Search Results (244)

Background and Objectives: Chronic adenoiditis is a major contributor to persistent middle ear dysfunction (PMED) in children; however, clinical evolution varies considerably despite similar anatomical obstruction. This study aimed to identify inflammatory endotypes of chronic adenoiditis using unsupervised clustering and to evaluate their association with PMED through mechanistic and predictive modeling. Materials and Methods: A retrospective cohort of 236 children (3–12 years) with chronic adenoiditis and otitis media with effusion was analyzed. Clinical, endoscopic, audiological, and hematologic inflammatory parameters (eosinophils, NLR, ELR, CRP, IgE) were included. K-means clustering identified inflammatory endotypes. Associations with PMED at six months were evaluated using multivariate logistic regression and mediation analysis. Predictive performance was compared using logistic regression, random forest, and gradient boosting models, with SHAP-based interpretability and decision curve analysis. Results: Three distinct endotypes were identified: eosinophilic (28%), neutrophilic (41%), and fibrotic–obstructive (31%). PMED occurred in 44% of the fibrotic endotype compared with 22% in the eosinophilic group (p < 0.001). In multivariate analysis, the fibrotic endotype independently predicted PMED (OR = 3.48, 95% CI 1.92–6.31), alongside PTA > 30 dB (OR = 2.91) and NLR > 3.5 (OR = 2.36). Mediation analysis showed that hearing impairment accounted for 34% of the effect of anatomical obstruction on persistence. Gradient boosting achieved superior discrimination (AUC = 0.90) and demonstrated the highest net clinical benefit. Conclusions: Chronic adenoiditis comprises biologically distinct inflammatory endotypes with differential risk of persistent middle ear dysfunction. Integrating inflammatory profiling with machine learning enhances mechanistic understanding and risk stratification, supporting precision-based management in pediatric otorhinolaryngology. Full article

Background and Objectives: In real-world NSCLC management, prognostic assessment extends beyond tumour staging and molecular profiling, which represent a partial timeframe of disease biology. Routinely collected inflammatory and haematological markers may better reflect the dynamic host–tumour interactions during treatment. This study assessed the prognostic significance of baseline and longitudinal neutrophil-to-lymphocyte ratio (NLR) and haemoglobin levels on survival outcomes in a real-world NSCLC cohort. Materials and Methods: We conducted a retrospective observational cohort study of 615 patients with histologically confirmed NSCLC diagnosed between 1 May 2022 and 30 April 2024 at a tertiary referral centre in western Romania. Survival outcomes, including progression-free and overall survival, were analysed through Kaplan–Meier curves, complemented by 12-month restricted mean survival time estimates. High NLR was defined as ≥3 and low haemoglobin as <12 g/dL. Longitudinal changes were evaluated at 6 and 12 months, with 12-month analyses restricted to patients alive at that landmark. Results: The cohort had a median age of 66 years (IQR 60–72) and was predominantly male (66.3%). Most patients presented with advanced disease (60.3% stage IV, 23.6% stage III). At baseline, 57.1% (n = 351) exhibited high NLR and 39.8% (n = 245) had low haemoglobin. Median PFS was 9.0 months (IQR 4.5–15.5), and median OS was 16.5 months (IQR 8.5–27.0). Stage IV disease was associated with shorter PFS than stages I–II (7.0 vs. 20.8 months; log-rank p < 0.001). High-baseline NLR showed a borderline association with shorter PFS (adjusted HR 1.40; 95% CI 0.98–1.95). Among the 436 patients alive at 12 months, NLR increased in 56.7% of cases, and this increase showed a non-significant trend toward shorter PFS (HR 1.35; 95% CI 0.95–1.90; p = 0.09) in a 12-month landmark analysis. Conclusions: Baseline systemic inflammation and anaemia are highly prevalent in real-world NSCLC patients and cluster with advanced disease. Elevated NLR was associated with poorer survival outcomes, whereas low haemoglobin did not demonstrate a significant independent association in adjusted analyses. These haematological parameters are accessible tools for prognostic assessment in routine clinical practice. Full article

