二代测序技术应用于脑脊液检测在结核性脑膜炎中的早期诊断价值

目的评价二代测序技术应用于脑脊液检测在结核性脑膜炎（TBM）患者中的早期诊断价值。 方法前瞻性纳入2018年2月2日至2018年8月2日于山东省胸科医院就诊的临床怀疑TBM的患者共50例,并跟踪随访其诊疗结局。送检脑脊液标本均进行二代测序,测序所得原始序列与病原微生物数据库进行对比得到最终结果。二代测序结果以检测到结核分枝杆菌复合群唯一比对序列为阳性,未检测到唯一比对序列为阴性。以符合脑脊液结核分枝杆菌培养阳性、涂片阳性、Xpert MTB/RIF检测阳性及结核分枝杆菌核酸检测阳性等4项中至少1项即为确诊TBM患者;临床可疑TBM且抗结核治疗有效为临床诊断患者;有其他病原学依据或临床排除TBM者为非TBM患者。分析二代测序在TBM早期诊断中的敏感性和特异度。 结果确诊为TBM患者22例中Xpert MTB/RIF检测阳性13例,培养阳性6例,结核分枝杆菌核酸PCR检测阳性5例,临床诊断为TBM患者12例,非TBM患者16例。在确诊及临床诊断患者中,二代测序技术检测到结核分枝杆菌复合群系列20例,敏感性为58.8%（20/34）,特异度为100%（16/16）。在确诊患者中,二代测序的敏感性为63.6%（14/22）;在同步进行结核分枝杆菌培养、Xpert MTB/RIF检测与二代测序的50例标本中,以临床诊断为标准,3种方法的特异度均为100%（16/16）;传统方法、Xpert MTB/RIF检测及二代测序的敏感性分别为29.4%（10/34）、38.2（13/24）和58.8（20/34）,前两种检测方法与二代测序敏感性差异均有统计学意义（McNemar检验：χ² = 8.333、P = 0.013,χ² = 8.333、P = 0.065）。传统方法与二代测序联合检测的敏感性高达82.4%（28/34）。 结论二代测序技术能够较快速地检测脑脊液中的结核分枝杆菌复合群,且其敏感性和特异度均较高,可作为TBM的早期诊断指标。二代测序联合传统检测方法可提高检出率。     

结核性胸膜炎患者外周血和胸水中Th17、Th1细胞检测分析

目的 探讨结核性胸膜炎患者Th17、Th1细胞免疫应答的特性及作用。方法 应用流式细胞术检测30例健康对照组（HD）、23例潜伏感染组（LTBI）、20例结核性胸膜炎组(TP) 患者外周血单个核细胞（PBMC）与胸水单个核细胞（PFMC）Th17、Th1细胞的变化情况。结果 结核性胸膜炎患组外周血非特异性Th17和Th1细胞百分比分别为（2.81±0.94）和（27.85±11.02）,低于健康对照组（4.63±1.63）、（36.34±9.39）和潜伏感染组（4.13±1.91）、（42.37±13.87）,差异有统计学意义（P<0.001,P<0.05）;结核性胸膜炎患者胸腔积液PFMC的非特异性Th17细胞百分比为（1.85±1.34）,低于外周血PBMC的（2.81±0.94）,差异有统计学意义(P<0.01);同时PFMC结核菌特异性Th17、Th1细胞的百分比分别为（0.68±0.13）和（6.91±1.16）,高于PBMC（0.25±0.11）和（1.98±0.56 ）,差异有统计学意义(P<0.01,P<0.001)。结论 结核性胸膜炎患者外周血非特异性Th17、Th1细胞应答及感染局部Th17的非特异性应答反应均受到抑制;感染局部特异性Th17、Th1应答处于高水平状态;Th17、Th1细胞应答在结核性胸膜炎的发病中发挥重要作用。     

