Association of the systemic immune-inflammation index (SII) and severity of diabetic ketoacidosis in patients with type 1 diabetes mellitus: a retrospective cohort study.

Background: Diabetic ketoacidosis (DKA) is the most serious metabolic complication of type 1 diabetes mellitus (T1DM). Insulin deficiency and inflammation play a role in the pathogenesis of DKA. The authors aimed to assess the systemic immune-inflammation index (SII) as a marker of severity among T1DM patients with DKA and without infection. Methods: The authors included T1DM patients older than or equal to 12 years hospitalized because of DKA. The authors excluded patients with infection or any condition that can change SII parameters or cause metabolic acidosis. The authors compared SII, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) between severe and non-severe DKA groups. The authors also assessed the need for an ICU, length of stay, and 90-day readmission rate between the groups. Results: The study included 241 patients with a median age of 17 (14, 24) years, and 44.8% were males. More patients with severe DKA (45%) required ICU admission (P<0.001). Median SII increased with DKA severity, and the difference was significant (P=0.033). No significant difference was observed as regards median NLR or PLR (P=0.380 and 0.852, respectively). SII, but not NLR or PLR, had a significant negative correlation with PH (r=-0.197, P=0.002) and HCO3 level (r=-0.144, P=0.026). Also, being in the highest SII quartile was an independent risk factor for DKA severity (OR, 2.522; 95% CI, 1.063-6.08; P=0.037). The authors estimated an SII cut-off value of 2524.24 to predict DKA severity with high specificity. Conclusion: Elevated SII is a risk factor for DKA severity in T1DM. It is better than NLR and PLR in prognosticating DKA patients. These findings highlight the role of inflammation in DKA. SII can help as a valuable and simple tool to assess DKA severity.

Evaluation of systemic immune inflammation index and neutrophil-to-lymphocyte ratio in schizophrenia, bipolar disorder and depression.

OBJECTIVES: Numerous studies consistently report on the frequent presence of low-grade systemic inflammation in individuals with schizophrenia, bipolar disorder (BD), and depression. Neutrophil-to-lymphocyte ratio (NLR) and a recently established marker, systemic immune inflammation index (SII), are markers used to assess systemic inflammation and immune response. In this study, NLR and SII index values were examined and compared across patients diagnosed with major psychiatric disorders and healthy controls. METHODS: The study included, totaling 129 patients, encompassed individuals who were diagnosed with schizophrenia in remission or BD in the euthymic period, and those undergoing treatment for major depressive disorder (MDD). The control group consisted of 62 healthy individuals. White blood cell (WBC), neutrophil, lymphocyte, platelet, and monocyte counts obtained retrospectively from complete blood profiles served as the basis for calculating NLR and SII values. RESULTS: In this study, higher WBC, neutrophil counts, NLR, and SII values were observed in schizophrenia and BD patients compared to the control group. In patients with MDD, no significant difference was found in terms of inflammatory blood cell markers compared to healthy controls. Higher NLR and SII values were found in patients with schizophrenia and BD compared to patients with MDD. CONCLUSION: The results of the study indicate that the significant difference in NLR and SII values persists after treatment in patients with schizophrenia and BD, and that the abnormal inflammatory response continues during the treatment process (Tab. 2, Ref. 41).

Rheumatoid arthritis reduces the risk of colorectal cancer through immune inflammation mediation.

There is a close relationship between immune-mediated inflammation and cancer, and there is still controversy over whether rheumatoid arthritis (RA) increases the risk of malignancy. We first used Mendelian randomization (MR) analysis to explore the potential causal relationship between RA and pan-cancer. And verify the effect of immune-mediated inflammation on cancer through intermediate MR analysis. Then we extracted the standardized incidence rate of malignancy in RA patients relative to the general population through large-scale meta-analysis. Finally, we performed pan-cancer analysis on the RA related genes obtained from MR analysis. And perform immune related analysis on key genes to reveal the association between RA and malignancy. The MR analysis demonstrated a negative correlation between RA and pan-cancer (p = 0.008). Autoimmune traits were the main mediating variable for the causal relationship between RA and pan-cancer. Based on the results of the meta-analysis, we validated that RA reduces the risk of developing colorectal cancer (SIR = 0.69, 95% CI 0.53-0.85). Pan-cancer analysis also showed that high expression of RA related genes was negatively correlated with colon adenocarcinoma. IL6R was the gene with the highest correlation among them, and its correlation with immune cells was higher in colorectal cancer than in other malignancy. Our MR study provides evidence that RA was associated with reduced risk of colorectal cancer. This effect is caused by immune-mediated inflammation, with IL6R being a key regulatory gene.

