Associations of Inflammatory Markers and Coronary Heart Disease in Different Gender Groups in Cohort NHANES 2003–2018

We preliminarily established the reference intervals for the systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) in healthy adults in Jiangsu region in Eastern China to guide the interpretation and application of these indicators in clinical practice. In total, 29,947 ostensibly healthy subjects from December 2020 to March 2021 were included in this study. The distributions of the SII, NLR, PLR, and LMR were analyzed using the Kolmogorov-Smirnov test. According to the C28-A3 guidelines, the 2.5th and 97.5th percentiles (P2.5 to P97.5) of the SII, NLR, PLR, and LMR were used to establish the reference intervals based on nonparametric methods. All SII, NLR, PLR, and LMR data were non-normally distributed. The levels of the SII, NLR, PLR, and LMR in healthy adults were significantly different between males and females (all p < 0.05). However, there were no significant differences in the SII, NLR, PLR or LMR among the different age groups, regardless of gender (all p > 0.05). Therefore, the reference intervals for the SII, NLR, PLR, and LMR were established based on the Sysmex testing platform for males (162 × 109/L - 811 × 109/L; 0.89 - 3.26; 63.15 - 191.34; 3.18 - 9.61) and females (165 × 109/L - 792 × 109/L; 0.87 - 3.16; 69.04 - 205.62; 3.46 - 10.96). We have established the reference intervals for SII, NLR, PLR, and LMR in healthy adults based on the Sysmex detection platform and large sample size, which may provide important guidance for its clinical application.

BackgroundThe objective of this research was to investigate the associations between inflammation markers and coronary artery disease (CAD), along with all-cause mortality and cardiovascular mortality.MethodsThis study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2003 and 2018. The platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune inflammation index (SII) were calculated based on blood test results. The diagnosis of CAD was obtained from self-reported cardiovascular health questionnaires. Participants’ survival status was sourced from the National Death Index (NDI) of the National Center for Health Statistics (NCHS). Logistic and Cox regression models were employed to investigate the associations between PLR, NLR, MLR, and SII with CAD, all-cause mortality, and cardiovascular mortality.ResultsA total of 32,683 individuals from the 2003–2018 NHANES were involved. After adjusting for potential confounders, each 1-unit increase in log (NLR) and log (MLR) was associated with a 29% (95% CI: 1.15–1.46, P < 0.001) and 67% (95% CI: 1.40–1.99, P < 0.001) increase in the risk of CAD, respectively. Notably, when log (PLR) exceeded 4.93(PLR = 138.38) and log (SII) surpassed 6.11(SII = 450.34), the risk of CAD increased sharply (P < 0.001). Furthermore, individuals in the highest quartiles (Q4) of PLR, NLR, MLR, and SII had significantly higher risks of all-cause mortality (13%, 88%, 91%, and 42%, respectively) and cardiovascular mortality (48%, 194%, 139%, and 90%, respectively) compared to those in the lowest quartile (Q1), with all P-values <0.001. Moreover, MLR had the highest the area under the curve (AUC) value (AUC:0.642, 95% CI: 0.629–0.654), followed by NLR (AUC:0.600, 95% CI: 0.587–0.612) for distinguishing CAD.ConclusionIn this study, we found that PLR, NLR, MLR, and SII were associated with increased prevalence of CAD, as well as increased risks of all-cause and cardiovascular mortality. These inflammatory markers may serve as valuable clinical indicators for CAD, all-cause and cardiovascular mortality in the general population.

