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Keywords = lymphocyte to white blood cell ratio

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15 pages, 626 KiB  
Review
Prediction of Mortality by Clinical Laboratory Parameters in Severe Fever with Thrombocytopenia Syndrome: A Meta-Analysis
by Shicui Yan, Xuebin Ding, Qiao Gao, Lili Zhao, Cong Li, Zhenlu Sun and Xuejun Ma
Trop. Med. Infect. Dis. 2025, 10(7), 193; https://doi.org/10.3390/tropicalmed10070193 - 9 Jul 2025
Viewed by 338
Abstract
Background: This study intended to fully assess the predictive efficiency of different clinical laboratory parameters for the mortality risk in severe fever with thrombocytopenia syndrome (SFTS). Methods: We systematically searched the Web of Science, PubMed, Cochrane Library, and Embase up to 13 December [...] Read more.
Background: This study intended to fully assess the predictive efficiency of different clinical laboratory parameters for the mortality risk in severe fever with thrombocytopenia syndrome (SFTS). Methods: We systematically searched the Web of Science, PubMed, Cochrane Library, and Embase up to 13 December 2024 for studies on the association of laboratory parameters with SFTS mortality. Two investigators were independently responsible for the study screening and data extraction, and they assessed the study quality using the Newcastle–Ottawa Scale (NOS). Stata17.0 was adopted for the meta-analyses. Results: We finally included 33 observational studies involving 9502 participants (1799 deaths and 7703 survivors). The results showed that increases in the viral load (odds ratio (OR) 1.93, 95% confidence interval (CI) 1.56–2.38), neutrophil-to-lymphocyte ratio (hazard ratio (HR) 1.31, 95% CI 1.13–1.51), neutrophil percentage (HR 1.02, 95% CI 1.01–1.03), white blood cells (HR 1.06, 95% CI 1.01–1.11), activated partial thromboplastin time (OR 1.07, 95% CI 1.04–1.09), prothrombin time (OR 1.31, 95% CI 1.03–1.65), creatine kinase-myocardial band (OR 1.01, 95% CI 1.01–1.02), and procalcitonin (HR 1.27, 95% CI 1.10–1.47) greatly increased the SFTS mortality, while decreases in the lymphocyte percentage (HR 0.96, 95% CI 0.94–0.98), platelets (HR 0.98, 95% CI 0.97–0.99), and albumin (HR 0.91, 95% CI 0.86–0.96) also greatly increased the SFTS mortality; the results were all statistically significant (p < 0.05). Conclusion: Abnormalities of laboratory parameters (e.g., viral load, blood routine, coagulation, multi-organ dysfunction, and inflammation indicators) are good predictors of SFTS mortality, which can provide valuable references in clinical practice. 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 704
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 562
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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18 pages, 1175 KiB  
Article
Association of Comorbidity and Inflammatory and Nutritional Markers with Epilepsy and Seizure Frequency
by Demet Aygun and Hafize Uzun
Nutrients 2025, 17(11), 1847; https://doi.org/10.3390/nu17111847 - 28 May 2025
Viewed by 626
Abstract
Background: Epilepsy is a chronic neurological disorder frequently influenced by systemic inflammation, nutritional status, and comorbid conditions, which may worsen seizure outcomes. Given the increasing recognition of these factors in disease progression, this study aimed to investigate the relationship between the Modified Charlson [...] Read more.