Prognostic value of systemic immune-inflammation index in patients with metastatic renal cell carcinoma treated with systemic therapy: a meta-analysis.

Objective: A novel systemic immune-inflammation index (SII), based on the neutrophils, lymphocytes, and platelet counts, is associated with the prognosis of several cancers, including non-metastatic renal cell carcinoma (RCC). In the present study, we evaluate the prognostic significance of SII in patients with metastatic RCC (mRCC) treated with systemic therapy. Method: Relevant studies were searched comprehensively from Web of Science, PubMed, Embase and the Cochrane Library up to January 2024. The pooled hazard ratio (HR) and 95% confidence interval (CI) were extracted from each study to evaluate the prognostic value of SII in patients with mRCC treated with tyrosine kinase inhibitor (TKI) or immune checkpoint inhibitor (ICI). Results: A total of 12 studies including 4,238 patients were included in the final analysis. High SII was significantly correlated to poor overall survival (OS, HR = 1.88; 95% CI 1.60-2.21; P < 0.001) and progression-free survival (PFS, HR = 1.66; 95% CI 1.39-1.99; P < 0.001). Stratified by therapy, high SII was also related to the poor OS (TKI: HR = 1.63, P < 0.001; ICI: HR = 2.27, P < 0.001) and PFS (TKI: HR = 1.67, P < 0.001; ICI: HR = 1.88, P = 0.002). Conclusion: In conclusion, high SII could serve as an unfavorable factor in patients with mRCC treated with systemic therapy. Stratified by therapies, the elevated SII was also associated with worse prognosis. Whereas, more prospective and large-scale studies are warranted to validate our findings. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024522831, identifier CRD42024522831.

A Clinical Nomogram for Predicting Overall Survival in Patients With T1/T2 Penile Squamous Cell Carcinoma.

BACKGROUND: To evaluate the overall survival (OS) and construct a nomogram to predict the OS of patients with penile squamous cell carcinoma (PSCC). METHODS: This retrospective study analyzed data of patients with PSCC from the First Affiliated Hospital of Soochow University between 2012 and 2022. R software was used to explore factors influencing OS in PSCC. Kaplan-Meier method and log-rank test were employed for OS estimation. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify these factors. A nomogram was created to identify the independent prognostic factors. The model was evaluated by concordance index, receiver operating characteristic (ROC) curves, and calibration plots. RESULTS: A total of 159 patients with T1/T2 PSCC were included in the analysis. Patients with T2/N2 stage, older age, larger tumor size, high preoperative systemic immune-inflammation index (SII), and poor preoperative nutrition had a higher incidence of poor OS. Age, T/N stage, tumor size, and SII were identified as independent prognostic indicators. A prognostic nomogram was formulated, and its predictive accuracy for estimating OS in PSCC patients was validated through ROC curves and calibration plots. CONCLUSION: The nomograms, based on age, T/N stage, tumor size, and high preoperative SII, provide a valuable tool for predicting 1-, 2-, and 3-year OS in patients with T1/T2 PSCC without distant metastases.

[(Auto)immunity in focal epilepsy: mechanisms of (auto­)immune-inflammatory epileptogenic neurodegeneration]. / (Auto­)Immunität bei fokaler Epilepsie: Mechanismen (auto­)immun-inflammatorischer epileptogener Neurodegeneration.