Psoriasis is an immune-mediated disorder which primarily affects skin and has systemic inflammatory involvement. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and monocyte-to-lymphocyte ratio (MLR) are novel complete blood count (CBC)-derived markers which can reflect systemic inflammation. This study aimed to systematically investigate the associations of NLR, PLR, SII, and MLR with psoriasis. This study was performed in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. A comprehensive search of Pubmed, Embase, Scopus, and Google Scholar was conducted for relevant studies. Observational studies evaluating the correlations of NLR, PLR, SII, or MLR with psoriasis were included. The primary outcomes were the associations of these inflammatory markers with the presence and severity of psoriasis. The random-effect model was applied for meta-analysis. 36 studies comprising 4794 psoriasis patients and 55,121 individuals in total were included in the meta-analysis. All inflammatory markers were significantly increased in psoriasis groups compared to healthy controls (NLR: MD = 0.59, 95% CI: 0.47-0.7; PLR: MD = 15.53, 95% CI: 8.48-22.58; SII: MD = 111.58, 95% CI: 61.49-161.68; MLR: MD = 0.034, 95% CI: 0.021-0.048; all p < 0.001). Between-group mean differences in NLR and PLR were positively correlated with the mean scores of Psoriasis Area Severity Index (NLR: p = 0.041; PLR: p = 0.021). NLR, PLR, SII, and MLR are associated with the presence of psoriasis. NLR and PLR serve as significant indicators of psoriasis severity. These novel CBC-derived markers constitute potential targets in the screening and monitoring of psoriasis.

BackgroundSystemic immune-inflammatory biomarkers including systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have been demonstrated to be associated with the risk and severity of various liver diseases. However, studies on their role and clinical significance in metabolic diseases, especially in nonalcoholic fatty liver disease (NAFLD), are limited and results are inconsistent.Methods10821 adults aged 20 years or older were enrolled in this cross-sectional study, sourced from six cycles of the National Health and Nutrition Examination Survey (NHANES). Survey-weighted logistic regression was employed to investigate the correlation between systemic immune-inflammatory biomarkers (SII, NLR, PLR, and LMR) and NAFLD risk. Restricted cubic spline regression models and segmented regression models were used to describe nonlinear relationships and threshold effects. Subgroup and sensitivity analyses were also conducted.ResultsAfter adjusting for all confounding variables, there was a significant positive association observed between ln-transformed SII (OR= 1.46, 95% CI: 1.27-1.69, P <0.001), NLR (OR= 1.25, 95% CI: 1.05-1.49, P =0.015), LMR (OR= 1.39, 95% CI: 1.14-1.69, P = 0.002) with NAFLD. A nonlinear dose-response relationship with an inverted “U”-shaped threshold of 4.64 was observed between ln(PLR) and NAFLD risk. When ln(PLR) was below 4.64, each unit increase in ln(PLR) was associated with a 0.55-fold increase in the risk of NAFLD (OR= 1.55, 95% CI: 1.05-2.31, P <0.05). Conversely, when ln(PLR) exceeded 4.64, each unit increase in ln(PLR) was associated with a 0.40-fold decrease in the risk of NAFLD (OR= 0.60, 95% CI. 0.44-0.81, P <0.05).Conclusionln-transformed SII, NLR, and LMR were linearly associated with NAFLD risk. ln(PLR) showed an inverted “U”-shaped nonlinear dose-response relationship with the risk of NAFLD.