Background: Epilepsy is a chronic neurological disorder frequently influenced by systemic inflammation, nutritional status, and comorbid conditions, which may worsen seizure outcomes. Given the increasing recognition of these factors in disease progression, this study aimed to investigate the relationship between the Modified Charlson Comorbidity Index (mCCI), inflammatory hematological parameters, and the prognostic nutritional index (PNI) with seizure frequency and clinical prognosis in patients with epilepsy. Methods: A total of 159 participants were enrolled between January 2021 and January 2023, including 53 healthy controls (mean age: 44 ± 14.2 years; female: 21, male: 32), 53 epilepsy patients without comorbidity (mean age: 33 ± 12.5 years; female: 28, male: 25), and 53 epilepsy patients with comorbidities (mean age: 56.2 ± 13.8 years; female: 22, male: 31). The participants were divided into three groups: 53 patients with isolated epilepsy, 53 patients with epilepsy and comorbid conditions, and 53 healthy individuals with no known diseases, matched for age and sex with the patient groups, who presented for routine check-ups. The mCCI was calculated for patients with comorbid epilepsy. Inflammatory hematological parameters and the PNI were assessed in all participants using previously obtained complete blood count data. Results: Inflammatory markers such as white blood cell count, neutrophil count, C-reactive protein (CRP), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and mean platelet distribution width (PDW) were significantly higher in epilepsy patients with comorbidities compared to other groups. Epilepsy patients with comorbidities had a higher seizure frequency compared to those without comorbidities (75.5% vs. 54.7%, p < 0.001). The PNI was lowest in epilepsy patients with comorbidities, showing a significant difference between all groups (p < 0.001). High comorbidity burden increased seizure risk by 4.56 times (95% CI: 1.30–16.01), each unit increase in the SII raised the risk by 1.13 times (95% CI: 1.08–1.19), and each unit decrease in the PNI increased the risk by 1.14 times (OR = 0.88, p < 0.001). Cerebrovascular disease and hemiplegia were also significant risk factors, increasing seizure risk by 4.15 and 4.48 times, respectively. Conclusions: Our study demonstrates that inflammatory hematological parameters, particularly SII and MCCI scores, are elevated in epilepsy patients and further increase with comorbidities. These markers are strongly associated with seizure occurrence, highlighting the prognostic significance of systemic inflammation and comorbidity burden in epilepsy. Given the frequent observation of low PNI values in patients with comorbid conditions, which may reflect compromised nutritional status, and given associations suggest a role in poor clinical outcomes, comprehensive management is essential. Monitoring the PNI and SII may help stratify high-risk patients for targeted nutritional and anti-inflammatory interventions. Full article
(This article belongs to the Section Nutritional Immunology)
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12 pages, 546 KiB  
Article
Low, Intermediate, and High Glutamine Levels Are Progressively Associated with Increased Lymphopenia, a Diminished Inflammatory Response, and Higher Mortality in Internal Medicine Patients with Sepsis
by Filippo Mearelli, Alessio Nunnari, Federica Chitti, Annalisa Rombini, Alessandra Macor, Donatella Denora, Luca Messana, Marianna Scardino, Ilaria Martini, Giulia Bolzan, Noemi Merlo, Fabio Di Paola, Francesca Spagnol, Chiara Casarsa, Nicola Fiotti, Venera Costantino, Verena Zerbato, Stefano Di Bella, Carlo Tascini, Daniele Orso, Filippo Giorgio Di Girolamo and Gianni Bioloadd Show full author list remove Hide full author list
J. Clin. Med. 2025, 14(10), 3313; https://doi.org/10.3390/jcm14103313 - 9 May 2025
Cited by 1 | Viewed by 801
Abstract
Background: The pathophysiological mechanisms underlying altered plasma glutamine concentrations in sepsis remain poorly understood. Identifying clinical, immunological, and metabolic correlates of glutamine fluctuations is crucial to advancing precision medicine, developing targeted therapies, and improving survival outcomes in septic patients. Methods: We enrolled 469 [...] Read more.