OBJECTIVE: While the neuronal mechanisms of epileptic hyperexcitability (HE) have been studied in detail, recent findings suggest that extraneuronal, mainly immune-mediated inflammatory and vascular mechanisms play an important role in the development and progression of HE in epilepsy and the cognitive and behavioral comorbidities. MATERIAL AND METHODS: Narrative review. RESULTS: As in autoimmune (limbic) encephalitis (ALE/AIE) or Rasmussen's encephalitis (RE), the primary adaptive and innate immune responses and associated changes in the blood-brain barrier (BBB) and neurovascular unit (NVU) can cause acute cortical hyperexcitability (HE) and the development of hippocampal sclerosis (HS) and other structural cortical lesions with chronic HE. Cortical HE, which is associated with malformation of cortical development (MCD) and low-grade epilepsy-associated tumors (LEAT), for example, can be accompanied by secondary adaptive and innate immune responses and alterations in the BBB and NVU, potentially modulating the ictogenicity and epileptogenicity. These associations illustrate the influence of adaptive and innate immune mechanisms and associated changes in the BBB and NVU on cortical excitability and vice versa, suggesting a dynamic and complex interplay of these factors in the development and progression of epilepsy in general. DISCUSSION: The described concept of a neuro-immune-vascular interaction in focal epilepsy opens up new possibilities for the pathogenetic understanding and thus also for the selective therapeutic intervention.

Association between admission pan-immune-inflammation value and short-term mortality in septic patients: a retrospective cohort study.

Pan-Immune-Inflammation Value (PIV) has recently received more attention as a novel indicator of inflammation. We aimed to evaluate the association between PIV and prognosis in septic patients. Data were extracted from the Medical Information Mart for Intensive Care IV database. The primary and secondary outcomes were 28-day and 90-day mortality. The association between PIV and outcomes was assessed by Kaplan-Meier curves, Cox regression analysis, restricted cubic spline curves and subgroup analysis. A total of 11,331 septic patients were included. Kaplan-Meier curves showed that septic patients with higher PIV had lower 28-day survival rate. In multivariable Cox regression analysis, log2-PIV was positively associated with the risk of 28-day mortality [HR (95% CI) 1.06 (1.03, 1.09), P < 0.001]. The relationship between log2-PIV and 28-day mortality was non-linear with a predicted inflection point at 8. To the right of the inflection point, high log2-PIV was associated with an increased 28-day mortality risk [HR (95% CI) 1.13 (1.09, 1.18), P < 0.001]. However, to the left of this point, this association was non-significant [HR (95% CI) 1.01 (0.94, 1.08), P = 0.791]. Similar results were found for 90-day mortality. Our study showed a non-linear relationship between PIV and 28-day and 90-day mortality risk in septic patients.

Association of the systemic immune-inflammation index with all-cause and cardiovascular mortality in individuals with rheumatoid arthritis.

The systemic immune-inflammation index (SII), a metric reflecting systemic inflammatory response and immune activation, remains underexplored concerning its correlation with mortality among rheumatoid arthritis (RA) patients. This study aimed to delineate the association between SII and both all-cause and cardiovascular mortality within the cohort of American adults diagnosed with RA, utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The investigation extracted data from NHANES cycles between 1999 and 2018, identifying RA patients through questionnaire responses. The SII was computed based on complete blood counts, employing the formula: (platelets × neutrophils) / lymphocytes. The optimal SII cutoff value for significant survival outcomes was determined using maximally selected rank statistics. Multivariable Cox proportional hazards models assessed the relationship between SII levels and mortality (all-cause and cardiovascular) among RA patients, with subgroup analyses examining potential modifications by clinical confounders. Additionally, restricted cubic spline (RCS) analyses were conducted to explore the linearity of the SII-mortality association. The study encompassed 2070 American adults with RA, among whom 287 exhibited a higher SII (≥ 919.75) and 1783 a lower SII (< 919.75). Over a median follow-up duration of 108 months, 602 participants died. After adjustments for demographic, socioeconomic, and lifestyle variables, a higher SII was associated with a 1.48-fold increased risk of all-cause mortality (hazard ratio [HR] = 1.48, 95% confidence interval [CI] 1.21-1.81, P < 0.001) and a 1.51-fold increased risk of cardiovascular mortality (HR = 1.51, 95% CI 1.04-2.18, P = 0.030) compared to a lower SII. Kaplan-Meier analyses corroborated significantly reduced survival rates within the higher SII cohort for both all-cause and cardiovascular mortality (Pall-cause mortality < 0.0001 and Pcardiovascular mortality = 0.0004). RCS analyses confirmed a positive nonlinear relationship between SII and mortality rates. In conclusion, the SII offers a straightforward indicator of the equilibrium between detrimental innate inflammation and beneficial adaptive immunity. Our investigation, utilizing a comprehensive and nationally representative sample, reveals that elevated SII levels independently forecast a greater risk of mortality from all causes, as well as cardiovascular-specific mortality, in individuals suffering from RA. These insights underscore the clinical relevance of the SII as an affordable and readily accessible biomarker. Its incorporation into regular clinical practice could significantly enhance the precision of risk assessment and forecasting for patients with RA, facilitating more tailored and effective management strategies. Specifically, patients with high SII levels could be identified for more stringent cardiovascular risk management, including closer monitoring, lifestyle interventions, and aggressive pharmacological treatments to mitigate their increased risk of mortality.