Background and aimsCurrently, most epidemiological investigations have concentrated on exploring the correlation between a singular indicator and the risk of cardiovascular disease. In clinical practice, a single indicator often fails to comprehensively represent a patient's health status. Consequently, it is crucial to thoroughly evaluate the influence of multiple indicators on disease prediction. Recently, the Triglyceride-Glucose Index (TyG Index) and inflammatory markers derived from CBC (CBC) have garnered increasing attention. Nevertheless, research on the individual and synergistic impacts of the TyG index and inflammatory indices on the risk of all-cause mortality and cardiovascular death in patients with coronary heart disease (CHD) remains scarce. To develop a more accurate risk assessment instrument for the clinic and to provide a novel strategy and framework for the management of individuals with coronary artery disease (CAD).Methods and resultsThis study identified patients with CHD aged 20 years and older from five cycles of National Health and Nutrition Examination Survey (NHANES) data spanning 2009 to 2018. We employed weighted logistic regression analysis and the restricted cubic spline (RCS) approach to investigate the TyG index and CBC-derived inflammatory indicators in relation to the risk of all-cause mortality and cardiovascular mortality in patients with CHD. The cumulative exposure effect of these measures was estimated utilizing a Weighted Quantitative Scoring (WQS) model. In the unadjusted model, ln(SII) (OR = 1.8, 95% CI = 1.05 ∼ 3.06, P = 0.032), ln(SIRI) (OR = 2.08, 95% CI = 1.45 ∼ 2.98, P < 0.001), ln(MLR) (OR = 2.53, 95% CI = 1.55 ∼ 4.13, P < 0.001), ln(NLR) (OR = 2.57, 95% CI = 1.44 ∼ 4.60, P = 0.002), and ln(PLR) (OR = 2.56, 95% CI = 1.53 ∼ 4.29, P < 0.001) exhibited a positive correlation with the risk of all-cause mortality. In the model, after comprehensive adjustment for confounders, it continued to exhibit a substantial association with the risk of mortality from CHD. RCS analysis revealed a nonlinear dose-response relationship between Monocyte-to-Lymphocyte Ratio (MLR), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Systemic Immune-Inflammation Index (SII), and Systemic Inflammation Response Index (SIRI) and the probability of all-cause mortality (P -nonlinear < 0.05). The WQS model indicated that simultaneous exposure to the TyG index and inflammatory markers derived from CBC was significantly and positively associated with the risk of all-cause mortality and cardiovascular death in patients with CAD (OR = 1.68, 95% CI = 1.22–2.30, P = 0.009, and OR = 2.2, 95% CI = 1.42–3.42, P = 0.0004), with the Neutrophil-to-Platelet Ratio (NPR) and SII being the most significant contributors to the overall risk.ConclusionOur investigation demonstrated that the TyG index and inflammatory indices generated from CBC are significant risk factors for all-cause mortality and cardiovascular mortality in patients with CHD, with NPR and SII representing the largest proportion of these factors.

This investigation examined the possibility of a relationship between neutrophil-to-lymphocyte ratio (NLR) and diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients. Adults with T2DM who were included in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2020 were the subjects of the current cross-sectional investigation. Low estimated glomerular filtration rate (eGFR) (< 60 mL/min/1.73 m2) or albuminuria (urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g) in T2DM patients were the diagnostic criteria for DKD. Weighted multivariable logistic regression models and generalized additive models were used to investigate the independent relationships between NLR levels with DKD, albuminuria, and low-eGFR. Additionally, we examined the relationships between DKD, albuminuria, and low-eGFR with other inflammatory markers, such as the aggregate index of systemic inflammation (AISI), systemic immune-inflammation index (SII), system inflammation response index (SIRI), and platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR). Their diagnostic capabilities were evaluated and contrasted using receiver operating characteristic (ROC) curves. 44.65% of the 7,153 participants who were recruited for this study were males. DKD, albuminuria, and low-eGFR were prevalent in 31.76%, 23.08%, and 14.55% of cases, respectively. Positive correlations were seen between the NLR with the prevalences of DKD, albuminuria, and low-eGFR. Subgroup analysis and interaction tests revealed that the associations of NLR with DKD, albuminuria, and low-eGFR were not significantly different across populations. In addition, MLR, SII and SIRI showed positive associations with the prevalence of DKD. ROC analysis discovered that when compared to other inflammatory markers (MLR, PLR, SII, SIRI, and AISI), NLR may demonstrate more discriminatory power and accuracy in assessing the risk of DKD, albuminuria, and low-eGFR. Compared to other inflammatory markers (MLR, PLR, SII, SIRI, and AISI), NLR may serve as the more effective potential inflammatory marker for identifying the risk of DKD, albuminuria, and low-eGFR in US T2DM patients. T2DM patients with elevated levels of NLR, MLR, SII, and SIRI should be closely monitored for their potential risk to renal function.

