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25 pages, 1966 KB  
Article
Monocyte-Containing Inflammatory Indices Show Stronger Association with 30-Day Mortality than the Systemic Immune-Inflammation Index in Elderly Sepsis: A Single-Center Retrospective Observational Cohort Study
by Alexandru-Ionut Irimie, Sorin-Nicolae Dinescu, Marius-Bogdan Novac, Ramona-Constantina Vasile, Alexandra-Daniela Rotaru-Zavaleanu, Mihai-Andrei Ruscu and Lucretiu Radu
J. Clin. Med. 2026, 15(12), 4799; https://doi.org/10.3390/jcm15124799 (registering DOI) - 20 Jun 2026
Abstract
Background. Hematological inflammatory indices from the complete blood count have been proposed as inexpensive prognostic markers in sepsis. The systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) are the most studied, but the performance of monocyte-containing alternatives (SIRI, AISI) in the elderly, in [...] Read more.
Background. Hematological inflammatory indices from the complete blood count have been proposed as inexpensive prognostic markers in sepsis. The systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) are the most studied, but the performance of monocyte-containing alternatives (SIRI, AISI) in the elderly, in whom immunosenescence may alter the leukocyte phenotype, remains poorly characterized. Methods. In a single-center retrospective cohort of patients aged ≥65 years admitted to a tertiary ICU with Sepsis-3-defined sepsis (n = 127, 33 deaths), we compared the discrimination of six indices (NLR, PLR, MLR, SII, SIRI, AISI) for 30-day all-cause mortality using AUROC with bootstrap confidence intervals and pairwise DeLong tests. Independent associations were assessed by logistic regression adjusted for APACHE II and age; incremental value over APACHE II was explored using IDI, cNRI, calibration and decision curve analysis, with bootstrap optimism correction. Results. Thirty-day mortality was 26.0%. The monocyte-containing indices (AISI, SIRI, MLR) discriminated better than SII and NLR, and AISI was significantly superior to SII, NLR and PLR on DeLong testing, though not to SIRI, MLR or APACHE II. After adjustment for APACHE II and age, AISI, SIRI and MLR remained independently associated with mortality, whereas SII and PLR did not. Adding AISI to APACHE II improved reclassification and calibration and yielded higher net clinical benefit across clinically relevant thresholds. Conclusions. In this exploratory, single-center analysis, monocyte-containing indices, particularly AISI, were more strongly associated with 30-day mortality in elderly ICU sepsis than SII or NLR. AISI, SIRI and MLR were strongly intercorrelated and near-equivalent, and AISI did not significantly exceed APACHE II in discrimination. These hypothesis-generating findings require prospective external validation before clinical use. Full article
(This article belongs to the Special Issue Sepsis: Current Updates and Perspectives)
16 pages, 905 KB  
Article
Adjunctive Value of Admission CBC-Derived Inflammation Indices for Catheter-Related Bloodstream Infection in Catheter-Dependent Hemodialysis Patients: A Retrospective Case–Control Study
by Muhammed Ali Coşkuner, Gökhan Köker, Gülhan Özçelik Köker, Gizem Zorlu Görgülügil, Gökay Güven, Yasin Şahintürk, Bilgin Bahadır Başgöz, Ayça İnci and Derya Seyman
Diagnostics 2026, 16(12), 1907; https://doi.org/10.3390/diagnostics16121907 (registering DOI) - 19 Jun 2026
Viewed by 117
Abstract
Background/objectives: Catheter-related bloodstream infection (CRBSI) is a frequent and morbid complication in catheter-dependent maintenance hemodialysis, and rapid risk stratification is needed while awaiting cultures. This study aimed to evaluate admission complete blood count-derived indices—neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic [...] Read more.
Background/objectives: Catheter-related bloodstream infection (CRBSI) is a frequent and morbid complication in catheter-dependent maintenance hemodialysis, and rapid risk stratification is needed while awaiting cultures. This study aimed to evaluate admission complete blood count-derived indices—neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and pan-immune-inflammation value (PIV)—for identifying CRBSI. Methods: This single-center retrospective study (1 January 2011–31 October 2024) included adult catheter-dependent hemodialysis patients classified as CRBSI or controls. CRBSI required compatible clinical findings and concordant growth of the same microorganism(s) in paired simultaneous catheter and peripheral blood cultures. Controls were hospitalized for non-infectious reasons without infection during the index admission. Indices were calculated from admission blood counts. Discrimination was assessed using ROC analysis, and adjusted associations were evaluated using multivariable logistic regression. Results: Among 286 patients (147 CRBSI, 139 controls), CRBSI cases had higher NLR, SII, and PIV and lower LMR; PLR did not differ. NLR showed the numerically highest discriminatory performance among the evaluated indices (AUC 0.737; cut-off 5.96; sensitivity 68.7%, specificity 68.3%; p < 0.001). SII (cut-off 1189.21; AUC 0.693) and PIV (cut-off 821.62; AUC 0.686) had moderate discrimination, and LMR was modest (cut-off 1.65; AUC 0.642); PLR was not discriminatory (AUC 0.559; p = 0.086). In models adjusted for age, sex, hypertension, and cardiovascular disease, NLR remained associated with CRBSI (OR 1.159; p < 0.001), together with hypertension (OR 2.441; p = 0.017) and cardiovascular disease (OR 2.626; p < 0.001). Conclusions: Admission hematologic inflammation indices, particularly NLR, showed moderate ability to discriminate CRBSI from non-infectious admissions in catheter-dependent hemodialysis patients and may provide rapid adjunctive information while awaiting microbiological confirmation. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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26 pages, 2448 KB  
Article
Distributional Characterization of CBC-Derived Inflammatory Indices in Hospitalized Patients with Schizophrenia
by Murat Yalçın and Mehmet Cudi Tuncer
Diagnostics 2026, 16(12), 1905; https://doi.org/10.3390/diagnostics16121905 (registering DOI) - 19 Jun 2026
Viewed by 98
Abstract
Background: Increasing evidence suggests that schizophrenia may be associated with peripheral immune–inflammatory alterations, although the distributional characteristics and heterogeneity of routinely available complete blood count (CBC)-derived inflammatory indices in real-world psychiatric inpatient settings remain insufficiently characterized. The present study aimed to descriptively evaluate [...] Read more.
