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Keywords = systemic inflammation index

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15 pages, 907 KB  
Article
Prognostic Impact of Postoperative Systemic Immune-Inflammation Index Changes in Epithelial Ovarian Cancer
by Young Eun Chung, E Sun Paik, Minji Kim, Na-Hyun Kim, Seongyun Lim, Jun-Hyeong Seo, Chel Hun Choi, Tae-Joong Kim, Jeong-Won Lee and Yoo-Young Lee
Cancers 2025, 17(21), 3422; https://doi.org/10.3390/cancers17213422 (registering DOI) - 24 Oct 2025
Abstract
Background: Epithelial ovarian cancer is an aggressive malignancy with poor prognosis despite advances in multimodal treatment. The systemic immune-inflammation index (SII) has emerged as a prognostic biomarker in various cancers; however, the impact of surgery-induced inflammatory changes remains unclear. Methods: This study evaluated [...] Read more.
Background: Epithelial ovarian cancer is an aggressive malignancy with poor prognosis despite advances in multimodal treatment. The systemic immune-inflammation index (SII) has emerged as a prognostic biomarker in various cancers; however, the impact of surgery-induced inflammatory changes remains unclear. Methods: This study evaluated the prognostic significance of postoperative changes in SII among patients with epithelial ovarian cancer undergoing primary surgery. Data from 374 patients treated at Samsung Medical Center and Kangbuk Samsung Hospital between 2016 and 2021 were retrospectively reviewed. SII was calculated from complete blood counts obtained within one month before surgery and on postoperative day 1. The percentage change in SII was analyzed, and the optimal cutoff was determined using receiver operating characteristic curve analysis. Survival outcomes were assessed using Kaplan–Meier and multivariable Cox regression models. Results: Patients with a postoperative SII increase > 98.4% (Group 2) had significantly poorer overall (HR = 1.86, p = 0.009) and progression-free survival (HR = 1.30, p = 0.112) compared with those with smaller changes (Group 1). Discussion: High-grade histology, serous subtype, and greater intraoperative blood loss were associated with higher postoperative SII. A marked postoperative increase in SII independently predicted poor survival, suggesting that dynamic inflammatory responses rather than static baseline levels provide additional prognostic information. Conclusions: Perioperative SII monitoring, easily obtainable from routine blood tests, may help identify high-risk patients who could benefit from intensified surveillance or adjuvant treatment. Prospective multicenter studies are warranted to validate these findings and explore whether perioperative modulation of systemic inflammation can improve outcomes. Full article
(This article belongs to the Special Issue Research on Surgical Treatment for Ovarian Cancer)
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12 pages, 639 KB  
Article
The Value of HALP Score, SII, and SIRI in Predicting the Need for Intensive Care and Assessing Disease Severity in Pediatric Diabetic Ketoacidosis Cases
by Muhammed Selçuk Sinanoğlu, Turgut Dolanbay, Bilgehan Demir, Süleyman Nogay, Can Celiloğlu and Muhammed Eyyüb Polat
Children 2025, 12(11), 1445; https://doi.org/10.3390/children12111445 (registering DOI) - 24 Oct 2025
Abstract
Objective: The aim of this study was to evaluate whether Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) scores, the Systemic Immune-Inflammation Index (SII), and the Systemic Inflammatory Response Index (SIRI) can predict intensive care unit (ICU) or inpatient admissions in pediatric diabetic ketoacidosis [...] Read more.
Objective: The aim of this study was to evaluate whether Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) scores, the Systemic Immune-Inflammation Index (SII), and the Systemic Inflammatory Response Index (SIRI) can predict intensive care unit (ICU) or inpatient admissions in pediatric diabetic ketoacidosis (DKA) cases and to determine their sensitivity and specificity. Methods: This retrospective study included 39 pediatric patients (<18 years) diagnosed with DKA (pH < 7.3, HCO3 < 15). HALP, SII, SIRI, and urine ketone values were collected from medical records. Statistical analyses included ROC curve analysis, correlation tests, and appropriate parametric or non-parametric comparisons to evaluate associations with 30-day outcomes. Results: The median age was 13 years (IQR: 8–15), 56.4% were male, and 64.1% required ICU monitoring. ICU patients had significantly lower pH (p = 0.005) and HCO3 (p = 0.012) and significantly higher monocyte, SII, and SIRI values (all p ≤ 0.018). ROC analysis showed SIRI had the highest predictive power for ICU admission (cut-off: 3911; sensitivity: 76%; specificity: 85.7%), followed by SII. HALP scores did not demonstrate any value in assessingdisease severity for predicting ICU admission (AUC = 0.25). Conclusion: SIRI and SII are reliable predictors of ICU admission in pediatric DKA. HALP scores do not predict ICU admission and should not be considered a marker of disease severity. Incorporating SIRI and SII into clinical decision-making may improve early risk stratification. Prospective multicenter studies are warranted to validate these results. Full article
(This article belongs to the Section Pediatric Emergency Medicine & Intensive Care Medicine)
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11 pages, 394 KB  
Article
Association Between Heavy Metals Exposure and Elevated High-Sensitivity C-Reactive Protein: Mediating Role of Body Mass Index
by Seong-Uk Baek and Jin-Ha Yoon
Biomolecules 2025, 15(11), 1491; https://doi.org/10.3390/biom15111491 - 23 Oct 2025
Abstract
Heavy metal exposure is linked to obesity and systemic inflammation. This study explored the mediating role of body mass index (BMI) in the association of heavy metal exposure with high-sensitivity C-reactive protein (hs-CRP). Blood levels of mercury (Hg), cadmium (Cd), and lead (Pb) [...] Read more.
