Search Results (270)

Background/Objectives: Metabolic syndrome (MetS) and dry eye disease (DED) share inflammatory mechanisms, yet few studies have examined objective tear function and serum inflammatory markers together in this population. The aim of this study was to compare tear function tests and a panel of systemic inflammatory indices between patients with MetS who did and did not have DED. Methods: This observational comparative study enrolled 104 adults with MetS (52 MetS-DED and 52 MetS-nonDED), with group-level comparability for age and sex. All participants underwent ophthalmologic evaluation, including the Ocular Surface Disease Index (OSDI), the Schirmer I test, and fluorescein tear break-up time (TBUT). DED was defined by a mean Schirmer I value of ≤5 mm/5 min. Routine blood tests were used to derive the neutrophil-, platelet-, monocyte-, and eosinophil-to-lymphocyte ratios (NLR, PLR, MLR, ELR), the neutrophil–lymphocyte–platelet ratio (NLPR), the C-reactive protein (CRP)-to-albumin ratio, and the monocyte-to-high density lipoprotein cholesterol (HDL) ratio. Between-group comparisons, receiver operating characteristic (ROC) analysis with Youden’s index, and age- and sex-adjusted binary logistic regression were performed. Results: TBUT and Schirmer I values were significantly lower in the MetS-DED group, whereas OSDI scores did not differ between the groups. NLR, MLR, NLPR, CRP, and the CRP-to-albumin ratio were significantly higher in MetS-DED patients (all p < 0.05), while classic metabolic parameters were comparable. ROC analysis revealed statistically significant but weak-to-modest discriminatory ability (areas under the curve (AUCs) 0.617–0.652). In age- and sex-adjusted models, MLR (odds ratio (OR) = 1.072 per 0.01 unit, p = 0.046), the CRP-to-albumin ratio (OR = 1.062 per 0.01 unit, p = 0.011), and NLPR (OR = 1.123 per 0.001 unit, p = 0.038) remained significantly associated with MetS-DED. Conclusions: Among individuals with MetS, the presence of DED was accompanied by impaired tear function and a more pronounced systemic inflammatory profile despite similar metabolic parameters. However, the modest discriminatory performance and borderline adjusted associations indicate that these findings should be regarded as preliminary signals rather than evidence supporting the clinical use of these markers for screening or risk identification. Full article

Background and Objectives: Neoadjuvant dual HER2 blockade combined with chemotherapy is the standard treatment approach for patients with high-risk early-stage or locally advanced HER2-positive breast cancer. However, the optimal chemotherapy backbone and the predictive value of systemic inflammatory biomarkers remain subjects of ongoing investigation. This study aimed to compare pathologic complete response (pCR) rates between neoadjuvant dose-dense doxorubicin/cyclophosphamide followed by paclitaxel plus trastuzumab and pertuzumab (ddAC+THP) and docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP), and to evaluate the predictive performance of pretreatment inflammatory biomarkers. Materials and Methods: In this multicenter retrospective study, patients with HER2-positive breast cancer treated with neoadjuvant ddAC+THP or TCHP between 2019 and 2025 at three tertiary centers were evaluated. Pretreatment inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and hemoglobin, albumin, lymphocyte, and platelet (HALP) score, were calculated from baseline laboratory parameters. Receiver operating characteristic analyses were performed to determine optimal cutoff values, and logistic regression analyses were used to identify predictors of pCR. Results: A total of 197 patients were included, of whom 138 received ddAC+THP and 59 received TCHP. Overall, 125 patients (63.5%) achieved pCR. The pCR rate was numerically higher in the ddAC+THP group than in the TCHP group (65.2% vs. 59.3%), although the difference was not statistically significant (p = 0.431). Among the evaluated biomarkers, SIRI demonstrated the highest discriminatory performance for predicting pCR (AUC: 0.725, 95% CI: 0.652–0.797), followed by NLR (AUC: 0.673, 95% CI: 0.595–0.750). In multivariable analysis, hormone receptor positivity (OR: 0.291, 95% CI: 0.131–0.645; p = 0.002) and elevated SIRI (>0.845) (OR: 0.088, 95% CI: 0.036–0.216; p < 0.001) were independently associated with lower odds of achieving pCR. No significant difference in pCR was observed between treatment regimens across predefined subgroup analyses. Conclusions: Neoadjuvant ddAC+THP and TCHP achieved comparable pCR outcomes in patients with HER2-positive breast cancer. SIRI was independently associated with a lower likelihood of achieving pCR and showed acceptable discriminatory performance. These findings suggest that SIRI may represent an exploratory, readily available inflammatory biomarker for pCR risk stratification; however, prospective validation is required before clinical application. Full article