Background: Acne in adult women is increasingly recognized as a condition with systemic endocrine–metabolic correlates. Evidence linking acne to thyroid-related abnormalities and cardiometabolic risk markers remains mixed, and integrated real-world evaluations combining thyroid biochemistry, ultrasound metrics, inflammatory indices, and lipid profile are limited. Methods: We performed a cross-sectional observational analysis of 80 women with acne who underwent routine laboratory testing and thyroid ultrasound assessment. Thyroid status was defined using TSH (reference 0.4–4.5 mIU/L) and free T4 (0.8–1.8 ng/dL), with an additional TSH-only sensitivity definition (high TSH >4.5 mIU/L). Low HDL-cholesterol (HDL-C) was defined as <50 mg/dL. Group comparisons used Mann–Whitney U tests with Hodges–Lehmann shifts; associations were summarized using odds ratios (ORs) with Fisher’s exact tests; correlations used Spearman’s ρ (TSH log-transformed for correlation analyses) with confidence intervals. Multiple testing was controlled within panels using Benjamini–Hochberg FDR. Analyses were complete-case per comparison. Results: Thyroid dysfunction and metabolic–inflammatory abnormalities were common in this cohort. Low HDL-C was more frequent in thyroid dysfunction, and in the TSH-only sensitivity analysis, high TSH (>4.5 mIU/L) was strongly associated with low HDL-C (OR 13.13, 95% CI 1.48–116.04; p = 0.020). In a minimal adjusted model including NLR, high TSH remained associated with low HDL-C (adjusted OR 12.93, 95% CI 1.44–115.70; p = 0.022). HDL-C showed an inverse association with NLR (ρ = −0.28; p = 0.023). Endocrine profiling suggested a positive association between ACTH and log(TSH) (ρ = 0.62; p = 0.004), although this did not remain significant after FDR correction. Thyroid ultrasound metrics showed limited correspondence with thyroid biochemistry. Conclusions: In women with acne, elevated TSH is associated with substantially higher odds of low HDL-C, independent of inflammatory burden as proxied by NLR, while thyroid ultrasound morphology contributes limited functional information. These findings support integrated thyroid–metabolic assessment in adult female acne and motivate prospective studies incorporating acne severity measures and standardized testing to clarify clinical implications. Full article

Background: Persistent inflammation and endothelial dysfunction have been proposed as key mechanisms of post-COVID cardiovascular sequelae and may contribute to atrial fibrillation (AF). We examined whether inflammatory/prothrombotic biomarkers and endothelial function differ between post-COVID patients and controls, and whether baseline inflammation/endothelial dysfunction relates to AF burden at 12 months. Methods: In this single-center, retrospective observational study, 198 outpatients were enrolled: 99 post-COVID patients evaluated 3–6 months after documented SARS-CoV-2 infection (Group 1) and 99 age- and sex-matched controls without prior COVID-19 (Group 2). At baseline (t0), clinical characteristics, inflammatory/prothrombotic biomarkers, brachial artery flow-mediated dilation (FMD), and 24 h Holter ECG were assessed in both groups. Univariable linear regression tested associations between baseline variables and FMD in Group 1. At 12 months (t1), 24 h Holter ECG was repeated in both groups. Quartile analyses were performed according to baseline neutrophil-to-lymphocyte ratio (NLR) to explore AF distribution across inflammatory strata. Results: At baseline, post-COVID patients had higher inflammatory and prothrombotic markers than controls (ESR, CRP, fibrinogen, and D-dimer; all p < 0.0001) and markedly lower FMD (7.72 vs. 13.72; p < 0.0001). In Group 1, FMD was inversely associated with multiple inflammatory/prothrombotic markers (all p < 0.0001), with the strongest association for ESR (R² = 0.6297). Holter-detected AF prevalence at baseline did not differ significantly between groups (25/99 [25.3%] vs. 18/99 [18.2%]). At 12 months, AF prevalence was numerically higher in the post-COVID group (32/99 [32.3%] vs. 21/99 [21.2%]); on two-sided testing, this difference was borderline (p = 0.047) and should be interpreted cautiously. Across increasing baseline NLR quartiles, AF prevalence increased stepwise in both groups (post-COVID: 2/25, 5/25, 10/24, 15/25; controls: 1/25, 3/25, 7/24, 10/25), consistent with the enrichment of AF in higher-inflammatory strata. Conclusions: Post-COVID patients exhibited a persistent inflammatory–prothrombotic profile and pronounced endothelial dysfunction at baseline. At 12 months, AF burden was numerically higher post-COVID, and AF clustered in strata characterized by higher baseline NLR and lower FMD, consistent with an inflammation–endothelial dysfunction axis associated with subsequent AF burden. Prospective studies with standardized rhythm monitoring and comprehensive multivariable adjustment are warranted. Full article