The association between systemic inflammation markers and paroxysmal atrial fibrillation.

BACKGROUND: Systemic inflammation markers have recently been identified as being associated with cardiac disorders. However, limited research has been conducted to estimate the pre-diagnostic associations between these markers and paroxysmal atrial fibrillation (PAF). Our aim is to identify potential biomarkers for early detection of PAF. METHODS: 91 participants in the PAF group and 97 participants in the non-PAF group were included in this study. We investigated the correlations between three systemic inflammation markers, namely the systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), and PAF. RESULTS: The proportion of patients with PAF gradually increased with increasing logSII, logSIRI, and logAISI tertiles. Compared to those in the lowest tertiles, the PAF risks in the highest logSII and logSIRI tertiles were 3.2-fold and 2.9-fold, respectively. Conversely, there was no significant correlation observed between logAISI and PAF risk within the highest tertile of logAISI. The restricted cubic splines (RCS) analysis revealed a non-linear relationship between the elevation of systemic inflammation markers and PAF risk. Specifically, the incidence of PAF is respectively increased by 56%, 95%, and 150% for each standard deviation increase in these variables. The ROC curve analysis of logSII, logSIRI and logAISI showed that they had AUC of 0.6, 0.7 and 0.6, respectively. It also demonstrated favorable sensitivity and specificity of these systemic inflammation markers in detecting the presence of PAF. CONCLUSIONS: In conclusion, our study reveals significant positive correlations between SII, SIRI, and AISI with the incidence of PAF.

Association between inflammatory biomarkers and hypertension among sedentary adults in US: NHANES 2009-2018.

Our study focuses on the relationship between inflammatory biomarkers and hypertension among sedentary adults in the United States, using data from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. We categorized 24,614 participants into two groups based on their daily sedentary time: 9607 individuals in the sedentary group (≥7 h) and 15,007 in the non-sedentary group (<7 h). We found that the sedentary group had a significantly higher prevalence of hypertension than the non-sedentary group. Using weighted multiple logistic regression and smoothing curves, we assessed the correlation between inflammatory biomarkers and hypertension among the sedentary adults. The odds ratios for hypertension were 1.92 for the monocyte to high-density lipoprotein ratio (MHR), 1.15 for the systemic inflammation response index (SIRI), and 1.19 for the natural logarithm of the systemic immune-inflammation index (lnSII), all showing nonlinear associations. Furthermore, a significant positive correlation was found between sedentary time and inflammatory biomarkers (MHR, SIRI, and lnSII). Our findings suggest that prolonged sedentary behavior in the US significantly increases hypertension risk, likely due to marked increases in inflammation markers.

Association Between Systemic Immune Inflammation Index and Diabetes Mellitus in the NHANES 2003-2018 Population.

