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14 pages, 1045 KB  
Article
Eustachian Tube Obstruction Grade as an Independent Determinant of Audiological and Quality-of-Life Outcomes in Pediatric Chronic Adenoiditis: A Retrospective Cohort Study
by Diana Szekely, Flavia Zara, Raul Patrascu, Cristina Stefania Dumitru, Alina Cristina Barb, Dorin Novacescu, Antonia Armega Anghelescu, Alexia Manole, Dan Iovanescu and Gheorghe Iovanescu
Medicina 2026, 62(7), 1297; https://doi.org/10.3390/medicina62071297 (registering DOI) - 5 Jul 2026
Abstract
Background and Objectives: Eustachian tube (ET) dysfunction links adenoidal disease to persistent middle ear dysfunction in children, yet the independent contribution of ET orifice obstruction grade to audiological outcomes and health-related quality of life remains unquantified after adjustment for anatomical and inflammatory [...] Read more.
Background and Objectives: Eustachian tube (ET) dysfunction links adenoidal disease to persistent middle ear dysfunction in children, yet the independent contribution of ET orifice obstruction grade to audiological outcomes and health-related quality of life remains unquantified after adjustment for anatomical and inflammatory confounders. Because conventional anatomical grading (e.g., the Cassano classification) does not directly characterize the degree of ET orifice compromise, it may underestimate the functional threat to middle ear ventilation; this study is the first to quantify the independent predictive value of endoscopic ET obstruction grade. This study aimed to evaluate ET obstruction grade as an independent determinant of hearing thresholds, middle ear pressure, and quality-of-life impairment in children with chronic adenoiditis and otitis media with effusion. Materials and Methods: A retrospective cohort of 236 children (aged 3–12 years) was analyzed. ET orifice obstruction was graded endoscopically as none, partial, or complete. Primary outcomes included pure tone average (PTA), middle ear pressure (MEP), and OSA-18 total score. Multivariate linear and logistic regression models were fitted, adjusting for age, sex, Cassano grade, neutrophil-to-lymphocyte ratio (NLR), allergic status, and acute otitis media frequency. The modifying role of mucosal appearance (edematous versus fibrotic/remodeling) on quality-of-life outcomes was also assessed. Results: ET obstruction was absent in 42 (17.8%), partial in 114 (48.3%), and complete in 80 (33.9%) children. PTA increased progressively across groups (22.2 ± 5.5 to 36.2 ± 6.7 dB; p < 0.001), as did OSA-18 scores (44.9 ± 7.9 to 80.4 ± 10.3; p < 0.001). In adjusted analysis, each obstruction increment independently predicted a 5.57 dB PTA increase (95% CI 4.37–6.77; p < 0.001), a 14.89-point OSA-18 increase (95% CI 12.87–16.92; p < 0.001), and 5.12-fold higher odds of PTA > 30 dB (95% CI 2.84–9.24; p < 0.001). Persistent middle ear dysfunction at six months occurred in 7.1%, 26.3%, and 61.3% across obstruction grades. Among children with complete obstruction, fibrotic mucosa was associated with higher OSA-18 scores than edematous mucosa (82.3 vs. 76.8; p = 0.02). Conclusions: ET obstruction grade independently determines audiological and quality-of-life outcomes in pediatric chronic adenoiditis. Mucosal remodeling further amplifies quality-of-life burden in complete obstruction. These findings support routine ET endoscopic grading in pediatric otorhinolaryngology risk stratification. Full article
(This article belongs to the Special Issue Advances in Otorhinolaryngologic Diseases)
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15 pages, 707 KB  
Article
The Fatigue Load Analysis of Wind Turbines in a Reconfigurable Floating Offshore Wind Farm
by Mohammad Mahdi Malayeri, Yue Niu and Ryozo Nagamune
J. Mar. Sci. Eng. 2026, 14(13), 1244; https://doi.org/10.3390/jmse14131244 (registering DOI) - 4 Jul 2026
Abstract
This paper analyzes the fatigue loads of wind turbines in a floating offshore wind farm (FOWF) whose layout can be reconfigured. Such wind farm reconfiguration will be useful for wake effect mitigation in varying wind conditions. As an example FOWF, a farm with [...] Read more.