Heavy metal exposure is linked to obesity and systemic inflammation. This study explored the mediating role of body mass index (BMI) in the association of heavy metal exposure with high-sensitivity C-reactive protein (hs-CRP). Blood levels of mercury (Hg), cadmium (Cd), and lead (Pb) were assessed in a nationwide sample of 4521 adults. Linear regressions were employed to examine associations among blood heavy metal levels, BMI, and hs-CRP levels. Mediation analyses were conducted to estimate the indirect effect of exposure to each heavy metal on the elevation of hs-CRP through an increase in BMI. The median (Q1; Q3) values for blood levels of heavy metals were 3.15 (2.10; 4.84) for Hg (μg/L), 0.95 (0.63; 1.38) for Cd (μg/L), and 1.67 (1.28; 2.21) for Pb (μg/dL). Blood Hg level was associated with both BMI (adjusted β: 0.73; 95% CI [confidence interval]: 0.51; 0.96) and a log-transformed hs-CRP level (adjusted β: 0.07; 95% CI: 0.02; 0.13). Blood Cd and Pb levels showed no clear associations with BMI and hs-CRP. The indirect effect of Hg exposure on hs-CRP via BMI was 0.069 (95% CI: 0.037; 0.102), and that of the direct effect was 0.003 (95% CI: −0.001; 0.007), with BMI accounting for 95.7% (95% CI: 88.6%, 102.0%) of the total association between Hg levels and hs-CRP levels. Hg exposure was linked to increased hs-CRP levels, with elevated BMI explaining most of this association. This research offers insights into the mechanisms through which Hg contributes to systemic inflammation, underscoring the potential role of BMI as a key mediator. Full article
(This article belongs to the Section Biological Factors)
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14 pages, 609 KB  
Article
Assessment of Hidden Nutritional Burden: High Prevalence of Disease-Related Malnutrition in Older Adults Without Cognitive Impairment Living in Nursing Homes in Madrid—A Multicentre Study
by Mar Ruperto, Dilek Ongan, Esmeralda Josa and Amalia Tsagari
Nutrients 2025, 17(21), 3325; https://doi.org/10.3390/nu17213325 - 22 Oct 2025
Abstract
Background/Objectives: Nutritional disorders are common conditions in older people. This study aimed to determine nutritional disorders in a Mediterranean cohort of nursing home residents without cognitive or functional impairment. Methods: A multicentre cross-sectional observational study was conducted in 10 Spanish geriatric centres. Socio-health, [...] Read more.
Background/Objectives: Nutritional disorders are common conditions in older people. This study aimed to determine nutritional disorders in a Mediterranean cohort of nursing home residents without cognitive or functional impairment. Methods: A multicentre cross-sectional observational study was conducted in 10 Spanish geriatric centres. Socio-health, clinical, and laboratory data were recorded from the participants’ medical records. The Mini-Nutritional Assessment (MNA) and Global Leadership Initiative in Nutrition (GLIM) diagnostic criteria [weight loss and serum C-reactive protein (CRP)] were used. Frailty risk was assessed using the FRAIL questionnaire. Anthropometric parameters [body mass index, weight loss, triceps skinfold thickness (TSF), muscle mass circumference (MAMC), and calf-circumference] were evaluated. Body composition [hydration pattern, fat-free mass, muscle mass (MM), fat mass, and phase angle (PhA)] was measured by bioelectrical impedance analysis. Laboratory parameters, such as haemoglobin, total lymphocyte count, serum albumin, transferrin, and CRP, were recorded. Participants were classified into two groups: the disease-related malnutrition (DRM) group and the no-DRM group. Using multivariate regression analysis, predictive factors for nutritional status were tested. Results: Among 340 participants, 63.2% were over 85 years old, 28.2% were men, and the median length of stay was 24 months (range: 6–119). Nutritional risk or malnutrition, as assessed by the MNA, was present in 60.8% of the residents. DRM was diagnosed in 39.4%, and frailty risk was diagnosed in 57.6%. Older adults with DRM had significantly lower MAMC, calfcircumference, MM, and serum albumin, as well as higher CRP concentrations compared with their No-DRM counterparts (all, at least, p < 0.05). The frailty risk (OR = 3.317), MM (OR = 0.732), PhA (OR = 0.033), serum albumin (OR = 0.070), and EuroQol visual