Background: The pathophysiological mechanisms underlying altered plasma glutamine concentrations in sepsis remain poorly understood. Identifying clinical, immunological, and metabolic correlates of glutamine fluctuations is crucial to advancing precision medicine, developing targeted therapies, and improving survival outcomes in septic patients. Methods: We enrolled 469 patients with sepsis and assessed inflammatory markers—including body temperature, white blood cell count, and C-reactive protein levels—upon admission to the internal medicine unit. Lymphocyte count and plasma concentrations of glutamine, glutamic acid, 5-oxoproline, phenylalanine, tyrosine, and leucine were measured using gas chromatography–mass spectrometry. Patients were stratified into three groups based on plasma glutamine levels. Mortality was recorded at 30 days and 6 months. Results: Low, intermediate, and high glutamine levels were observed in 46% (n = 217), 47% (n = 218), and 7% (n = 34) of patients, respectively. Patients with hyperglutaminemia exhibited significantly lower body temperature, white blood cell and lymphocyte counts, C-reactive protein levels, and glutamic acid-to-5-oxoproline ratio (a surrogate marker of glutathione availability), along with elevated phenylalanine levels, leucine levels, and tyrosine-to-phenylalanine ratio (all p < 0.01). Metabolic disruption and mortality increased progressively across glutamine level groups. Kaplan–Meier analysis demonstrated significantly higher mortality in patients with elevated glutamine levels at both 30 days (log-rank p = 0.03) and 6 months (log-rank p = 0.05). Conclusions: At baseline, increasing plasma glutamine levels are associated with progressively deeper lymphopenia, more pronounced metabolic derangement, and higher short- and long-term mortality in patients with sepsis. Full article
(This article belongs to the Special Issue Sepsis: New Insights into Diagnosis and Treatment)
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8 pages, 422 KiB  
Article
An Important Biomarker in Patients with Bell’s Palsy: Serum Calprotectin
by Cihan Türker, Elif Emre, Süleyman Aydın, Mustafa Dalgıç and Deniz Baklacı
Medicina 2025, 61(4), 747; https://doi.org/10.3390/medicina61040747 - 18 Apr 2025
Viewed by 416
Abstract
Background and Objectives: This study aimed to examine the relationship between serum calprotectin levels and facial paralysis in patients with Bell’s palsy and to determine its prognostic significance. Materials and Methods: This study included 40 patients diagnosed with Bell’s palsy and [...] Read more.
Background and Objectives: This study aimed to examine the relationship between serum calprotectin levels and facial paralysis in patients with Bell’s palsy and to determine its prognostic significance. Materials and Methods: This study included 40 patients diagnosed with Bell’s palsy and 20 healthy individuals as controls. The patients were categorized into three groups based on their response to treatment: complete response, partial response, and no response. Blood samples were taken before treatment and in the third month after treatment to measure C-reactive protein, white blood cell count, lymphocyte count, neutrophil count, neutrophil-to-lymphocyte ratio, and calprotectin levels. Results: Serum calprotectin levels were found to be elevated in patients with BP compared to the healthy controls; however, no significant correlation was observed between calprotectin levels and disease prognosis. Conclusions: The findings suggest that Bell’s palsy patients have elevated serum calprotectin levels compared to healthy individuals, indicating the potential use of calprotectin as a biomarker in Bell’s palsy. However, no significant difference in calprotectin levels was observed between patients with varying degrees of treatment response, suggesting that calprotectin may be limited in predicting disease prognosis. Full article
(This article belongs to the Special Issue Update on Otorhinolaryngologic Diseases (2nd Edition))
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14 pages, 2871 KiB  
Article
Disrupted Redox Regulation and Inflammatory Response in Pyoderma Gangrenosum
by Simona Roxana Georgescu, Clara Matei, Corina Daniela Ene, Cristina Capusa, Mircea Tampa, Madalina Irina Mitran, Cristina Iulia Mitran, Gheorghe Nicolae and Ilinca Nicolae
Life 2025, 15(4), 611; https://doi.org/10.3390/life15040611 - 6 Apr 2025
Cited by 1 | Viewed by 625
Abstract
Introduction. The pathophysiology of Pyoderma Gangrenosum (PG) involves altered innate and adaptive immunity, mutagenic and epigenetic changes, the autoinflammatory state, and the overexpression of cytokines. This study investigated the potential contribution of inflammation, redox signaling, and the immune system in the pathogenesis of [...] Read more.