Background: Increasing evidence suggests that schizophrenia may be associated with peripheral immune–inflammatory alterations, although the distributional characteristics and heterogeneity of routinely available complete blood count (CBC)-derived inflammatory indices in real-world psychiatric inpatient settings remain insufficiently characterized. The present study aimed to descriptively evaluate the distributional properties of CBC-derived inflammatory markers in hospitalized patients with schizophrenia using an exploratory panel-based analytical framework. Methods: We conducted a retrospective cross-sectional analysis using anonymized CBC laboratory panels obtained from hospitalized patients with schizophrenia at a tertiary psychiatric center. Following panel reconstruction and quality control procedures, 858 structurally valid CBC panels were included in the analyses. Primary inflammatory indices included neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune–inflammation index (SII). Descriptive distributional analyses, threshold-based prevalence estimation, Spearman correlation analyses, and exploratory unsupervised clustering procedures were performed to evaluate inflammatory variability and internal distributional patterns within the dataset. Results: Median NLR was 2.51 (IQR: 1.95–3.55), median MLR was 0.25 (IQR: 0.19–0.31), median PLR was 124.10 (IQR: 100.40–163.94), and median SII was 686.96 (IQR: 484.81–1045.85). Threshold-based analyses demonstrated substantial variability in inflammatory burden distributions, with 35.9% of panels showing NLR > 3 and 27.0% demonstrating SII > 1000. Correlation analyses revealed strong positive associations among NLR, PLR, and SII, whereas RDW-CV and MPV demonstrated weaker and more heterogeneous relationships with the principal inflammatory indices. Exploratory clustering analyses generated two distributional clusters, including a smaller cluster exhibiting relatively higher NLR, MLR, PLR, SII, WBC, and platelet values than the remaining panels. Female panels demonstrated significantly higher PLR and SII distributions following false discovery rate (FDR) correction. Conclusions: The present findings suggest that CBC-derived inflammatory indices demonstrate substantial distributional variability within this panel-based schizophrenia dataset. Although the exploratory design, absence of patient-level linkage, and lack of clinical confounder adjustment substantially limit biological interpretation, routinely available hematological inflammatory markers may still provide a pragmatic framework for descriptive characterization of inflammatory variability patterns in real-world psychiatric populations. Future patient-level longitudinal studies integrating clinical, pharmacological, and molecular variables will be necessary to determine the potential clinical relevance of inflammatory heterogeneity in schizophrenia. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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14 pages, 1453 KB  
Article
Platelet-to-Lymphocyte Ratio as a Predictor of Lymphovascular Space Invasion in Endometrioid Endometrial Cancer: Development and Internal Validation of a Continuous Parameter-Based Nomogram
by Kasim Akay, Gorkem Ulger, Hamza Yildiz, Zeynep Kucukolcay Coskun, Sevki Goksun Gokulu, Tolgay Tuyan Ilhan and Hakan Aytan
Medicina 2026, 62(6), 1190; https://doi.org/10.3390/medicina62061190 (registering DOI) - 19 Jun 2026
Viewed by 76
Abstract
Background and Objectives: The relationship between preoperative inflammatory markers and lymphovascular space invasion (LVSI) in endometrioid-type endometrial cancer (EC) remains incompletely defined and warrants evaluation using robust statistical methods. This study aimed to evaluate the independent association of preoperative inflammatory markers, analyzed [...] Read more.