Background: Although gemcitabine-based palliative chemotherapy remains widely used for advanced biliary tract cancer (BTC), practical pretreatment prognostic factors are needed. This study identified baseline prognostic factors associated with overall survival (OS) and explored a simple risk stratification approach for 12-month survival in advanced BTC patients treated with gemcitabine-based chemotherapy. Methods: This retrospective cohort study included advanced BTC patients treated with gemcitabine-based palliative chemotherapy between 2011 and 2025. Baseline clinical and laboratory variables were collected at treatment initiation. The Kaplan–Meier method estimated OS. Univariable and multivariable Cox proportional hazards regression analyses identified prognostic factors. A post hoc exploratory risk score was developed using routinely available factors independently associated with OS. Results: A total of 154 patients were included, gemcitabine plus cisplatin was administered to 95 patients, whereas 59 received gemcitabine plus carboplatin. Median OS was 9.43 months. Multivariable analysis showed that ECOG performance status ≥ 2 (adjusted HR, 5.68; 95% CI, 2.52–12.81), alkaline phosphatase (ALP) ≥ 2 × ULN (adjusted HR, 1.53; 95% CI, 1.01–2.33), and neutrophil-to-lymphocyte ratio (NLR) ≥ 3 (adjusted HR, 1.51; 95% CI, 1.03–2.20) were associated with worse OS. An exploratory score assigning one point to each factor stratified patients into low-, intermediate-, and high-risk groups. The estimated 12-month OS rates were 59.6%, 40.4%, and 10.8%, respectively. Conclusions: Poor performance status, elevated ALP, and elevated NLR were associated with worse OS in advanced BTC patients receiving gemcitabine-based palliative chemotherapy. However, the associations for ALP and NLR were modest and should be interpreted cautiously. A simple exploratory score based on routinely available factors demonstrated distinct 12-month survival across risk groups and may help inform prognostic discussions in routine practice. This approach should be considered hypothesis-generating, and external validation is warranted. Full article

Background/Objectives: Systemic inflammatory markers may predict relapse in ulcerative colitis (UC), but whether histologic activity modifies their prognostic value remains unclear. We evaluated whether baseline neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and neutrophil-to-platelet ratio (NPR) predict clinical relapse in UC patients with endoscopic improvement and whether these associations differ by histologic status. Methods: This retrospective cohort study included UC patients with Mayo Endoscopic Subscore 0 or 1. Histologic status was assessed using the Geboes score and classified as histologic improvement (<3.1) or histologic activity (≥3.1). Baseline NLR, LMR, and NPR were calculated. Clinical relapse was the primary outcome. Cox proportional hazards models and Kaplan–Meier analyses were performed. Results: Histologic activity was present in 132 patients (30.3%). Baseline inflammatory indices did not differ between groups. Higher baseline NLR was associated with relapse in the histologic activity subgroup (hazard ratio [HR], 1.72; 95% confidence interval [CI], 1.06–2.92; p = 0.028), but not in the histologic improvement subgroup (HR, 0.98; 95% CI, 0.70–1.38; p = 0.901). After adjustment for endoscopic activity, high NLR remained independently associated with relapse in patients with histologic activity (HR, 1.83; 95% CI, 1.10–2.05; p = 0.021), with significant interaction by histologic status (p = 0.019). LMR and NPR were not associated with relapse. Conclusions: Histologic activity modifies the prognostic value of baseline NLR in UC patients with endoscopic improvement. Combining NLR with histologic assessment may improve relapse risk stratification. Full article