ABSTRACTObjectiveThis study aimed to explore the associations between inflammatory markers and the severity of early neurological dysfunction and prognosis in patients with progressive stroke (PS) and evaluated the predictive value of inflammatory markers for PS.MethodsAmong 711 acute ischemic stroke (AIS) patients, 210 patients with PS and 501 patients without PS were included. Six inflammatory markers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), systemic immune‐inflammation index (SII), systemic inflammatory response index (SIRI), and pan‐immune‐inflammation value (PIV), were measured and compared between two groups. Correlation analysis was used to analyze the correlation between inflammatory markers and early neurological dysfunction in patients with PS. Univariate and multivariate regression analyses were applied to screen the factors for the prognosis of PS patients. The receiver operating characteristic (ROC) curve was utilized to evaluate the predictive value for the prognosis of PS patients.ResultsElevated levels of NLR, LMR, SII, and PIV were observed in PS patients. Correlation analysis revealed positive correlations between NLR, PLR, SII, SIRI, PIV, and early neurological deficits, while LMR showed a negative correlation in PS patients. Multivariate analysis identified LMR and the National Institutes of Health Stroke Score (NIHSS) as independent risk factors for poor outcome of PS patients. The predictive value of LMR alone was limited (AUC = 0.59), but combining it with NIHSS improved predictive accuracy (AUC = 0.73) (p < 0.05).ConclusionThese findings suggest that inflammatory markers, particularly LMR, should be considered in PS management, and their combination with NIHSS enhances outcome prediction.

Objective: To compare the prognostic evaluation value of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) in rectal cancer patients. Nomogram survival prediction model based on inflammatory markers was constructed. Methods: The clinical and survival data of 585 patients with rectal cancer who underwent radical resection in the First Affiliated Hospital of Xi'an Jiao tong University from January 2013 to December 2016 were retrospectively analyzed. The optimal cut-off values of NLR, PLR, LMR, and SII were determined by the receiver operating characteristic (ROC) curve. The relationship between different NLR, PLR, LMR and SII levels and the clinic pathological characteristics of the rectal cancer patients were compared. Cox proportional risk model was used for univariate and multivariate regression analysis. Nomogram prediction models of overall survival (OS) and disease-free survival (DFS) of patients with rectal cancer were established by the R Language software. The internal validation and accuracy of the nomograms were determined by the calculation of concordance index (C-index). Calibration curve was used to evaluate nomograms' efficiency. Results: The optimal cut-off values of preoperative NLR, PLR, LMR and SII of OS for rectal cancer patients were 2.44, 134.88, 4.70 and 354.18, respectively. There was statistically significant difference in tumor differentiation degree between the low NLR group and the high NLR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative carcinoembryonic antigen (CEA) level between the low PLR group and the high PLR group (P<0.05). There was statistically significant difference in tumor differentiation degree between the low LMR group and the high LMR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative CEA level between the low SII group and the high SII group (P<0.05). The multivariate Cox regression analysis showed that the age (HR=2.221, 95%CI: 1.526-3.231), TNM stage (Ⅲ grade: HR=4.425, 95%CI: 1.848-10.596), grade of differentiation (HR=1.630, 95%CI: 1.074-2.474), SII level (HR=2.949, 95%CI: 1.799-4.835), and postoperative chemoradiotherapy (HR=2.123, 95%CI: 1.506-2.992) were independent risk factors for the OS of patients with rectal cancer. The age (HR=2.107, 95%CI: 1.535-2.893), TNM stage (Ⅲ grade, HR=2.850, 95%CI: 1.430-5.680), grade of differentiation (HR=1.681, 95%CI: 1.150-2.457), SII level (HR=2.309, 95%CI: 1.546-3.447), and postoperative chemoradiotherapy (HR=1.837, 95%CI: 1.369-2.464) were independent risk factors of the DFS of patients with rectal cancer. According to the OS and DFS nomograms predict models of rectal cancer patients established by multivariate COX regression analysis, the C-index were 0.786 and 0.746, respectively. The calibration curve of the nomograms showed high consistence of predict and actual curves. Conclusions: Preoperative NLR, PLR, LMR and SII levels are all correlated with the prognosis of rectal cancer patients, and the SII level is an independent prognostic risk factor for patients with rectal cancer. Preoperative SII level can complement with the age, TNM stage, differentiation degree and postoperative adjuvant chemoradiotherapy to accurately predict the prognosis of rectal cancer patients, which can provide reference and help for clinical decision.