Background and Objectives: The relationship between preoperative inflammatory markers and lymphovascular space invasion (LVSI) in endometrioid-type endometrial cancer (EC) remains incompletely defined and warrants evaluation using robust statistical methods. This study aimed to evaluate the independent association of preoperative inflammatory markers, analyzed strictly as continuous variables, with the presence of LVSI, and to develop a refined predictive nomogram adjusted for established clinical confounders. Materials and Methods: Data from 156 patients who underwent standard staging surgery for endometrioid-type EC were retrospectively analysed. To preserve statistical power and avoid structural artifacts from data forcing, preoperative glucose-to-lymphocyte ratio (GLR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) were modeled on their original continuous scale. Multivariable logistic regression analysis was performed to identify independent risk factors for LVSI, adjusting for patient age and maximum tumor diameter. Internal validation was conducted using bootstrap resampling (1000 iterations). Results: In the multivariable logistic regression model, continuous PLR emerged as a significant independent risk factor for the presence of LVSI (adjusted OR: 1.013 per 1-unit increase, 95% CI: 1.001–1.024; p = 0.033). Among clinical parameters, maximum tumor diameter demonstrated the strongest independent association with LVSI (adjusted OR: 1.595 per 1 cm increase, 95% CI: 1.211–2.099; p = 0.001). Continuous NLR (p = 0.513) and GLR (p = 0.545) did not retain statistical significance due to overlapping explanatory variance and shared hematological components. The optimized 3-variable nomogram (PLR, tumor size, and age) demonstrated an apparent C-index of 0.816 (95% bootstrap CI: 0.719–0.920) and a robust optimism-corrected C-index of 0.794. The bootstrap-corrected calibration slope was 0.909, and Decision Curve Analysis (DCA) demonstrated a positive net clinical benefit across clinically relevant threshold probabilities. Conclusions: Preoperative PLR, evaluated as a continuous parameter, provides a statistically stable framework for preoperative risk stratification in endometrioid EC. When integrated with tumor size and age, the proposed nomogram demonstrates promising discriminative performance and potential clinical utility pending external validation for predicting LVSI. However, given the limited number of LVSI-positive events (n = 17), these findings should be regarded as exploratory and hypothesis-generating and require external validation before clinical use. Full article
(This article belongs to the Section Obstetrics and Gynecology)
17 pages, 4543 KB  
Article
Albuminuria Levels and Geriatric Outcomes in Predialysis: Chronic Kidney Disease: Falls, Fear of Falling, and Frailty in a Cross-Sectional Study
by Vedat Gençer, Yavuz Sultan Selim Akgül, Burcu Eren Cengiz and İsmail Altıntop
J. Clin. Med. 2026, 15(12), 4772; https://doi.org/10.3390/jcm15124772 (registering DOI) - 19 Jun 2026
Viewed by 64
Abstract
Background: Chronic kidney disease (CKD) accelerates biological aging and amplifies the risk of adverse geriatric outcomes. Albuminuria reflects systemic endothelial dysfunction beyond renal damage, yet its specific relationship with falls, fear of falling, and frailty in predialysis CKD patients remains underexplored. Objectives: We [...] Read more.
Background: Chronic kidney disease (CKD) accelerates biological aging and amplifies the risk of adverse geriatric outcomes. Albuminuria reflects systemic endothelial dysfunction beyond renal damage, yet its specific relationship with falls, fear of falling, and frailty in predialysis CKD patients remains underexplored. Objectives: We aimed to evaluate the association between albuminuria levels (urinary albumin-to-creatinine ratio, ACR) with falls, fear of falling (Falls Efficacy Scale, FES), and frailty (FRAIL scale and Clinical Frailty Scale, CFS) in older adults with CKD. Methods: This cross-sectional study analyzed 295 patients aged ≥60 years attending nephrology and geriatrics clinics at Kayseri City Hospital, Turkey (April–June 2025). ACR was categorized per KDIGO (A1: <30, A2: 30–300, A3: ≥300 mg/g). Inflammatory indices (NLR, SII, CAR) were calculated. Hierarchical multivariable logistic regression and ROC analyses were performed. Results: Fall prevalence showed a clear dose-response across ACR categories: 31.2% (A1), 72.0% (A2), and 93.2% (A3) (p < 0.001). In the fully adjusted model, each unit increase in log-ACR was associated with a 3.84-fold increase in fall odds (OR 3.84, 95% CI 2.74–6.65). Although bivariate ACR-frailty associations were non-significant, fully adjusted models uncovered independent associations across both instruments and thresholds: FRAIL ≥ 3 (OR 1.41, 95% CI 1.05–2.03), FRAIL ≥ 2 (OR 1.49, 95% CI 1.08–2.21), CFS ≥ 5 (OR 1.87, 95% CI 1.38–2.83), and CFS ≥ 4 (OR 1.37, 95% CI 1.02–1.93). ACR showed good discriminative ability for falls (AUC 0.773, optimal cut-off 21.70 mg/g) but poor discrimination for frailty (AUC 0.50–0.54). The ACR–fall association was stronger in patients with GFR < 60 (OR 4.48) than GFR ≥ 60 (OR 2.18). Conclusions: Albuminuria is a strong, independent, and graded predictor of falls in older CKD patients, with a nearly 4-fold increase in risk per log-unit ACR increase after full adjustment. ACR measurement, already routine in CKD monitoring, could help identify older patients at increased fall risk and guide targeted geriatric assessment. However, ACR showed poor standalone discriminative ability for frailty across all definitions (AUC 0.50–0.54), establishing that it cannot serve as a frailty screening tool in isolation. Full article
(This article belongs to the Special Issue Chronic Disease Management and Rehabilitation in Older Adults)
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18 pages, 1553 KB  
Article
Preliminary Findings on the Predictive Value of Hematologic Inflammatory Indices for Survival in Treatment-Naïve Non-Metastatic Nasopharyngeal Carcinoma: A Retrospective Cohort Study
by Muhammed Ali Coşkuner, Gökhan Köker, Gizem Zorlu Görgülügil, Gülhan Özçelik Köker, Bilgin Bahadır Başgöz, Asım Armağan Aydın and Mustafa Yıldız
J. Clin. Med. 2026, 15(12), 4760; https://doi.org/10.3390/jcm15124760 (registering DOI) - 18 Jun 2026
Viewed by 153
Abstract
Background/Objectives: Prognostic stratification in non-metastatic nasopharyngeal carcinoma (NPC) remains challenging, particularly among patients within the same TNM stage. Readily available hematologic inflammatory indices may reflect host–tumor interactions and provide additional prognostic information beyond conventional clinicopathologic factors. This study evaluated the prognostic value [...] Read more.
