Clinical relevance of increased neuron-specific enolase concentration in cerebrospinal fluid

Neuron-specific enolase (NSE) concentrations in cerebrospinal fluid (CSF) and serum have been studied by an EIA-method using monoclonal antibodies against human NSE. In a control group (n = 24) the mean NSE value (+/- SD) in CSF was 10.8 (+/- 4.5) ng/ml. Increased NSE values in CSF (greater than or equal to 20 ng/ml, ie greater than or equal to means + 2s) have been detected in 33/172 patients with the following neurological diseases: CNS tumors (6/30), infarctions (6/36), cerebral ischemias (5/25), inflammatory diseases (7/33), epilepsias (3/10) and miscellaneous neurological diseases (6/38). The NSE assay in CSF was not specific for a single neurological disease. In 9% of all patients with an organic neurological disease the increased NSE concentration was the only abnormal result in the CNS out of variables routinely determined in CSF. The discrimination between an organic and psychogenic origin of epilepsy may be possible by an NSE analysis in CSF. The NSE assay in CSF can be recommended as an unspecific screening parameter for pathological organic CNS processes.     

Technical performance and diagnostic utility of the new Elecsys neuron-specific enolase enzyme immunoassay.

This international multicenter study was designed to evaluate the technical performance of the new double-monoclonal, single-step Elecsys neuron-specific enolase (NSE) enzyme immunoassay (EIA) and to assess its utility as a sensitive and specific test for the diagnosis of small-cell lung cancer (SCLC). Intra- and interassay coefficients of variation, determined in five control or serum specimens in six laboratories, ranged from 0.7 to 5.3 (inter-laboratory median: 1.3%) and from 1.3 to 8.5 (inter-laboratory median: 3.4%), respectively. Laboratory-to-laboratory comparability was excellent with respect to recovery and inter-assay coefficients of variation. The test was linear between 0.0 and 320 ng/ml (highest measured concentration). There was a significant correlation between NSE concentrations measured using the Elecsys NSE and the established Cobas Core NSE EIA II in all subjects (n = 723) and in patients with lung cancer (n = 333). However, NSE concentrations were systematically lower (approximately 9%) with the Elecsys NSE than with the comparison test. Based on a specificity of 95% in comparison with the group suffering from benign lung diseases (n = 183), the cut-off value for the discrimination between malignant and benign conditions was set at 21.6 ng/ml. NSE was raised in 73.4% of SCLC patients (n = 188) and was significantly higher (p < 0.01) in extensive (87.8%) as opposed to limited disease (56.7%). NSE was also elevated in 16.0% of the cases with non-small cell lung cancer (NSCLC, n = 374). It is concluded that the Elecsys NSE EIA is a reliable and accurate diagnostic procedure for the measurement of NSE in serum samples. The special merits of this new assay are the wide measuring range (according to manufacturer's declaration up to 370 ng/ml) and a short incubation time of 18 min.     

Population-based validation of a German-language self-administered headache questionnaire

We validated a German-language self-administered headache questionnaire for migraine (M), tension-type headache (TTH) and trigeminal autonomic cephalalgia (TAC) in a general population sample of people with headache. Randomly selected subjects ( n  = 240) diagnosed by the questionnaire as M ( n  = 60), TTH ( n  = 60), a combination of M and TTH (M+TTH, n  = 60) and TAC ( n  = 60) were invited for examination by headache specialists. One hundred and ninety-three subjects (80%) were studied. Sensitivity and specificity for M were 0.85 and 0.85, for TTH 0.6 and 0.88, for M+TTH 0.82 and 0.87, respectively. Cohen's κ was 0.6 (95% confidence interval 0.50, 0.71). Of 45 patients with TAC according to the questionnaire, physicians diagnosed cluster headache in two patients only. We conclude: (i) the questionnaire can be used to diagnose M, TTH and M+TTH, but not TAC; (ii) screening questionnaires for epidemiological research should be validated in a general population sample but not in a tertiary headache clinic.     