analogue scale (OR = 0.961) were risk predictors of DRM in nursing home residents. Conclusions: This study supports the importance of conducting comprehensive nutritional assessments to ensure the earliest recognition of nutrition disorders in nursing homes. Older adults with DRM had greater unintentional weight loss, inflammation, and a high risk of frailty, as well as reduced MM, compared to those without DRM. Subclinical low-grade systemic inflammation is a risk factor for DRE and functional decline in older adults living in nursing homes. The generalisation of the study results is limited to institutionalised older adults without cognitive impairment who are clinically stable and functionally independent. Full article
(This article belongs to the Special Issue Nutritional Risk in Older Adults in Different Healthcare Settings)
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22 pages, 1939 KB  
Article
Development and Validation of Prognostic Models for Treatment Response of Patients with B-Cell Lymphoma: Standard Statistical and Machine-Learning Approaches
by Adugnaw Zeleke Alem, Itismita Mohanty, Nalini Pati, Cameron Wellard, Eliza Chung, Eliza A. Hawkes, Zoe K. McQuilten, Erica M. Wood, Stephen Opat and Theophile Niyonsenga
J. Clin. Med. 2025, 14(20), 7445; https://doi.org/10.3390/jcm14207445 - 21 Oct 2025
Viewed by 125
Abstract
Background: Achieving a complete response after therapy is an important predictor of long-term survival in lymphoma patients. However, previous predictive models have primarily focused on overall survival (OS) and progression-free survival (PFS), often overlooking treatment response. Predicting the likelihood of complete response before [...] Read more.
Background: Achieving a complete response after therapy is an important predictor of long-term survival in lymphoma patients. However, previous predictive models have primarily focused on overall survival (OS) and progression-free survival (PFS), often overlooking treatment response. Predicting the likelihood of complete response before initiating therapy can provide more immediate and actionable insights. Thus, this study aims to develop and validate predictive models for treatment response to first-line therapy in patients with B-cell lymphomas. Methods: The study used 2763 patients from the Lymphoma and Related Diseases Registry (LaRDR). The data were randomly divided into training (n = 2221, 80%) and validation (n = 553, 20%) cohorts. Seven algorithms: logistic regression, K-nearest neighbor, support vector machine, random forest, Naïve Bayes, gradient boosting machine, and extreme gradient boosting were evaluated. Model performance was assessed using discrimination and classification metrics. Additionally, model calibration and clinical utility were evaluated using the Brier score and decision curve analysis, respectively. Results: All models demonstrated comparable performance in the validation cohort, with area under the curve (AUC) values ranging from 0.69 to 0.70. A nomogram incorporating the six variables, including stage, lactate dehydrogenase, performance status, BCL2 expression, anemia, and systemic immune-inflammation index, achieved an AUC of 0.70 (95% CI: 0.65–0.75), outperforming the international prognostic index (IPI: AUC = 0.65), revised IPI (AUC = 0.61), and NCCN-IPI (AUC = 0.63). Decision curve analysis confirmed the nomogram’s superior net benefit over IPI-based systems. Conclusions: While our nomogram demonstrated improved discriminative performance and clinical utility compared to IPI-based systems, further external validation is needed before clinical integration. Full article
(This article belongs to the Section Oncology)
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12 pages, 534 KB  
Article
Beyond Hyperferritinemia: Evaluating Ferritin as a Predictor of Advanced Therapy in Adult-Onset Still’s Disease
by Ji-Hyoun Kang
Diagnostics 2025, 15(20), 2630; https://doi.org/10.3390/diagnostics15202630 - 18 Oct 2025
Viewed by 194
Abstract
Background: Ferritin is a hallmark biomarker of systemic inflammation in adult-onset Still’s disease (AOSD), but its potential role in guiding escalation to advanced therapy has not been established. This study aimed to evaluate whether ferritin, alone or in combination with simple clinical variables, [...] Read more.