Background/Object: Early allograft dysfunction (EAD) and 90-day mortality are major challenges after liver transplantation (LT). Combined predictive utility of the delta neutrophil index (DNI), lactate clearance, and C-reactive protein/albumin ratio (CAR) in the post-LT setting remains unexplored. Methods: We conducted a single-center retrospective cohort study of 548 adult elective LT recipients (January 2010–December 2023). Serial DNI, lactate clearance, CRP, albumin, bilirubin, and INR were measured during the first postoperative week. Multivariate logistic regression identified MELD score and five postoperative predictors of 90-day mortality: Results: DNI ≥ 2.5 at POD 7 (OR 8.42, 95% CI 3.56–19.92), lactate clearance < 15% at 6 h post-reperfusion (OR 4.65), CRP/albumin ratio ≥ 8.5 at POD 3 (OR 3.28), total bilirubin ≥ 10 mg/dL at POD 7 (OR 2.94), and INR ≥ 1.6 at POD 7 (OR 2.18). A five-variable postoperative DLC composite score (0–5 points) achieved an AUC of 0.876 (95% CI 0.831–0.921) for 90-day mortality, significantly outperforming DNI alone (AUC 0.742), MELD (AUC 0.663; both p < 0.001), and a bilirubin/INR subset of the Olthoff EAD criteria (AUC 0.784; p = 0.014). In a secondary concordance analysis, the DLC score showed concordance with patients meeting EAD criteria (AUC 0.854). Risk stratification produced 90-day mortality of 2.7%, 18.4%, and 55.3% for Low-, Intermediate-, and High-risk groups. Conclusions: The DLC score demonstrates promising internal performance for risk stratification within the first postoperative week and warrants prospective external validation prior to clinical adoption. Full article

Background: Inflammation and lipid metabolism play critical roles in coronary artery calcium (CAC) progression. This study aimed to investigate the relationship between neutrophil-to-high-density lipoprotein-cholesterol ratio (NHR) and CAC score. Methods: This cross-sectional study included 2193 eligible participants from Sichuan Provincial People’s Hospital between November 2015 and July 2025. The correlation between NHR and CAC score was evaluated using multivariable logistic and multinomial logistic regression models. Restricted cubic splines (RCS) were employed to assess potential nonlinear relationships. Sensitivity analyses and subgroup analyses were performed to test the robustness of the findings. Results: Among 2193 eligible participants, 64.89% had detectable CAC. Higher NHR levels were significantly associated with increased CAC prevalence. After adjustment for multiple confounders, each 1-unit increase in NHR was associated with 9.0% higher odds of CAC (odds ratio (OR): 1.09, [95% confidence interval (CI) 1.03–1.16], p = 0.002). Compared with the lowest NHR quartile, the highest quartile was associated with modestly higher odds of CAC (OR: 1.43 [95% CI 1.05–1.95], p = 0.022). In multinomial analyses, NHR was modestly but significantly associated with CAC across mild, moderate, and severe calcification stages. The RCS analysis showed a linear relationship between NHR and CAC. Subgroup analyses and sensitivity analyses confirmed the robustness of the findings. Conclusions: Elevated NHR was associated with an increased likelihood of CAC. As a simple and readily available marker, NHR may reflect inflammatory and lipid metabolic status related to subclinical atherosclerosis, although its clinical utility requires further confirmation. Full article