脑卒中患者血清 Hcy及 NSE水平与癫痫发作的相关性研究

目的　探讨脑卒中患者血清同型半胱氨酸 (homocysteine, Hcy)及神经元特异性烯醇化酶 (neuron speci.c enolase, NSE)对其癫痫发作的影响。方法　研究对象为 2016年 1月～ 2019年 6月期间到保定市第四中心医院就诊的脑卒中患者,其中并发癫痫患者 160例,纳入癫痫组,随机抽取同期未并发癫痫患者 160例,纳入对照组。采用 ELISA(酶联免疫吸附试验 )法检测所有患者血清中 Hcy和 NSE的表达水平。采用单因素考察癫痫发作影响因素;采用 Pearson相关分析 Hcy和 NSE与癫痫患者卒中评分的关系;选取单因素中具有统计学差异的关键因素进行多因素 logistic回归;绘制癫痫发作的 ROC曲线,并计算曲线下面积 (AUC)。结果　癫痫组和对照组的年龄 ( ≥ 80岁 )、卒中类型 (梗死 /出血 )、脑血管疾病家族史、高脂血症、同型半胱氨酸尿症、肺部感染、 NIHSS评分 ( ≥ 25分 ),BI评分≥ 55分 )及病灶范围 9个参数差异均有统计学意义 (χ2 =5.472~18.315,均 P<0.01);癫痫组的血清 Hcy为 51.34±7.48μmol/L,高于对照组的31.85±5.04μmol/L,经 t检验具有显著差别（ t=27.333,P<0.001）;癫痫组的血清 NSE为 62.47±8.11ng/ml,高于对照组的 35.40±5.43ng/ml,经 t检验,差异有统计学意义（t=35.083,P<0.001）。Pearson相关分析显示,血清 Hcy水平 (r=0.314, P<0.001),NSE(r=0.352,P<0.001)与脑卒中 NIHSS评分呈正相关,而血清 Hcy水平 (r= -0.338,P<0.001),NSE(r =-0.257, P<0.001)与 BI评分呈负相关。 Logistic回归分析可知, NIHSS评分 ( ≥ 25分 )(OR=3.781,95%CI 1.441~9.919),BI评分 (<55分 )(OR=3.546,95%CI 1.220~10.305)、大的病灶范围 (OR=2.996,95%CI 1.137~7.738)、血清 Hcy(OR=4.014, 95%CI 1.590~10.134)及血清 NSE(OR=4.325,95%CI 1.776~10.530)是影响脑卒中患者癫痫发作的独立危险因素。 ROC曲线分析结果显示:血清 Hcy的 ROC曲线下面积为 0.820,敏感度和特异度分别为 79.2%和 70.3%,血清 NSE的 ROC曲线下面积为 0.873,预测的敏感度和特异度分别为 83.7%和 84.0%。结论　脑卒中患者血清 Hcy和 NSE与其癫痫发作的关系密切,可作为预测其发作的潜在标志物。     

Effect of ketoconazole on ritonavir and saquinavir concentrations in plasma and cerebrospinal fluid from patients infected with human immunodeficiency virus

AIM: Our aim was to evaluate the effect of ketoconazole on ritonavir and saquinavir plasma and cerebrospinal fluid (CSF) concentrations. METHODS: Twelve patients who were human immunodeficiency virus-seropositive and who were receiving 400 mg of ritonavir and 400 mg of saquinavir twice daily completed a nonfasted, two-period, two-group, longitudinal pharmacokinetic study. Blood samples were collected over the daytime 12-hour dosing interval of the protease inhibitors at baseline (period 1, day 0) and after 10 days of coadministration of 200 mg (n = 6) or 400 mg (n = 6) of ketoconazole once daily (period 2, day 10). One set of paired CSF and blood samples was collected between 4 and 5 hours after the dose on both days. RESULTS: Ketoconazole significantly increased area under the plasma concentration-time curve, plasma concentration at 12 hours after the dose, and half-life of ritonavir by 29% (95% confidence interval (CI), 13%-46%), 62% (95% CI, 37%-92%), and 31% (95% CI, 13%-51%), respectively. Similar increases of 37% (95% CI, 4%-81%), 94% (95% CI, 41%-167%), and 38% (95% CI, 15%-66%), respectively, were observed for these parameters for saquinavir. Ketoconazole significantly elevated ritonavir CSF concentration by 178% (95% CI, 59%-385%), from 2.4 to 6.6 ng/mL, with no change in paired unbound plasma level (26 ng/mL); this led to a commensurate 181% increase (95% CI, 47%-437%) in CSF/plasma unbound ratio. All pharmacokinetic changes were unrelated to ketoconazole dose or plasma exposures. Corresponding changes for saquinavir CSF pharmacokinetics were insignificant (P > .06); saquinavir CSF levels were unmeasurable in 7 patients (<0.2 ng/mL). Conclusions: The disproportionate increase in CSF compared with plasma concentrations of ritonavir is consistent with ketoconazole inhibiting both drug efflux from CSF and systemic clearance.     