Objective: To analyze the comprehensive blood inflammation index of the patients with stage I pneumoconiosis complicated with pulmonary infection, and to explore its value in predicting the patients' disease. Methods: In September 2023, 83 patients with stage I pneumoconiosis who were treated in Tianjin Occupational Diseases Precaution and Therapeutic Hospital from November 2021 to August 2023 were selected and divided into non-infected group (56 cases) and infected group (27 cases) according to whether they were combined with lung infection. Workers with a history of dust exposure but diagnosed without pneumoconiosis during the same period were selected as the control group (65 cases) . By referring to medical records and collecting clinical data such as gender, age, occupational history, past medical history, hematology testing, the differences in the comprehensive blood inflammation indexes among the three groups were compared, ROC curve was drawn, and the relationship between comprehensive blood inflammation indexes and stage I pneumoconiosis and its combined lung infection was analyzed. Results: There were significtant differences in the number of neutrophils (N) , the number of lymphocytes (L) , the number of monocytes (M) , C-reactive protein (CRP) , the neutrophil to lymphocyte ratio (NLR) , the monocyte to lymphocyte ratio (MLR) , the platelet to lymphocyte ratio (PLR) , the systemic immune-inflammatory index (SII) , the systemic inflammation response index (SIRI) , the aggregate index of systemic inflammation (AISI) , the derived neutrophil to lymphocyte ratio (dNLR) , the neutrophil to lymphocyte and platelet ratio (NLPR) , and the C-reactive protein to lymphocyte ratio (CLR) (P<0.05) . Compared with the control group, MLR, SIRI and AISI in the non-infected group were significantly increased (P<0.05) . NLR, MLR, PLR, SII, SIRI, AISI, dNLR, NLPR, CLR were significantly increased (P<0.05) . Compared with the non-infected group, NLR, PLR, SII, SIRI, AISI, dNLR, NLPR and CLR were significantly increased in the infected group (P<0.05) . ROC analysis showed that NLR, MLR, PLR, SII, SIRI and AISI had a certain predictive capability for stage I pneumoconiosis (P<0.05) , among which MLR had the highest efficacy, with an AUC of 0.791 (95% CI: 0.710-0.873) , the cut-off value was 0.18, the sensitivity was 71.4%, and the specificity was 78.5%. NLR, MLR, PLR, SII, SIRI, AISI, dNLR, NLPR and CLR all had a certain predictive capability forstage I pneumoconiosis combined lung infection (P<0.05) , among which CLR had the highest efficacy, with an AUC of 0.904 (95%CI: 0.824~0.985) , the cut-off value was 5.33, sensitivity was 77.8%, specificity was 98.2%. Conclusion: The comprehensive blood inflammation index may be an auxiliary predictor of stage I pneumoconiosis and its combined lung infections.

