil-to-lymphocyte ratio—NLR; platelet-to-lymphocyte ratio—PLR; lymphocyte-to-monocyte ratio—LMR; systemic immune inflammation index—SII; systemic inflammatory response index—SIRI; aggregate index of systemic inflammation—AISI; derived neutrophil-to-lymphocyte ratio—dNLR; C-reactive protein-to-albumin ratio—CAR; and fibrinogen-to-albumin ratio—FAR. In the analysis of patients with colorectal cancer, we have also introduced two new recently developed inflammatory markers: the cumulative inflammatory index (IIC) and the ratio between the mean corpuscular volume and lymphocytes (MCVL). This study aimed to correlate the inflammatory markers’ levels with the colorectal cancer diagnostic stage, the tumor and clinical characteristics of the colorectal cancer patients, and 36 months’ survival time and to evaluate the diagnostic and prognostic capacity and accuracy of these inflammatory markers in this type of cancer. Results: We showed that the levels of the analyzed inflammation markers correlate with the TNM stage, the tumor pathological differentiation grade, the age and gender of the patients, and overall survival, with their increased levels being associated with a lower survival rate. Conclusions: The analyzed markers, which are easy to perform right from the patient’s admission, can be helpful both in diagnosis and, mostly, in prognosis, sustaining the role of inflammation in cancer. By comparing them, we showed which one can be useful for increased sensitivity and specificity in the diagnosis and prognosis of colorectal cancer patients. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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14 pages, 3281 KB  
Article
Thromboinflammatory Biomarkers in Lymphomas: Linking Inflammation to Thrombosis Risk
by Emilija Živković, Olivera Mitrović-Ajtić, Tijana Subotički, Jelena Ivanović, Vladimir Otašević, Dragoslava Đikić, Miloš Diklić, Milica Vukotić, Teodora Dragojević, Dejana Stanisavljević, Darko Antić and Vladan P. Čokić
Int. J. Mol. Sci. 2025, 26(5), 2058; https://doi.org/10.3390/ijms26052058 - 26 Feb 2025
Cited by 1 | Viewed by 1811
Abstract
Thrombosis is a critical complication in lymphomas, driven by chronic inflammation. To observe this systemic mechanism, we evaluated inflammatory cytokines, neutrophil and monocyte activation, and platelet function in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Hodgkin lymphoma (HL), with and without [...] Read more.
Thrombosis is a critical complication in lymphomas, driven by chronic inflammation. To observe this systemic mechanism, we evaluated inflammatory cytokines, neutrophil and monocyte activation, and platelet function in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Hodgkin lymphoma (HL), with and without thrombosis using ELISA and flow cytometry according to laboratory and clinical data. Interleukin-1β was elevated across lymphomas and inversely correlated with the Khorana score for venous thromboembolism, while increased tumor necrosis factor-alpha (TNF-α) was inversely associated with the International Prognostic Index (IPI) in thrombosis-associated lymphomas. Neutrophil activation was increased in DLBCL, while elevated neutrophil extracellular traps (NETs) biomarkers were inversely consistent with thrombosis and the ThroLy score. NETs were elevated in HL. Classical monocytes were increased in all lymphoma subtypes, with intermediate and tissue factor (TF)-carrying monocytes elevated in DLBCL and HL. Platelet activation was pronounced, with platelet–monocyte aggregates and platelet-associated TF elevated in DLBCL and FL but not HL. P-selectin was increased in lymphomas with thrombosis, aligned with Khorana and ThroLy scores, and reflected clinical stage while inversely correlating with IPI in non-thrombotic lymphomas. These findings highlight distinct thromboinflammatory mechanisms across lymphoma subtypes, providing insights into biomarkers for thrombosis risk and therapeutic targets in lymphoma management. Full article
(This article belongs to the Section Molecular Immunology)
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17 pages, 2642 KB  
Article
The Prognostic Value of Inflammatory Indices in Acute Pulmonary Embolism
by Mihai Ștefan Cristian Haba, Oana Mădălina Manole, Ana Maria Buburuz, Ionuț Tudorancea, Irina-Iuliana Costache-Enache and Viviana Onofrei
Diagnostics 2025, 15(3), 312; https://doi.org/10.3390/diagnostics15030312 - 29 Jan 2025
Cited by 4 | Viewed by 2550
Abstract
Background: Acute pulmonary embolism (PE) is a condition with increased morbidity and mortality. It is important to identify patients with high mortality risk. Inflammation and thrombosis are interconnected in the pathophysiology of PE. The aim of the study was to investigate the prognostic [...] Read more.
Background: Acute pulmonary embolism (PE) is a condition with increased morbidity and mortality. It is important to identify patients with high mortality risk. Inflammation and thrombosis are interconnected in the pathophysiology of PE. The aim of the study was to investigate the prognostic value of multiple blood cellular indices such as neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte platelet ratio (NLPR), systemic immune–inflammation index (SII), systemic inflammation response index (SIRI) and aggregate index of systemic inflammation (AISI) in acute PE. Methods: A total of 157 patients with acute PE confirmed by chest computed tomographic angiography (CTPA) were enrolled. These patients were divided into two categories according to the simplified pulmonary embolism severity index (sPESI): high risk and low risk. Results: Univariate logistic regression analysis showed that right ventricle dysfunction, NLR, SII and SIRI were significantly associated with high risk of acute PE. NLR of 4.32 was associated with high-risk PE with a sensitivity of 57.4% and specificity of 65.7% (AUC = 0.635). SII of 1086.55 was associated with high-risk PE with a sensitivity of 55.7% and specificity of 71.4% (AUC = 0.614). SIRI of 2.87 was associated with high-risk PE with a sensitivity of 59% and specificity of 62.9% (AUC = 0.624). Multivariate logistic regression analysis demonstrated that right ventricle dysfunction, NLR, PLR and NLPR are independent predictors of high-risk acute PE. Secondly, NLR, NLPR, SII and SIRI were significantly correlated with in-hospital mortality of acute PE. Based on receiver-operating characteristic (ROC) curve values of 7.66 for NLR (AUC 0.911, sensitivity of 85.7% and sensibility of 83%), 0.02 for NLPR (AUC 0.871, sensitivity of 85.7% and sensibility of 70%), 1542.71 for SII (AUC 0.782, sensitivity of 71.4% and sensibility of 72%) and 5.72 for SIRI (AUC 0.788, sensitivity of 71.4% and sensibility of 73%) could predict in-hospital mortality. Conclusions: The blood cellular indices (NLR, NLPR, SII and SIRI) are associated with high-risk acute PE and in-hospital mortality. Right ventricular dysfunction, NLR and NLPR are independent predictors for high-risk acute PE. Full article
(This article belongs to the Special Issue Biochemical Testing Applications in Clinical Diagnosis)
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