This paper analyzes the fatigue loads of wind turbines in a floating offshore wind farm (FOWF) whose layout can be reconfigured. Such wind farm reconfiguration will be useful for wake effect mitigation in varying wind conditions. As an example FOWF, a farm with three 5 MW floating offshore wind turbine (FOWT) models on semi-submersible platforms, developed by the National Laboratory of the Rockies (NLR) (formerly the National Renewable Energy Laboratory (NREL)), is considered. Simulations for the example FOWF are conducted with various realistic turbulent wind and irregular wave conditions in the medium-fidelity wind farm simulator FAST.Farm. Using the simulation data, fatigue analysis is conducted by calculating the damage equivalent loads (DELs) using the computational tool MLife at critical components of the three FOWTs. The analysis results demonstrate the potential of reconfigurable FOWFs in not only increasing power outputs but also reducing fatigue loads for many critical components of turbines. Full article
(This article belongs to the Section Ocean Engineering)
13 pages, 883 KB  
Article
The Global Immune–Nutrition–Inflammation Index Is Associated with Survival Outcomes and Enhances Prognostic Discrimination in Metastatic Pancreatic Cancer
by Kamuran Yüceer, Oktay Bozkurt, Mevlüde Inanç and Metin Ozkan
Medicina 2026, 62(7), 1279; https://doi.org/10.3390/medicina62071279 - 2 Jul 2026
Viewed by 110
Abstract
Background and Objectives: Metastatic pancreatic ductal adenocarcinoma (PDAC) continues to carry a poor prognosis despite advances in treatment, underscoring the need for simple and accessible biomarkers that reflect tumor–host interactions. The Global Immune–Nutrition–Inflammation Index (GINI), which combines inflammatory, immune, and nutritional parameters, [...] Read more.
Background and Objectives: Metastatic pancreatic ductal adenocarcinoma (PDAC) continues to carry a poor prognosis despite advances in treatment, underscoring the need for simple and accessible biomarkers that reflect tumor–host interactions. The Global Immune–Nutrition–Inflammation Index (GINI), which combines inflammatory, immune, and nutritional parameters, may offer improved prognostic stratification compared with conventional indices. Materials and Methods: This retrospective cohort study included 126 patients with metastatic PDAC treated between 2015 and 2024. GINI, neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) were calculated using baseline laboratory data. Discriminative ability was evaluated by receiver operating characteristic (ROC) analysis. Survival outcomes were assessed using Kaplan–Meier curves and Cox proportional hazards models. Results: Among the evaluated indices, GINI showed the best discriminative performance (AUC, 0.769; 95% CI, 0.637–0.900), with a sensitivity of 78.8% and specificity of 76.9%. Patients with lower GINI values had significantly longer overall survival than those with higher values (median OS, 11.0 vs. 7.0 months; p = 0.014). Although progression-free survival differed statistically (p = 0.006), median PFS was the same in both groups (5.0 months). In univariable analysis, higher GINI was associated with worse OS (HR, 1.67; p = 0.022) and PFS (HR, 1.75; p = 0.012). However, in multivariable analysis, ECOG performance status remained the only consistent independent predictor, and GINI was no longer significant. Conclusions: GINI is a practical and biologically meaningful biomarker that improves risk discrimination in metastatic PDAC. While it does not retain independent prognostic significance, its ability to capture the overall tumor–host interaction  supports its use as a complementary tool for baseline risk assessment. Full article
(This article belongs to the Special Issue Pancreatic Cancer: Advances in Treatment and Future Prospects)
14 pages, 249 KB  
Article
Associations of Systemic Immune-Inflammation Index and Hematological Markers with Symptom Burden and Radiological Stage in Sarcoidosis
by Ezgi Erdem Türe, Berna Akıncı Özyürek, Fulsen Bozkuş, Nilgün Yilmaz Demirci, Celal Satıcı, Ayshan Mammadova, Gözde Kalbaran Kismet, Zeynep Erayman Ozen, Onur Yazıcı, Şule Taş Gülen, Burcu Akkök, Ayşegül Erinç, Nevin Fazlıoğlu, Pelin Pınar Deniz, Pınar Yıldız Gülhan, Yasemin Söyler and Aysun Şengül
Diagnostics 2026, 16(13), 2082; https://doi.org/10.3390/diagnostics16132082 (registering DOI) - 2 Jul 2026
Viewed by 156
Abstract
Background/Objectives: Sarcoidosis is a multisystem inflammatory disease characterized by heterogeneous clinical manifestations and variable disease severity. Hematological inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), red cell distribution width (RDW), and systemic immune-inflammation index (SII), have recently [...] Read more.