ObjectivesConvulsive status epilepticus (CSE) is a major subtype of status epilepticus that is known to be closely associated with systemic inflammation. Some important inflammatory biomarkers of this disorder include the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune inflammation index (SII), and pan-immune inflammation value (PIV). This study aimed to determine the NLR, PLR, MLR, SII, and PIV levels before and after treatment in adult patients with CSE and investigated the relationship of these parameters with disease severity.MethodsThis retrospective study analyzed data from 103 adult patients with CSE and 103 healthy controls. The neutrophil, monocyte, platelet, and lymphocyte counts, as well as the NLR, PLR, MLR, SII, and PIV, were compared in adult patients with CSE during acute seizures (within 2 h of admission) and after treatment relief (1–2 weeks of complete seizure control). Furthermore, multivariate linear regression analysis investigated the relationship between NLR, PLR, MLR, SII, and PIV with the Status Epilepticus Severity Score (STESS).ResultsThe data revealed significant differences (p < 0.05) in neutrophils, monocytes, lymphocytes, NLR, PLR, MLR, SII, and PIV between adult patients with CSE during acute seizures and after treatment relief. The average neutrophil count was high during acute seizures in the patient group and decreased after remission. In contrast, the average lymphocyte count was lower after remission (p < 0.05). Furthermore, significant differences (p < 0.05) were observed in monocytes, lymphocytes, platelets, NLR, PLR, MLR, and PIV levels between adult patients with CSE after remission and the healthy control group. Multivariate linear regression analysis showed no significant correlation between NLR, PLR, MLR, SII, and PIV with STESS.ConclusionThe results of this study indicated that adult patients with CSE experienced a transient systemic inflammatory response during acute seizures, which gradually returned to baseline levels after remission. However, there was a lack of robust clinical evidence correlating the severity of adult CSE and systemic inflammatory response.

This study aimed to evaluate the association between six complete blood count (CBC)-derived inflammatory markers [neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), systemic inflammatory response index (SIRI), and pan-immune inflammation value (PIV)] and the risk of frailty and mortality. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Mortality was identified using the National Death Index until December 31, 2019. Multiple logistic regression analysis was conducted to evaluate the association between six CBC-derived inflammatory markers and frailty. The Cox regression model assessed the association between six CBC-derived inflammatory markers and mortality in frail populations. Restricted cubic spline (RCS) was used to visualize the association of the six CBC-derived inflammatory markers with mortality risk. The predictive value of CBC-derived inflammatory markers for mortality was further assessed using a random survival forest (RSF) approach. This study analyzed data from a total of 16,705 middle-aged and older participants. Among them, 6,503 participants were frail, with a mortality rate of 41.47%. Multiple logistic regression analysis showed that NLR, MLR, PLR, SII, SIRI, and PIV were positively associated with frailty risk. The Cox regression model revealed that participants in the highest quartile had a significantly increased risk of death compared to those in the lowest quartile: NLR (HR = 1.73, 95% CI:1.54, 1.94), MLR (HR = 1.71, 95% CI:1.51, 1.93), PLR (HR = 1.28, 95%CI: 1.15, 1.43), SII (HR = 1.50, 95%CI:1.34, 1.68), SIRI (HR = 1.88, CI 95%:1.67, 2.12), PIV (HR = 1.55, 95%CI:1.38, 1.73). Random survival forest (RSF) analyses demonstrated that MLR had the highest predictive value for mortality risk middle-aged and older adult frail participants. The results suggest that CBC-derived inflammatory markers are associated with a higher risk of frailty as well as mortality in the middle and old-aged population of the United States.

We conducted this study to evaluate the diagnostic value of Inflammatory Factors (IFs) in the pathology of bladder cancer patients. The patients who were diagnosed with urothelial bladder carcinoma (bladder cancer) and underwent surgical treatment in our center from 2014 to 2019 were enrolled. The values of Neutrophil to Lymphocyte Ratio (NLR), derived Neutrophil to Lymphocyte Ratio (dNLR), Platelet to Lymphocyte Ratio (PLR), Lymphocyte to Monocyte Ratio (LMR), Systemic Immune-inflammation Index (SII), and Prognostic Nutritional Index (PNI) were calculated by blood routine test results before operation. After obtaining the postoperative pathology of the patients, the Area Under Curve (AUC) of Receiver Operating Characteristic (ROC) curves was calculated to evaluate the diagnostic value of these IFs in pathology and their corresponding cut-off values. A total of 641 bladder cancer patients were enrolled. The median values of NLR, dNLR, PLR, LMR, SII, and PNI were 6.33, 4.09, 156.47, 2.66, 1114.29, and 51.45, respectively. Grouped patients according to the pathological grade, the NLR, dNLR, PLR, and SII of the high-grade group were significantly higher than those of the low-grade group (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively), while the LMR and PNI were significantly lower than those of the low-grade group (P = 0.003 and P < 0.001). Divided patients into non-muscle invasion group (Tis + Ta + T1) and muscle invasion group (T2 + T3 + T4), in which NLR, dNLR, PLR, and SII in the muscle invasion group were significantly higher than those in the non-muscle invasion group (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively), while LMR and PNI were significantly lower than those in the low-grade group (P = 0.012 and P < 0.001). ROC curves analyses showed that NLR, dNLR, PLR, LMR, SII, and PNI had predictive value for pathological grade (P < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively) and muscle invasion (P < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively). The results suggest the higher NLR, dNLR, PLR, SII, and lower LMR and PNI are associated with higher risk of high-grade and muscle invasive disease. However, this conclusion needs to be further clarified in the future.