Background/Objectives: Prognostic stratification in non-metastatic nasopharyngeal carcinoma (NPC) remains challenging, particularly among patients within the same TNM stage. Readily available hematologic inflammatory indices may reflect host–tumor interactions and provide additional prognostic information beyond conventional clinicopathologic factors. This study evaluated the prognostic value of pretreatment hematologic inflammatory indices for overall survival (OS) and progression-free survival (PFS) in patients with non-metastatic NPC. Methods: This single-center retrospective cohort study included adult patients with non-metastatic NPC diagnosed at a tertiary referral center between 20 February 2014 and 2 May 2023, with outcomes ascertained through 12 December 2023. Pretreatment complete blood count and biochemical parameters were used to calculate the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, pan-immune-inflammation value (PIV), and hemoglobin–albumin–lymphocyte–platelet score. Receiver operating characteristic analysis determined optimal cut-off values for mortality discrimination. Associations with OS and PFS were assessed using Cox regression models. Results: Forty-six patients were analyzed, including 37 males. Median OS and PFS were 45.90 and 37.05 months, respectively. Compared with survivors, non-survivors were older and had lower hemoglobin and albumin levels, higher PIV, NLR, PLR, and SII values, and lower HALP scores. Although NLR showed the highest conventional ROC performance for mortality discrimination, PIV retained prognostic significance in multivariable Cox models and showed stable time-dependent discrimination for PFS. Conclusions: These preliminary findings suggest that pretreatment inflammatory indices, particularly composite markers such as PIV, may provide adjunctive prognostic information in treatment-naïve non-metastatic NPC, pending larger prospective validation. Full article
(This article belongs to the Section Oncology)
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14 pages, 1238 KB  
Article
Two-Step Vibrio parahaemolyticus Challenge Reveals Transcriptional Reprogramming of Trained Immunity in Shrimp Hemocytes
by Zhongying Li, Shihao Li, Xinjia Lv and Fuhua Li
Biology 2026, 15(12), 956; https://doi.org/10.3390/biology15120956 (registering DOI) - 18 Jun 2026
Viewed by 79
Abstract
Invertebrates rely exclusively on innate immunity but exhibit memory-like responses termed immune priming or trained immunity. In the commercially vital whiteleg shrimp (Litopenaeus vannamei), infection by Vibrio parahaemolyticus causes severe economic losses, yet the molecular networks driving secondary immune recall remain [...] Read more.
Invertebrates rely exclusively on innate immunity but exhibit memory-like responses termed immune priming or trained immunity. In the commercially vital whiteleg shrimp (Litopenaeus vannamei), infection by Vibrio parahaemolyticus causes severe economic losses, yet the molecular networks driving secondary immune recall remain poorly understood. In this study, we established a two-step immune challenge model in L. vannamei using formaldehyde-inactivated V. parahaemolyticus and performed transcriptomic analysis on hemocytes to compare primary and secondary immune responses. Differentially expressed gene (DEG) screening and enrichment analyses (GO, KEGG, and GSEA) suggest that shrimp hemocytes undergo a broad and coordinated transcriptional reprogramming rather than uniform upregulation of immune genes. Transcriptomic data show potential associations between secondary immune priming and the modulation of cell fate processes: genes related to cell cycle progression (e.g., CDK1, CCNB3) and spindle assembly (e.g., MPS1) were significantly upregulated alongside apoptosis inhibition (CASP6 downregulation). Concurrently, metabolic remodeling was observed through the upregulation of lipid synthesis (SREBF1, FASN) and carbohydrate uptake pathways, potentially providing anabolic support for hemocyte growth and immune activation. Furthermore, the humoral effector responses appear to be strengthened, characterized by upregulated antimicrobial peptides (PEN, ALF) and the proPO melanization cascade (PPAF3, PPO3), whereas the expression of intracellular NLR was relatively suppressed, which might help mitigate excessive immune inflammation and immunopathological damage. Collectively, these transcriptomic findings identify a putative coordinated transcriptional signature of hemocyte recall responses in L. vannamei. This study expands our understanding of innate immune memory in invertebrates and provides candidate molecular markers for further study in disease-resistant breeding research in shrimp aquaculture. Full article
(This article belongs to the Section Marine and Freshwater Biology)
18 pages, 992 KB  
Article
Prognostic Significance of Inflammatory Markers in Patients with Immune Thrombocytopenia
by Nur Oğuz Davutoğlu, Ali İhsan Gemici, Merve Kocaköse, Selçuk Uylaş, Şeyma Tanır, Gökhan Pektaş and Mehmet Bilgehan Pektaş
Int. J. Mol. Sci. 2026, 27(12), 5528; https://doi.org/10.3390/ijms27125528 (registering DOI) - 18 Jun 2026
Viewed by 78
Abstract
Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by immune-mediated platelet destruction and impaired platelet production. Increasing evidence suggests that systemic inflammation plays a significant role in disease pathogenesis and clinical outcomes. This study aimed to evaluate the prognostic significance of inflammatory [...] Read more.
Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by immune-mediated platelet destruction and impaired platelet production. Increasing evidence suggests that systemic inflammation plays a significant role in disease pathogenesis and clinical outcomes. This study aimed to evaluate the prognostic significance of inflammatory indices and their association with complications, mortality, treatment response, and relapse in patients with ITP. In this single-center retrospective study, 166 adult patients diagnosed with primary ITP between January 2015 and December 2024 were analyzed. Demographic, clinical, and laboratory data at diagnosis were collected. Inflammatory indices derived from complete blood count parameters, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), were evaluated. Their associations with clinical outcomes were assessed using appropriate statistical methods. During the observation period based on retrospective medical records, complications occurred in 12% of patients, and mortality was observed in 6.6%. Patients with complications had significantly higher D-dimer levels and reduced bone marrow megakaryocyte production. In group comparisons, mortality was significantly associated with advanced age, male sex, and comorbidities. Laboratory findings revealed that lower hemoglobin, lymphocyte count, mean platelet volume, and albumin levels, along with higher PLR, erythrocyte sedimentation rate, bilirubin, and D-dimer levels, were significantly associated with mortality. Inflammatory indices such as NLR and PLR were not associated with complication development, but PLR was significantly associated with mortality. Response to intravenous immunoglobulin (IVIG) therapy was significantly associated with higher total protein, albumin, and fibrinogen levels, and lower erythrocyte sedimentation rate. Relapse was significantly associated in group comparisons with increased inflammatory activity, higher reticulocyte count, and positivity for antinuclear antibodies and Helicobacter pylori antigen. Systemic inflammation and impaired megakaryopoiesis play critical roles in the prognosis of ITP. While conventional inflammatory indices showed limited predictive value for complications, markers such as PLR, D-dimer, and albumin were associated with mortality and clinical outcomes. These findings suggest that readily available laboratory parameters may provide valuable insights for risk stratification and personalized management in patients with ITP. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
21 pages, 1045 KB  
Article
Integrated Assessment of Skeletal Muscle Quantity and Quality Is Associated with Survival in Patients with Oesophagogastric Malignancies: A Retrospective Cohort Study
by Yannick Deswysen, Pierre Trefois, Etienne Danse, Alix Collard, Marc Van den Eynde and Nicolas Lanthier
Cancers 2026, 18(12), 1987; https://doi.org/10.3390/cancers18121987 - 18 Jun 2026
Viewed by 186
Abstract
Background: Oesophagogastric cancer is associated with poor survival and major alterations in body composition. This study investigated the relationship between myopenia and myosteatosis in patients with oesophagogastric cancer and evaluated their prognostic significance and association with systemic inflammation. Methods: In this retrospective single-centre [...] Read more.
