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Background: Two novel systemic inflammation indices, SII and SIRI, are associated with increased risk of cardiovascular diseases (CVD). However, SII and SIRI are prone to change over time and the association between changeable status and long-term outcome risk remains to be uncovered. This study aims to examine the association between the dynamic status of SII and SIRI and risk of CVD. Methods: This prospective study included a total of 45,809 subjects without MI, stroke and cancer prior to or in 2010 (baseline of this study). The dynamic status of SII and SIRI during 2006, 2008, and 2010 was assessed by dynamic trajectories (primary exposure), annual increase, and average value. The outcome was CVD incidence during 8.6 years' follow-up. Multiple Cox regression models were used to calculate the adjusted hazard ratios (HRs) and confidence intervals (95% CIs). Results: Four dynamic trajectories of SII and SIRI were identified as follows: low stable pattern, moderate stable pattern, increase pattern, and decrease pattern. For SII, compared with \"low stable pattern\", after controlling confounders and level of SII in 2006, adjusted HRs were 1.24 (95% CI = 1.02-1.51) for \"increase pattern\" and 1.11 (95% CI = 1.00-1.23) for \"moderate-stable pattern\" while the association was not significant for \"decrease pattern\". Additionally, the highest group of annual SII increase and average SII had respective HR of 1.20 (95% CI = 1.05-1.37) and 1.32 (95% CI = 1.13-1.55). The results were consistent for SIRI. \"Increase pattern\" and \"moderate stable pattern\" increased the risk of CVD by 38% (HR = 1.38, 95% CI = 1.17-1.63) and 12% (HR = 1.12, 95% CI = 1.01-1.25), while no significant association was found for \"decrease pattern\". The highest group of annual SIRI increase and average SIRI had respective HR of 1.25 (95% CI = 1.09-1.44) and 1.39 (95% CI = 1.19-1.63). Conclusion: Dynamic status of SII and SIRI was significantly associated with risk of CVD, which highlighted that we should focus on the dynamic change of SII and SIRI. Keywords: systemic inflammation, dynamic status, prospective study, cardiovascular diseases

Inflammatory mechanisms play important roles in intracerebral hemorrhage (ICH) and have been linked to the development of stroke-associated pneumonia (SAP). The neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) are inflammatory indexes that influence systemic inflammatory responses after stroke. In this study, we aimed to compare the predictive value of the NLR, SII, SIRI and PLR for SAP in patients with ICH to determine their application potential in the early identification of the severity of pneumonia. Patients with ICH in four hospitals were prospectively enrolled. SAP was defined according to the modified Centers for Disease Control and Prevention criteria. Data on the NLR, SII, SIRI and PLR were collected at admission, and the correlation between these factors and the clinical pulmonary infection score (CPIS) was assessed through Spearman's analysis. A total of 320 patients were enrolled in this study, among whom 126 (39.4%) developed SAP. The results of the receiver operating characteristic (ROC) analysis revealed that the NLR had the best predictive value for SAP (AUC: 0.748, 95% CI: 0.695-0.801), and this outcome remained significant after adjusting for other confounders in multivariable analysis (RR=1.090, 95% CI: 1.029-1.155). Among the four indexes, Spearman's analysis showed that the NLR was the most highly correlated with the CPIS (r=0.537, 95% CI: 0.395-0.654). The NLR could effectively predict ICU admission (AUC: 0.732, 95% CI: 0.671-0.786), and this finding remained significant in the multivariable analysis (RR=1.049, 95% CI: 1.009-1.089, P=0.036). Nomograms were created to predict the probability of SAP occurrence and ICU admission. Furthermore, the NLR could predict a good outcome at discharge (AUC: 0.761, 95% CI: 0.707-0.8147). Among the four indexes, the NLR was the best predictor for SAP occurrence and a poor outcome at discharge in ICH patients. It can therefore be used for the early identification of severe SAP and to predict ICU admission.