Background/Objectives: Sarcoidosis is a multisystem inflammatory disease characterized by heterogeneous clinical manifestations and variable disease severity. Hematological inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), red cell distribution width (RDW), and systemic immune-inflammation index (SII), have recently attracted attention as accessible indicators of systemic inflammation in sarcoidosis. This study aimed to evaluate radiological stage, symptom burden, pulmonary function parameters, and hematological markers in patients with sarcoidosis. Methods: This retrospective multicenter cohort study included histopathologically confirmed sarcoidosis patients from 10 centers. Demographic characteristics, clinical manifestations, pulmonary function test parameters, serum angiotensin-converting enzyme (ACE) levels, and hematological inflammatory markers (MPV, RDW, NLR, PLR, SII) were evaluated. Patients were categorized according to radiological stage (stage 0–I vs. stage II–IV), symptomatic status, and symptom burden (<3 vs. ≥3 symptoms). Results: Among 458 patients included in the study, stage I (47.8%) and stage II (46.9%) disease were the predominant radiological presentations. Patients with stage II–IV disease were older and demonstrated significantly lower forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and diffusing capacity for carbon monoxide (DLCO) values together with higher serum ACE levels compared with stage 0–I disease. Dyspnea, weight loss, and extrapulmonary involvement were more frequent in stage 2–4 disease. No significant associations were observed between radiological stage and NLR, PLR, or SII values. MPV and RDW values differed significantly between symptomatic and asymptomatic patients. Patients with ≥3 symptoms demonstrated significantly lower pulmonary function parameters together with statistically significant higher NLR, PLR, and SII values. In multivariate analyses, only the SII demonstrated an independent association with a high symptom burden. Conclusions: Serum ACE levels were associated with advanced radiological stage, whereas hemogram-derived inflammatory indices, particularly the NLR, PLR, and SII, were associated with symptom burden rather than radiological stage in sarcoidosis and may reflect symptomatic inflammatory activity. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
16 pages, 1633 KB  
Systematic Review
The Neutrophil-to-Lymphocyte Ratio in Fibromyalgia: A Systematic Review with a Neuroimmune Perspective
by Sanam Mohammadzadeh, Shokufe Khanzade, Sarvin Es Haghi and Richard K. Shields
Brain Sci. 2026, 16(7), 703; https://doi.org/10.3390/brainsci16070703 - 30 Jun 2026
Viewed by 128
Abstract
Background/Objectives. Alterations in systemic immune balance, reflected by changes in neutrophil and lymphocyte proportions, index a peripheral immune state relevant to central nervous system function. This systematic review and meta-analysis aimed to assess the differences in the neutrophil-to-lymphocyte ratio (NLR) between fibromyalgia patients [...] Read more.
Background/Objectives. Alterations in systemic immune balance, reflected by changes in neutrophil and lymphocyte proportions, index a peripheral immune state relevant to central nervous system function. This systematic review and meta-analysis aimed to assess the differences in the neutrophil-to-lymphocyte ratio (NLR) between fibromyalgia patients and healthy controls and offer a framework to study fibromyalgia. Methods. We adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered our work on PROSPERO (CRD420251001424). Two authors performed a comprehensive search of databases, including PubMed, Embase, Web of Science, and Scopus, until August 2025. The Newcastle–Ottawa Scale (NOS) was used for bias risk assessment, and STATA 19.0 software was used for statistical analyses. The standardized mean difference (SMD) and 95% confidence interval (CI) of the NLR were reported. Finally, 24 studies with 3143 fibromyalgia patients and 1610 healthy controls were included in our meta-analysis. Results. The results indicated that patients with fibromyalgia had elevated NLRs compared to healthy controls (SMD = 0.30; 95% CI = 0.07–0.52; p = 0.01). Our results showed no publication bias. A bivariate random-effects meta-analysis on the diagnostic accuracy of the NLR showed a summary sensitivity of 0.74 (95% CI: 0.62–0.83) and a summary specificity of 0.63 (95% CI: 0.51–0.73). Conclusions. Our meta-analysis supports the fact that the NLR is significantly different between patients with fibromyalgia and healthy controls. We conceptualize the idea that the NLR may be used as a “state-dependent” peripheral marker indexing the susceptibility of central nervous system sensitization, pain amplification, and responsiveness to future therapies. Full article
(This article belongs to the Section Neuropharmacology and Neuropathology)
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26 pages, 6295 KB  
Article
Melatonin Attenuates Glucolipotoxicity-Induced Cardiac Oxidative Stress, Inflammation, Pyroptosis, and Fibrotic Remodeling in STZ/HFD-Treated ApoE/ Mice
by Chia-Hui Lin, I-Ning Tsai, Ai-Ting Jou, Chau-Jong Wang, Ming-Chih Chou, Hui-Pei Huang and Chien-Ning Huang
Antioxidants 2026, 15(7), 825; https://doi.org/10.3390/antiox15070825 - 30 Jun 2026
Viewed by 112
Abstract
Diabetic cardiomyopathy (DCM) under glucolipotoxic stress is sustained by a reactive oxygen species (ROS)-driven circuit in which oxidative DNA damage and nitrosative injury prime NLR family pyrin domain containing 3 (NLRP3) inflammasome assembly, triggering caspase-1 activation, gasdermin D (GSDMD) cleavage, and pyroptotic cardiomyocyte [...] Read more.