Background: Ferritin is a hallmark biomarker of systemic inflammation in adult-onset Still’s disease (AOSD), but its potential role in guiding escalation to advanced therapy has not been established. This study aimed to evaluate whether ferritin, alone or in combination with simple clinical variables, could predict the need for advanced therapy in AOSD. Methods: A retrospective review was conducted of 113 patients with AOSD fulfilling the Yamaguchi criteria at Chonnam National University Hospital. Baseline demographic, clinical, and laboratory data were collected at the index episode. The primary endpoint was defined as the use of advanced therapy—namely, intravenous immunoglobulin (IVIG), anakinra, or tocilizumab—during the index hospitalization. Ferritin was log-transformed and analyzed both as a continuous variable and in quartiles. A pragmatic Ferritin-Guided Escalation Rule (FGER) points score was constructed by combining ferritin quartiles with malignancy and ANA status. Logistic regression, Fisher’s exact test, and bootstrapped receiver operating characteristic (ROC) analyses were applied. Results: The cohort was predominantly male (64.6%) with a mean age of 44.9 years. Median ferritin was 4626.6 µg/L (IQR 1169.3–14,239.8). Advanced therapy was required in 15 patients (13.3%), including 14 who received tocilizumab, 1 IVIG, and 1 anakinra. When stratified by ferritin quartiles, advanced therapy occurred in 10.7% of Q1, 21.4% of Q2, 10.7% of Q3, and 10.7% of Q4 patients. Comparison of Q4 versus Q1–Q3 yielded an odds ratio of 0.67 (p = 0.47). Discriminatory performance was poor for both continuous ferritin (AUC 0.49, 95% CI 0.30–0.68) and the FGER points score (AUC 0.51, 95% CI 0.32–0.71). Calibration analysis also demonstrated limited agreement between predicted and observed risks. Conclusions: In this retrospective cohort, ferritin—whether assessed continuously, by quartiles, or within a simple bedside score—did not predict the need for advanced therapy (IVIG, anakinra, or tocilizumab) in AOSD. Although advanced therapies were administered to 13.3% of patients, ferritin was not a reliable escalation biomarker. Full article
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39 pages, 3698 KB  
Review
From Steatosis to Immunosenescence: The Impact of Metabolic Dysfunction on Immune Aging in HIV and Non-HIV Populations
by Carlo Acierno, Maria Frontuto, Giulio Francesco De Stefano, Ana Erezanu, Andrea Limone, Simona Morella, Francesco Picaro, Donatella Palazzo and Michele Gilio
Biomedicines 2025, 13(10), 2513; https://doi.org/10.3390/biomedicines13102513 - 15 Oct 2025
Viewed by 453
Abstract
Immunosenescence, defined as the progressive decline of immune function with age, is increasingly recognized as a determinant of morbidity in people living with HIV (PLWH) and in individuals with metabolic dysfunction. The coexistence of chronic viral infection and systemic metabolic alterations—including metabolic dysfunction-associated [...] Read more.
Immunosenescence, defined as the progressive decline of immune function with age, is increasingly recognized as a determinant of morbidity in people living with HIV (PLWH) and in individuals with metabolic dysfunction. The coexistence of chronic viral infection and systemic metabolic alterations—including metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus—creates a pro-inflammatory state (“metaflammation”) that accelerates immune aging. This narrative review synthesizes current clinical, translational, and experimental evidence on the cellular, molecular, and metabolic mechanisms underlying immunosenescence in HIV-positive and HIV-negative populations with metabolic dysfunction. Key converging pathways include chronic inflammation, mitochondrial dysfunction, microbial translocation, and altered immunometabolic signaling, leading to features such as CD8+CD28 T-cell expansion, reduced CD4/CD8 ratios, and impaired vaccine responses. Biomarkers such as iAge, IMM-AGE, and the triglyceride–glucose (TyG) index have emerged as promising tools to quantify immune aging beyond chronological measures. Understanding these interconnected mechanisms offers opportunities for targeted interventions—such as metabolic reprogramming, microbiota modulation, and geroscience-based strategies—aimed at preserving immune resilience and promoting healthy aging in high-risk populations. Full article
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12 pages, 256 KB  
Article
Inflammatory and Nutritional Markers Predicting Pathological Complete Response to Neoadjuvant Therapy in HER2-Positive Breast Cancer: A Multicenter Real-World Study
by Zeliha Birsin, İsmail Nazlı, Onur Alkan, Hülya Odabaşı Bükün, Murat Günaltılı, Emir Çerme, Vali Aliyev, Selin Cebeci, Seda Jeral, Hamza Abbasov, Türkkan Evrensel, Çiğdem Papila, Berrin Papila, Ceyda Sönmez Wetherilt, Nebi Serkan Demirci and Özkan Alan
J. Clin. Med. 2025, 14(20), 7271; https://doi.org/10.3390/jcm14207271 - 15 Oct 2025
Viewed by 276
Abstract
Background: Pathological complete response (pCR) following neoadjuvant therapy (NAT) is a key surrogate marker for long-term outcomes in HER2-positive breast cancer. Identifying clinical and biological predictors of pCR, including systemic inflammatory and nutritional markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), [...] Read more.