新型隐球菌脑膜炎45例临床分析

目的 探讨新型隐球菌脑膜炎（CNM）患者的临床特点,为诊断和治疗提供经验与参考。 方法 回顾性分析2010年1月—2019年6月海南省人民医院收治的45例CNM患者的临床表现及治疗情况。 结果 4.44%（2例）有明确鸽子接触史,22.22%（10例）合并有艾滋病,28.89%（13例）合并有肺结核、肝病等其他基础疾病。主要临床症状为头痛（36/45,80%）,发热（31/45,68.89%）,恶心、呕吐（15/45,33.33%）,复视、视力下降（3/45,6.67%）,意识障碍（4/45,8.89%）,抽搐（2/45,4.44%）,听力下降（1/45,2.22%）,脑膜刺激征阳性（11/45,24.44%）。80%(36例)出现高颅压,20例脑脊液压力大于300 mmH₂O。脑脊液检查显示颅内压升高,脑脊液蛋白、糖、氯化物呈现一高二低现象;20例患者脑脊液培养阳性,分离菌株对氟康唑、5-氟胞嘧啶(5-FC)、两性霉素B(AmB)和伏立康唑的敏感性较高;45例患者中,18例给予AmB联合5-FC治疗,12例接受AmB联合氟康唑治疗,4例接受氟康唑+5-FC治疗,8例单用AmB,3例单用氟康唑治疗,治愈24例,好转2例,有效率57.78%。 结论 CNM患者主要以颅内高压为特点,患者出现发热、头痛、脑膜刺激征阳性,应及时行腰穿,反复行脑脊液涂片及培养明确诊断,隐球菌对多种抗真菌药敏感,临床可个体化采用AmB、氟康唑（或）5-FC的联合方案治疗。     

促炎因子在低龄化脓性脑膜炎患儿病情严重程度及预后中的应用价值

目的探讨4种促炎因子在低龄化脓性脑膜炎（purulent meningitis,PM）患儿早期诊断、病情评估和预后中的价值。 方法选取2岁以下的PM患儿25例,其中普通PM组17例,重症PM组8例,同时选取对照组18例,入院后12 h内采集脑脊液（cerebrospinal fluid,CSF）和血液。应用酶联免疫吸附剂测定法测定CSF和血清中肿瘤坏死因子α（tumor necrosis factor-α,TNF-α）、白细胞介素（interleukin,IL）1β、IL-6和IL-8的浓度。随访6个月,评估患儿的预后情况。 结果CSF IL-6和CSF IL-8诊断小儿PM的受试者工作特征(receiver operating characteristic,ROC)曲线的曲线下面积（area under curve,AUC）分别为0.932和0.916,其诊断效能高于其他指标。重症PM组CSF中TNF-α、IL-1β、IL-6和IL-8水平均高于普通PM组的水平（P＜0.05）,普通PM组CSF促炎因子水平高于对照组（P＜0.05）。在区分普通PM和重症PM的ROC曲线中,CSF TNF-α的AUC最大,当CSF TNF-α取截断值为70.4 ng/L时,其区分重症PM的敏感度为100%、特异度为94.1%。预后不良组CSF IL-6水平显著高于预后轻度不良组,预后轻度不良组CSF IL-6水平明显高于预后良好组（P＜0.05）。 结论CSF中的IL-6和IL-8可作为低龄儿童PM的早期辅助诊断指标。CSF中TNF-α水平有助于反映低龄儿童PM病情的严重程度。CSF中IL-6水平可能对PM患儿的远期预后有一定的预测作用。     