Diabetic cardiomyopathy (DCM) under glucolipotoxic stress is sustained by a reactive oxygen species (ROS)-driven circuit in which oxidative DNA damage and nitrosative injury prime NLR family pyrin domain containing 3 (NLRP3) inflammasome assembly, triggering caspase-1 activation, gasdermin D (GSDMD) cleavage, and pyroptotic cardiomyocyte death that propagates apoptosis and fibrotic remodeling. Whether melatonin can disrupt this oxidative-pyroptotic axis when both hyperglycemia and dyslipidemia coexist, the metabolic context most refractory to current therapy has not been established. Apolipoprotein E-deficient (ApoE/) mice were subjected to streptozotocin-induced hyperglycemia and high-fat diet-induced dyslipidemia, then treated with oral melatonin (20 mg/kg/day) for 8 weeks. Despite unchanged fasting glycemia, melatonin attenuated cardiac oxidative stress, reducing 8-OHdG and inducible nitric oxide synthase while restoring Nrf2. Suppression of nuclear factor-κB and NLRP3 was accompanied by lowered interleukin-1β, caspase-1, and GSDMD, indicating disrupted inflammasome priming and pyroptotic execution. Downstream pathology was concurrently attenuated, with reduced TUNEL-positive cardiomyocytes, normalized Bax/Bcl-2 ratio, lower natriuretic peptide expression, diminished interstitial fibrosis, and improved electrocardiographic parameters. These findings position melatonin as a cardioprotective agent that operates despite persistent fasting hyperglycemia, acting through combined attenuation of lipid burden, cumulative glycemic stress, oxidative stress, and inflammatory signaling to arrest downstream apoptotic and fibrotic remodeling under glucolipotoxic conditions, providing a mechanistic rationale for adjunctive melatonin therapy in DCM. Full article
13 pages, 560 KB  
Article
Prognostic Nutritional Index Predicts In-Hospital Mortality Among Patients with Clostridioides difficile Infection: A Real-World Retrospective Study
by Edison Jahaj, Dimitris C. Kounatidis, Eleni Mylona, Fotis Panagopoulos, Andreas Adamou, Sofia Kargioti, Maria Masouridi and Natalia G. Vallianou
Antibiotics 2026, 15(7), 650; https://doi.org/10.3390/antibiotics15070650 - 30 Jun 2026
Viewed by 172
Abstract
Background/Objectives: Clostridioides difficile infection (CDI) remains a major cause of morbidity and mortality, particularly among hospitalized older adults. This study evaluated the prognostic performance of routinely available inflammatory and nutritional biomarkers for predicting in-hospital mortality in patients with CDI. Methods: We conducted [...] Read more.
Background/Objectives: Clostridioides difficile infection (CDI) remains a major cause of morbidity and mortality, particularly among hospitalized older adults. This study evaluated the prognostic performance of routinely available inflammatory and nutritional biomarkers for predicting in-hospital mortality in patients with CDI. Methods: We conducted a retrospective observational study of 110 adults with confirmed CDI admitted to the Internal Medicine Department of a tertiary-care hospital in Athens, Greece, between January 2022 and December 2025. Demographic, clinical, and laboratory data obtained within 24 h of admission were analyzed. The prognostic value of the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), C-reactive protein-to-albumin ratio (CAR), and Prognostic Nutritional Index (PNI) was assessed using univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis evaluated the discriminatory performance of PNI. Results: Twenty-two patients (20.0%) died during hospitalization. Compared with survivors, non-survivors exhibited significantly higher NLR (p = 0.035), dNLR (p = 0.012), and CAR (p = 0.015) values, whereas serum albumin and PNI were significantly lower (both p < 0.001). In univariate analysis, dNLR, CAR, and PNI were associated with mortality. After adjustment for age, sex, length of stay, and cancer diagnosis, only PNI remained independently associated with in-hospital mortality (p = 0.018). PNI showed good predictive performance (p < 0.001). Conclusions: PNI is a simple, inexpensive, and readily obtainable biomarker independently associated with in-hospital mortality in CDI. These findings highlight the importance of immune-nutritional status in CDI and support the potential utility of PNI for early risk stratification in hospitalized patients. Full article
19 pages, 27995 KB  
Article
Region-Aware 3D Tensor Decomposition Exploiting Spectral Symmetry for Hyperspectral Image Denoising
by Jiaxian Long and Chaowei Yuan
Symmetry 2026, 18(7), 1120; https://doi.org/10.3390/sym18071120 - 30 Jun 2026
Viewed by 174
Abstract
Spectral fidelity is critical for accurate hyperspectral image (HSI) processing. A key characteristic of HSI data is the strong correlation between spectral bands, which manifests as structured symmetry in spectral covariance matrices. While global low-rank tensor decompositions leverage this spectral structure, they often [...] Read more.
Spectral fidelity is critical for accurate hyperspectral image (HSI) processing. A key characteristic of HSI data is the strong correlation between spectral bands, which manifests as structured symmetry in spectral covariance matrices. While global low-rank tensor decompositions leverage this spectral structure, they often neglect the significant spatial heterogeneity present in real-world scenes. To address this limitation, we propose a Region-Aware 3D Tensor Decomposition (RA-3DTD) framework that balances global spectral consistency with local spatial adaptation. Our approach first performs residual energy-based region detection to identify complex regions within the hyperspectral cube, and then applies localized Higher-Order Orthogonal Iteration (HOOI) specifically to those regions requiring enhanced detail preservation. This two-phase design incorporates global low-rank constraints with local spatial processing, improving denoising accuracy. Extensive experiments on four benchmark datasets (Pavia_80, Indian Pines, Salinas, and Pavia University) demonstrate the effectiveness of our method compared to five leading model-based baselines including BM3D, LRMR, NLR, LRTD, and FastHyDe. Our approach achieves a 1.33 dB increase in PSNR over a leading model-based competitor (FastHyDe) in complex urban scenes while maintaining strong structure fidelity as measured by SSIM and SAM metrics. Full article
(This article belongs to the Special Issue Studies of Symmetry and Asymmetry in Cryptography)
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11 pages, 335 KB  
Article
Analysis of Circadian Blood Pressure Patterns and Their Clinical, Metabolic, and Structural Correlates in Newly Diagnosed Hypertensive Patients
by Kaya Özen and Süleyman Akkaya
Biomedicines 2026, 14(7), 1491; https://doi.org/10.3390/biomedicines14071491 - 30 Jun 2026
Viewed by 200
Abstract
Background: This study aimed to investigate the relationships of AHA/ACC blood pressure stages and circadian blood pressure patterns with clinical, metabolic, inflammatory, and structural echocardiographic parameters in newly diagnosed hypertensive (HT) patients, and to identify independent predictors of high-risk circadian disruptions. Methods [...] Read more.