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

Background/Objectives: Identifying aggressive tumor biology within early-stage hepatocellular carcinoma (HCC) remains challenging. Scores based on liver function, systemic inflammation, and HCC biomarkers have been linked to overall survival prognosis; however, the combined ability of these scores to assess tumor-specific prognosis in early-stage disease is unclear. In this single-center, prospective study, biomarker profiling with AFP, AFP-L3, and DCP, along with modified albumin–bilirubin (mALBI), and neutrophil–lymphocyte ratio (NLR)/platelet–lymphocyte ratios (PLRs) were evaluated to determine their prognostic role in assessing clinical manifestations of aggressive biology by stratifying HCC progression risk. Methods: Indices and biomarkers were assessed at BCLC-A-stage HCC diagnosis and prior to liver-directed therapy (LDT). The primary prospective study endpoint was time-to-advanced-stage tumor progression (TTP). Results: The cohort included 232 patients diagnosed with early-stage HCC who underwent treatment with LDT. A multivariate model revealed that mALBI grade (p = 0.021), cumulative lesion size (p = 0.005), and elevations in HCC biomarkers (p < 0.001) were associated with TTP. Biomarker profile stratified TTP (p < 0.001) in which patients with complex profiles (3+) had 1-year progression risks of 69%. The biomarker system retained the ability to stratify TTP within small (≤3 cm) and large (>3 cm) cumulative tumor burden (p < 0.001, p = 0.005). While PLR was not prognostic for TTP, NLR disappeared from the multivariate model and mALBI stratified long-term progression risk (p = 0.003). In low-complex biomarker patients (0–1+), mALBI stratified progression risk (p = 0.001). Conclusions: Multi-positive biomarker profiling in early-stage HCC identifies a population with clinical manifestations of aggressive tumor biology at high risk of rapid post-treatment disease progression that may benefit from more aggressive treatment approaches. In patients with low-risk biomarker profiles (0–1+), mALBI can assess longer-term (>1-year) post-treatment disease progression risk, while scores based on systemic inflammation were not associated with tumor-restricted outcomes. Full article

Objective: To evaluate the association of routine complete blood count (CBC)-derived inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation response index (SIRI), with disease activity and exploratory neuropsychiatric risk stratification in patients with systemic lupus erythematosus (SLE). Methods: In this multi-center retrospective study, 579 SLE patients and 282 healthy controls (HCs) were recruited from five clinical centers between 2018 and 2025. NLR, MLR, PLR, and SIRI were calculated from routine CBC parameters. Disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K), with high activity defined as SLEDAI-2K ≥ 10. The comparison between SLE patients and HCs was performed as an exploratory descriptive analysis to characterize systemic inflammatory profiles, whereas the primary analyses focused on associations with disease activity and NPSLE-related risk stratification. Results: SLE patients exhibited significantly higher levels of SIRI, NLR, PLR, and MLR compared to HCs (all p < 0.001). In this exploratory comparison, MLR showed the largest area under the curve for distinguishing SLE patients from HCs (AUC: 0.849, Cut-off: 0.263). In regression analyses, MLR, NLR, PLR, and SIRI were positively associated with SLEDAI-2K score. In multivariable linear regression analysis, MLR was associated with a higher SLEDAI-2K score (B = 4.600, 95% CI: 2.039–7.160, p < 0.001). In patients with available neuropsychiatric data, MLR, NLR, and SIRI were higher in patients with NPSLE than in those with non-NPSLE, whereas PLR showed no significant difference. SIRI showed modest exploratory discriminatory ability for NPSLE and may provide auxiliary information for NPSLE risk stratification (AUC: 0.710, p < 0.001, Cut-off: 1.438). Conclusions: Routine CBC-derived inflammatory biomarkers, particularly MLR, NLR, and SIRI, are associated with SLE disease activity and may serve as accessible, low-cost adjunctive tools for rapid clinical assessment. SIRI may provide additional auxiliary information for identifying patients at higher risk of neuropsychiatric involvement. However, these biomarkers should be interpreted as complementary screening or risk-stratification tools rather than substitutes for established disease activity indices or organ-specific evaluations. Further prospective studies are warranted to validate their clinical utility. Full article

Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection (Sepsis-3 definition), associated with high mortality in intensive care unit (ICU) patients. Composite immune–nutritional indices derived from routine laboratory data have emerged as accessible prognostic tools; however, their comparative value in critically ill septic patients remains insufficiently characterised. This study aimed to compare the prognostic performance of the haemoglobin–albumin–lymphocyte–platelet (HALP) score, pan-immune-inflammation value (PIV), and Naples Prognostic Score (NPS) for predicting in-hospital mortality in ICU patients with sepsis as the primary outcome, and to assess their incremental predictive value as the secondary objective. Methods: In this retrospective, two-centre cohort study, 1020 consecutive eligible adult patients fulfilling Sepsis-3 criteria (suspected or confirmed infection with an acute increase in SOFA score ≥ 2 points) admitted to the ICUs of Necmettin Erbakan University Hospital and Beyhekim Training and Research Hospital between January 2016 and June 2025 were included. HALP was calculated as haemoglobin (g/L) × albumin (g/L) × lymphocyte count (×10⁹/L) ÷ platelet count (×10⁹/L); PIV as (neutrophil × platelet × monocyte) ÷ lymphocyte (all ×10⁹/L). NPS was computed from serum albumin, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio, with the total-cholesterol component imputed due to availability in only 31.7% of patients. Discriminative performance was evaluated by receiver operating characteristic (ROC) analysis, pairwise DeLong tests, bootstrap resampling (1000 iterations), Hosmer–Lemeshow calibration, and net reclassification improvement (NRI)/integrated discrimination improvement (IDI) analyses. Five pre-specified nested multivariable logistic regression models were constructed. Results: Of 1020 patients (median age 76 years, IQR 67–83; 59.8% male), 521 (51.1%) died during hospitalisation. HALP showed the highest discriminative ability among individual indices (AUC 0.626, 95% CI 0.594–0.658), while PIV was non-discriminatory (AUC 0.504, p = 0.78) and NPS showed limited performance (AUC 0.563, 95% CI 0.531–0.595). HALP remained an independent predictor of mortality after multivariable adjustment (OR 0.98, 95% CI 0.97–0.99, p = 0.002). NRI and IDI analyses showed no incremental value with NPS addition. Conclusions: HALP demonstrated modest but independently consistent discrimination for in-hospital mortality in ICU patients with sepsis, outperforming PIV and NPS. However, an AUC of 0.626 does not support standalone clinical use; external validation and comparison with established severity models are required before integration into risk stratification frameworks. Full article

Background: Here, we propose a novel predictive scoring system incorporating age and the systemic inflammation response index (SIRI), which is calculated using neutrophil, monocyte, and lymphocyte counts, for patients with newly diagnosed primary central nervous system lymphoma (PCNSL). Methods: The study included 55 consecutive patients with sufficient blood test data and follow-up at our institution between November 2006 and May 2022. Age and SIRI were identified as prognostic factors and incorporated into a predictive multivariate Cox proportional hazards model. A scoring system of 0–2 points was created, with 1 point each assigned to age ≥ 65 years and high SIRI score (≥1.43 × 10⁹/L). We subsequently validated the predictive scoring system in an independent external validation cohort. Results: Patients with 0, 1, and 2 points were assigned to groups 1, 2, and 3, respectively. The median overall survival (OS) was 35.9 months in the entire training cohort and 57.8, 37.2, and 16.1 months in groups 1, 2, and 3, respectively. The three groups showed significant differences in median OS (p < 0.001), with lower scores corresponding to longer survival times. The performance of our new scoring system was significant in the training cohort and in the external validation cohort. Conclusion: Our new scoring system incorporating age and SIRI may serve as a preliminary prognostic model for predicting OS in patients with PCNSL. This score may be beneficial for disease risk stratification and clinical decision-making in the future. Full article