Background: Oesophagogastric cancer is associated with poor survival and major alterations in body composition. This study investigated the relationship between myopenia and myosteatosis in patients with oesophagogastric cancer and evaluated their prognostic significance and association with systemic inflammation. Methods: In this retrospective single-centre study, 161 consecutive patients diagnosed with oesophagogastric cancer between 2019 and 2023 underwent computed tomography-based body-composition analysis at diagnosis. Skeletal muscle index (SMI) and skeletal muscle density (SMD) were measured at the third lumbar vertebra. Myopenia and myosteatosis were defined using Martin’s criteria. Associations with overall survival (OS) and progression-free survival (PFS), and systemic inflammation assessed using C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), were analysed using Kaplan–Meier and Cox regression analyses. Results: Among the 161 patients included (67.1% male; median age 66 years), myopenia and myosteatosis were highly prevalent (62.7% and 87.6%, respectively), despite a median body mass index (BMI) within the normal range. Lowest SMI tertile was significantly associated with poorer OS and PFS, whereas lowest SMD tertile showed markedly reduced OS. On multivariate analyses, lower SMD remained independently associated with OS and with PFS, whereas SMI lost significance after adjustment for clinical and inflammatory factors. The coexistence of myopenia and myosteatosis was associated with significantly worse survival outcomes. An exploratory continuous muscle score integrating muscle quantity and muscle quality was associated with OS (hazard ratio 1.28 per SD increase) and demonstrated moderate prognostic discrimination (concordance-index 0.63). Conclusions: Muscle quantity and quality represent complementary dimensions of cancer-associated muscle impairment in oesophagogastric cancer. Collectively, these results suggest that a continuous measure integrating both muscle quantity and muscle quality provides a more clinically informative assessment of muscle impairment than traditional binary definitions of myopenia and myosteatosis. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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22 pages, 2506 KB  
Article
Clinical and Inflammatory Predictors of Neurocognitive Decline in Long COVID: A Two-Year Longitudinal Study with Propensity Score Matching
by Iulia Elena Diaconu, Maria Ioana Onofrei, Andrei Vâță, Florin Manuel Roșu, Emilian Bogdan Ignat, Iulian Dan Cuciureanu, Mihnea Eudoxiu Hurmuzache and Mihaela Cătălina Luca
Medicina 2026, 62(6), 1180; https://doi.org/10.3390/medicina62061180 - 18 Jun 2026
Viewed by 221
Abstract
Background and Objectives: Neurological complications of SARS-CoV-2 infection frequently impair patients’ long-term quality of life. This study aimed to identify clinical and laboratory risk factors—including inflammatory markers and micronutrients—for the occurrence or worsening of neurocognitive disorders in long COVID patients. Materials and [...] Read more.
Background and Objectives: Neurological complications of SARS-CoV-2 infection frequently impair patients’ long-term quality of life. This study aimed to identify clinical and laboratory risk factors—including inflammatory markers and micronutrients—for the occurrence or worsening of neurocognitive disorders in long COVID patients. Materials and Methods: In this prospective observational study, patients presenting with long COVID neurological manifestations were stratified by baseline MoCA score into two groups (≥23 and <23). Clinical, laboratory (inflammatory markers, 25-hydroxy vitamin D, vitamin B12, folic acid), and neuroimaging assessments (global cortical atrophy scale, Fazekas score) were performed over 24 months. Propensity score matching (PSM) for age, gender, and neurological comorbidities yielded 54 patients per group. Results: In the MoCA ≥ 23 group, significant predictors of cognitive decline included severe COVID-19 (OR = 2.211, 95% CI = 1.819–5.973, p = 0.012), autoimmune comorbidities (OR = 1.676, 95% CI = 1.191–2.390, p = 0.043), and elevated neutrophil-to-lymphocyte ratio (NLR; OR = 1.586, 95% CI = 1.431–2.122, p = 0.011). In the MoCA < 23 group, independent predictors were diabetes mellitus (OR = 3.021, 95% CI = 2.65–14.004, p = 0.016), autoimmune comorbidities (OR = 4.987, 95% CI = 1.412–6.033, p = 0.021), and NLR (OR = 5.944, 95% CI = 2.353–19.321, p = 0.015). Serum vitamin D levels were significantly associated with MoCA scores in both groups. Conclusions: COVID-19 severity, autoimmune comorbidities, NLR, and serum vitamin D represent key risk factors for neurocognitive decline in long COVID, highlighting potential targets for early intervention. Full article
(This article belongs to the Section Infectious Disease)
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14 pages, 1823 KB  
Article
Inflammatory Biomarkers and Their Associations with Arrhythmic Burden Following SGLT2-I Treatment in Chronic Heart Failure—A Subanalysis of the ERASe Trial
by Martin Benedikt, Markus Herrmann, Faisal Aziz, Norbert J. Tripolt, Peter Pferschy, Martin Manninger, Markus Wallner, Raffaela Planka, Andreas Zirlik, Harald Sourij, Abderrahim Oulhaj, Markus Stühlinger, Daniel Scherr and Dirk von Lewinski
J. Clin. Med. 2026, 15(12), 4681; https://doi.org/10.3390/jcm15124681 - 17 Jun 2026
Viewed by 165
Abstract
Background: Sodium glucose-linked transport 2 inhibitors (SGLT2-Is) are well known to exert beneficial effects in chronic heart failure (CHF) independent of left ventricular ejection fraction (LVEF). As inflammation plays a key role in cardiac diseases, data on the association of inflammatory biomarkers [...] Read more.