Background: This study aimed to investigate the relationships of AHA/ACC blood pressure stages and circadian blood pressure patterns with clinical, metabolic, inflammatory, and structural echocardiographic parameters in newly diagnosed hypertensive (HT) patients, and to identify independent predictors of high-risk circadian disruptions. Methods: A total of 539 patients undergoing 24 h Ambulatory Blood Pressure Monitoring (ABPM) between 2022 and 2024 were retrospectively analyzed. Patients were grouped by nocturnal blood pressure dipping percentages and HT stages; laboratory markers (TyG index(Triglyceride–Glucose İndex), AIP(Atherogenic İndex of Plasma), SII(Systemic Immune-Inflammation Index), AISI(Aggregate Index of Systemic Inflammation), NLR(Neutrophil-to-Lymphocyte Ratio)) and echocardiographic data were evaluated via multivariable logistic regression. Results: The mean cohort age was 46.49 ± 13.98 years. Progressing HT stages were associated with significant increases in metabolic risk indicators: TyG index (p = 0.002) and AIP (p = 0.004). The prevalence of left ventricular hypertrophy (LVH) increased significantly from 7.3% in the normal group to 34.5% in Stage 2 HT (p < 0.001). The highest-risk “reverse-dipper” group had a significantly higher mean age (50.32 ± 14.55 years) than other groups (p < 0.001). In multivariable logistic regression, left atrial diameter (LAd) was the only common independent structural predictor of circadian disruption across all models (Extreme-Dipper OR: 1.19, p = 0.003; Non-Dipper OR: 1.11, p = 0.001). In the Reverse-Dipper model score analysis, both LAd (p < 0.001) and LVH (p = 0.001) demonstrated strong independent predictive potential. Inflammatory indices (SII, AISI, NLR) showed no independent predictive value (p > 0.05). Conclusions: Advanced HT stages and disrupted circadian rhythms are strongly associated with metabolic impairment, left atrial dilatation, and LVH. In older hypertensive patients presenting with left atrial enlargement and LVH, echocardiographic screening and close ABPM are crucial for early “reverse-dipper” pattern detection. Full article
(This article belongs to the Special Issue New Insights into Biomarkers in Cardiovascular Diseases)
13 pages, 7715 KB  
Article
Variation of the Neutrophil-to-Lymphocyte Ratio and Mean Platelet Volume in a Multicenter Study of Critically Ill Patients with COVID-19 Living at Different Altitudes
by Pablo Andrés Vélez-Páez, Jorge Luis Vélez-Páez, Iván Best, Luis Arturo Herrera-León, Pedro René-Torres, Jorge Vasconez-Gonzalez, Juan S. Izquierdo-Condoy and Esteban Ortiz-Prado
Med. Sci. 2026, 14(3), 363; https://doi.org/10.3390/medsci14030363 - 30 Jun 2026
Viewed by 180
Abstract
Background: Evidence on the prognostic utility of biological markers in critically ill patients with COVID-19 across different geographic altitudes remains limited. Objectives: The aim of this study was to determine the prognostic value of inflammatory and hematological markers, particularly the neutrophil-to-lymphocyte ratio (NLR) [...] Read more.