Background Inflammation and hyperuricemia are closely associated with chronic kidney disease (CKD). The systemic inflammation response index (SIRI), systemic immune-inflammation index (SII), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are emerging as novel biomarkers. While, the synergistic effects of these biomarkers with hyperuricemia on CKD remain unclear. Method We analyzed 10,226 participants from 2015–2020 National Health and Nutrition Examination Survey (NHANES). The relationships among inflammatory biomarkers (SIRI, SII, MLR, NLR, and PLR), hyperuricemia and CKD were assessed by multivariate logistic regression models. Restricted cubic splines (RCS) and segmented regression models were used to evaluate the nonlinear relationships. The diagnostic performance was evaluated using receiver operating characteristic (ROC) curve, and incremental predictive value was further calculated by Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI). The interaction analysis was performed to explore the combined effects. Results SIRI, SII, MLR, and NLR were significantly linked with CKD. MLR exhibited a threshold effect at 0.22 (p-non-linear < 0.05), with significantly stronger association with CKD above this cutoff. SIRI demonstrated the best diagnostic accuracy among these biomarkers. Significant interactions were observed between hyperuricemia and inflammatory biomarkers (SIRI, SII, MLR, NLR), indicating that the association between inflammatory biomarkers and CKD is more pronounced in the presence of hyperuricemia. Conclusion There were significant associations between inflammatory biomarkers (SII, SIRI, NLR, MLR) and CKD, with particularly stronger correlations observed in patients with hyperuricemia.

3048 Background: Indications for immune checkpoint inhibitor (ICI) in cancer care are expanding rapidly. There is increasing need for accurate decision tool to better guide treatment. We have constructed a new prognostic scoring system, neutrophil-lymphocyte score (NRS), based on the nonlinear dynamic change of neutrophil to lymphocyte ratio (NLR) in relation to survival over the first cycle of ICI treatment. We compared this novel system to existing indices such as NLR, lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR), Advanced Lung Cancer Inflammation Index (ALI), and Systemic Immune-inflammation Index (SII). Methods: This is a retrospective analysis of 837 patients at Ohio State University from 2011-18. Neutrophil (ANC), lymphocyte (ALC), platelet (plt), monocyte (AMC), albumin (alb), and body mass index (BMI) were collected at baseline. Repeat labs were collected at cycle 2. NLR = ANC/ALC, ALI = BMI x alb / NLR, LMR = ALC/AMC, SII = platelet x NLR, PLR = plt/ALC. NLR Ratio = baseline NLR / repeat NLR. Based on the association between NLR and the overall survival, we assigned 1 point (p) for baseline NLR &lt; 0.7, 6p for 0.7 to &lt; 2, 5p for 2 to &lt; 3, 4 p for 3 to &lt; 4, 3 for 4 to 5, 2p for 5 to &lt; 9, and 1p for ≥9. We also assigned 1p for NLR ratio &lt; 0.6, 2p for 0.6 to &lt; 0.8, 3p for 0.8 to &lt; 1.2, 5p for 1.25 to &lt; 1.4, 3p for 1.4 to &lt; 1.6, and 2p for ≥1.6. NLS = sum of these 2 scores . NLS_A = NLS*alb. Time-dependent receiver operator characteristic (ROC) curves with integrated time-dependent area under the curve (TD AUC) values were used to evaluate the predictive accuracy of each index for survival. Results: For baseline and repeat values, all indices were statistically significant (P &lt; 0.001) in predicting survival. Baseline integrated TD AUC were: ALI 0.704, NLR 0.692, SII 0.663, LMR 0.645, and PLR 0.612. All of the repeat indices at cycle 2 had higher prognostic value than their baseline counterparts. Integrated TD AUC for indices at cycle 2 were: ALI 0.740 (with baseline BMI), NLR 0.729, SII 0.694, LMR 0.671, and PLR 0.652. NLS_A was a composite score based on the dynamic change of NLR from cycle 1 to 2 and the treatment alb with integrated TD-AUC at 0.754. Conclusions: Indices constructed from ANC, ALC, AMC, Plt, alb, and BMI can be obtained inexpensively and provide great prognostic value for pts on ICI. We have constructed a novel scoring system (NLS_A) and demonstrated its improvement over the current prognostic indices. Studies with a larger cohort are needed to further improve and validate this system.