Background: Sodium glucose-linked transport 2 inhibitors (SGLT2-Is) are well known to exert beneficial effects in chronic heart failure (CHF) independent of left ventricular ejection fraction (LVEF). As inflammation plays a key role in cardiac diseases, data on the association of inflammatory biomarkers and ventricular arrhythmic (VA) burden in SGLT2-I-treated patients is lacking. Methods: This pre-defined subanalysis investigated changes in pre-specified inflammatory biomarkers from baseline to week 52 in response to 5 mg Ertugliflozin compared to placebo and their associations to the incidence of VA burden. Results: A total of 36 patients (18 versus 18) with available biobank samples were included in the analysis. At week 52, leukocyte and neutrophil counts, as well as high-sensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6), were numerically higher in the Ertugliflozin group. In contrast, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were lower in the Ertugliflozin group, although these differences did not reach statistical significance. Notably, lymphocyte counts were significantly higher in Ertugliflozin showing a mean difference of 19.0 ± 10.78% (p = 0.028). Further, a significantly higher incidence of VA burden was observed among Ertugliflozin-treated patients with elevated hsCRP levels (incidence rate ratio [IRR] 3.58; 95% Confidence interval [CI], 1.12–11.40, p = 0.031). Conclusions: In patients with CHF, Ertugliflozin treatment was associated with a higher incidence of VA burden in those with elevated hsCRP levels. This may suggest a potential higher risk for VA in SGLT2-I-treated patients in the setting of heightened inflammatory activity. However, this finding is based on a single interaction analysis in a small sample size, and the results should therefore be considered exploratory and hypothesis-generating, and must be interpreted cautiously. Full article
(This article belongs to the Special Issue Clinical Aspects of Cardiac Arrhythmias and Arrhythmogenic Disorders)
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16 pages, 2242 KB  
Article
Characterization and Immune Function of NOD1 in Snakehead (Channa argus)
by Beibei Wang, Yiying Liu, Xiaochen Zhu, Min Cao, Qiang Fu, Yang Li, Ning Yang, Xiaoyan Zhang, Guangzhou Wu and Chao Li
Biology 2026, 15(12), 942; https://doi.org/10.3390/biology15120942 - 16 Jun 2026
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Abstract
The innate immune response is a critical defense mechanism by which vertebrates recognize and eliminate invading pathogens. Pattern recognition receptors (PRRs) detect pathogen-associated molecular patterns and activate downstream signaling pathways. NOD1, a classic PRR of the NLR family, recruits the adaptor protein [...] Read more.
The innate immune response is a critical defense mechanism by which vertebrates recognize and eliminate invading pathogens. Pattern recognition receptors (PRRs) detect pathogen-associated molecular patterns and activate downstream signaling pathways. NOD1, a classic PRR of the NLR family, recruits the adaptor protein RIPK2 to initiate antibacterial signaling. In this study, we cloned and characterized the NOD1 gene from snakehead (Channa argus). Briefly, the full-length NOD1 cDNA is 2829 bp encoding 943 amino acids, showing high homology with Perciformes. The qPCR analysis revealed widespread NOD1 gene expression in various tissues, with significant upregulation in the gill (p < 0.05) and spleen (p < 0.05) following bacterial infection. Overexpression of the NOD1 gene activated the NF-κB signaling pathway in a dose- and time-dependent manner, and specifically responded to the bacterial ligand iE-DAP but not to other tested ligands. Furthermore, NOD1 synergized with the downstream adaptor RIPK2 to enhance NF-κB activity, and direct protein interaction between NOD1 and RIPK2 was confirmed by co-immunoprecipitation. Taken together, these findings demonstrate that snakehead NOD1 plays a critical role in the host antimicrobial immune response. Full article
(This article belongs to the Section Immunology)
20 pages, 2072 KB  
Article
Oxidative Stress Biomarkers and Systemic Inflammatory Indices in Metabolic Dysfunction-Associated Steatotic Liver Disease with Type 2 Diabetes Mellitus: A Comparative and Longitudinal Analysis
by Vlad Pădureanu, Lidia Boldeanu, Anca Bobîrcă, Diana Clenciu, Rodica Pădureanu, Adina Mitrea, Veronica Gheorman, Ștefan Pătrașcu, Beatrice Elena Vladu, Albert Georgescu, Ionela Mihaela Vladu and Virginia Maria Radulescu
Int. J. Mol. Sci. 2026, 27(12), 5432; https://doi.org/10.3390/ijms27125432 - 16 Jun 2026
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Abstract
Metabolically dysfunction-associated steatotic liver disease (MASLD) complicated by type 2 diabetes mellitus (T2DM) represents a clinically aggressive phenotype associated with accelerated hepatic fibrosis progression. The interplay among oxidative stress, systemic inflammation, and the risk of hepatic fibrosis in this context remains incompletely characterised. [...] Read more.