Introduction. The pathophysiology of Pyoderma Gangrenosum (PG) involves altered innate and adaptive immunity, mutagenic and epigenetic changes, the autoinflammatory state, and the overexpression of cytokines. This study investigated the potential contribution of inflammation, redox signaling, and the immune system in the pathogenesis of PG. Materials and Methods. This case–control study included 36 patients with PG and 30 controls. We have determined the serum concentrations of acute phase proteins (C-reactive protein—CRP, alpha1 glycoprotein acid—AGPA, Albumin), interleukin-17A -IL-17A, β2 microglobulin-β2MG, reduced glutathione-GSH, oxidized glutathione- GSSG, the GSH/GSSG ratio, and hematological parameters (white blood cells-WBC, neutrophil-lymphocyte ratio-NLR, erythrocyte sedimentation rate-ESR) in patients with PG compared with controls. Furthermore, we have evaluated the variations in these markers before and after treatment in PG patients. Results. The serum concentrations of acute phase proteins (CRP, AGPA, and Albumin) and the IL-17A, β2MG, GSH, GSSG, and GSH/GSSG ratio were significantly different between the PG group and controls. Hematological parameters (WBC, NLR, and ESR), acute phase proteins (CRP, AGPA, and albumin), and IL-17A showed an exaggerated and persistent inflammatory response in patients with PG. In patients with PG associated with systemic diseases, the dysregulation of the biochemical events was more severe. Conclusions. The acute phase proteins, β2MG-MHC class I complex, and the GSH-GSSG system are unbalanced in PG. Our results could improve the diagnosis and our understanding of the pathogenic basis of PG. Full article
(This article belongs to the Special Issue Skin Diseases and Dermatologic Comorbidities)
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24 pages, 4975 KiB  
Article
Enhancement of NK Cell Cytotoxic Activity and Immunoregulatory Effects of a Natural Product Supplement Across a Wide Age Span: A 30-Day In Vivo Human Study
by Sergei Boichuk, Aigul Galembikova and David Vollmer
Int. J. Mol. Sci. 2025, 26(7), 2897; https://doi.org/10.3390/ijms26072897 - 22 Mar 2025
Viewed by 1784
Abstract
The purpose of this study was to examine whether supplementation of ultra- and nanofiltered colostrum-based products, combined with egg yolk extract, nicotinamide mononucleotide (NMN), quercetin, alpha-ketoglutarate, white button mushroom, and celery seed extracts (the formula was patented by 4Life Research Company, USA and [...] Read more.
The purpose of this study was to examine whether supplementation of ultra- and nanofiltered colostrum-based products, combined with egg yolk extract, nicotinamide mononucleotide (NMN), quercetin, alpha-ketoglutarate, white button mushroom, and celery seed extracts (the formula was patented by 4Life Research Company, USA and named as AgePro), modulate the functional activity of natural killer (NK) cells in vivo. We found that this supplement, taken orally in two capsules twice a day for 30 days, significantly enhanced the cytotoxic activity of NK cells. This was evidenced by the increased NK cell-mediated killing of carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled K562 human myeloid leukemia cells. As expected, this effect was dependent on the ratio between the effector (E) (e.g., peripheral blood mononuclear cells (PBMCs)) and target (T) (e.g., K562) cells, illustrating maximal killing of K562 cells at a 50:1 E/T ratio. Of note, increased NK-mediated killing of K562 cells after taking AgePro correlated with increased perforin release, evidenced by the CD107a degranulation assay. In concordance with these findings, taking of AgePro for 1 month increased production of several cytokines and chemokines, including IL-1β, IL-1Rα, IL-6, IL-8, IL-10, IFN-γ, TNF-α, G-CSF, PDGF-AA, PDGF-AB/BB, GRO, MCP-1, MCP-3, and MIP-1α, in PBMCs co-cultured with K562 cells. Of note, increased production of the cytokines correlated with the activation state of PBMCs, as evidenced by increased expression of the surface activation markers (e.g., the interleukin-2 receptor alpha chain—CD25). A strong correlation was found between NK-based cytotoxic activity and the production of IL-1β, IL-6, TNF-α, and MIP-1α. Importantly, no increase in the aforementioned soluble factors and activation markers was detected in PBMCs cultured alone, thereby illustrating the potent immunoregulatory