Objects: This study aimed to explore the association between the Systemic Immune-Inflammation Index (SII) and diabetes mellitus (DM) and to assess its influence on the prognosis of the DM and no-DM groups. Methods: The study used data from the National Health and Nutrition Examination Survey; 9643 participants were included. Logistic regression analysis was employed to evaluate connections between SII and DM. We used the Cox proportional hazards model, restricted cubic spline, and Kaplan-Meier curve to analyze the relationship between SII and mortality. Results: The logistic regression analysis indicated that a significant increase in the likelihood of developing DM with higher SII levels (odds ratio, 1.31; 95% CI, 1.09-1.57, P = .003). The Cox model showed that there is a positive association between increased SII and higher all-cause mortality. The hazard ratios for SII were 1.53 (1.31, 1.78), 1.61 (1.31, 1.98), and 1.41 (1.12, 1.78) in the total, DM and non-DM groups, respectively. We observed a linear correlation between SII and all-cause mortality in DM participants, whereas non-DM participants and the total population showed a nonlinear correlation. Conclusion: Elevated SII levels are linked to an augmented risk of DM. Those with DM and higher SII levels demonstrated an elevated risk of mortality.

The Construction of a Nomogram Using the Pan-Immune-Inflammation Value Combined with a PILE Score for Immunotherapy Prediction Prognosis in Advanced NSCLC.

Purpose: The purpose of this study was to investigate the predictive value of Pan-Immune-Inflammation Value (PIV) combined with the PILE score for immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) and to construct a nomogram prediction model to provide reference for clinical work. Patients and Methods: Patients with advanced NSCLC who received ICIs treatment in Qingdao Municipal Hospital from January 2019 to December 2021 were selected as the study subjects. The chi-square test, Kaplan-Meier survival analysis, and Cox proportional risk regression analysis were used to evaluate the prognosis. The results were visualized by a nomogram, and the performance of the model was judged by indicators such as the area under the subject operating characteristic curve (AUC) and C-index. The patients were divided into high- and low-risk groups by PILE score, and the prognosis of patients in different risk groups was evaluated. Results: Multivariate Cox regression analysis showed that immune-related adverse events (irAEs) were prognostic factors for overall survival (OS) improvement, and ECOG PS score ≥2, bone metastases before treatment, and high PIV expression were independent risk factors for OS. The C index of OS predicted by the nomogram model is 0.750 (95% CI: 0.677-0.823), and the Calibration and ROC curves show that the model has good prediction performance. Compared with the low-risk group, patients in the high-risk group of PILE were associated with a higher inflammatory state and poorer physical condition, which often resulted in a poorer prognosis. Conclusion: PIV can be used as a prognostic indicator for patients with advanced NSCLC treated with ICIs, and a nomogram prediction model can be constructed to evaluate the survival prediction of patients, thus contributing to better clinical decision-making and prognosis assessment.

The association between systemic immune-inflammation index and cardiotoxicity related to 5-Fluorouracil in colorectal cancer.

BACKGROUND AND AIMS: The cardiotoxicity related to 5-Fluorouracil (5-FU) in cancer patients has garnered widespread attention. The systemic immune-inflammation index (SII) has recently been identified as a novel predictive marker for the development of cardiovascular illnesses in individuals without pre-existing health conditions. However, it remains unclear whether the levels of SII are linked to cardiotoxicity related to 5-FU. This retrospective study aims to fill this knowledge gap by examining the correlation between SII and cardiotoxicity related to 5-FU in a colorectal cancer cohort. METHODS: The study comprised colorectal cancer patients who received 5-FU-based chemotherapy at the affiliated cancer hospital of Guizhou Medical University between January 1, 2018 and December 31, 2020. After adjustment for confounders and stratification by tertiles of the interactive factor, linear regression analyses, curve fitting and threshold effect analyses were conducted. RESULTS: Of the 754 patients included final analysis, approximately 21% (n = 156) of them ultimately experienced cardiotoxicity related to 5-FU. Monocytes (M) was found as an influential element in the interaction between SII and cardiotoxicity related to 5-FU. In the low tertile of M (T1: M ≤ 0.38 × 109/L), increasing log SII was positively correlated with cardiotoxicity related to 5-FU (Odds Ratio [OR], 8.04; 95% confidence interval [95%CI], 1.68 to 38.56). However, a curvilinear relationship between log SII and cardiotoxicity was observed in the middle tertile of M (T2: 0.38 < M ≤ 0.52 × 109/L). An increase in log SII above 1.37 was shown to be associated with a decreased risk of cardiotoxicity (OR, 0.14; 95%CI, 0.02 to 0.88), indicating a threshold effect. In the high tertile of M (T3: M > 0.52 × 109/L), there was a tendency towards a negative linear correlation between the log SII and cardiotoxicity was observed (OR, 0.85; 95%CI, 0.37 to 1.98). CONCLUSION: Our findings suggest that SII may serve as a potential biomarker for predicting cardiotoxicity related to 5-FU in colorectal cancer patients. SII is an independent risk factor for cardiotoxicity related to 5-FU with low monocytes levels (T1). Conversely, in the middle monocytes levels (T2), SII is a protective factor for cardiotoxicity related to 5-FU but with a threshold effect.