Background/Objectives: Emergency surgery for complicated colon cancer carries high morbidity and mortality, largely driven by systemic inflammation and organ dysfunction. This study aims to investigate the predictive value of preoperative inflammatory biomarkers for postoperative outcomes. Methods: We retrospectively analyzed 219 patients undergoing emergency surgery for complicated colon cancer. Patients were classified as uncomplicated (n = 164) or complicated (Clavien–Dindo ≥ IIIA; n = 55). Preoperative clinical data, comorbidity indices, laboratory values, and inflammatory markers: C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were assessed. Logistic regression and ROC (Receiver Operating Characteristic) curves analyses identified predictors of Clavien Dindo complications graded as IIIA or higher, anastomotic leak (AL), and in-hospital mortality. Results: Most patients included in the study were males (75.02%), with a mean age of 69.63 (±11.54) years. Patients included in the complicated group had higher comorbidity burden, ASA (American Society of Anesthesiologists) grade, rates of diabetes, organ failure, and systemic inflammatory response. All inflammatory biomarkers were significantly elevated in the complicated group (p < 0.001). CRP (>62.8 mg/dL), NLR (>6.89), and PLR (>334.2) showed good discrimination for Clavien Dindo complications graded as IIIA or higher, with AUC (area under curve) ranging from 0.726 to 0.799. A multivariable model including Charlson Comorbidity Index (CCI), CRP, PLR, and diabetes predicted Clavien–Dindo ≥ IIIA complications with excellent accuracy (AUC 0.870). PLR, creatinine, and diabetes independently predicted AL (AUC 0.834). Mortality (20.5%) was strongly associated with peritonitis, CRP, and NLR (AUC 0.891). Conclusions: Preoperative inflammatory biomarkers, combined with comorbidity and renal function, reliably predict adverse outcomes after emergency colon cancer surgery. Multivariate models may be useful for early risk stratification and support individualized perioperative management. Full article

Background: Immune-mediated cholangitis (IMC) is a rare complication of immune checkpoint inhibitor (ICI) therapy, and its clinical characteristics and prognostic implications remain unclear. This study aimed to clarify the characteristics, risk factors, and outcomes of IMC compared with non-cholangitis cases of immune-mediated hepatotoxicity (IMH). Methods: In this single-center retrospective study, 1332 patients who received ICIs between 2014 and 2023 were analyzed. IMH was diagnosed based on liver enzyme elevation and exclusion of other liver diseases, while IMC was identified through characteristic imaging findings. Baseline factors, clinical presentations, treatment responses, and overall survival (OS) were evaluated. Multivariate analysis identified IMC risk and IMH prognostic factors. Results: Among the cohort, 81 (6.1%) patients had IMH, including 10 (0.8%) with IMC. Baseline eosinophil count > 270/μL (odds ratio [OR] 10.33, p = 0.004) and C-reactive protein (CRP) levels > 0.8 mg/dL (OR 6.260, p = 0.027) were independent predictors of IMC. IMC was associated with delayed onset, cholestatic liver injury, abdominal pain, and neutrophil-predominant inflammation. In prognostic analysis, IMC was not associated with OS. However, cholestatic liver injury (hazard ratio [HR] 2.318, p = 0.023) and neutrophil-to-lymphocyte ratio (NLR) ≥ 4.0 (HR 3.622, p = 0.001) were independent predictors of poor OS. Bile duct imaging abnormalities before or after onset were common in patients with treatment-resistant IMC. Conclusions: Baseline eosinophil count and CRP may help predict IMC. While IMC was not a prognostic factor, cholestatic injury and high NLR were associated with worse outcomes. IMC exhibits distinct clinical features, and radiologic findings may support earlier diagnosis and management. Full article