Metabolically dysfunction-associated steatotic liver disease (MASLD) complicated by type 2 diabetes mellitus (T2DM) represents a clinically aggressive phenotype associated with accelerated hepatic fibrosis progression. The interplay among oxidative stress, systemic inflammation, and the risk of hepatic fibrosis in this context remains incompletely characterised. We conducted a single-centre observational study enrolling 110 adult MASLD patients, stratified into two groups: Group 1 (G1, n = 20), patients with concurrent T2DM, followed longitudinally at three successive time points, and Group 2 (G2, n = 90), non-diabetic controls. Serum oxidative stress biomarkers were assessed using malondialdehyde (MDA) and 8-isoprostaglandin F2α (8-iso-PGF2α). Systemic inflammatory status was quantified through the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR). Hepatic fibrosis risk was estimated using the FIB-4 index. Diabetic MASLD patients exhibited significantly elevated levels of 8-iso-PGF2α (p = 0.014) and NLR (p = 0.016) compared with controls, indicating greater oxidative membrane damage and systemic neutrophilic inflammation. A robust inverse correlation between PLR and FIB-4 was observed across all analytical strata (combined cohort: Spearman r = −0.680, p < 0.001). MLR emerged as the only independent predictor of MDA in G1 (β = 841.78, p = 0.013). Longitudinal analysis demonstrated biomarker stability over time, except for a significant increase in ALT from T1 to T2 (p_adj = 0.014). These findings support the clinical utility of routinely available haematological inflammatory ratios and lipid peroxidation biomarkers for phenotypic characterisation of MASLD in the diabetic context, highlighting the need for larger prospective studies with histological validation. Full article
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17 pages, 1378 KB  
Review
Regulation of Innate Immune Signaling by Autophagy
by Daniel Oña-Sánchez, Julia Bandera-Linero and Felipe X. Pimentel-Muiños
Int. J. Mol. Sci. 2026, 27(12), 5413; https://doi.org/10.3390/ijms27125413 - 16 Jun 2026
Viewed by 187
Abstract
The first line of defense against infection is provided by the innate immune system, which is able to recognize molecular patterns in a variety of infectious agents through the action of different families of pattern recognition receptors (PRRs). These effectors detect the invading [...] Read more.
The first line of defense against infection is provided by the innate immune system, which is able to recognize molecular patterns in a variety of infectious agents through the action of different families of pattern recognition receptors (PRRs). These effectors detect the invading agent and trigger powerful inflammatory responses that help fight the infection from the very beginning. However, inflammatory reactions can be damaging for the host and must be properly controlled to prevent pathological consequences. Here we provide a comprehensive review of the important role of autophagy, a catabolic pathway that degrades cellular components for quality control and regulatory purposes, in the regulation of innate immune responses, and the underlying mechanisms involved. Inflammatory pathways discussed in this review include those triggered by Toll-like receptors (TLRs), Retinoic acid-Inducible Gene (RIG)-I-like receptors (RLRs), Nucleotide-binding Oligomerization Domain (NOD)-like receptors (NLRs), and the receptor for cyclic GMP–AMP Stimulator of Interferon Genes (STING). Finally, we also consider examples where autophagy plays context-dependent or even pro-inflammatory roles, reflecting a complex involvement that remains to be fully characterized. Full article
(This article belongs to the Special Issue Autophagy in Physiology and Pathophysiology: Recent Advances)
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17 pages, 2472 KB  
Article
Enhanced Nonlinear Optical Properties and Optical Limiting Performance of Perylenediimide Derivative/Semiconductor Nanocomposites Under Femtosecond Laser Light Excitation
by Tarek Mohamed, Majed H. El-Motlak, Fatma Abdel Samad, Mohamed E. El-Khouly, Sulaiman Wadi Harun and Alaa Mahmoud
Materials 2026, 19(12), 2587; https://doi.org/10.3390/ma19122587 - 16 Jun 2026
Viewed by 196
Abstract
The linear and third-order nonlinear optical (NLO) properties of a water-soluble perylenediimide derivative, N,N′-di(2-(trimethylammonium iodide) ethylene) perylenediimide (TAIPDI), doped with semiconductor nanoparticles (NPs), were systematically investigated under femtosecond laser excitation. ZnO and TiO2 NPs were synthesized using a pulsed laser ablation technique. [...] Read more.
The linear and third-order nonlinear optical (NLO) properties of a water-soluble perylenediimide derivative, N,N′-di(2-(trimethylammonium iodide) ethylene) perylenediimide (TAIPDI), doped with semiconductor nanoparticles (NPs), were systematically investigated under femtosecond laser excitation. ZnO and TiO2 NPs were synthesized using a pulsed laser ablation technique. Nanocomposite systems were prepared by incorporating different concentrations of ZnO and TiO2 NPs into the TAIPDI dye solution. The optical properties were characterized using UV–visible absorption spectroscopy together with open- and closed-aperture Z-scan measurements at 800 nm. Linear absorption measurements revealed concentration-dependent modifications in the optical band gap, indicating electronic interaction between the dye molecules and the semiconductor NPs. Open-aperture Z-scan results demonstrated strong nonlinear absorption (NLA) behavior dominated by two-photon absorption and excited-state absorption processes. Closed-aperture measurements showed a negative nonlinear refractive (NLR) index, corresponding to self-defocusing behavior. Both the NLA coefficient and the NLR index increased with increasing NP concentration, resulting in a significant enhancement of the third-order nonlinear susceptibility of the nanocomposite systems. In addition, optical limiting measurements revealed a pronounced reduction in the limiting threshold with increasing nanoparticle concentration, demonstrating improved laser attenuation capability. These findings indicate that ZnO@TAIPDI and TiO2@TAIPDI nanocomposites are promising candidates for applications in optical limiting, all-optical switching, and advanced photonic devices. Full article
(This article belongs to the Section Optical and Photonic Materials)
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