Background: Evidence on the prognostic utility of biological markers in critically ill patients with COVID-19 across different geographic altitudes remains limited. Objectives: The aim of this study was to determine the prognostic value of inflammatory and hematological markers, particularly the neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV), for mortality risk in critically ill patients with COVID-19 receiving invasive mechanical ventilation and living at different geographic altitudes. Methods: A multicenter retrospective cohort study was conducted using secondary data from a clinical database. A total of 362 critically ill patients with COVID-19 admitted to intensive care units (ICUs) between April 2020 and March 2022 were included. Patients were treated at three hospitals in Ecuador located at different altitudes: sea level (4 m above sea level [masl]), moderate altitude (2200 masl), and high altitude (2850 masl). Clinical, laboratory, and outcome data were obtained from electronic medical records. Results: The mean age was 54.44 years, and 71.27% of patients were male. Post hoc, altitude-stratified NLR and MPV thresholds were associated with increased odds of ICU mortality: at sea level, NLR ≥ 12.50 and MPV ≥ 8.80 fL; at moderate altitude, NLR ≥ 11.50 and MPV ≥ 9.80 fL; and at high altitude, NLR ≥ 16.30 and MPV ≥ 9.00 fL. Conclusions: In mechanically ventilated patients with critical COVID-19, NLR and MPV values above post hoc, altitude-stratified cutoff points were associated with higher ICU mortality. However, because each altitude stratum corresponded to a different hospital and these thresholds were not ROC-derived or internally/externally validated, these findings should be interpreted as exploratory and hypothesis-generating. Full article
(This article belongs to the Section Pneumology and Respiratory Diseases)
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21 pages, 2304 KB  
Article
Systemic Inflammatory Biomarkers as Prognostic Indicators in Metastatic Colorectal Cancer: A Retrospective Study
by Diana-Ioana Panaite, Simona-Ruxandra Volovat, Madalina Ostafe, Cezara-Ioana Litcanu, Cristian-Constantin Volovat, Maria-Luiza Baean, Ingrid-Andrada Vasilache and Constantin Volovat
Medicina 2026, 62(7), 1259; https://doi.org/10.3390/medicina62071259 - 30 Jun 2026
Viewed by 192
Abstract
Background and Objectives: Systemic inflammatory biomarkers have emerged as potential prognostic indicators in metastatic colorectal cancer (mCRC). However, the prognostic robustness of inflammatory indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), C-reactive protein-to-albumin ratio (CAR), and Glasgow Prognostic [...] Read more.
Background and Objectives: Systemic inflammatory biomarkers have emerged as potential prognostic indicators in metastatic colorectal cancer (mCRC). However, the prognostic robustness of inflammatory indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), C-reactive protein-to-albumin ratio (CAR), and Glasgow Prognostic Score (GPS) remains incompletely characterized. In this study, we aimed to evaluate the prognostic significance of NLR, PLR, CRP, CAR, and GPS for progression-free survival in metastatic colorectal cancer in a cohort of patients from Romania. Materials and Methods: This retrospective observational study included 148 patients diagnosed with mCRC. Inflammatory biomarkers were determined from baseline laboratory parameters. Progression-free survival (PFS) was the primary endpoint. Statistical analyses included correlation testing, Kaplan–Meier survival analysis, Cox proportional hazards regression, Firth penalized Cox regression, restricted cubic spline modeling, time-dependent receiver operating characteristic (ROC) analysis, LASSO penalized regression, multiple imputation, and parsimonious multivariable Cox models adjusted for major clinicopathologic confounders. Results: Median PFS was 21 months (95% CI 19–24). In univariable Cox analyses, elevated NLR (HR 1.98, 95% CI 1.11–3.51, p = 0.020), PLR (HR 1.89, 95% CI 1.25–2.85, p = 0.002), CRP (HR 1.45, 95% CI 1.15–1.83, p = 0.002), and CAR (HR 1.44, 95% CI 1.05–1.98, p = 0.022) were associated with shorter PFS. Restricted cubic spline analysis demonstrated a significant nonlinear association between NLR and PFS (p = 0.0025). After multiple imputation, NLR remained associated with shorter PFS (HR 2.04, 95% CI 1.13–3.68, p = 0.018). However, in a multivariable model adjusted for major clinicopathologic confounders, this association was not retained (HR 1.41, 95% CI 0.81–2.43, p = 0.221) and time-dependent ROC analyses demonstrated its limited discriminatory performance. Conclusions: Although some inflammatory markers were associated with shorter PFS in univariable analyses, the prognostic effect of NLR was attenuated after adjustment and was not consistently confirmed across all analyses. Full article
(This article belongs to the Section Oncology)
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18 pages, 810 KB  
Article
Serum Copper-to-Zinc Ratio and Oxidative Stress Are Associated with Anemia in Older Adults with Cardiovascular–Kidney–Metabolic Syndrome
by Giuseppe Bruschetta, Guido Gembillo, Lorenzo Lo Cicero, Angela D’Ascola, Fabio Bruno, Andrea Corsonello, Domenico Santoro, Mirko Di Rosa and Luca Soraci
Int. J. Mol. Sci. 2026, 27(13), 5840; https://doi.org/10.3390/ijms27135840 - 28 Jun 2026
Viewed by 176
Abstract
Chronic oxidative stress is a molecular hallmark of cardiovascular–kidney–metabolic (CKM) syndrome, yet its contribution to CKM-associated anemia beyond erythropoietin deficiency and iron restriction is poorly characterized. The serum copper-to-zinc (Cu/Zn) ratio reflects impaired Cu/Zn-SOD1 antioxidant capacity and inflammatory trace-element imbalance, but its relationships [...] Read more.
