Pretreatment neutrophil-to-lymphocyte ratio as an important prognostic marker in stage III locally advanced non-small cell lung cancer: confirmatory results from the PROCLAIM phase III clinical trial

BackgroundNeutrophil-to-lymphocyte ratio (NLR) is an important pretreatment marker of systemic inflammation and tumor aggressiveness. Increased levels of this ratio have been associated with reduced survival in several observational studies of lung cancer. However, supporting analyses from large clinical trial data are lacking.MethodsTo validate the prognostic role of NLR, the current study evaluated data from a randomized phase III study (PROCLAIM; clinicaltrial.gov ID: {"type":"clinical-trial","attrs":{"text":"NCT00686959","term_id":"NCT00686959"}}NCT00686959) of patients with stage IIIA/B, unresectable, non-squamous, non-small cell lung cancer (NSCLC), originally comparing combination pemetrexed-cisplatin chemoradiotherapy with etoposide-cisplatin chemoradiotherapy. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for survival were estimated using a Cox proportional hazards model. Models were adjusted for age, race, sex, stage, treatment, and body mass index (BMI). Patients were followed for a median of 24 months.ResultsIncreased NLR levels at baseline were associated with reduced overall (P_Trend <0.0001) and progression-free survival (P_Trend <0.005). A similar but decreasing linear trend was not observed for lymphocytes count alone.ConclusionsThese findings provide substantiating evidence that NLR, which is routinely available from standard blood testing of patients diagnosed with NSCLC, is an important inflammation-based prognostic marker for survival among patients with locally advanced disease undergoing chemoradiation. Future research will benefit by assessing the prognostic potential of NLR in the context of genetic mutations and molecular markers.     

NLR及ESE-3转录因子在胃癌患者中表达及其与预后的关系

目的探讨中性粒细胞淋巴细胞比值(NLR)及上皮转录调控因子(ESE)-3转录因子在胃癌组织中的表达及其与预后的关系。方法选择初次行胃癌根治术患者82例,采用免疫组化法检测胃癌组织及癌旁组织ESE-3、CD133蛋白表达情况,并检测术前NLR及血小板与淋巴细胞比率(PLR)水平,分析胃癌组织ESE-3、CD133及NLR、PLR与患者临床病理特征相关性,采用Kaplan-Meier法绘制生存曲线,分析NLR及ESE-3对胃癌患者预后的影响。结果胃癌组织中ESE-3阳性表达(81.7%)显著高于癌旁组织(54.9%,P0.05),阳性颗粒主要定位于细胞核中;胃癌组织中CD133阳性表达为51.2%,癌旁组织均为阴性;胃癌组织ESE-3表达阳性率与患者TNM分期及浸润深度明显相关,胃癌组织CD133表达阳性率、NLR高水平及PLR高水平与患者肿瘤分化程度、TNM分期及浸润深度明显相关(P0.05),而与患者性别、年龄、肿瘤大小、淋巴结转移无相关(P0.05);胃癌组织中ESE-3阴性表达患者术后生存时间明显优于阳性表达患者,NLR低水平患者术后生存时间明显优于NLR高水平患者(P0.05)。结论 NLR及ESE-3表达与胃癌发生发展及预后密切相关,ESE-3可能是胃癌一种潜在的预后标志物和治疗靶点。     

Immune inflammation indicators and ALBI score to predict liver cancer in HCV-patients treated with direct-acting antivirals

BackgroundUnexpectedly high occurrence or recurrence rate of hepatocellular carcinoma (HCC) has been observed in patients with chronic hepatitis C receiving direct-acting antivirals (DAAs) therapy.AimsWe evaluated the predictive value of albumin-bilirubin (ALBI) score and immune-inflammation indicators to identify the risk of occurrence or recurrence of HCC in patients treated with DAAs in a real life setting.MethodsIn this retrospective cohort study, we analysed data from 514 patients with cirrhosis who were prospectively enrolled for treatment with DAAs. We assessed baseline neutrophil to lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet to lymphocyte ratio (PLR), aspartate aminotransferase-lymphocyte ratio (ALRI) index and ALBI score.ResultsIn patients with no history of HCC (N = 416), increased AST, bilirubin, ALRI, and ALBI score, and decreased albumin and platelets were significantly associated with an increased risk of HCC development, at univariate analysis. At multivariate analysis, increase in ALBI grade (p = 0.038, HR: 2.35, 95% CI: 1.05–5.25) and decrease in platelets (p = 0.048, HR: 0.92, 95% CI: 0.85–1.0) were independently associated with HCC development. In patients with previous HCC (N = 98), adjusting for the time from HCC treatment, increased ALRI (p = 0.008, HR: 1.05, 95% CI: 1.01–1.09) was significantly associated with a risk of recurrence.ConclusionALBI score, platelet count and ALRI are promising, easy to perform and inexpensive tools for identifying patients with higher risk of HCC after treatment with DAAs.     