Background: Gastric cancer remains a leading cause of cancer mortality, and additional prognostic tools reflecting host inflammation and nutritional status are needed, particularly in patients receiving neoadjuvant regimens such as fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT). This study aimed to evaluate the prognostic significance of the Gustave Roussy Immune (GRIm) score in patients with locally advanced gastric cancer treated with neoadjuvant FLOT. Methods: This retrospective single-center study included 128 patients with locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma treated with neoadjuvant FLOT between 2018 and 2022. The GRIm score, based on albumin, lactate dehydrogenase (LDH), and neutrophil-to-lymphocyte ratio (NLR), was used to stratify patients into low- and high-risk groups. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier and Cox proportional hazards regression models. Results: Among 128 patients (mean age, 61.5 years; 63.3% male), 69.5% underwent surgical resection, and 24.7% achieved a pathological complete response. During a median follow-up of 36.9 months, 57.0% of patients experienced disease progression and 48.4% died. The median OS and PFS were 49.9 and 25.5 months, respectively. The GRIm score demonstrated moderate discriminative ability for mortality (area under the curve [AUC]: 0.704) and was significantly associated with survival. The median OS was shorter in the high-risk group than in the low-risk group (35.2 vs. 69.6 months, p < 0.001), and the median PFS was also shorter in the high-risk group (17.2 months vs. not reached, p < 0.001). In the multivariate analysis, high GRIm risk remained independently associated with worse OS (hazard ratio [HR]: 1.832, p = 0.030) and PFS (HR: 2.491, p < 0.001), along with age, clinical stage, and surgical resection status. Conclusions: In this single-center retrospective cohort study, the GRIm score was associated with survival outcomes in patients with locally advanced gastric or GEJ adenocarcinoma receiving neoadjuvant FLOT. These findings suggest that the GRIm score may provide additional risk stratification when interpreted in conjunction with established clinical factors. However, external validation in larger prospective cohorts is required before it can be applied in routine clinical practice. Full article

Background/Objectives: Peripheral-blood transcriptomic profiling can capture molecular heterogeneity in systemic lupus erythematosus (SLE), but discovery-stage signatures often show limited transportability across cohorts and validation layers. This study aimed to establish a staged whole-blood transcriptomic framework and to derive a compact, biologically interpretable activity score. Methods: Public whole-blood bulk transcriptome cohorts were organised into discovery, public validation, and single-cell reference layers. Local orthogonal validation included a peripheral blood mononuclear cell (PBMC) reverse transcription quantitative PCR (RT-qPCR)/flow-cytometric cohort and an expanded whole-blood RT-qPCR validation set. Discovery-stage BloodGen3 profiling included 233 samples, comprising 170 SLE and 63 healthy controls, and endotype discovery was restricted to SLE samples. Candidate genes were compressed into two 6-gene panels, with final selection adjudicated through staged public validation. Results: Two working whole-blood endotypes were identified, characterised by lymphoid versus myeloid/neutrophil-inflammatory polarisation. Although pre6-any showed a marginal discovery-stage advantage, the predefined integrated public-stage adjudication favoured pre6-balanced (MMP9, MYL9, HAL, CTLA4, CD40LG, VPREB3), which was locked as the final panel. In the PBMC cohort, the locked score discriminated SLE from healthy controls (AUC 0.838) and high from low/moderate disease activity (AUC 0.719), with associations with SLEDAI, complement C3/C4, and monocyte subpopulations. In the expanded whole-blood validation set, the score showed SLE-versus-HC discrimination (AUC 0.888, 95% CI 0.821–0.954), high versus low/moderate activity discrimination (AUC 0.918, 95% CI 0.831–0.980), and association with SLEDAI (ρ = 0.819, p = 1.25 × 10⁻¹⁵). Conclusions: This staged framework yielded a compact myeloid–lymphoid activity score supported across public and local validation layers. The score should be interpreted as a research-grade relative activity score and warrants prospective evaluation in SLE. Full article