activity of AgePro only in the presence of the harmful target cells. Hematological parameters also remained unchanged over the entire study period. Collectively, we show herein the significant enhancement of the cytotoxic activity of NK cells against target tumor cells after taking AgePro for 1 month. Notably, this effect was observed for all age groups, including young, adult, and elderly participants. Moreover, a significant improvement in NK cytotoxic activity was also detected for participants with low basal (e.g., before taking AgePro) numbers of NK-mediated killing. The enhancement of NK-based cytotoxicity was associated with an increased release of several cytokines and chemokines involved in regulating a broad spectrum of mechanisms outside the cell-mediated cytotoxicity and killing of target cells. Of note, spontaneous activation of PBMCs, particularly NK cells, was not detected after taking AgePro. Given that spontaneous activation of autoreactive lymphocytes is a feature associated with autoimmunity and taking into account our data illustrating the AgePro-induced activation of NK cells detected only in the presence of the potentially harmful cells, we conclude that our innovative product exhibits potent immunoregulatory activity and high safety profile. Full article
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds: 3rd Edition)
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15 pages, 6304 KiB  
Article
Polydatin Alleviates Cyclophosphamide-Induced Mouse Immunosuppression by Promoting Splenic Lymphocyte Proliferation and Thymic T Cell Development and Differentiation
by Na Sun, Huimin Yan, Xiuping Liu, Xingdi Xu, Wei Zhao, Jing Zhang, Meng Wang, Yuxuan Liu and Lin Miao
Int. J. Mol. Sci. 2025, 26(6), 2800; https://doi.org/10.3390/ijms26062800 - 20 Mar 2025
Viewed by 699
Abstract
Immunosuppression increases disease risk, and the natural compound polydatin (PD) has been reported to modulate immune-related disorders. In cyclophosphamide-induced immunosuppressed mice, PD was evaluated for its immunomodulatory effects. Immune organ indices were measured, while H&E staining and ELISA assessed spleen pathology and serum [...] Read more.
Immunosuppression increases disease risk, and the natural compound polydatin (PD) has been reported to modulate immune-related disorders. In cyclophosphamide-induced immunosuppressed mice, PD was evaluated for its immunomodulatory effects. Immune organ indices were measured, while H&E staining and ELISA assessed spleen pathology and serum cytokine levels. The proliferation of splenic lymphocytes, both total and subpopulation, was determined using concanavalin A or lipopolysaccharide stimulation, with flow cytometry analyzing peripheral blood and splenic lymphocytes, thymic T cell subtypes, cell cycling, and bromodeoxyuridine incorporation. Western blotting was used to assess Ki67, PCNA expression, and MAPK activation. PD significantly alleviated cyclophosphamide-induced reductions in spleen and thymus indices, improved the organization of red and white pulp in the spleen, and restored TNF-α and IFN-γ levels. It reversed cyclophosphamide-induced cell cycle arrest, characterized by increased PCNA and decreased Ki67, and corrected the diminished numbers of B and T cells and the reduced CD4+/CD8+ ratio in the thymus. In vitro, PD directly promoted splenic lymphocyte proliferation and cell cycling via MAPK activation. Overall, our findings demonstrated that PD alleviated mouse immunosuppression by activating splenic lymphocyte proliferation and re-organizing thymic T cell development and differentiation. Full article
(This article belongs to the Section Molecular Pharmacology)
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12 pages, 528 KiB  
Article
Association of Inflammatory and Metabolic Markers with Mortality in Patients with Postoperative Femur Fractures in the Intensive Care Unit
by Metin Kilinc, Enes Çelik, Ibrahim Demir, Semih Aydemir and Hakan Akelma
Medicina 2025, 61(3), 538; https://doi.org/10.3390/medicina61030538 - 19 Mar 2025
Cited by 2 | Viewed by 627
Abstract
Background and Objectives: Postoperative femur fracture in elderly patients is associated with high morbidity and mortality, especially in the intensive care unit (ICU). Various factors, including demographic and laboratory parameters, may influence mortality in this population. The aim of this study was [...] Read more.