血清CEA,ProGRP,NSE和CYFRA21-1联合检测在肺癌诊断中的应用研究

目的 研究血清癌胚抗原(CEA)、胃泌素释放前体(ProGRP)、神经元特异性烯醇化酶(NSE)和细胞角蛋白19片段(CYFRA21-1)联合检测在肺癌诊断中的应用。方法 空腹取诊断明确的133例肺癌患者、67例肺部良性病变患者及同期66例体检健康者(对照组)的静脉血,用化学发光法检测血清CYFRA21-1,CEA,NSE和ProGRP水平,并计算敏感度、准确度和特异度。结果 CYFRA21-1,CEA,NSE和ProGR水平,肺癌患者血清分别为6.31±1.04 ng/ml,20.58±2.41 ng/ml,32.74±3.24 ng/ml和125.78±15.32 pg/ml,肺良性病变患者血清分别为1.93±0.52 ng/ml,2.93±0.82 ng/ml,10.49±1.93 ng/ml和48.32±6.72 pg/ml,对照组血清分别为1.56±0.45 ng/ml,2.67±0.74 ng/ml,8.34±1.2 ng/ml和35.78±4.2 pg/ml,肺癌患者血清CEA,ProGRP,NSE,CYFRA21-1水平均高于肺良性病变患者(t=1.48～2.78,P=0.13～0.25)和对照组(t=1.981～2.371,P=0.21～0.41),差异均有统计学意义(P<0.05)。CYFRA21-1,NSE,CEA和ProGRP单项检测肺癌的敏感度分别为61.65%,45.86%,52.63%和63.91%,准确度为72.36%,63.81%,67.34%和74.87%。联合两项、三项检测肺癌,敏感度为72%～89%,准确度为78.89%～89.44%。四项联合检测肺癌的敏感度(92.48%)、准确度(90.45%)最高。结论 血清标志物能较好地诊断肺癌,联合多种血清学指标检测可提高肺癌诊断的敏感度、准确度。     

The Prevalence of Headache and Its Association With Socioeconomic Status Among Schoolchildren in Istanbul, Turkey

Objective.— The etiology and pathogenesis of migraine and other types of headache are still under discussion. An interaction of organic, psychological, and psychosocial factors is operative. In this study, we aimed to determine the prevalence of headache and its association with socioeconomic status among schoolchildren.
Study Design.— A cross-sectional study was performed on 2669 schoolchildren via a parental questionnaire. Socioeconomic status was determined according to the Turkish socioeconomic status scale.
Results.— The mean age of the students was 8.2 ± 2.4 years. The headache prevalence was 46.2% (95% CI: 44.3-48.1). The prevalence of migraine was 3.4% (95% CI: 2.8-4.1), the prevalence of probable migraine was 8.7% (95% CI: 7.6-9.8), and that of non-migraine headache was 34.1% (95% CI: 32.3-35.9). Multivariate analysis revealed that older age, being a girl, having a family history of headache, and exposure to passive smoking at home were independently associated with headache. There was an inverse association between socioeconomic status and all 3 types of headaches after adjusting for age, sex, family history of headache, and presence of passive smoking. When the group with the lowest socioeconomic status was taken as the reference category, the odds ratios for the highest socioeconomic group were 0.33 (95% CI: 0.16-0.69, P  = .003) for the migraine, 0.30 (95% CI: 0.11-0.89, P  = .029) for the probable migraine, and 0.34 (95% CI: 0.16-0.72, P  = 0.005) for the non-migraine headache.
Conclusion.— Headache is more common among children with lower socioeconomic groups. Social causation can play a role in the pathogenesis of headache.     