Background: Hematological parameters derived from complete blood count (CBC) are inexpensive and widely available markers with potential utility in risk stratification of acute coronary syndrome (ACS). However, their incremental prognostic value when used alongside contemporary risk stratification tools such as the Troponin-only Manchester Acute Coronary Syndrome (T-MACS) score remains unclear. Methods: In this prospective, single-center cohort study, 521 patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina were enrolled. Admission CBC parameters (white blood cell count, neutrophils, monocytes, red cell distribution width, mean platelet volume) and derived inflammatory indices (neutrophil-to-lymphocyte ratio, white blood cell-to-mean platelet volume ratio, lymphocyte-to-monocyte ratio, mean platelet volume-to-platelet ratio, and red cell distribution width-to-platelet ratio) were recorded. T-MACS risk scores were calculated, and patients were followed for 30-day major adverse cardiac events (MACE), mortality, and coronary interventions. Associations were assessed using univariate and multivariate logistic regression analyses. Results: Patients experiencing 30-day MACE or mortality had significantly higher white blood cell counts, neutrophil counts, and WMR values (all p < 0.05). Several hematological indices showed significant associations with T-MACS risk categories. In multivariate analysis, intermediate- and high-risk T-MACS classifications independently predicted 30-day MACE (OR 4.49, 95% CI:1.46–13.77, p = 0.009; OR 9.34, 95% CI:3.00–29.03, p < 0.001, respectively), whereas white blood cell count, neutrophil count, and WMR did not demonstrate independent prognostic value beyond T-MACS classification. Conclusions: Admission white blood cell count, neutrophil count, and WMR are associated with short-term adverse outcomes and T-MACS risk severity in patients with NSTE-ACS. However, these markers do not provide additional prognostic value beyond T-MACS classification. These findings suggest that CBC-derived inflammatory markers primarily reflect disease severity rather than incremental prognostic information in the contemporary high-sensitivity troponin era. Full article

Introduction: Immunotherapy with immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis has become an established treatment strategy across various malignancies. In this context, PD-L1 expression plays a key role in the clinical management of cancer patients. However, the prognostic significance of PD-L1 expression remains inconsistent across different cancer types. This study aimed to evaluate the prevalence of PD-L1 expression in three cancer types and to examine its association with key clinicopathological parameters, systemic inflammatory markers and patient outcomes. Methods: A retrospective cohort of 141 patients with lung, breast and head and neck cancers diagnosed between 2016 and 2021 was analysed. PD-L1 expression was analysed by immunohistochemistry using clone 22C3 and the scoring system for positivity was determined according to standard clinical scoring practices for each tumour type. Systemic inflammatory markers, including the platelet-to-lymphocyte ratio (PLR), were calculated from pre-treatment blood counts. Correlation and survival analyses were performed to evaluate the associations between PD-L1 expression levels, clinicopathological characteristics and prognosis. Bioinformatics analyses using GeneMania, STRING and TIMER (v.3) databases were conducted to explore functional enrichment, protein–protein interactions and immune-cell infiltration associated with PD-L1 expression. Results: PD-L1 positivity (≥1%) was observed in 56.75% of lung cancer cases, 44% of breast cancer cases and 92.85% of head and neck cancer cases. PD-L1 expression alone was not significantly associated with overall survival across the cancer cohorts. However, it was significantly associated with PLR in the lung cancer cohort (p = 0.036). Notably, low PLR was associated with improved survival in both lung cancer (p = 0.007) and breast cancer (p = 0.031). Bioinformatics analysis identified several PD-L1-interacting genes, including PD-1, CTLA4 and PTPN and demonstrated strong positive correlations between PD-L1 expression and the infiltration of CD8+ T cells, neutrophils and dendritic cells across the analysed malignancies. Conclusions: Despite its high expression in advanced solid tumours, PD-L1 showed limited prognostic value in our cancer cohort. In contrast, systemic inflammatory markers particularly PLR, emerged as a potential indicator of clinical outcome. Our data suggest that integrating PD-L1 status with systemic inflammatory markers may improve outcome prediction and help inform therapeutic decision-making in patients with advanced malignancies. Full article