Background: Diabetic foot ulceration represents one of the most severe diabetic complications, with 50–60% progressing to diabetic foot infection (DFI). All diabetic wounds and diseases originate from peripheral vasculopathy and neuropathy, which are caused by oxidative stress and inflammatory processes. We investigated the utility of neutrophil-to-lymphocyte ratio (NLR) and CRP-to-albumin ratio (CAR) as cost-effective inflammatory biomarkers in DFI. Methods: The study included 58 DFI patients and 45 healthy controls. Disease severity was assessed using PEDIS staging. Routine laboratory parameters, NLR, derived NLR (d-NLR), and CAR were measured and compared. Results: In DFI patients, statistically significant increases (p < 0.001) were observed in NLR (3.12 vs. 1.99, p < 0.001), d-NLR (2.13 vs. 1.49, p = 0.003), CAR (0.91 vs. 0.03, p < 0.001), CRP (30.5 vs. 1.3 mg/L, p < 0.001) and PCT (0.1 vs. 0.02 μg/L, p < 0.001) values compared to the control group. Strong correlations existed between NLR, CAR and disease severity markers (CRP, PCT, HbA1c, osteomyelitis, PEDIS stage). ROC analysis revealed excellent discriminatory power for CAR (AUC = 0.915), PCT (AUC = 0.952), and CRP (AUC = 0.902), while NLR showed moderate performance (AUC = 0.702). Conclusions: NLR/CAR demonstrate excellent discrimination vs. healthy controls (AUC 0.915/0.702). The proposed workflow (NLR screening → CAR severity → PCT confirmation) requires prospective validation against with guidelines. Full article

Background: Mitral annular calcification (MAC) is associated with systemic atherosclerosis and cardiometabolic risk factors. Although hematologic inflammatory indices have been reported to be correlated with MAC, whether these associations persist after accounting for the cardiometabolic context in which MAC occurs remains unclear. Methods: In a prospective, cross-sectional study of consecutive adults, patients with mild MAC were compared to those without MAC. Individuals with major inflammatory conditions, advanced chronic kidney disease, cirrhosis, malignancy, autoimmune/acute inflammatory disorders, significant valvular disease, prosthetic valves/pacing devices, psychiatric disorders, or moderate-severe MAC were excluded. C-reactive protein (CRP) and hematological inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), Systemic Inflammatory Response Index (SIRI), and lymphocyte-to-leukocyte ratio (LLR), were analyzed in relation to MAC status. Results: Among 205 patients, 134 had mild MAC and 71 had no MAC. Patients with MAC were older and displayed higher cardiometabolic burden, including more frequent dysglycemia, higher blood pressure, and greater adiposity. In unadjusted comparisons, inflammatory markers differed according to MAC status: CRP (0.31 mg/dL vs. 0.18 mg/dL, p = 0.002), NLR (2.52 vs. 1.99, p = 0.032), SIRI (1.27 vs. 1.04, p = 0.039), and LLR (0.26 vs. 0.29, p = 0.032). In multivariable logistic regression models, none of the inflammatory markers remained independently associated with MAC. In contrast, age (ORs 1.056–1.063 per year increase, p ≤ 0.001), prediabetes (ORs 2.43–3.63, p ≤ 0.001), and type 2 diabetes (OR 5.91 and 6.19, p ≤ 0.001) demonstrated consistent independent associations with MAC across all models. Conclusions: In this cardiometabolic population with mild MAC, inflammatory indices showed unadjusted differences but no independent associations with MAC after comprehensive cardiometabolic adjustment. These findings are most compatible with inflammatory markers primarily reflecting the cardiometabolic milieu in which MAC occurs rather than representing MAC-specific processes. Age and glucose metabolism abnormalities emerged as the dominant independent factors associated with mild MAC, reinforcing the central role of metabolic dysfunction in MAC pathogenesis. Full article