Background and Objectives: Postoperative femur fracture in elderly patients is associated with high morbidity and mortality, especially in the intensive care unit (ICU). Various factors, including demographic and laboratory parameters, may influence mortality in this population. The aim of this study was to evaluate the association of inflammatory and metabolic markers with mortality in ICU patients with postoperative femur fractures and to identify key predictors to enhance risk stratification and improve patient outcomes. Materials and Methods: In this retrospective single-center study, we analyzed 121 patients aged over 65 years with postoperative femur fractures who were admitted to the ICU between January 2023 and January 2024. Demographic and clinical data, including comorbidities, Charlson Comorbidity Index (CCI), and Acute Physiology and Chronic Health Evaluation (APACHE II) score, were collected. Laboratory parameters such as white blood cell count (WBC), albumin, C-reactive protein (CRP), D-dimer, Pan-Immune-Inflammation Value (PIV), CRP-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), and others were analyzed. Linear regression, logistic regression, and Receiver Operating Characteristic (ROC) analyses were performed to determine the predictive value of these markers for ICU mortality. Results: The mean age of the patients was 76.3 ± 9.6 years, and 52.1% were female. The most common comorbidities were hypertension (67.8%) and diabetes (49.6%). ICU mortality occurred in 24 patients (20%). Significant predictors of mortality included higher CRP (>62.8 mg/L), NLR (>10.0), PIV (>450), and APACHE II scores (>23) (p < 0.001 for all). Lower albumin levels (<2.5 g/dL) were strongly associated with increased mortality (p < 0.001). ROC analysis demonstrated that the APACHE II score had the highest predictive accuracy for mortality (AUC = 0.83), followed by albumin (AUC = 0.79) and PIV (AUC = 0.76). Extended ICU stay (>10 days) was also significantly correlated with increased mortality (p < 0.001). Conclusions: This study successfully demonstrates the utility of combining traditional clinical markers, such as APACHE II score, with novel inflammatory markers, such as PIV, CAR, and NLR, in predicting mortality in ICU patients following femur fracture surgery. The integration of emerging biomarkers with well-established scoring systems offers enhanced predictive accuracy and provides valuable insights into patient management. Full article
(This article belongs to the Section Intensive Care/ Anesthesiology)
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9 pages, 381 KiB  
Article
The Association of Systemic Inflammatory Response with Hepatitis B Vaccine Unresponsiveness
by Oguz Karabay, Kaan Furkan Hamarat, Gamze Guney Eskiler and Ayhan Aydin
Viruses 2025, 17(3), 338; https://doi.org/10.3390/v17030338 - 28 Feb 2025
Viewed by 607
Abstract
(1) Background: Hepatitis B virus (HBV) infection remains a major health challenge. Although vaccination protects people from HBV infection, 5–10% of people at risk of HBV infection and associated liver diseases do not respond to vaccination. The association of hematological indices with vaccine [...] Read more.
(1) Background: Hepatitis B virus (HBV) infection remains a major health challenge. Although vaccination protects people from HBV infection, 5–10% of people at risk of HBV infection and associated liver diseases do not respond to vaccination. The association of hematological indices with vaccine response is a crucial contributing factor in HBV-associated liver damage and the outcome of patients. In this context, we clinically assessed the interaction between inflammatory parameters and Hepatitis B vaccine response for the first time. (2) Methods: In total, 90 volunteers (44 non-responders and 46 responders) were included in this retrospective study. The demographic data and the hemogram parameters of the volunteers were recorded and statistically analyzed. Additionally, systemic inflammation index (SII), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) were calculated. (3) Results: Our results indicate that higher median levels of white blood cells (8.61), lymphocytes (2.37), neutrophils (5.71), and platelets (280) were determined in the non-responders compared to the responders. SII and NLR indices were significantly higher in the non-responders than in the responders (p < 0.05). (4) Conclusions: The non-responders exerted higher systemic inflammation indicators than the responders, and the NLR value partially distinguished Hepatitis B vaccine response. Nevertheless, further studies with larger cohorts are essential to confirm the clinical utility of systemic inflammatory response as a reliable criterion for predicting Hepatitis B vaccine responsiveness. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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15 pages, 1479 KiB  
Article
Obesity-Induced PVAT Dysfunction and Atherosclerosis Development: The Role of GHSR-1a in Increased Macrophage Infiltration and Adipocytokine Secretion
by Sorin Nicolae Peiu, Florin Zugun-Eloae, Bogdan Stoica, Ecaterina Anisie, Diana Gabriela Iosep, Mihai Danciu, Iustina Silivestru-Crețu, Fawzy Akad, Andrei Nicolae Avadanei, Laura Condur, Radu Florin Popa and Veronica Mocanu
J. Cardiovasc. Dev. Dis. 2025, 12(3), 87; https://doi.org/10.3390/jcdd12030087 - 26 Feb 2025
Viewed by 843
Abstract
In obesity, recent research revealed that increased expression of the growth hormone secretagogue receptor (GHSR) in macrophages plays a pivotal role in the development of meta-inflammation, promoting macrophage infiltration and pro-inflammatory polarization. This study aimed to examine the association between GHSR-1a expression in [...] Read more.