Cardiac biomarkers for risk stratification in non-massive pulmonary embolism: a multicenter prospective study

Summary.  Background: Troponins (cTnI and cTnT), N-terminal pro-Brain Natriuretic Peptide (NT-proBNP), myoglobin, heart-type fatty acid-binding protein (H-FABP) and fibrin D-Dimer are emergent candidates for risk stratification in pulmonary embolism (PE). Objective: To compare the respective prognostic values of biomarker with non-massive PE to predict an adverse outcome at 3 months. Patients/Methods: One hundred and forty-six consecutive patients with non-massive PE were included in this multicenter prospective study. The combined outcome consisted of intensive care monitoring on admission, death or hospitalization attributable to either a PE-related complication [defined by PE/deep vein thrombosis (DVT) relapse or major bleeding under anticoagulation] or to dyspnoea with or without chest pain during follow-up. Results: The outcome was met in 12% of patients. In univariate analysis, a NT-proBNP level above 300 pg/ml was the strongest predictor of unfavorable outcome with an odds ratio (OR) of 15.8 [95% confidence interval (CI): 2.05–122). ORs for the other variables were: 8.0 for D-dimer >2000 ng/ml (95% CI: 1.1–64), 4.7 for H-FABP >6ng/ml (95% CI:1.5–14.8), 3.5 for cTnI >0.09 ng/ml (95% CI:1.2–9.7), 3.4 for myoglobin >70 ng/ml (95% CI:0.9–12.2). Receiver operating curve (ROC) analysis indicated that NT-proBNP was the best predictor [area under the curve (AUC) 0.84; 95%CI: 0.76–0.92; P  < 0.0001] with a negative predictive value of 100% (95% CI: 91–100) at 300 pg/ml. At that cut-off, the true negative rate for NT-proBNP was 40%. In multivariate analysis, NT-proBNP was the only significant independent predictors. Conclusions: NT-proBNP appears to be a good risk stratification marker in identifying low-risk patients with non-massive PE who could be treated in an outpatient setting.     

Effectiveness of an educational and physical programme in reducing headache, neck and shoulder pain: a workplace controlled trial

This study was an 8-month controlled trial to evaluate the effectiveness of a workplace educational and physical programme in reducing headache and neck and shoulder pain. Central registry office employees ( n  = 192; study group) and 192 peripheral registry office and central tax office employees (controls) in the city of Turin, Italy were given diaries for the daily recording of pain episodes. After 2 months, the study group only began the educational and physical programme. The primary end-point was the change in frequency of headache and neck and shoulder pain expressed as the number of days per month with pain, and as the proportion of subjects with a ≥ 50% reduction of frequency (responder rate). The number of days of analgesic drug consumption was also recorded. Diaries completed for the whole 8 months were available for 169 subjects in the study group and 175 controls. The baseline frequency of headache (days per month) was 5.87 and 6.30 in the study group and in controls; frequency of neck and shoulder pain was 7.12 and 7.79, respectively. Mean treatment effects [days per month, 95% confidence interval (CI)] on comparing the last 2 months vs. baseline were: headache frequency −2.45 (−3.48, −1.43); frequency of neck pain −2.62 (−4.09, −1.16); responder rates (odds ratio, 95% CI) 5.51 (2.75, 11) for headache, 3.10 (1.65, 5.81) for neck and shoulder pain, and 3.08 (1.06, 8.90) for days with analgesic drug consumption. The study suggests that an educational and physical programme reduces headache and neck and shoulder pain in a working community.     

脑梗死及多梗死性痴呆患者脑脊液S-100、NSE的测定

目的　研究脑梗死 (CI)及多梗死性痴呆 (MID)患者脑脊液 (CSF)S - 10 0、神经元特异性烯醇化酶 (NSE)含量的变化及意义。方法　采用放免法及ELISA法对 72例CI及 2 1例MID患者CSFS - 10 0、NSE含量进行测定。MID患者的智能水平采用简易智能量表 (MMSE)测定 ,并参考Hachinski缺血评分及DSM -Ⅳ诊断标准进行确诊。结果　CI急性期组患者CSFS- 10 0、NSE浓度明显高于对照组 (P <0 0 1) ;而CI恢复期组患者CSFS - 10 0、NSE的浓度与对照组无显著差异 (P >0 0 5 )。MID患者CSFS - 10 0浓度高于对照组及CI恢复期组 (P <0 0 5 ) ;而NSE浓度低于对照组及CI恢复期组 (P <0 0 5 )。结论　NSE、S - 10 0蛋白可反映MID患者脑神经细胞、神经胶质细胞的损害情况和功能状态 ,对MID患者的病情及预后判断有重要意义。     

The RANTES -403G>A promoter polymorphism in Korean men: association with serum RANTES concentration and coronary artery disease