Systemic immune-inflammation index mediates the association between metabolic dysfunction-associated fatty liver disease and sub-clinical carotid atherosclerosis: a mediation analysis.

Background: Limited research has been conducted to quantitatively assess the impact of systemic inflammation in metabolic dysfunction-associated fatty liver disease (MAFLD) and sub-clinical carotid atherosclerosis (SCAS). The systemic immune-inflammation index (SII), which integrates inflammatory cells, has emerged as a reliable measure of local immune response and systemic inflammation Therefore, this study aims to assess the mediating role of SII in the association between MAFLD and SCAS in type 2 diabetes mellitus (T2DM). Method: This study prospectively recruited 830 participants with T2DM from two centers. Unenhanced abdominal CT scans were conducted to evaluate MAFLD, while B-mode carotid ultrasonography was performed to assess SCAS. Weighted binomial logistic regression analysis and restricted cubic splines (RCS) analyses were employed to analyze the association between the SII and the risk of MAFLD and SCAS. Mediation analysis was further carried out to explore the potential mediating effect of the SII on the association between MAFLD and SCAS. Results: The prevalence of both MAFLD and SCAS significantly increased as the SII quartiles increased (P<0.05). MAFLD emerged as an independent factor for SCAS risk across three adjusted models, exhibiting odds ratios of 2.15 (95%CI: 1.31-3.53, P < 0.001). Additionally, increased SII quartiles and Ln (SII) displayed positive associations with the risk of MAFLD and SCAS (P < 0.05). Furthermore, a significant dose-response relationship was observed (P for trend <0.001). The RCS analyses revealed a linear correlation of Ln (SII) with SCAS and MAFLD risk (P for nonlinearity<0.05). Importantly, SII and ln (SII) acted as the mediators in the association between MAFLD and SCAS following adjustments for shared risk factors, demonstrating a proportion-mediated effect of 7.8% and 10.9%. Conclusion: SII was independently correlated with MAFLD and SCAS risk, while also acting as a mediator in the relationship between MAFLD and SCAS.

Exploring the mechanism of luteolin improving immune and inflammatory responses in systemic sclerosis based on systems biology and cell experiments.

There is a growing trend of applying traditional Chinese medicine (TCM) to treat immune diseases. This study reveals the possible mechanism of luteolin, an active ingredient in the core prescription of TCM, in alleviating systemic sclerosis (SSc) inflammation. Bibliometrics was performed to retrieve the core keywords of SSc inflammation. The key inflammatory indicators in the serum samples of 50 SSc patients were detected by ELISA. Data mining was applied for correlation analysis, association rule analysis, and binary logistic regression analysis on the clinical indicators and medication of 50 SSc patients before and after treatment to determine the core prescription. Network pharmacology was used for identifying candidate genes and pathways; molecular docking was conducted to determine the core monomer components of the prescription, providing a basis for subsequent in vitro molecular mechanism research. The effect of luteolin on SSc-human dermal fibroblasts (HDF) viability and inflammatory factors was evaluated by means of ELISA, RT-PCR, and Western blot. The role of TNF in inflammation was explored by using a TNF overexpression vector, NF-κB inhibitor (PKM2), and SSc-HDF. The involvement of TNF/NF-κB pathway was validated by RT-PCR, Western blot, and immunofluorescence. TCM treatment partially corrected the inflammatory changes in SSc patients, indicating its anti-inflammatory effects in the body. Atractylodes, Yam, Astragalus root, Poria cocos, Pinellia ternata, Salvia miltiorrhiza, Safflower, Cassia twig, and Angelica were identified as the core prescriptions for improving inflammatory indicators. Luteolin was the main active ingredient in the prescription and showed a strong binding energy with TNF and NF-κB. Luteolin exerted anti-inflammatory effects in vitro by reducing inflammatory cytokines in SSc-HDF and inhibiting the activation of TNF/NF-κB. Mechanistically, luteolin inhibited the activation of the TNF/NF-κB pathway in SSc-HDF, as manifested by an increase in extranuclear p-P65 and TNF but a decrease in intranuclear p-P65. Interestingly, the addition of PKM2 augmented the therapeutic function of luteolin against inflammation in SSc-HDF. Our study showed the TCM alleviates the inflammatory response of SSc by inhibiting the activation of the TNF/NF-κB pathway and is an effective therapeutic agent for the treatment of SSc.