Chronic oxidative stress is a molecular hallmark of cardiovascular–kidney–metabolic (CKM) syndrome, yet its contribution to CKM-associated anemia beyond erythropoietin deficiency and iron restriction is poorly characterized. The serum copper-to-zinc (Cu/Zn) ratio reflects impaired Cu/Zn-SOD1 antioxidant capacity and inflammatory trace-element imbalance, but its relationships with circulating redox biomarkers and its hematological relevance in CKM syndrome has never been explored in a community-dwelling cohort of older adults. We analyzed 2,391 NHANES 2011–2016 participants ≥ 50 years of age with CKM stage I-IV. To explore whether the serum Cu/Zn ratio was associated with oxidative stress and immunomodulatory biomarkers as well as with the odds of anemia, we used survey-weighted Spearman correlations, linear regression (outcome: hemoglobin), and logistic regression (outcome: anemia); multivariate models were adjusted for a panel of antioxidant or immunomodulatory biomarkers (selenium, vitamin D), pro-oxidant biomarkers (lead, cadmium, cotinine, uric acid), red cell distribution width (RDW) as a composite biomarker of erythrocyte stress, neutrophil-to-lymphocyte ratio (NLR), CKM stage, and comorbidities. The molecular targets of the nine biomarkers were mapped onto a protein–protein interaction network using the STRING database v12.0 to contextualize regression findings within a systems biology framework. Anemia was present in 205 participants (8.6%). The Cu/Zn ratio was inversely correlated with the antioxidant marker selenium (r = −0.19; p < 0.001) and positively correlated with the pro-oxidant markers RDW (r = +0.21; p < 0.001) and cadmium (r = +0.10; p < 0.001), consistent with its role as a hub within the CKM redox network. In fully adjusted models, a higher Cu/Zn ratio was independently associated with prevalent anemia (OR = 2.94; 95% CI: 1.61–5.37) and lower hemoglobin (β = −0.55 g/dL); among included biomarkers, selenium and cadmium were independently protective (OR = 0.76 per 10 µg/L and 0.23 per µg/dL, respectively), and RDW and uric acid were independently harmful (OR = 2.20 per 1% and 1.33 per mg/dL, respectively). The Cu/Zn ratio correlated with both antioxidant depletion and pro-oxidant accumulation in CKM syndrome and was independently associated with anemia within this oxidative network. Together with selenium, cadmium, RDW, and uric acid, it defines an oxidative stress-driven hematological pathway that may contribute to the development and progression of anemia in patients with CKM syndrome. Full article
(This article belongs to the Special Issue Oxidative Stress and Disease: Basic and Biochemical Approaches)
15 pages, 3734 KB  
Article
Association of Pretreatment Immune-Inflammatory Biomarkers with Pathological Tumor Regression Following Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer
by Ahmet Sencer Ergin, Burcin Cakan Demirel, Sahin Bedir, Nida Sünnetci Arıkan, Alparslan Saylar, Ali Karabulut, Nihat Bugdayci, Tevhide Bilgen Özcan and Hüsniye Esra Pasaoglu
J. Clin. Med. 2026, 15(13), 5039; https://doi.org/10.3390/jcm15135039 - 28 Jun 2026
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Abstract
Background: Predicting tumor regression following neoadjuvant chemoradiotherapy (nCRT) remains a major challenge in the management of locally advanced rectal cancer (LARC). Readily available inflammatory biomarkers may provide useful information regarding treatment response. Methods: This retrospective single-center study included 88 patients with stage II–III [...] Read more.
Background: Predicting tumor regression following neoadjuvant chemoradiotherapy (nCRT) remains a major challenge in the management of locally advanced rectal cancer (LARC). Readily available inflammatory biomarkers may provide useful information regarding treatment response. Methods: This retrospective single-center study included 88 patients with stage II–III rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy followed by curative-intent surgery between 2017 and 2025. Patients were classified according to the College of American Pathologists tumor regression grading system as CAP 0 (pathological complete response, n = 22), CAP 2 (partial response, n = 50), or CAP 3 (poor/no response, n = 16). Pretreatment C-reactive protein, carcinoembryonic antigen (CEA), neutrophil, platelet, monocyte, and lymphocyte counts, together with NLR, PLR, and PIV, were compared across groups. Receiver operating characteristic and logistic regression analyses were performed for pathological complete response (pCR). Results: None of the evaluated biomarkers differed significantly across CAP groups. The smallest omnibus p-values were observed for neutrophil count (p = 0.052), monocyte count (p = 0.075), and CEA (p = 0.088). Monocyte count showed the highest discriminatory performance for pathological complete response (AUC = 0.663), followed by CEA (AUC = 0.640). In sensitivity analyses adjusted for baseline clinical T stage and receipt of total neoadjuvant therapy, CEA, neutrophil count, and monocyte count were not independently associated with pathological complete response. More favorable tumor regression was associated with lower residual tumor burden and reduced nodal involvement. Conclusions: Pretreatment inflammatory biomarkers showed biologically plausible numerical patterns across tumor regression groups, but their discriminatory and independent predictive performance was limited. These markers should not be considered stand-alone clinical prediction tools and should be validated within larger, multimodal prospective models. Full article
(This article belongs to the Section General Surgery)
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12 pages, 321 KB  
Article
Hematological Changes Associated with Thrombotic Events in Cancer Patients: A Retrospective Exploratory Study
by Yavuz Katırcılar, İrfan Buğday, Hacer Demir and Mevlüde İnanç
J. Clin. Med. 2026, 15(13), 4998; https://doi.org/10.3390/jcm15134998 - 26 Jun 2026
Viewed by 127
Abstract
Background: Cancer-associated thrombosis is a major cause of morbidity and mortality in oncology patients. Routinely available hematological parameters, including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and neutrophil-to-lymphocyte ratio (NLR), may reflect thrombo-inflammatory alterations accompanying thrombotic events in [...] Read more.