In obesity, recent research revealed that increased expression of the growth hormone secretagogue receptor (GHSR) in macrophages plays a pivotal role in the development of meta-inflammation, promoting macrophage infiltration and pro-inflammatory polarization. This study aimed to examine the association between GHSR-1a expression in atherosclerotic plaques and adjacent perivascular adipose tissue (PVAT) from 11 patients with obesity and peripheral artery disease (PAD) who underwent revascularization procedures. Immunohistochemistry was used to assess the expression of CD68, CD80, and CD14, while tissue homogenate levels of adiponectin, leptin, IL-6, and CRP were quantified via ELISA. Serum markers of inflammation were also measured. Among patients with GHSR-1a-positive (+) macrophages in atherosclerotic plaques, we observed significantly higher white blood cell counts and platelet-to-lymphocyte ratios in serum, a lower adiponectin-to-leptin ratio, and elevated IL-6 levels in both arterial and PVAT homogenates. Our findings suggest a link between GHSR-1a and macrophage/monocyte infiltration, macrophage polarization, and adipocytokine secretion in atherosclerotic plaques associated with obesity-induced PVAT dysfunction. Full article
(This article belongs to the Section Basic and Translational Cardiovascular Research)
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10 pages, 242 KiB  
Article
The Long-Term Survivorship and Cause of Failure of Metal-on-Metal Total Hip Arthroplasty
by Hiroki Wakabayashi, Masahiro Hasegawa, Yohei Naito, Shine Tone and Akihiro Sudo
Antibiotics 2025, 14(2), 161; https://doi.org/10.3390/antibiotics14020161 - 6 Feb 2025
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Abstract
Background: Complications associated with metal-on-metal (MOM) prostheses, such as adverse reactions to metal debris (ARMDs), include pseudotumor (PT) formation, metallosis, and soft tissue necrosis. High short-term failure rates have been reported for various MOM total hip arthroplasties (THAs) due to ARMDs. ARMDs in [...] Read more.
Background: Complications associated with metal-on-metal (MOM) prostheses, such as adverse reactions to metal debris (ARMDs), include pseudotumor (PT) formation, metallosis, and soft tissue necrosis. High short-term failure rates have been reported for various MOM total hip arthroplasties (THAs) due to ARMDs. ARMDs in MOM THAs can potentially lead to secondary failure modes, such as dislocation or infection. Objectives: This study aims to examine the cumulative incidence of revisions due to ARMDs and periprosthetic joint infection (PJI) in primary MOM total hip arthroplasty and to compare the outcomes of ARMD and PJI cases. Methods: Between 2006 and 2011, 247 primary MOM THAs were performed on 230 patients (39 men, 191 women) with a mean age of 64.1 years. The average follow-up duration was 10.5 years. Results: Thirty-eight hips were converted to metal-on-polyethylene articulation between 1.2 and 14.7 years postoperatively (mean: 7.2 years) due to pain, swelling, infection, and/or implant failure. Eight hips (3.2%) were complicated by infection, while 30 hips (12.1%) were diagnosed with ARMDs. Rheumatoid arthritis (RA) was significantly more prevalent in patients with PJI. Preoperative C-reactive protein (CRP) levels were significantly elevated in THAs diagnosed with PJI compared to ARMD cases. Additionally, the preoperative white blood cell (WBC) counts, neutrophil counts, and neutrophil-to-WBC ratios were significantly higher in THAs with PJI, while the lymphocyte-to-WBC ratios were significantly lower. Conclusion: The incidence of postoperative infection in MOM THA cases was 3.2%, with a notable occurrence of late-onset infections. Differentiating ARMDs from PJI in MOM THA cases remains crucial. Full article
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14 pages, 1645 KiB  
Article
Association of Altered Baseline Hematological Parameters with Adverse Tuberculosis Treatment Outcomes
by Arul Nancy Pandiarajan, Nathella Pavan Kumar, Kadar Moideen, Kannan Thiruvengadam, Syed Hissar, Shanmugam Sivakumar, Ramalingam Bethunaickan, Vijay Viswanathan, Hardy Kornfeld and Subash Babu
Pathogens 2025, 14(2), 146; https://doi.org/10.3390/pathogens14020146 - 4 Feb 2025
Viewed by 1253
Abstract
Tuberculosis (TB) treatment monitoring is an essential tool for effective TB treatment management. Identifying parameters that predict adverse TB treatment outcomes could significantly improve clinical management. The association of hematological parameters with poor TB treatment outcomes is not well defined. To study the [...] Read more.