Background: Pathological complete response (pCR) following neoadjuvant therapy (NAT) is a key surrogate marker for long-term outcomes in HER2-positive breast cancer. Identifying clinical and biological predictors of pCR, including systemic inflammatory and nutritional markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-albumin ratio (NAR), C-reactive protein-to-albumin ratio (CAR), systemic immune-inflammation index (SII), and prognostic nutritional index (PNI), may help refine treatment strategies and improve patient outcomes. Methods: We retrospectively analyzed 174 patients with stage II–III HER2-positive breast cancer who received neoadjuvant anti-HER2-based regimens at multiple centers between 2010 and 2025. Demographic, clinicopathological, and laboratory data were collected, and inflammatory and nutritional indices (NLR, PLR, LMR, NAR, CAR, SII, PNI) were calculated. Predictors of pCR were evaluated using univariate and multivariate logistic regression analyses. Results: Overall, 49% of patients achieved pCR. In multivariate analysis, independent predictors of pCR were hormone receptor negativity, smaller tumor size, HER2 IHC 3+ expression, dual HER2 blockade, and a higher prognostic nutritional index (PNI ≥ 55). In contrast, systemic inflammatory indices such as NLR, PLR, LMR, NAR, CAR, and SII were not significantly associated with pCR. Conclusions: This multicenter real-world study demonstrates that conventional inflammatory markers have limited predictive value, whereas the PNI emerges as a simple and practical biomarker reflecting nutritional and immune status. Integrating PNI with clinicopathological factors may enhance risk stratification and help guide individualized neoadjuvant treatment strategies in HER2-positive breast cancer. Full article
(This article belongs to the Section Oncology)
10 pages, 402 KB  
Article
The Role of Immature Granulocytes in Fibromyalgia: An Indicator of Subclinical Inflammation?
by Mehmet Serhat Topaloğlu, Medeni Arpa, Bayram Şen, Hacer Bilgin Topaloğlu and Osman Cüre
Biomedicines 2025, 13(10), 2511; https://doi.org/10.3390/biomedicines13102511 - 15 Oct 2025
Viewed by 354
Abstract
Background: Fibromyalgia (FM) is a chronic musculoskeletal disorder characterized by widespread body pain and various symptoms. Its etiology remains unclear to date. It has been associated with various pathogenic mechanisms, primarily inflammation. Immature granulocytes (IGs) have been proposed as a potential biomarker, playing [...] Read more.
Background: Fibromyalgia (FM) is a chronic musculoskeletal disorder characterized by widespread body pain and various symptoms. Its etiology remains unclear to date. It has been associated with various pathogenic mechanisms, primarily inflammation. Immature granulocytes (IGs) have been proposed as a potential biomarker, playing a role in both inflammatory responses and prognosis in numerous diseases. No other study has investigated the count of immature granulocytes (IG#) and percentage of immature granulocytes (IG%) in FM patients. The aim of this study is to investigate the IG# and IG% in FM patients and to evaluate the relationship between these parameters and disease parameters. Methods: This retrospective observational study included 95 patients diagnosed with FM and 63 healthy control subjects matched for body mass index and gender. Biochemical, hematological parameters, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and other inflammatory markers were recorded for both groups. Fibromyalgia Survey Diagnostic Criteria and Severity Scale (FSDC) and Fibromyalgia Impact Questionnaire (FIQ) scores were recorded for FM patients. Results: In FM patients, the IG% and IG# were significantly higher than in the healthy control group (p < 0.001, p: 0.006, respectively). There was no significant difference between the CRP and ESR values of the two groups. The platelet large cell count (PLCC) was significantly lower in the FM group (p < 0.032). Conclusions: IG levels can be used as a systemic early, sensitive, and low-cost marker in patients with FM. Based on our current knowledge, and considering the heterogeneous nature of FM, IG levels may serve as a meaningful tool in identifying subgroup elements reflecting an inflammatory phenotype. However, these findings require further validation through larger sample size, prospective studies, and advanced analyses including cytokine levels. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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14 pages, 1530 KB  
Article
miR-129 as a Molecular Biomarker in Gastric Cancer and Its Association with Neurodegenerative and Vascular Pathology
by Sabrina Birsan, Adrian-Gheorghe Boicean, Paula Anderco, Cristian Ichim, Samuel Bogdan Todor, Roman Iulian, Blanca Grama, Anca-Rafila Stîngaciu, Olga Brusnic, Tiberia Ilias and Corina Roman-Filip
Life 2025, 15(10), 1603; https://doi.org/10.3390/life15101603 - 14 Oct 2025
Viewed by 341
Abstract
Background: MicroRNA-129 (miR-129) is a tumor suppressor involved in regulating oncogenic pathways, but its role in gastric adenocarcinoma and its potential connections to vascular and neurological dysfunction remain insufficiently defined. Objectives: To assess gastric juice-derived miR-129 as a diagnostic and prognostic biomarker for [...] Read more.