In the present study we investigated the association of the RANTES (regulated upon activation, normal T-cell expressed and secreted) -28C>G and -403G>A promoter polymorphisms with the concentration of serum RANTES and CAD (coronary artery disease) in Korean men. We included 553 male CAD patients with (n=176) or without (n=377) Type 2 diabetes, aged 40-65 years with previous myocardial infarction ( approximately 50%) or angiographically confirmed CAD ( approximately 50%), and 416 aged-matched healthy male controls. The main outcome measures were the OR (odds ratio) of CAD risk and the serum RANTES concentration evaluated by sandwich ELISA. Although the RANTES -28C>G genotype had no significant association with CAD risk, the presence of the minor allele of the RANTES -403G>A single nucleotide polymorphism was associated with a lower risk of CAD {OR 0.70 [95% CI (confidence interval) 0.54-0.92], P=0.011} after adjusting for age, BMI (body mass index), cigarette smoking and alcohol consumption. Serum RANTES concentrations were significantly associated with the -403G>A genotype in controls (G/G: 44.7+/-3.3 ng/ml, G/A: 36.5+/-2.0 ng/ml, A/A: 28.7+/-2.5 ng/ml; P<0.001), non-diabetic CAD patients (G/G: 50.9+/-3.0 ng/ml, G/A: 42.2+/-2.6 ng/ml, A/A: 41.3+/-4.4 ng/ml; P<0.05) and diabetic CAD patients (G/G: 58.5+/-3.5 ng/ml, G/A: 49.6+/-4.1 ng/ml, A/A: 42.2+/-4.3 ng/ml; P<0.05); however, such associations were not observed in the subgroup of CAD patients taking lipid-lowering medication. Moreover, serum RANTES was positively correlated with C-reactive protein (r=0.289, P<0.001) and platelet counts (r=0.253, P<0.001). The results of the present study demonstrate that the RANTES -403A allele is associated with lower serum RANTES concentrations and consequently with reduced CAD risk.     

Cough headache: a study of 83 consecutive patients

To delineate the differences in clinical characteristics and evaluate the outcome between primary and secondary cough headache, 83 consecutive patients (59M/24F, mean age 61.5 ± 17.7 years) with cough headache (1.2%) out of 7100 patients in a headache clinic were studied. All of them received brain imaging studies. Most did not have relevant brain lesions ( n  = 74, 89.2%, primary group) except for nine patients (10.8%, the secondary group). Most of the intracranial lesions were located in the posterior fossa ( n  = 6, 67%), including only two patients with Chiari malformation. The primary group had a higher response rate to indomethacin than the secondary group (72.7% vs. 37.5 %, P  = 0.046). Mild to moderate headache intensity and age onset < 50 years predicted a favourable response. At a mean follow-up of 51.4 months, 83.9% of patients with primary cough headache completely remitted. Inconsistent with the proposed International Classification of Headache Disorders, 2nd edn criteria, 10.8% of patients with primary cough headache had headache duration of > 30 min. Clinical features, neurological examinations and drug response could not safely differentiate primary from secondary cough headache. Neuroimaging studies are required in each patient.     

Prostaglandin E2 (PGE2) induces headache in healthy subjects

The role of prostanoids in nociception is well established. The headache-eliciting effects of prostaglandin E₂ (PGE₂) and its possible mechanisms have previously not been systematically studied in man. We hypothesized that infusion of PGE₂ might induce headache and vasodilation of cranial vessels. PGE₂ (0.40 µg kg⁻¹ min⁻¹) or saline was infused for 25 min into 11 healthy subjects in a cross-over, double-blind study. Headache intensity was scored on a verbal rating scale from 0 to 10. In addition, we recorded mean flow in the middle cerebral artery (V_MCA) by transcranial Doppler and diameter of the superficial temporal artery (STA) by high-resolution ultrasonography. All 11 subjects reported headache on the PGE₂ day and no subjects reported headache on the placebo day ( P  = 0.001). During the immediate phase (0–30 min) ( P  = 0.005) and the postinfusion phase (30–90 min) ( P  = 0.005), the area under the curve for headache score was significantly larger on the PGE₂ day compared with the placebo day. PGE₂ caused dilatation of the STA (23.5%; 95% CI 14.0, 37.8) and the MCA (8.3%; 95% CI 4.0, 12.6). We suggest that PGE₂ induces headache by activation and sensitization of cranial perivascular sensory afferents.     