BackgroundCardiovascular-kidney-metabolic (CKM) syndrome is a major public health concern associated with increased mortality. Inflammation plays a critical role in CKM progression and outcomes. This study investigates the relationship between inflammatory indices and mortality risk in CKM patients.MethodsA comprehensive analysis of data from 26,265 participants in the National Health and Nutrition Examination Survey (NHANES) database (2007–2016) with CKM syndrome stages 0–4 was conducted. The primary outcomes of the study were all-cause and cardiovascular mortality. The inflammatory indices encompassed the systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), aggregate index of systemic inflammation (AISI), and neutrophil-to-albumin ratio (NAR). Multivariable Cox models, adjusted for demographic and clinical confounders, were employed to examine nonlinearity, alongside restricted cubic splines and threshold analyses. The present study sought to compare the prognostic accuracy of the time-dependent ROC (Receiver Operating Characteristic) at 93 months.ResultsDuring a median follow-up of 93.4 months, 2,292 subjects experienced all-cause mortality and 701 experienced cardiovascular deaths. In the adjusted models, elevated SIRI (all-cause HR 1.11, 95% CI 1.06–1.15; cardiovascular HR 1.18, 1.10–1.27), NLR (all-cause HR 1.08, 1.05–1.12; cardiovascular HR 1.11, 1.05–1.17) and MLR (all-cause HR 2.27, 1.71–3.01; cardiovascular HR 3.37, 2.09–5.44) were independently associated with mortality (all p < 0.0001). Dose–response analyses revealed nonlinear J-shaped relationships: MLR showed marked risk above 0.19 (HR 2.59), NLR risk was greatest below 3 (HR 1.14), and SIRI thresholds differed for all-cause (> 1.74, HR 1.09) versus cardiovascular (> 0.38, HR 1.17) outcomes. At 93 months, MLR demonstrated the highest discriminatory ability (AUC 0.630; C-index 0.667; p < 0.001), outperforming SIRI (AUC 0.611) and NLR (AUC 0.602). PLR, AISI, SII and NAR showed limited predictive value due to imbalanced sensitivity–specificity. The impact of age and the early stages of CKD on the modification of associations was investigated.ConclusionSystemic inflammatory indices demonstrated nonlinear, J-shaped associations with mortality in CKM syndrome, with the MLR showing the strongest association across disease trajectories. MLR, NLR, and SIRI were identified as potential risk indicators, with stronger associations observed in younger patients and those with early-stage CKM syndrome.HighlightsSystemic inflammatory markers (SIRI, NLR, MLR) were significantly associated with increased mortality risk in CKM syndrome.Most inflammation indices exhibited nonlinear, J-shaped associations with mortality.Nonlinear threshold analyses identified specific risk inflection points for SIRI, NLR, and MLR.These associations were stronger in younger patients (≤ 60 years) and those with early CKM stages (1–2).Supplementary InformationThe online version contains supplementary material available at 10.1007/s12026-025-09707-5.