Background: MicroRNA-129 (miR-129) is a tumor suppressor involved in regulating oncogenic pathways, but its role in gastric adenocarcinoma and its potential connections to vascular and neurological dysfunction remain insufficiently defined. Objectives: To assess gastric juice-derived miR-129 as a diagnostic and prognostic biomarker for gastric cancer and to explore its associations with systemic inflammation, vascular impairment, and neurodegenerative changes. Methods: A prospective study was conducted in 38 patients undergoing upper gastrointestinal endoscopy (22 with histologically confirmed gastric adenocarcinoma, 16 controls). Gastric juice was aspirated prior to biopsy, and miR-129-2-3p expression was quantified by means of RT-qPCR normalized to U6 RNA. Tumor stage, serum biomarkers (CEA, CA 19-9, LDH, and CRP), carotid index (Doppler ultrasound), and neuroimaging (MRI) were recorded. Statistical analyses included ANOVA, Mann–Whitney U, ROC curve analysis, and correlation testing. Results: miR-129 expression was significantly reduced in gastric cancer compared with controls (ANOVA: F(3,34) = 3.70, p = 0.021, η2 = 0.25). ΔCt values increased progressively from controls to T2–T4 tumors, indicating stage-dependent downregulation. ROC analysis demonstrated moderate diagnostic performance (AUC = 0.75, 95% CI 0.54–0.92). Lower miR-129 levels correlated inversely with serum tumor markers (CEA, CA 19-9), LDH, and CRP. Patients with elevated carotid index (>1.3) and abnormal brain imaging findings exhibited significantly lower miR-129 expression (both p < 0.05). Conclusion: Gastric juice-derived miR-129 is downregulated in gastric adenocarcinoma, with progressive decline across tumor stages. Its inverse association with systemic tumor and inflammatory markers, as well as vascular and neurological impairment, suggests that miR-129 may function as a minimally invasive, multi-system biomarker for integrated cancer and vascular–neurological risk assessment. Full article
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23 pages, 2027 KB  
Article
Bayesian Network Modeling of Environmental, Social, and Behavioral Determinants of Cardiovascular Disease Risk
by Hope Nyavor and Emmanuel Obeng-Gyasi
Int. J. Environ. Res. Public Health 2025, 22(10), 1551; https://doi.org/10.3390/ijerph22101551 - 12 Oct 2025
Viewed by 506
Abstract
Background: Cardiovascular disease (CVD) is the leading global cause of death and is shaped by interacting biological, environmental, lifestyle, and social factors. Traditional models often treat risk factors in isolation and may miss dependencies among exposures and biomarkers. Objective: To map interdependencies among [...] Read more.
Background: Cardiovascular disease (CVD) is the leading global cause of death and is shaped by interacting biological, environmental, lifestyle, and social factors. Traditional models often treat risk factors in isolation and may miss dependencies among exposures and biomarkers. Objective: To map interdependencies among environmental, social, behavioral, and biological predictors of CVD risk using Bayesian network models. Methods: A cross-sectional analysis was conducted using NHANES 2017–2018 data. After complete-case procedures, the analytic sample included 601 adults and 22 variables: outcomes (systolic/diastolic blood pressure, total/LDL/HDL cholesterol, triglycerides) and predictors (BMI, C-reactive protein (CRP), allostatic load, Dietary Inflammatory Index, income, education, age, gender, race, smoking, alcohol, and serum lead, cadmium, mercury, and PFOA). Spearman’s correlations summarized pairwise associations. Bayesian networks were learned with two approaches: Grow–Shrink (constraint-based) and Hill-Climbing (score-based, Bayesian Gaussian equivalent score). Network size metrics included number of nodes, directed edges, average neighborhood size, and Markov blanket size. Results: Correlation screening reproduced expected patterns, including very high systolic–diastolic concordance (p ≈ 1.00), strong LDL–total cholesterol correlation (p = 0.90), inverse HDL–triglycerides association, and positive BMI–CRP association. The final Hill-Climbing network contained 22 nodes and 44 directed edges, with an average neighborhood size of ~4 and an average Markov blanket size of ~6.1, indicating multiple indirect dependencies. Across both learning algorithms, BMI, CRP, and allostatic load emerged as central nodes. Environmental toxicants (lead, cadmium, mercury, PFOS, PFOA) showed connections to sociodemographic variables (income, education, race) and to inflammatory and lipid markers, suggesting patterned exposure linked to socioeconomic position. Diet and stress measures were positioned upstream of blood pressure and triglycerides in the score-based model, consistent with stress-inflammation–metabolic pathways. Agreement across algorithms on key hubs (BMI, CRP, allostatic load) supported network robustness for central structures. Conclusions: Bayesian network modeling identified interconnected pathways linking obesity, systemic inflammation, chronic stress, and environmental toxicant burden with cardiovascular risk indicators. Findings are consistent with the view that biological dysregulation is linked with CVD and environmental or social stresses. Full article
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31 pages, 2225 KB  
Review
Interferons in Autoimmunity: From Loss of Tolerance to Chronic Inflammation
by Grigore Mihaescu, Gratiela Gradisteanu Pircalabioru, Claudiu Natanael Roznovan, Lia-Mara Ditu, Mihaela Maria Comanici and Octavian Savu
Biomedicines 2025, 13(10), 2472; https://doi.org/10.3390/biomedicines13102472 - 11 Oct 2025
Viewed by 348
Abstract
Interferons (IFNs) are key cytokines at the intersection of innate and adaptive immunity. While their antiviral and antitumor roles are well recognized, emerging evidence implicates IFNs—particularly types I, II, and III—in the initiation and progression of autoimmune diseases (ADs). This review synthesizes current [...] Read more.