Associations between sleep disturbance and primary headaches: the third Nord-Trøndelag Health Study

The aim of the study was to evaluate the association between sleep disturbance and headache type and frequency, in a random sample of participants in the third Nord-Trøndelag Health Survey. The headache diagnoses were set by neurologists using the ICHD-2 criteria performing a semi structured face-to-face interview. Sleep problems were measured by the two validated instruments Karolinska Sleep Questionnaire (KSQ) and Epworth Sleepiness Scale (ESS). Among 297 participants, 77 subjects were headache-free, whereas 135 were diagnosed with tension-type headache (TTH), 51 with migraine, and 34 with other headache diagnoses. In the multivariate analyses, using logistic regression, excessive daytime sleepiness, defined as ESS ≥ 10, was three times more likely among migraineurs compared with headache-free individuals (OR = 3.3, 95% CI 1.0–10.2). Severe sleep disturbances, defined as KSQ score in the upper quartile, was five times more likely among migraineurs (OR = 5.4, 95% CI 2.0–15.5), and three times more likely for subjects with TTH (OR = 3.3, 1.4–7.3) compared with headache-free individuals. Subjects with chronic headache were 17 times more likely to have severe sleep disturbances (OR = 17.4, 95% CI 5.1–59.8), and the association was somewhat stronger for chronic migraine (OR = 38.9, 95% CI 3.1–485.3) than for chronic TTH (OR = 18.3, 95% CI 3.6–93.0). In conclusion, there was a significant association between severe sleep disturbances and primary headache disorders, most pronounced for those with chronic headache. Even though one cannot address causality in the present study design, the results indicate an increased awareness of sleep problems among patients with headache.     

急性CO中毒后迟发性脑病神经元特异性烯醇化酶测定的临床意义

目的　探讨急性CO中毒后迟发性脑病 (DEACMP)患者脑脊液 (CSF)和血清神经元特异性烯酶化酶(NSE)的变化及临床意义。方法　对 49例DEACMP患者均在急性期入院 3d内抽取CSF和血标本进行NSE测定 ,其中 34例于治疗 30d后再次采取标本复查 ,对比分析治疗前后NSE的变化。结果　患者组急性期CSF和血清NSE含量较对照组明显增高 (P <0 .0 0 1) ;治疗后明显下降 (P <0 .0 0 1,P <0 .0 0 5 ) ,与对照组比较差异无显著性 (P >0 .0 5 ) ;患者组CSF和血清NSE呈明显正相关 (r =0 .46 14,P <0 .0 0 1)。结论　CSF和血清NSE测定可作为DEACMP诊断和病情判断的有效指标。     

联合检测血清SIRT1和CTRP5水平对慢性阻塞性肺疾病急性加重期患者预后的预测价值研究

目的　探讨沉默信息调节因子 2相关酶 1(silent information regulator 2 related enzyme 1,SIRT1)联合补体 1q/肿瘤坏死因子相关蛋白 5(complement 1q/tumor necrosis factor-related protein 5 ,CTRP5)对慢性阻塞性肺疾病急性加重期 (acute exacerbation of chronic obstructive pulmonary disease,AECOPD)患者预后的预测价值。方法　选取海南省东部中心医院收治的 152例 COPD患者,根据病情程度分为急性加重期组 (n=84)和稳定期组 (n=68),随访 1年根据预后情况将急性加重期组分为预后不良组 (n=32)和预后良好组 (n=52)。比较各组血清 SIRT1和 CTRP5水平,采用多因素逐步 Logistics回归分析 AECOPD患者预后的影响因素,绘制 ROC曲线分析 SIRT1联合 CTRP5对 AECOPD患者预后不良的预测价值。结果　急性加重期组血清 SIRT1水平 (0.68±0.19ng/ml)低于稳定期组 (0.93±0.22ng/ml),CTRP5水平 (51.98±6.82ng/ml)高于稳定期组 (41.36±8.35ng/ml),差异具有统计学意义 (t=-7.451,8.630,均 P＜ 0.001)。预后不良组血清 SIRT1水平 (0.57±0.13ng/ml)低于预后良好组 (0.75±0.19ng/ml),CTRP5水平 (56.51±6.06ng/ml)高于预后良好组 (49.19±5.71ng/ml),差异具有统计学意义 (t=-4.759,5.582,均 P＜ 0.001)。多因素逐步 Logistics回归分析显示,年龄≥ 60岁 (OR=1.389,95%CI 1.052～ 1.632)、并发肺心病 (OR=4.575,95%CI 2.143～ 8.322)、机械通气 (OR=3.804, 95%CI 1.695～ 7.705)、高血清 CTRP5水平 (OR=4.073,95%CI 2.604～ 8.082)为 AECOPD患者预后不良独立危险因素,高血清 SIRT1水平 (OR=0.976,95%CI 0.881～ 1.082)为独立保护因素 (均 P＜ 0.05)。ROC曲线显示,SIRT1联合 CTRP5(AUC=0.905,95%CI 0.821～ 0.958)预测 AECOPD患者预后不良的曲线下面积 (AUC)大于 SIRT1(AUC=0.816, 95%CI 0.716～ 0.892),CTRP5(AUC=0.810,95%CI 0.709～ 0.887)单独预测 (Z=2.296,3.328,P=0.022,0.001),联合检测的敏感度和特异度分别为 78.12%,90.38%。结论　AECOPD患者血清 SIRT1水平降低, CTRP5水平提高,二者均为预后不良独立影响因素,联合检测能提高预后不良预测价值。     