Background: Cholestatic liver injury (CLI) is characterized by complex pathogenesis; however, oxidative stress-mediated inflammatory response due to bile acid accumulation in the liver is considered a primary cause. Cynarin (CN), an artichoke phytochemical, has demonstrated different biological activities, including antioxidant and anti-inflammatory ones. The current study aimed to explore the potential hepatoprotective effect of CN on CLI induced by alpha-naphthyl isothiocyanate (ANIT) in mice and investigate the possible involved mechanisms. Methods: Mice received CN (25 and 50 mg/kg) for four consecutive days and were challenged with ANIT (75 mg/kg) once on the second day. Liver injury was examined through biochemical determination of liver injury biomarkers and confirmed by histopathological evaluation. Oxidative stress biomarkers and pro-inflammatory cytokines were detected in the hepatic tissue. RT-PCR, Western blotting, and ELISA were applied to address gene and protein expression of potential underlying molecular targets, including thioredoxin-interacting protein (TXNIP), NLR family pyrin domain-containing 3 (NLRP3) inflammasome, and high-mobility group box 1 (HMGB1). Moreover, nuclear factor kappa-B (NF-κB) activation was determined by immunohistochemical analysis. Results: Our findings revealed that CN remarkably ameliorated ANIT-induced hepatic necro-inflammatory changes and biliary duct injury and restored redox balance in the liver. Mechanistically, CN markedly decreased the expression of TXNIP, NLRP3, active caspase-1, gasdermin D N-terminal (GSDMD-N), interleukin (IL)-1β, and IL-18, which were elevated upon ANIT administration. Moreover, CN suppressed ANIT-induced expression of HMGB1 and NF-κB. Conclusions: Our findings suggest that CN has a protective effect against ANIT-induced CLI in mice that is associated with modulation of the TXNIP/NLRP3 and HMGB1/NF-κB signaling cascades. Full article

Background/Objectives: Postoperative atrial fibrillation (POAF) is a common and serious complication after coronary artery bypass grafting (CABG), leading to increased morbidity and healthcare utilization. Although systemic inflammation is a well-established driver of POAF pathogenesis, no composite preoperative inflammatory biomarker has been validated for risk stratification in this population. This study aimed to evaluate the novel Inflammatory Burden Index (IBI)—the first composite biomarker combining acute-phase (C-reactive protein, CRP) and chronic cellular (neutrophil-to-lymphocyte ratio, NLR) inflammation—as a preoperative predictor of POAF after CABG. Methods: In this large retrospective cohort study, we included 3481 consecutive patients who underwent isolated CABG at a high-volume cardiac center between 2019 and 2024. Preoperative IBI was calculated as CRP (mg/dL) × NLR. The primary outcome was new-onset POAF within the first 7 postoperative days, confirmed by continuous telemetry on 12-lead ECG. Predictive performance was assessed using multivariable logistic regression, receiver operating characteristic (ROC) curve analysis (area under the curve, AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), and internal validation via bootstrapping (1000 resamples). Results: POAF developed in 866 patients (24.9%). Patients with POAF exhibited significantly higher preoperative IBI levels (39.4 ± 18.6 vs. 26.3 ± 16.7, p < 0.01). In multivariable analysis adjusted for age, hypertension, left atrial diameter, and other clinical covariates, IBI emerged as a strong independent predictor of POAF (adjusted OR 1.041, 95% CI 1.036-1.046, p < 0.01). The IBI alone demonstrated moderate-to-good discriminative performance (AUC 0.72, 95% CI 0.70–0.74), significantly outperforming the Systemic Immune/Inflammation Index (SII; AUC 0.61, DeLong test p < 0.001) and providing superior reclassification (NRI 0.150, IDI 0.032) and model fit (lower AIC). Combining IBI with established clinical risk factors further improved predictive accuracy (combined AUC 0.74, specificity 72.4%). Tertile-based stratification revealed a clear graded relationship with POAF incidence (low IBI: 16.6%, medium: 21.3%, high: 35.1%; p = 0.02). Notably, the medium IBI stratum (11.18-25.44) displayed the highest discriminative power (AUC 0.87, 95% CI 0.85-0.88), with bootstrap validation confirming model stability (minimal bias, robust 95% CI). Conclusions: This study establishes the preoperative Inflammatory Burden Index (IBI) as the first validated composite inflammatory biomarker independently associated with POAF following CABG. Its superior performance over existing indices (SII), graded risk stratification, and peak accuracy in the moderate inflammation window highlight its potential for personalized preoperative risk assessment and targeted perioperative intervention strategies. Full article