Interferons (IFNs) are key cytokines at the intersection of innate and adaptive immunity. While their antiviral and antitumor roles are well recognized, emerging evidence implicates IFNs—particularly types I, II, and III—in the initiation and progression of autoimmune diseases (ADs). This review synthesizes current data on IFN biology, their immunoregulatory and pathogenic mechanisms, and their contributions to distinct AD phenotypes. We conducted a comprehensive review of peer-reviewed literature on IFNs and autoimmune diseases, focusing on publications indexed in PubMed and Scopus. Studies on molecular pathways, immune cell interactions, disease-specific IFN signatures, and clinical correlations were included. Data were extracted and thematically organized by IFN type, signaling pathway, and disease context, with emphasis on rheumatic and systemic autoimmune disorders. Across systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, systemic sclerosis, idiopathic inflammatory myopathies, multiple sclerosis, type 1 diabetes, psoriasis, and inflammatory bowel diseases, IFNs were consistently associated with aberrant activation of pattern recognition receptors, sustained expression of interferon-stimulated genes (ISGs), and dysregulated T cell and B cell responses. Type I IFNs often preceded clinical onset, suggesting a triggering role, whereas type II and III IFNs modulated disease course and severity. Notably, IFNs exhibited dual immunostimulatory and immunosuppressive effects, contingent on tissue context, cytokine milieu, and disease stage. IFNs are central mediators in autoimmune pathogenesis, functioning as both initiators and amplifiers of chronic inflammation. Deciphering the context-dependent effects of IFN signaling may inform targeted therapeutic strategies and advance precision immunomodulation in autoimmune diseases. Full article
(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 3rd Edition)
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12 pages, 842 KB  
Article
Integrating Nutrition, Inflammation, and Immunity: The CALLY Index as a Novel Prognostic Biomarker in Acute Geriatric Care
by Francesca Mancinetti, Anna Giulia Guazzarini, Martina Gaspari, Michele Francesco Croce, Rocco Serra, Patrizia Mecocci and Virginia Boccardi
Nutrients 2025, 17(20), 3192; https://doi.org/10.3390/nu17203192 - 10 Oct 2025
Viewed by 360
Abstract
Background/Objectives: Malnutrition, systemic inflammation, and immune dysfunction are key determinants of adverse outcomes in older adults following acute illness. Composite biomarkers integrating these domains could enhance early risk stratification. This study investigates, for the first time in acute geriatric care, the prognostic value [...] Read more.
Background/Objectives: Malnutrition, systemic inflammation, and immune dysfunction are key determinants of adverse outcomes in older adults following acute illness. Composite biomarkers integrating these domains could enhance early risk stratification. This study investigates, for the first time in acute geriatric care, the prognostic value of the C-reactive protein–albumin–lymphocyte (CALLY) index—a composite marker of nutritional, inflammatory, and immune status—in predicting short-term survival. Methods: We retrospectively analyzed 264 patients admitted to the acute geriatrics ward of Santa Maria della Misericordia Hospital in Perugia. The CALLY index was calculated as: (Albumin × Lymphocytes)/(CRP × 104). The optimal prognostic cut-off was determined using receiver operating characteristic (ROC) curve analysis. Three-month survival was assessed by Kaplan–Meier analysis. Results: The cohort included 167 women (63.3%) and 97 men (36.7%), with a mean age of 88.0 ± 6.4 years. At 3-month follow-up, 80 patients (30.3%) had died. The CALLY index showed an area under the ROC curve of 0.647 (95% CI: 0.576–0.718; p < 0.001), with a cut-off of 0.055 (sensitivity: 68.5%, specificity: 46.3%). Among deceased patients, 42.5% had a CALLY index <0.055. After multivariable adjustment, a lower CALLY index remained independently associated with increased mortality (B = −0.805; OR = 0.45; 95% CI: 0.215–0.930; p = 0.031). Kaplan–Meier analysis demonstrated significantly higher survival in patients with a CALLY index ≥ 0.055 (Log-rank test: 13.71; p < 0.001). Conclusions: The CALLY index shows a modest but statistically significant discriminative ability for predicting short-term mortality in acutely ill older adults. As a simple, low-cost marker derived from routine laboratory tests, it holds potential for integration into clinical workflows to guide nutritional, metabolic, and prognostic management strategies in geriatric acute care. Full article
(This article belongs to the Special Issue Nutritional Support for Critically Ill Patients)
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16 pages, 1105 KB  
Article
Chronic Kidney Disease and Oral Health: A Cross-Sectional Study
by Michele Basilicata, Manuela Di Lauro, Giovanni Bruno, Kevin Cornali, Giulia Marrone, Claudia Masci, Giuseppe Troiano, Simone Manca di Villahermosa, Anna Paola Mitterhofer, Patrizio Bollero and Annalisa Noce
Appl. Sci. 2025, 15(19), 10804; https://doi.org/10.3390/app151910804 - 8 Oct 2025
Viewed by 504
Abstract
Objective: This pilot study investigated the association between chronic kidney disease (CKD) and oral health, focusing on the prevalence and severity of periodontal disease (PD) in the different CKD stages. Moreover, we explored how systemic alterations related to kidney dysfunction may influence oral [...] Read more.