Background: Cancer-associated thrombosis is a major cause of morbidity and mortality in oncology patients. Routinely available hematological parameters, including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and neutrophil-to-lymphocyte ratio (NLR), may reflect thrombo-inflammatory alterations accompanying thrombotic events in malignancy. Methods: This retrospective exploratory study included 93 patients with solid malignancies who developed radiologically confirmed thrombotic events between 2006 and 2018. Clinical and laboratory data were retrospectively reviewed. Hematological parameters obtained within seven days before and after thrombotic events were compared using appropriate parametric and non-parametric statistical methods. Results: Thrombotic events were most frequently observed in patients with lung, colorectal, breast, and gastric cancers. Gastrointestinal malignancies accounted for 47.3% of cases. Venous thrombotic events represented the majority of cases (63.4%), whereas arterial thrombosis was observed in a smaller subset of patients (10.7%). Pulmonary embolism was identified in 23.7% of patients. Central venous catheter use was significantly associated with subclavian/femoral vein thrombosis (p < 0.001). PLT significantly decreased following thrombotic events (329.3 × 103/µL vs. 260.8 × 103/µL, p < 0.001), whereas MPV increased modestly (9.23 ± 1.57 fL vs. 9.40 ± 1.45 fL, p < 0.001). PDW significantly decreased (14.37 ± 2.78 vs. 13.63 ± 3.24, p = 0.011). NLR increased numerically (3.33 ± 2.32 vs. 4.26 ± 4.74) but did not reach statistical significance (p = 0.089). An inverse correlation was observed between PLT and MPV (r = −0.268, p = 0.009). Conclusions: Routinely available hematological parameters, including PLT, MPV, PDW, and NLR, demonstrated measurable alterations in cancer patients with thrombotic events and may reflect thrombo-inflammatory processes associated with malignancy. However, because of the retrospective design, heterogeneous study population, and absence of a non-thrombotic control group, these findings should be considered exploratory and hypothesis-generating rather than evidence of predictive biomarkers. Larger prospective controlled studies are required to clarify their clinical significance. Full article
(This article belongs to the Section Hematology)
13 pages, 248 KB  
Article
Routine Haematological Parameters Associated with HbA1c and Estimated Whole-Blood Viscosity in Diabetes Management: An Exploratory AIC-Based Regression Analysis
by Jovita I. Mbah, Phillip T. Bwititi, Prajwal Gyawali, Lin K. Ong and Ezekiel U. Nwose
J. Clin. Med. 2026, 15(13), 4995; https://doi.org/10.3390/jcm15134995 - 26 Jun 2026
Viewed by 173
Abstract
Background: Routine full blood count (FBC) testing is part of the haematological workup in diabetes management. There is limited information regarding the contributions of individual haematological parameters to regression models for glycated haemoglobin (HbA1c), estimated whole-blood viscosity (eWBV) and the resulting blood [...] Read more.
Background: Routine full blood count (FBC) testing is part of the haematological workup in diabetes management. There is limited information regarding the contributions of individual haematological parameters to regression models for glycated haemoglobin (HbA1c), estimated whole-blood viscosity (eWBV) and the resulting blood viscosity complications. Importantly, because association and prediction represent distinct concepts, this study extends previous work with a focus on comparative and exploratory relationships. The objective was to compare FBC parameters between higher and lower HbA1c and eWBV groups and identify variables contributing to the Akaike Information Criterion (AIC)-based regression model among diabetics. Methods: This laboratory-based mixed quantitative study involved cross-sectional and regression analyses. Fifteen parameters were evaluated, including the following: red blood cell count (RBC) and indices (MCV, MCH, MCHC); platelet count and derived ratios (PRR, PWR, RPR); and white blood cell count (WBC) with lymphocyte ratios (MLR, NLR, PLR). HbA1c and eWBV data were used to create dichotomous subgroups for univariate comparison, followed by exploratory AIC-based model identification of variables. Results: HbA1c, RDW, MCV, and RPR, differed significantly between HbA1c groups (p < 0.1). Regression analysis identified RDW, MCV, RPR, MCH and RBC as contributors to the HbA1c model. For eWBV, five out of seven parameters (HCT, HB, RBC, WBC, and MLR) showed a significant association. Conclusions: These findings highlight haematological parameters with potential values for future predictive model development. Overall, the study supports the usefulness of selected FBC variables as adjuncts in diabetes monitoring with potential utility in understanding glycaemia control and blood viscosity-related complications. Full article
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