The systemic immune‐inflammation index (SII = N × P/L) based on neutrophil (N), platelet (P) and lymphocyte (L) counts is used to predict the survival of patients with malignant tumours and can fully reflect the balance between host inflammatory and immune status. This study is conducted to explore the potential prognostic significance of SII in patients with breast cancer undergoing neoadjuvant chemotherapy (NACT). A total of 262 patients with breast cancer received NACT were enrolled in this study. According to the receiver operating characteristic curve, the optimal cut‐off value of SII was divided into two groups: low SII group (<602 × 109/L) and high SII group (≥602 × 109/L). The associations between breast cancer and clinicopathological variables by SII were determined by chi‐squared test or Fisher's exact test. The Kaplan‐Meier plots and log‐rank test were used to determine clinical outcomes of disease‐free survival (DFS) and overall survival (OS). The prognostic value of SII was analysed by univariate and multivariate Cox proportional hazards regression models. The toxicity of NACT was accessed by National Cancer Institute Common Toxicity Criteria (NCICTC). According to univariate and multivariate Cox regression survival analyses, the results showed that the value of SII had prognostic significance for DFS and OS. The patients with low SII value had longer DFS and OS than those with high SII value (31.11 vs 40.76 months, HR: 1.075, 95% CI: 0.718‐1.610, P = .006; 44.47 vs 53.68 months, HR: 1.051, 95% CI: 0.707‐1.564, P = .005, respectively). The incidence of DFS and OS in breast cancer patients with low SII value was higher than that in those patients with high SII value in 3‐, 5‐ and 10‐year rates. The common toxicities after NACT were haematological and gastrointestinal reaction, and there were no differences by SII for the assessment of side effects of neoadjuvant chemotherapy. Meanwhile, the results also proved that breast cancer patients with low SII value and high Miller and Payne grade (MPG) survived longer than those breast cancer with high SII value and low MPG grade. In patients without lymph vessel invasion, these breast cancer patients with low SII value had better prognosis and lower recurrence rates than those with high SII value. Pre‐treatment SII with the advantage of reproducible, convenient and non‐invasive was a useful prognostic indicator for breast cancer patients undergoing neoadjuvant chemotherapy and is a promising biomarker for breast cancer on treatment strategy decisions.

Background. The rapid onset of a systemic pro-inflammatory state followed by acute respiratory distress syndrome is the leading cause of mortality in patients with COVID-19. We performed a retrospective observational study to explore the capacity of different complete blood cell count (CBC)-derived inflammation indexes to predict in-hospital mortality in this group. Methods. The neutrophil to lymphocyte ratio (NLR), derived NLR (dNLR), platelet to lymphocyte ratio (PLR), mean platelet volume to platelet ratio (MPR), neutrophil to lymphocyte × platelet ratio (NLPR), monocyte to lymphocyte ratio (MLR), systemic inflammation response index (SIRI), systemic inflammation index (SII), and the aggregate index of systemic inflammation (AISI) were calculated on hospital admission in 119 patients with laboratory confirmed COVID-19. Results. Non-survivors had significantly higher AISI, dNLR, NLPR, NLR, SII, and SIRI values when compared to survivors. Similarly, Kaplan–Meier survival curves showed significantly lower survival in patients with higher AISI, dNLR, MLR, NLPR, NLR, SII, and SIRI. However, after adjusting for confounders, only the SII remained significantly associated with survival (HR = 1.0001; 95% CI, 1.0000–1.0001, p = 0.029) in multivariate Cox regression analysis. Conclusions. The SII on admission independently predicts in-hospital mortality in COVID-19 patients and may assist with early risk stratification in this group.

BackgroundAs a novel inflammatory marker, Systemic Immune-Inflammation Index (SII) has not been studied with hepatic steatosis. The aim of this study was to investigate the possible relationship between SII and hepatic steatosis.MethodsIn the cross-sectional investigation, adults having complete information on SII, hepatic steatosis, and bariatric surgery from the 2015–2018 National Health and Nutrition Examination Survey (NHANES) were included. Hepatic steatosis was evaluated with heaptic steatosis index (HSI). The platelet count × neutrophil count/lymphocyte count was used to compute SII. We investigated the independent interaction between SII and hepatic steatosis using weighted multivariable regression analysis and subgroup analysis. To explore the potential relationship between SII, bariatric surgery and hepatic steatosis by controlling potential confounders by propensity score matching.ResultsThe study involved 10505 participants in total, 5937 (56.5%) of whom had hepatic steatosis according to the diagnosis. After adjusted for covariates, multivariable logistic regression revealed that high SII level was an independent risk factor for hepatic steatosis (OR = 1.30, 95% CI: 1.10-1.52, P 0.01). Unexpectedly, bariatric surgery reduced SII even after PSM corrected for differences of BMI and HSI.ConclusionsIn US adults, SII was positively correlated with an increase in hepatic steatosis. The SII may be a simple and affordable way to identify hepatic steatosis. Bariatric surgery may reduce SII without resorting to weight loss. This needs to be verified in additional prospective research.