Systematic review of prediction of poor outcome in anoxic-ischaemic coma with biochemical markers of brain damage

OBJECTIVE: To investigate whether accurate prognostic rules can be derived from the combined results of studies concerning prediction of poor prognosis in anoxic-ischaemic coma with biochemical markers of brain damage in cerebrospinal fluid (CSF) or serum. DESIGN: A meta-analysis of prognostic studies in anoxic-ischaemic coma, selected from Medline and EMBASE databases, according to predefined criteria. SUBJECTS: Twenty-eight studies, with a total of 802 unselected, consecutive patients, in which tests, sampling time and outcome measures were described unequivocally and results were described using clear cut-off values or raw data. MAIN OUTCOME MEASURES: Poor outcome, defined as death or vegetative state, versus good outcome, defined as any other outcome state. ANALYSES: The overall prognostic accuracy of these variables was expressed as the 95% CIs of the pooled false-positive test rate and the pooled positive-likelihood ratios. RESULTS: Only markers in CSF (creatine kinase isoenzyme (CKBB) >204 U/l, neuron specific enolase (NSE) >33 ng/ml, lactate dehydrogenase (LDH) >82 U/l and glutamate oxaloacetate (GOT) >62 U/l) reached a 0% false-positive rate. However, due to small sample sizes, the confidence limits were wide. The accuracy of prediction of poor outcome seemed acceptably high for CSF-CKBB (pooled false-positive rate 0% [95% CI 0-2.3%]; pooled positive-likelihood ratio 33.2 [95% CI 4.8-230.2]), but this result was based on two retrospective studies without blinding of the treating physicians for the test result. CONCLUSIONS: Because of small numbers of patients studied and methodological limitations the combined results are not sufficiently accurate to provide a solid basis for non-treatment decisions.     

Serum neuron-specific enolase: A promising biomarker of silicosis

BACKGROUNDSilicosis is a type of chronic pulmonary fibrosis caused by long-term inhalation of silica dust particles. There has been no ideal biomarker for the diagnosis and differential diagnosis of silicosis until now. Studies have found that elevated neuron-specific enolase (NSE) concentration in the serum of silicosis patients is helpful for diagnosis and severity assessment of the disease. However, the number of cases in these studies was not enough to arouse attention.AIMTo investigate the clinical significance of serum NSE in the diagnosis and staging of silicosis.METHODSFrom January 2017 to June 2019, 326 cases of silicosis confirmed in Quanzhou First Hospital Affiliated to Fujian Medical University were included in the silicosis group. A total of 328 healthy individuals or medical patients without silicosis were included in the control group. Serum NSE concentrations of all subjects were determined by electrochemical luminescence.RESULTSThere were no significant differences in sex, age, smoking index and complications between the silicosis and control groups. The mean serum NSE concentration was 26.57 ± 20.95 ng/mL in the silicosis group and 12.42 ± 2.68 ng/mL in the control group. The difference between the two groups was significant (U = 15187, P = 0.000). Among the 326 patients with silicosis, 103 had stage I silicosis, and the mean serum NSE concentration was 15.55 ± 6.23 ng/mL. The mean serum NSE concentration was 21.85 ± 12.05 ng/mL in 70 patients with stage II silicosis. The mean serum NSE concentration was 36.14 ± 25.72 ng/mL in 153 patients with stage III silicosis. Kruskal–Wallis H test suggested that the difference in serum NSE concentration in silicosis patients in the three groups was significant (H = 130.196, P = 0.000). Receiver operating characteristic curve analysis indicated that the area under the curve was 0.858 (95% confidence interval: 0.828-0.888; P = 0.000). When the NSE concentration was 15.82 ng/mL, the Jorden index was the largest, the sensitivity was 72%, and the specificity was 90%.CONCLUSIONSerum NSE concentration may be a promising biomarker for the diagnosis and assessment of severity of silicosis.     