Background: Predicting natural conception following surgical treatment remains a clinical challenge for endometriosis, a chronic inflammatory condition often associated with infertility. This study aimed to determine if simple, low-cost inflammatory biomarkers, such as NLR, dNLR, LMR, PLR, SIRI, PIV, and SII calculated from routine preoperative blood tests are associated with spontaneous pregnancy in women with endometriosis-related infertility after laparoscopic surgery. Methods: A retrospective analysis was conducted on 78 women between the ages of 18 and 48 who underwent standardized laparoscopic surgery and were monitored for up to 18 months. Results: The pregnancy group had significantly lower NLR, dNLR, PLR, SIRI, and especially SII values than the non-pregnancy group. Among the evaluated markers, SII, NLR, and dNLR demonstrated the highest discriminative ability for spontaneous conception. In regression analyses, lower values of NLR and dNLR were associated with higher odds of spontaneous pregnancy. Conclusions: These findings suggest a correlation between preoperative inflammatory status and postoperative reproductive outcomes in women with endometriosis. Full article

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children presents with a heterogeneous clinical spectrum, whereas multisystem inflammatory syndrome in children (MIS-C) is a distinct immunological entity characterized by a hyperinflammatory phenotype and a distinct biological architecture. Identifying routine biomarkers with early discriminatory utility is essential for rapid differentiation between MIS-C and coronavirus disease 2019 (COVID-19). Methods: We conducted a retrospective comparative study of 144 pediatric patients with COVID-19 or MIS-C admitted to a single specialized medical center. The analyses integrated classical statistical methods, Benjamini–Hochberg false discovery rate correction (FDR), penalized regression models, and machine learning algorithms to identify biomarkers with discriminative value, using only routine laboratory tests. Results: MIS-C was associated with an intense inflammatory profile, characterized by increases in C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), lymphopenia, and selective electrolyte disturbances, highlighting a coherent biological architecture. In contrast, COVID-19 showed limited associations with traditional inflammatory markers. Predictive models identified a stable core of biomarkers with excellent performance in Random Forest analysis (area under the curve, AUC = 0.95), and reproducible thresholds (CRP ~3.7 mg/dL, NLR ~3.3, PLR ~376; potassium ~4.2 mmol/L). These findings were independently confirmed using penalized Ridge regression, where the reduced model achieved superior discrimination compared to the full 13-variable model (AUC = 0.93 vs. 0.89) and maintained stable performance under internal cross-validation, reinforcing the clinical relevance of this compact biomarker panel. Conclusions: MIS-C is clearly distinguished from COVID-19 by a specific and reproducible immunological signature. The identified biomarkers may represent a potential foundation for the development of simple clinical algorithms for pediatric triage and risk stratification, opening the prospect of a simplified scoring tool applicable in emergency settings. Full article

Diabetic retinopathy (DR) is a major microvascular complication of type 2 diabetes (T2D) and is strongly associated with chronic inflammation. Neutrophils contribute to this inflammatory milieu, and the hyperosmolar stress-responsive transcription factor NFAT5 and its downstream effector aldose reductase (AR) may play crucial roles in this process. NFAT5 regulates AR, which converts glucose to sorbitol; excessive sorbitol accumulation promotes endothelial and retinal cell damage. Given the links between NFAT5, metabolic stress and immune activation, dysregulation of the NFAT5–AR axis in neutrophils may contribute to DR pathophysiology. This study evaluated NFAT5 and AR expression in peripheral blood neutrophils from 150 individuals classified as nondiabetic (n = 50), T2D without DR (n = 50), or T2D with DR (n = 50). Clinical, metabolic, and ophthalmic assessments were performed, and neutrophils were isolated to quantify NFAT5 and AR via ELISA. Associations with renal function, plasma osmolarity (pOSM), and hematological inflammatory ratios (NLR, NMR, NPAR, and SII) were analyzed. T2D-DR subjects presented impaired renal parameters, increased pOSM, reduced eGFR, and elevated NLR and NPAR. NFAT5 and AR levels were significantly increased in T2D-DR neutrophils and correlated positively with pOSM and the inflammatory ratios, whereas NFAT5 correlated inversely with the eGFR. These findings suggest that activation of the NFAT5–AR pathway contributes to neutrophil-driven inflammatory and hyperosmolar dysregulation in T2D and may influence DR progression. Full article