Background Previous studies have confirmed that systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) can predict the prognosis and chemotherapy efficacy of various malignant tumors. However, to the best of our knowledge, no study investigated the SII combined with PNI score to predict the efficacy of anti-programmed death 1 (anti-PD-1) antibody sintilimab and XELOX regimen (capecitabine plus oxaliplatin) in the treatment of locally advanced gastric cancer. This study aims to evaluate the predictive value of pre-treatment SII-PNI score on the sensitivity of sintilimab immunotherapy combined with XELOX chemotherapy in patients with locally advanced gastric cancer. Methods We registered a prospective clinical study involving 30 locally advanced gastric cancer patients from March 2020 to July 2021. The pre-treatment SII and PNI were calculated from peripheral blood samples, and the cut-off value was calculated by receiver operating characteristic. The SII-PNI score ranged from 0 to 2 and were categorized into the following: score of 2, high SII (≥ 568.5) and low PNI (≤ 52.7); score of 1, either high SII or low PNI; score of 0, no high SII nor low PNI. Results All patients were evaluated by RECIST1.1 criteria after four cycles of sintilimab immunotherapy combined with XELOX chemotherapy, including 5 patients with TRG 3 and 25 patients with non-TRG 3. The SII-PNI score of non-TRG 3 patients was significantly lower than that of TRG 3 patients ( P  = 0.017). The medial progression free survival of patients with low SII-PNI score was significantly better than that of patients with high SII-PNI score ( P  < 0.001). Multivariate analysis showed that SII-PNI score was an independent prognostic factor for predicting progression-free survival ( P  = 0.003). Conclusion The pre-treatment SII-PNI score is a significant indicator for predicting chemosensitivity of locally advanced patients after sintilimab immunotherapy combined with XELOX chemotherapy, which can help to identify high-risk groups and predict prognosis. Trial registration : The registered name of the trial is “Prospective clinical study of sintilimab combined with chemotherapy for neoadjuvant therapy in locally advanced gastric cancer”. Its Current Controlled Trials number is ChiCTR2000030414. Its date of registration is 01/03/2020.

The current investigation examines the potential clinical value and prognostic significance of a systemic immune-inflammation index (SII) in patients with breast cancer. A total of 477 individuals underwent neoadjuvant chemotherapy, and 308 individuals did not at our center between January 1998 and December 2016 were selected. An optimized SII threshold was generated using a receiver operating characteristic curve (ROC). The relationship between various factors and breast cancer in predicting disease-free survival (DFS) and overall survival (OS) were analyzed. The SII < 560 group (Low SII group) and SII ≥ 560 group (High SII group) are divided according to the threshold value. SII was an independent predictor for breast cancer DFS and OS based on univariate and multivariate analyses. Low SII patients had higher mean DFS and OS in contrast to those in the high SII groups (46.65 vs 27.37 months and 69.92 vs 49.53 months). Those in the low SII cohort who also had early or advanced breast cancer, different molecular subtypes, and with or without lymph vessel invasion all had higher mean survival time of DFS and OS in contrast to those with raised SII values (P<0.05). The mean DFS and OS durations also varied based on different Miller and Payne grades (MPG) (P <0.005), and different response groups (P<0.05). SII can be used as an easily accessible and minimally invasive potential prognostic factor in individuals with breast cancer and may also guide clinicians in treating and prognosticating patients with breast cancer.

A novel systemic immune-inflammation index (SII) has been proven to be associated with outcomes in patients with cancer. Although some studies have shown that the SII is a potential and valuable tool to diagnose and predict the advise outcomes in stroke patients. Nevertheless, the findings are controversial, and their association with clinical outcomes is unclear. Consequently, we conducted a comprehensive review and meta-analysis to explore the relationship between SII and clinical outcomes in stroke patients. A search of five English databases (PubMed, Embase, Cochrane Library, Scopus, and Web of Science) and four Chinese databases (CNKI, VIP, WanFang, and CBM) was conducted. Our study strictly complied with the PRISMA (the Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We used the NOS (Newcastle-Ottawa Scale) tool to assess the possible bias of included studies. The endpoints included poor outcome (the modified Rankin Scale [mRS] ≥ 3 points or > 3 points), mortality, the severity of stroke (according to assessment by the National Institute of Health stroke scale [NIHSS] ≥ 5 points), hemorrhagic transformation (HT) were statistically analyzed. Nineteen retrospective studies met the eligibility criteria, and a total of 18609 stroke patients were included. Our study showed that high SII is significantly associated with poor outcomes (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02-1.09, P = 0.001, I = 93%), high mortality (OR 2.16, 95% CI 1.75-2.67, P < 0.00001, I = 49%), and the incidence of HT (OR 2.09, 95% CI 1.61-2.71, P < 0.00001, I = 42%). We also investigated the difference in SII levels in poor/good outcomes, death/survival, and minor/moderate-severe stroke groups. Our analysis demonstrated that the SII level of the poor outcome, death, and moderate-severe stroke group was much higher than that of the good outcome, survival, and minor stroke group, respectively (standard mean difference [SMD] 1.11, 95% CI 0.61-1.61, P < 0.00001 [poor/good outcome]; MD 498.22, 95% CI 333.18-663.25, P < 0.00001 [death/survival]; SMD 1.35, 95% CI 0.48-2.23, P = 0.002 [severity of stroke]). SII, on the other hand, had no significant impact on recanalization (OR 1.50, 95% CI 0.86-2.62, P = 0.16). To the best of our knowledge, this may be the first meta-analysis to look at the link between SII and clinical outcomes in stroke patients. The inflammatory response after a stroke is useful for immunoregulatory treatment. Stroke patients with high SII should be closely monitored, since this might be a viable treatment strategy for limiting brain damage after a stroke. As a result, research into SII and the clinical outcomes of stroke patients is crucial. Our preliminary findings may represent the clinical condition and aid clinical decision-makers. Nonetheless, further research is needed to better understand the utility of SII through dynamic monitoring. To generate more robust results, large-sample and multi-center research are required. https://www.crd.york.ac.uk/prospero/, identifier CRD42022371996.