Tuberculosis (TB) treatment monitoring is an essential tool for effective TB treatment management. Identifying parameters that predict adverse TB treatment outcomes could significantly improve clinical management. The association of hematological parameters with poor TB treatment outcomes is not well defined. To study the relationship of hematological parameters with TB treatment outcomes, we examined data from pulmonary tuberculosis (PTB) patients with successful (controls) and unsuccessful (cases) treatment outcomes. We enrolled 68 cases and 133 controls through a nested 1:2 case–control study, matching for age, sex, body mass index, diabetes status, alcohol and smoking. Hematological profiling showed significant difference in the absolute counts of white blood cells, lymphocytes, neutrophils and monocytes between cases and controls. In addition, increased neutrophil to lymphocyte ratio (NL) ratio and monocyte to lymphocyte (ML) ratio were present in cases in comparison to controls. Similarly, decreased hematocrit and red blood cell counts were detected in cases when compared with controls. Univariate and multivariate analysis demonstrated a significant association of absolute counts of WBC, neutrophils, monocytes, NL and ML ratios with poor treatment outcomes. The altered baseline hematological parameters are clearly associated with the poor TB treatment outcomes, showing potential for clinical prediction to enhance management of at-risk cases. Full article
(This article belongs to the Section Immunological Responses and Immune Defense Mechanisms)
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16 pages, 3472 KiB  
Article
The Development and Validation of a Nomogram for Predicting Sepsis Risk in Diabetic Patients with Urinary Tract Infection
by Hua-Qiao Tan, Xiang-Jie Duan, Wan Qu, Mi Shu, Guang-Yao Zhong, Li-Hong Liang, Dong-Mei Bin and Yu-Ming Chen
Medicina 2025, 61(2), 225; https://doi.org/10.3390/medicina61020225 - 27 Jan 2025
Viewed by 1367
Abstract
Background and Objectives: Urinary tract infection (UTI) is a common comorbidity in diabetic patients, making up one of the causes of sepsis. This study aims to develop a nomogram to predict the risk probability of sepsis in diabetic patients with UTI (DPUTIs). [...] Read more.
Background and Objectives: Urinary tract infection (UTI) is a common comorbidity in diabetic patients, making up one of the causes of sepsis. This study aims to develop a nomogram to predict the risk probability of sepsis in diabetic patients with UTI (DPUTIs). Materials and Methods: This is a retrospective observational study. Clinical data for DPUTIs were extracted from the Medical Information Mart for Intensive Care IV database. Eligible DPUTIs were randomly divided into training and validation cohorts in a 7:3 ratio. Independent prognostic factors for sepsis risk were determined using least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression. A corresponding nomogram based on these factors was constructed to predict sepsis occurrence in DPUTIs. The discrimination of the nomogram was assessed by multiple indicators, including the area under the receiver operating characteristic curve (AUC), net reclassification improvement index (NRI), and integrated discrimination improvement (IDI). In addition, a calibration curve and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. Results: A total of 1990 DPUTIs were included. Nine independent prognostic factors were identified as predictive factors for sepsis risk in DPUTIs. The prognostic factors included urine red blood cell classification (urine RBC cat), urine white blood cell classification (urine WBC cat), blood glucose, age, temperature, white blood cells (WBCs), sequential organ failure assessment (SOFA) score, lymphocytes, and hematocrit. The AUC, NRI, and IDI of the nomogram indicated robust discrimination. The calibration curve and Hosmer–Lemeshow test showed good calibration of the nomogram. The DCA curve demonstrated a better clinical utility of the nomogram. Conclusions: The nomogram established in this study helps clinicians predict the probability of sepsis in DPUTIs, providing evidence for optimizing the management of related risk factors. Full article
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