Prognostic and clinicopathological significance of systemic immune-inflammation index in upper tract urothelial carcinoma: a meta-analysis of 3911 patients.

Background: Systemic immune-inflammation index (SII), a novel prognostic indicator, is being more commonly utilized in different types of cancer. This research project involved combining information from previously published studies to examine how pre-treatment SII can predict outcomes in individuals with upper tract urothelial carcinoma (UTUC). Further examination of the correlation between SII and clinical and pathological features in UTUC. Methods: We thoroughly chose pertinent articles from various databases including PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), WanFang database, and Chinese Scientific Journal Database (VIP) until March 10, 2022.The data collected was analyzed using Stata 17.0 software (Stat Corp, College Station, TX). Subsequently, the impact of SII on the survival outcomes of UTUC patients was evaluated by combining HRs with 95% confidence intervals. Results: Six included studies were finally confirmed, including 3911 UTUC patients in seven cohorts. The results showed that high SII before treatment predicted poor overall survival (HR =1.87, 95%CI 1.20-2.92, p=0.005), cancer specific survival (HR=2.70, 95%CI 1.47-4.96, P=0.001), and recurrence-free survival (HR =1.52, 95%CI 1.12-2.07, P=0.007). And the elevated SII may be related to LVI (present vs. absent) (OR=0.83, 95% CI=0.71-0.97, p=0.018), pT stage (pT ≥3 vs. < 3) (OR=1.82, 95% CI=1.21-2.72, p=0.004), and pN stage (N+ vs. N0) (OR=3.27, 95% CI=1.60-6.71, p=0.001). Conclusion: A comprehensive analysis of all included articles in this study showed that higher pretreatment SII was related to poorer survival outcomes and adverse pathological features independently. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022316333.

Meaningful nomograms based on systemic immune inflammation index predicted survival in metastatic pancreatic cancer patients receiving chemotherapy.

OBJECTIVE: The purpose of the study is to construct meaningful nomogram models according to the independent prognostic factor for metastatic pancreatic cancer receiving chemotherapy. METHODS: This study is retrospective and consecutively included 143 patients from January 2013 to June 2021. The receiver operating characteristic (ROC) curve with the area under the curve (AUC) is utilized to determine the optimal cut-off value. The Kaplan-Meier survival analysis, univariate and multivariable Cox regression analysis are exploited to identify the correlation of inflammatory biomarkers and clinicopathological features with survival. R software are run to construct nomograms based on independent risk factors to visualize survival. Nomogram model is examined using calibration curve and decision curve analysis (DCA). RESULTS: The best cut-off values of 966.71, 0.257, and 2.54 for the systemic immunological inflammation index (SII), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR) were obtained by ROC analysis. Cox proportional-hazards model revealed that baseline SII, history of drinking and metastasis sites were independent prognostic indices for survival. We established prognostic nomograms for primary endpoints of this study. The nomograms' predictive potential and clinical efficacy have been evaluated by calibration curves and DCA. CONCLUSION: We constructed nomograms based on independent prognostic factors, these models have promising applications in clinical practice to assist clinicians in personalizing the management of patients.

Association of systemic immune-inflammation index with asthma and asthma-related events: a cross-sectional NHANES-based study.