炎性小体在脑缺血中的作用

固有免疫在脑缺血后炎性损伤中发挥重要作用,其中炎性小体被认为是一个关键因素.炎性小体是一种大分子蛋白质复合物,可识别各种病原体相关分子模式和损伤相关分子模式介导免疫炎性反应.研究显示,脑缺血或脑缺血再灌注可诱导NLRP1和NLRP3炎性小体激活.文章对炎性小体的结构、活化、调控以及在脑缺血中的作用进行了综述.     

Neutrophil lymphocyte ratio significantly improves the Framingham risk score in prediction of coronary heart disease mortality: Insights from the National Health and Nutrition Examination Survey-III

Background

Neutrophil lymphocyte ratio (NLR) has been shown to predict cardiovascular events in several studies. We sought to study if NLR predicts coronary heart disease (CHD) in a healthy US cohort and if it reclassifies the traditional Framingham risk score (FRS) model.

Methods

We performed post hoc analysis of National Health and Nutrition Examination Survey-III (1998–94) including subjects aged 30–79 years free from CHD or CHD equivalent at baseline. Primary endpoint was death from ischemic heart disease. NLR was divided into four categories: < 1.5, ≥ 1.5 to < 3.0, 3.0–4.5 and > 4.5. Statistical analyses involved multivariate Cox proportional hazards models as well as discrimination, calibration and reclassification.

Results

We included 7363 subjects with a mean follow up of 14.1 years. There were 231 (3.1%) CHD deaths, more in those with NLR > 4.5 (11%) compared to NLR < 1.5 (2.4%), p < 0.001. Adjusted hazard ratio of NLR > 4.5 was 2.68 (95% CI 1.07–6.72, p = 0.035). There was no significant improvement in C-index (0.8709 to 0.8713) or area under curve (0.8520 to 0.8531) with addition of NLR to FRS model. Model with NLR was well calibrated with Hosmer–Lemeshow chi-square of 8.57 (p = 0.38). Overall net reclassification index (NRI) was 6.6% (p = 0.003) with intermediate NRI of 10.1% (p < 0.001) and net upward reclassification of 5.6%. Absolute integrated discrimination index (IDI) was 0.003 (p = 0.039) with relative IDI of 4.3%.

Conclusions

NLR can independently predict CHD mortality in an asymptomatic general population cohort. It reclassifies intermediate risk category of FRS, with significant upward reclassification. NLR should be considered as an inflammatory biomarker of CHD.     

Neutrophil to lymphocyte ratio (NLR) and cardiovascular diseases: an update

As we know, inflammatory and oxidative stresses have a role in the pathogenesis of cardiovascular disease. This knowledge has triggered many investigations targeted to inflammatory markers. One such example, the neutrophil to lymphocyte ratio (NLR), is an inexpensive and easily accessible inflammatory marker whose role in cardiovascular disease has been studied extensively in the past few years. The neutrophil lymphocyte ratio has been shown to predict cardiac arrhythmias as well as short- and long-term mortality in patients with acute coronary syndromes (ACS). It has correlated well with ACS risk prediction models such as the GRACE and SYNTAX scores. A higher NLR has also been associated with frequent congestive heart failure decompensation and long-term mortality. The neutrophil to lymphocyte ratio also appears to have a prognostic role in patients undergoing transaortic valve replacement and the progression of valvular heart diseases. Despite the science of inflammatory biomarkers having been described decades ago, NLR appears to be enjoying a renaissance as a cost-effective biomarker with immediate clinical predictability and prognostication.     

Placental TLR/NLR expression signatures are altered with gestational age and inflammation

Objective: To quantify changes in placental expression of Toll-like receptors (TLRs) and nuclear oligomerization domain (NOD)-like receptors (NLRs) gene with (1) advancing gestational age (GA) and (2) exposure to chorioamnionitis (CA) and preterm premature rupture of membrane (PPROM).

Methods: Placental tissue was collected at the time of birth from 83 subjects with live birth pregnancies from 24- to 40-week gestation between 2009 and 2013. Real-time RT-PCR analysis of 13 TLR/NLR genes involved in bacterial sensing was performed using specific probes.

Results: Of 83 patients enrolled, 61 were preterm (<37 weeks). 23 (27%) had evidence of CA; and 33 (39.8%) had PPROM. 15 (18%) had both CA and PPROM (CP). 42 (50%) had neither CA nor PPROM (C/P). Only RIPK2 (p?=?0.0025) and TLR4 (p?=?0.0005) were found to increase progressively with GA. We found significant changes in TLR5 (p?=?0.01) with CA, NFKBIA (p?=?0.016) with PPROM, NKKBIA (p?=?0.003), and NFKB1 (p?=?0.009) with CA and PPROM.

Conclusion: RIPK2 (mediator of NOD-dependent NF-kB signaling) and TLR4 progressively increased with GA. We speculate this upregulation may be involved in initiating labor and delivery at term. Increase in NFKBIA seen in PPROM and CA might represent a counter regulatory mechanism to decrease inflammation in these conditions. This study provides new information on relationships between GA, CA/PPROM, and TLR/NLR signaling in the placenta.