Neutrophil–lymphocyte ratio: a novel predictor for short‐term prognosis in acute‐on‐chronic hepatitis B liver failure

Acute‐on‐chronic hepatitis B liver failure (ACHBLF) has a poor prognosis in patients with hepatitis B virus infection. The role of the neutrophil–lymphocyte ratio (NLR), which reflects the inflammatory status of the patient before treatment, has never been studied in this setting. To investigate the predictive value of NLR in patients with ACHBLF, a retrospective cohort with 216 patients and a prospective validation cohort with 73 patients were recruited. Multivariate analyses showed that total bilirubin (TBIL), NLR, age and model for end‐stage liver disease (MELD) score had prognostic significance for survival. Both NLR (0.781) and MELD score (0.744) had higher ROC curves, which differed significantly from those for age (0.615) and TBIL (0.691), but not from each other (P = 0.94). NLR ≤2.36 predicted lower mortality (with 91.6% sensitivity and 86.0% negative predictive value), and NLR >6.12 was a warning sign for higher mortality risk (with 90.1% specificity and 80.3% positive predictive value). These results demonstrated that pretreatment NLR was associated with the prognosis of patients with ACHBLF, and elevated NLR predicted poor outcome within 8 weeks. We suggest that NLR cut‐offs of ≤2.36 and >6.12 are powerful markers for predicting mortality in ACHBLF.     

Evolving concepts of pathogenesis of heparin‐induced thrombocytopenia: Diagnostic and therapeutic implications

Heparin‐induced thrombocytopenia (HIT) is an immune reaction to heparin. It often causes severe thrombosis which may lead to limb gangrene and thrombosis‐associated death. The concept of its pathogenesis has been evolving during the past five decades. Initially, HIT was thought to be caused by disseminated intravascular coagulation. Later it became clear that HIT was mediated by an immune mechanism whereby an IgG antibody induced platelet aggregation, release of procoagulant materials and consequently thrombus formation. The antigen comprises Platelet Factor 4 (PF4) and heparin which have a tendency to form ultralarge complexes. The HIT immune response has atypical features. IgG antibody appears early without IgM precedence and lasts transiently. One explanation is that there is prior priming by bacterial infection. Another unique characteristic is that it is processed as if it is a particulate antigen involving complement activation and B cells. Antigen‐presenting cells/monocytes are also involved but the role of T cells is controversial. Recent advances have provided new insights into the underlying mechanisms of HIT‐related thrombosis. Previously, platelets were believed to play a central role; their activation and consequently the induction of blood coagulation was the basis of the hypercoagulability in HIT. More recently, several studies have provided clear evidence that neutrophil and NETosis, monocytes and endothelial cells contribute significantly to the thrombosis in HIT. These new insights may result in development of better diagnostic laboratory assays and more effective treatments for HIT.     

Delta Neutrophil Index as an Early Marker for Differential Diagnosis of Adult-Onset Still's Disease and Sepsis

Purpose

To investigate clinical implications of delta neutrophil index (DNI) to discriminate adult onset Still''s disease (AOSD) from sepsis.

Materials and Methods

We reviewed the medical records of 13 patients with AOSD and 33 gender and age-matched patients with sepsis. In all subjects, microbial tests were performed to exclude or confirm sepsis. All laboratory data were measured two or three times during the first 3 days and represented by their mean levels. DNI was measured automatically by ADVIA 2120 for the first 3 days.

Results

There were no significant differences in white blood cell counts, neutrophil proportion, erythrocyte sedimentation rate and C-reactive protein between two groups. AOSD patients had notably lower DNI than sepsis patients regardless of the presence of bacteremia or not. However, both DNI and ferritin were not significant independent factors for predicting sepsis in the multivariate logistic regression analysis. Meanwhile, the area under the receiver operating characteristic curve (AUROC) of DNI was slightly higher than that of ferritin. When we set DNI of 2.75% as the cut-off value for predicting sepsis, 11 (84.6%) of AOSD patients had a DNI value below 2.75% and 2 (15.4%) of them had a DNI over 2.75% (relative risk for sepsis 176).

Conclusion

We suggest that DNI may be a useful marker for differential diagnosis of AOSD from sepsis in the early phase as supplementary to ferritin.     