Background: Asthma is associated with persistent airway inflammation, and numerous studies have investigated inflammatory markers causing asthma. However, the systemic immune-inflammation index (SII) is a novel inflammatory marker, with scarce research reporting on the correlation between SII and asthma and asthma-related events. Objective: The purpose of this study was to assess the relationship between SII and asthma and asthma-related events (including whether asthma is still present, asthma flare-ups in the past year, and asthma duration) using data from the National Health and Nutrition Examination Survey (NHANES). Methods: The study utilized data from NHANES 2009-2018 with asthma and asthma-related events as dependent variables and SII as an independent variable. Multifactor logistic regression was employed to assess the correlation between the independent and dependent variables. Smoothed curve-fitting and threshold effect analyses were also carried out to determine the presence of non-linear relationships. Subgroup analyses were then performed to identify sensitive populations. Results: In this study, we analyzed data from 40,664 participants to elucidate the association between SII and asthma and its related events. The study findings indicated a positive correlation between SII and asthma, with a relative risk increase of 0.03% for asthma incidence per one percentage point increase in SII (OR = 1.0003, 95% CI: 1.0002, 1.0004). For individuals still suffering from asthma, higher SII also indicated a positive correlation with ongoing asthma (OR = 1.0004, 95% CI: 1.0001, 1.0006). However, no statistically significant association was observed between SII and asthma exacerbations within the following year (OR = 1.0001, p > 0.05). When considering the duration of asthma, we observed a slight positive correlation with SII (ß = 0.0017, 95% CI: 0.0005, 0.0029). Additionally, a significant non-linear relationship between SII and asthma duration emerged at the threshold of 504.3 (ß = 0.0031, 95% CI: 0.0014-0.0048, p = 0.0003). Subgroup analysis revealed a stronger correlation between SII and asthma in male patients (OR = 1.0004, 95% CI: 1.0002-1.0006) and individuals aged 60 and above (OR = 1.0005, 95% CI: 1.0003-1.0007). No gender differences were observed for individuals still suffering from asthma. However, the positive correlation between SII and asthma was more pronounced in participants under 20 years old (OR = 1.0004 in Model 3, 95% CI: 1.0002-1.0006). Specific sensitive subgroups for asthma exacerbation recurrence within the past year were not identified. When considering asthma duration, we observed this association to be significant in male individuals (ß = 0.0031 in Model 3, 95% CI: 0.0014-0.0049) as well as individuals aged 20 to 39 (ß = 0.0023 in Model 3, 95% CI: 0.0005-0.0040). Conclusion: Our study concludes that SII is positively correlated with the persistence of asthma yet has limited predictive power for asthma recurrence. This highlights SII's potential as a tool for assessing asthma risk and formulating targeted management strategies.

The Importance of Pan-Immune Inflammation Value (PIV) in Predicting Coronary Collateral Circulation in Stable Coronary Artery Patients.

In this study, the correlation between pan-immune-inflammation value (PIV) and coronary collateral circulation (CCC) in patients with chronic coronary syndrome (CCS) was analyzed. The study included 663 patients with CCS who underwent coronary angiography and had coronary stenosis of ≥95% in at least one major coronary vessel. The participants were divided into two groups: good CCC (Rentrop score 2-3) and poor CCC (Rentrop score 0-1). PIV score was calculated as monocyte x platelet x neutrophil/lymphocyte count. When the patient groups who developed good and poor CCC were compared, neutrophil/lymphocyte ratio (NLR) (P < .001), C-reactive protein (CRP) levels, CRP/albumin ratio (CAR) (P < .001), systemic immune-inflammation index (SII) (P < .001), and PIV (P < .001) were higher in patients with poor CCC. In multivariate logistic regression analysis, age, SII, NLR, CRP, CAR, and PIV were found to be independent predictors of poor CCC (P < .001, for all). Receiver operating characteristic (ROC) analysis demonstrated that a cut-off value of 442.2 for PIV predicted poor CCC slightly better compared to other markers, with 76.8% sensitivity and 70.1% specificity (area under ROC curve = 0.808 (95% CI: 0.764-0.851), P < .001). These findings suggest that PIV can be used as an independent predictor of CCC development.