Objective: This pilot study investigated the association between chronic kidney disease (CKD) and oral health, focusing on the prevalence and severity of periodontal disease (PD) in the different CKD stages. Moreover, we explored how systemic alterations related to kidney dysfunction may influence oral conditions. Methods: A cross-sectional observational study was conducted on seventy-five adult CKD patients (stages G1–G5) under conservative therapy. Participants underwent clinical, biochemical, and dental assessments. Periodontal parameters, such as the plaque index, bleeding on probing, clinical attachment loss, and gingival recession, were evaluated. Results: A significant inverse relationship was found between the estimated glomerular filtration rate (e-GFR) and PD severity, plaque index, and gingival inflammation. Advanced CKD patients exhibited a higher prevalence of generalized gingivitis and more severe PD stages and grades. Patients with e-GFR below 44 mL/min/1.73 m2 had a 3.3-fold higher risk of developing PD. In our population, the prevalence of xerostomia and dysgeusia was 45% and 15%, respectively, with taste alteration correlating directly with declining kidney function. Conclusions: CKD patients demonstrate compromised oral health, with an increased risk of PD. Renal dysfunction appears to be a significant factor influencing the onset and progression of PD. Further studies are necessary to clarify the underlying mechanisms and to develop integrated management strategies. Full article
(This article belongs to the Section Applied Dentistry and Oral Sciences)
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16 pages, 1095 KB  
Article
Inflammation-Based Cell Ratios Beyond White Blood Cell Count for Predicting Postimplantation Syndrome After EVAR and TEVAR
by Ebubekir Sönmez, İzatullah Jalalzai and Ümit Arslan
Int. J. Mol. Sci. 2025, 26(19), 9753; https://doi.org/10.3390/ijms26199753 - 7 Oct 2025
Viewed by 577
Abstract
Postimplantation syndrome (PIS) is an early inflammatory response following endovascular stent-graft implantation (EVAR and TEVAR), defined by culture-negative fever and leukocytosis. The patient’s preoperative inflammatory status is thought to play a central role in its development. This study aimed to evaluate whether the [...] Read more.
Postimplantation syndrome (PIS) is an early inflammatory response following endovascular stent-graft implantation (EVAR and TEVAR), defined by culture-negative fever and leukocytosis. The patient’s preoperative inflammatory status is thought to play a central role in its development. This study aimed to evaluate whether the systemic inflammatory response index (SIRI) and the eosinophil-to-lymphocyte ratio (ELR) can serve as preoperative predictors of PIS. Clinical data from 300 patients who underwent aortic endograft implantation and laboratory results obtained 24 h before the procedure, and at 24 h, 72 h, and 1 week postoperatively, were prospectively recorded. PIS was defined as culture-negative fever ≥ 37.8 °C accompanied by leukocytosis ≥ 12,000/µL. Inflammation-based indices derived from complete blood count (SIRI and ELR), along with serum C-reactive protein (CRP) and albumin levels, were compared between patients with and without PIS. Logistic regression and receiver operating characteristic (ROC) analyses were performed to identify independent predictors. PIS developed in 55 patients (18.3%). Patients with PIS were younger (70.1 ± 8.6 vs. 72.7 ± 7.3 years; p = 0.042) and had larger aneurysm diameters and greater mural thrombus thickness. Preoperatively, leukocyte count, SIRI, and CRP levels were significantly higher in patients who developed PIS, whereas ELR and albumin levels were lower. Multivariable analysis showed that a larger aneurysm diameter (OR: 1.2; 95% CI: 1.0–1.3; p = 0.003), greater mural thrombus thickness (OR: 1.3; 95% CI: 1.0–1.6; p = 0.012), EVAR procedure (OR: 3.7; 95% CI: 1.2–6.3; p = 0.033), elevated SIRI (OR: 1.9; 95% CI: 1.2–3.1; p = 0.005), and higher CRP (OR: 1.4; 95% CI: 1.1–3.2; p = 0.003) were significantly associated with PIS. In contrast, increasing age, higher ELR, and higher albumin levels were associated with a reduced risk of PIS. Simple biomarkers routinely obtained from standard laboratory tests can contribute meaningfully to the preoperative prediction and postoperative identification of PIS. Their integration into risk stratification models and confirmation against definitive diagnostic criteria will require validation in larger, multicenter studies. Full article
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