Nitric oxide production by polymorphonuclear leucocytes in infected cystic fibrosis sputum consumes oxygen

Chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients is characterized by persisting mucoid biofilms in hypoxic endobronchial mucus. These biofilms are surrounded by numerous polymorphonuclear leucocytes (PMNs), which consume a major part of present molecular oxygen (O₂) due to production of superoxide (O₂⁻). In this study, we show that the PMNs also consume O₂ for production of nitric oxide (NO) by the nitric oxide synthases (NOS) in the infected endobronchial mucus. Fresh expectorated sputum samples (n = 28) from chronically infected CF patients (n = 22) were analysed by quantifying and visualizing the NO production. NO production was detected by optode measurements combined with fluorescence microscopy, flow cytometry and spectrophotometry. Inhibition of nitric oxide synthases (NOS) with N^G-monomethyl-L-arginine (L-NMMA) resulted in reduced O₂ consumption (P < 0·0008, n = 8) and a lower fraction of cells with fluorescence from the NO-indicator 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate (DAF-FM) (P < 0·002, n = 8). PMNs stained with DAF-FM and the superoxide indicator hydroethidine (HE) and host cells with inducible NOS (iNOS) were identified in the sputum. In addition, the production of the stable end-products of NO in CF sputum was correlated with the concentration of PMNs; NO₃⁻ (P < 0·04, r = 0·66, n = 10) and NO₂⁻ (P< 0·006, r = 0·78, n = 11). The present study suggests that besides consumption of O₂ for production of reactive oxygen species, the PMNs in CF sputum also consume O₂ for production of NO.     

外周血中性粒细胞/淋巴细胞比值与透析患者冠状动脉钙化的关系

目的 通过透析患者资料分析该人群冠状动脉钙化(CAC)的危险因素,探讨中性粒细胞/淋巴细胞比值(NLR)对CAC的预测价值。方法 采用横断面调查方法,对163例透析患者(包括血液透析102例,腹膜透析61例)进行回顾性研究,根据多层螺旋CT评估结果,采用Agatston冠状动脉钙化积分(CACS)进行冠状动脉钙化程度的评估,将透析患者分成无钙化组59例(CACS 0～10分)和钙化组104例(CACS≥11分)。对两组患者的NLR、年龄、透析龄、高敏C反应蛋白(hs-CRP)、血钙、血磷、全段甲状旁腺激素(iPTH)、白蛋白(Alb)、血红蛋白、血清肌酐等指标进行统计学比较。应用Spearman相关性分析得出与CAC相关的因素,二元Logistic回归分析CAC发生的危险因素,受试者工作特征(ROC)曲线探讨NLR对CAC的预测价值。结果 163例透析患者中CAC总检出率为63.8%。钙化组NLR显著高于无钙化组(P＜0.001)。将钙化组分为轻度钙化组(CACS 11~400分)和重度钙化组(CACS＞400分),两亚组间NLR差异无统计学意义。Spearman相关性分析显示NLR与CAC显著相关(r＝0.403,P＜0.001)。二元Logistic回归分析结果显示年龄(OR=1.069,P＜0.001)、透析龄(OR=1.024,P＜0.001)、糖尿病(OR=15.871,P＝0.012)、NLR(OR=1.720,P＝0.001)是CAC的危险因素。ROC曲线分析结果显示,NLR与年龄的联合指标预测透析患者发生CAC时,曲线下面积为0.810(95%CI 0.739~0.880,P＜0.001),显著高于NLR(0.742,95%CI 0.666~0.818,P＜0.001)和年龄(0.754,95%CI 0.674~0.834,P＜0.001)单独分析时的曲线下面积。结论 高龄、透析龄和高水平NLR的透析患者发生CAC的风险较高,且NLR与年龄的联合指标对CAC的发生有着较好的预测价值。     

2型糖尿病患者尿微量白蛋白/尿肌酐比值与血糖波动的影响因素分析*

目的 探讨2型糖尿病患者尿微量白蛋白/尿肌酐比值（uACR）与血糖波动的影响因素。方法 选取339例确诊的2型糖尿病患者,应用动态血糖监测系统监测血糖,收集其临床资料。首先依据平均血糖波动幅度（MAGE）分组,MAGE<3.9?mmol/L 99例（血糖波动正常组）,MAGE≥3.9?mmol/L 240例（血糖波动异常组）,分析影响血糖波动的因素;再依据uACR分组,uACR<30?mg/g 197例（uACR正常组）,uACR≥30?mg/g 142例（uACR异常组）,分析影响uACR的因素。结果 血糖波动正常组与血糖波动异常组比较,病程、空腹血糖、糖化血红蛋白、总胆固醇、中性粒细胞/淋巴细胞比值（NLR）、uACR差异有统计学意义（P?<0.05）。糖尿病病程[OlR=1.040（95% CI：0.958,1.758）]、总胆固醇[OlR=1.332（95% CI：1.061,1.672）]是血糖波动的影响因素。uACR正常组与uACR异常组比较,年龄、病程、低密度脂蛋白胆固醇、NLR、MAGE差异有统计学意义（P?<0.05）。病程[OlR=1.055（95% CI：1.014,1.096）]、NLR [OlR=2.186（95% CI：1.602,2.983）]、MAGE [OlR=1.438（95% CI：1.226,1.688）]是uACR的影响因素。结论 随着2型糖尿病患者病程的进展,血糖波动幅度逐渐增大,总胆固醇可影响血糖波动;随着病情的进展,机体的炎症反应增强,血糖波动幅度的增大可影响uACR。