老年脓毒症患者血清循环Netrin-1表达水平对发生脑损伤风险的预测价值研究

目的　探讨神经导向因子-1(Netrin-1) 在老年脓毒症并发脑损伤（sepsis-associated encephalopathy,SAE）患者血清中表达情况及临床意义。方法　选择2017 年1 月～ 2020 年12 月在唐山市丰润区人民医院就诊的老年脓毒症患者162例为观察对象,其中并发脑损伤患者67 例作为SAE 组,未并发脑损伤患者95 例作为对照组;根据患者28 天内死亡情况,将SAE 患者分为存活组35 例和死亡组32 例。酶联免疫吸附法（enzyme-linked immunosorbent assay,ELISA）检测血清中Netrin-1 和神经元特异性烯醇化酶（neuron specific enolase,NSE）表达水平,免疫层析法检测中枢神经特异蛋白（S100β）表达水平,对患者进行急性生理健康与慢性疾病（acute physical health and chronic diseases,APACHE Ⅱ）评分、序贯器官衰竭估计（Sequential Organ Failure Assessment, SOFA）评分,Pearson 分析血清 Netrin-1 水平与NSE,S100β,APACHE Ⅱ和SOFA 评分相关性,受试者工作特征（receiver operating characteristic,ROC）曲线分析血清Netrin-1 对SAE 的预测价值。结果　SAE 患者住重症加强护理病房（intensive care unit, ICU）时间8.72±1.81 天, APACHE Ⅱ为20.10±6.46分和SOFA 为11.57±4.83 分,显著高于对照组的ICU 时间4.52±1.34 天,APACHE Ⅱ 14.20±5.31 分和SOFA 8.41±3.56 分,差异均有统计学意义（t=4.794~16.971,均P ＜ 0.001）。SAE 患者血清Netrin-1 水平为114.57±30.21 ng/ml,显著低于对照组（162.81±35.43 ng/ml）的表达水平;NSE 和S100β 分别为9.62±1.76 ng/ml 和1.03±0.32μg/ml,显著高于对照组（7.32±1.35ng/ml 与0.75±0.21μg/ml）,差异均有统计学意义（t=6.723~9.408,均P ＜ 0.001）。死亡组SAE 患者血清 Netrin-1 水平为93.78±25.62ng/ml,显著低于存活组的134.26±28.05ng/ml;NSE 和S100β 高于存活组（13.01±1.81 ng/ml vs 7.23±1.14 ng/ml;1.29±0.35μg/ml vs 0.81±0.19μg/ml）,其APACHE Ⅱ和SOFA 显著高于对照组（22.15±6.21 分vs 18.23±5.64 分;13.25±3.42 分vs 10.45±2.95 分）,差异具有统计学意义（t=2.708~15.782,均P ＜ 0.05）。相关性分析结果显示,SAE 患者血清 Netrin-1 水平与NSE,S100β,APACHE Ⅱ和SOFA 评分呈负相关性（r=-0.451,-0.503,-0.514,-0.409,均P ＜ 0.001）。血清Netrin-1 联合NSE 和S100β 预测老年脓毒症患者发生脑损伤风险敏感度和特异度分别为95.52% 和89.47%（AUC=0.969,95%CI:0.942~0.996,P ＜ 0.001）,联合诊断优于血清Netrin-1 单独检测（AUC=0.873,95%CI:0.819~0.928,P ＜ 0.001）。结论　老年SAE 患者血清Netrin-1 水平降低。血清Netrin-1 单独或联合NSE 和S100β 检测对预测老年脓毒症患者发生脑损伤风险具有一定临床应用价值。