A novel systemic immune-inflammation index named SII (SII=N×P/L), which is based on neutrophil (N), platelet (P) and lymphocyte (L) counts, has emerged and reflects comprehensively the balance of host inflammatory and immune status. We aimed to evaluate the potential prognostic significance of SII in patients with advanced gastric cancer who received neoadjuvant chemotherapy. The retrospective analysis included data from 107 patients with advanced gastric cancer undergoing neoadjuvant chemotherapy and 185 patients with pathology-proven gastric cancer. The optimal cutoff value of SII by receiver operating characteristic curve stratified patients into low SII (<600×10 /L) and high SII (SII ≥600×10 /L) groups. The clinical outcomes of disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier survival curves and compared using log-rank test. Univariate and multivariate Cox proportional hazards regression models were used to analyze the prognostic value of SII. The results indicated that SII had prognostic significance using the cutoff value of 600×10 /L on DFS and OS in univariate and multivariate Cox regression survival analyses. Low SII was associated with prolonged DFS and OS, and the mean DFS and OS for patients with low SII were longer than for those with high SII (57.22 vs 41.56 months and 62.25 vs 45.60 months, respectively). Furthermore, we found that patients with low SII had better 1-, 3- and 5-year rates of DFS and OS than those with high SII. In addition, patients with low SII were likely to receive DFS and OS benefits from neoadjuvant chemotherapy and postoperative chemotherapy. SII may qualify as a noninvasive, cost-effective, convenient and reproducible prognostic indicator for patients with advanced gastric cancer undergoing neoadjuvant chemotherapy. It may help clinicians to identify those patients who will benefit from treatment strategy decisions.

BackgroundInflammatory biomarkers in the peripheral blood have been established as predictors for immunotherapeutic efficacy in advanced non-small cell lung cancer (NSCLC). Whether they can also predict major pathological response (MPR) in neoadjuvant setting remains unclear.MethodsIn this multi-center retrospective study, 122 and 92 stage I-IIIB NSCLC patients from six hospitals who received neoadjuvant chemoimmunotherapy followed by surgery were included in the discovery and external validation cohort, respectively. Baseline and on-treatment neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII) were calculated and associated with MPR. Furthermore, resected tumor samples from 37 patients were collected for RNA-sequencing to investigate the immune-related tumor microenvironment.ResultsIn both the discovery and validation cohorts, the on-treatment NLR, dNLR, PLR, and SII levels were significantly lower in the patients with MPR versus non-MPR. On-treatment SII remained an independent predictor of MPR in multivariate logistic regression analysis. The area under the curve (AUC) of on-treatment SII for predicting MPR was 0.75 (95%CI, 0.67–0.84) in the discovery cohort. Moreover, the predictive value was further improved by combining the on-treatment SII and radiological tumor regression data, demonstrating an AUC of 0.82 (95%CI, 0.74–0.90). The predictive accuracy was validated in the external cohort. Compared with the SII-high group, patients with SII-Low were associated with the activated B cell receptor signaling pathway and a higher intratumoral immune cell infiltration level.ConclusionsOn-treatment SII was independently associated with MPR in NSCLC patients receiving neoadjuvant chemoimmunotherapy. Further prospective studies are warranted.