Background: Chronic urticaria (CU) is characterized by recurrent wheals and/or angioedema persisting for more than six weeks. While disease triggers are often unidentified, seasonal and environmental factors may modulate disease activity; however, evidence regarding their clinical impact remains limited. Objective: This study aimed to evaluate the effects of seasonal, meteorological, and pollutant-specific environmental factors on urticaria control using the Urticaria Control Test (UCT), and to compare these effects between chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIU) in relation to inflammatory serum biomarkers. Materials and Methods: This prospective observational study was conducted at the Allergy and Clinical Immunology outpatient clinic of Kirikkale University Faculty of Medicine between 1 June 2023 and 1 April 2024. Patients with CU were classified as CSU or CIU according to international guidelines. Each participant was evaluated during summer and winter seasons. Area-level air pollution data and meteorological parameters were obtained from national monitoring systems. Disease control was assessed using the UCT, and inflammatory biomarkers were analyzed. Results: Urticaria control showed significant seasonal variation, with lower UCT scores during summer and higher scores during winter in both CSU and CIU patients. Among environmental factors, ozone (O₃) was the only pollutant consistently associated with poorer urticaria control, whereas particulate matter and traffic-related pollutants, despite being higher in winter, showed no clinically relevant association. Summer months were characterized by increased inflammatory activity, including elevated leukocyte counts, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), and D-dimer levels, particularly in CSU patients. D-dimer emerged as an independent marker associated with poor disease control during summer. Conclusions: CU demonstrates marked seasonal variation, with disease worsening during summer months. Pollutant-specific effects, particularly O₃ exposure, rather than overall air pollution burden, appear to be clinically relevant in urticaria control. Inflammatory and coagulation-related biomarkers may provide additional insight into disease activity. These findings support a season-aware and individualized management approach and highlight the need for future studies incorporating individual-level exposure assessment and biomarker-guided strategies. Full article

Objective: The aim of this study was to assess the association between the Lung Immune Prognostic Index (LIPI) measured at diagnosis and both event-free survival (EFS) and overall survival (OS) in patients with stage III non-small cell lung cancer (NSCLC). Methods: This retrospective cohort included patients diagnosed with stage III NSCLC between September 2022 and July 2024, all of whom had a minimum follow-up duration of six months. LIPI was calculated using the derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase levels at diagnosis. Clinical, demographic, and treatment-related data were systematically collected. Survival outcomes were estimated using the Kaplan–Meier approach, while factors associated with prognosis were examined through Cox proportional hazards models. Results: The study population consisted of 68 patients, predominantly male (86.8%), with a mean age of 63.4 ± 8.7 years. According to the Lung Immune Prognostic Index classification, 29 patients (42.6%) were categorized as having a good score, 27 (39.7%) as intermediate, and 12 (17.6%) as poor. During a median follow-up of 15.4 months, a total of 40 progressions and 22 deaths occurred. Median EFS was 17.7, 9.4, and 5.8 months for good, intermediate, and poor LIPI groups, respectively (p < 0.001). Median OS was 25.7 months in the good LIPI group, was not reached in the intermediate group due to insufficient events, and was 6.7 months in the poor group (p < 0.001). In multivariate Cox analysis, poor LIPI was independently associated with inferior survival (EFS: HR = 2.87, 95% CI: 1.85–4.46, p < 0.001; OS: HR = 2.59, 95% CI: 1.40–4.78, p = 0.002). Conclusions: LIPI calculated at diagnosis is an independent prognostic factor for both EFS and OS in stage III NSCLC. Validation in larger, prospective cohorts is warranted to further define its prognostic role in stage III NSCLC. Full article