儿童化脓性脑膜炎近期不良预后危险因素分析

目的 探讨儿童化脓性脑膜炎近期不良预后的危险因素。方法收集化脓性脑膜炎患儿209例,分为预后良好组33例和预后不良组176例。筛选出可能影响近期预后的因素,单因素分析两组在这些因素方面的差异。结果结果显示,预后不良组年龄小于预后良好组,意识障碍/昏迷、前囟隆起、瞳孔异常、肌张力异常及并发症发生率;脑脊液蛋白含量、糖浓度、乳酸浓度,血白细胞＜4×10⁹/L或血白细胞＞12×10⁹/L、血钙＜3.5 mmol/L、血钠＜135mmol/L、颅脑CT或MRI检查异常及使用丙种球蛋白患儿比例高于预后良好组,差异有统计学意义(P＜0.05)。Logistic多因素分析结果显示,低龄、意识障碍或昏迷、瞳孔不等大、脑脊液乳酸升高、血白细胞＜4×10⁹/L或血白细胞＞20×10⁹/L与化脓性脑膜炎患儿预后不良独立相关。结论低龄、意识障碍或昏迷、瞳孔不等大、脑脊液乳酸升高、血白细胞＜4×10⁹/L或＞血白细胞20×10⁹/L是化脓性脑膜炎近期不良预后的危险因素。临床上应及早识别,早期积极防治。     

Asbestos exposure and tuberculous pleurisy as developmental causes of progressive unilateral upper-lung field pulmonary fibrosis radiologically consistent with pleuroparenchymal fibroelastosis

BackgroundUnilateral upper-lung field pulmonary fibrosis (upper-PF), which is radiologically consistent with pleuroparenchymal fibroelastosis, develops after thoracic surgery. In most patients with unilateral upper-PF, aberrant intra-/extra thoracic air commonly emerges and an autopsy shows chronic pleuritis, which indicates that pleural involvement is associated with upper-PF development. If so, there may be patients with unilateral upper-PF who have a history of pleural involvement, including tuberculous pleurisy (TP) or asbestos exposure (AE). This study aimed to examine this supposition.MethodsWe examined the radiological reports of all consecutive patients from 2012 to 2018 to investigate whether there were patients having unilateral upper-PF and a history of TP or AE.ResultsEight patients were included in the study. Five patients had a history of TP, and the remaining three had that of AE. All patients were men and had respiratory symptoms, and seven patients presented with restrictive ventilatory impairment. The interval between TP or last AE and upper-PF development was long, with a median of over 20 years. The upper-PF lesion was commonly located in the right lung, and aberrant intrathoracic air was observed in five patients during their clinical course. Additionally, the upper-PF lesion transformed into a cystic lesion in six patients, which resulted in Aspergillus infection in two patients. The prognosis was poor, with a median overall survival of 38 months.ConclusionsUnilateral upper-PF developed even in patients with a history of pleural involvement. Our results indicate that pleural involvement plays an important role in the development of unilateral upper-PF.     

糖皮质激素在结核性脑膜炎治疗中效果的探析

目的：探讨糖皮质激素在结核性脑膜炎中的治疗效果。方法整群选取该院于2008年1月-2012年12月收治的96例结核性脑膜炎患者为研究对象,随机分为对照组和观察组,对照组采用常规治疗,观察组在常规治疗的基础上配合糖皮质激素。比较两组患者治疗后的转归率和各项指标改善情况。结果观察组良好转归率为72.91豫,高于对照组的43.75豫,差异具有统计学意义(P<0.05);观察组患者的意识恢复时间、白细胞计数、蛋白质含量等指标改善程度均优于对照组,差异具有统计学意义(P<0.05)。结论对结核性脑膜炎患者采用糖皮质激素配合治疗可以提高良好转归率,提高治疗效果。     

Conventional- versus high-dose vancomycin regimen in patients with acute bacterial meningitis: a randomized clinical trial

Objective: Efficacy of the conventional- versus high-dose vancomycin regimen in patients with acute bacterial meningitis was compared.

Methods: In a randomized clinical trial 44 patients with acute bacterial meningitis were randomly assigned to the conventional- or high-dose vancomycin groups. Clinical and laboratory parameters were used for evaluation of response to the treatment regimens.

Results: In the high-dose group, leukocytosis and fever resolved significantly faster than those in the conventional group. Furthermore, the length of hospitalization was shorter and Glasgow Coma Scale at the end of 10th day was significantly lower in the high dose compared to the conventional group. Trend of creatinine clearance changes did not differ significantly between the two groups.

Conclusion: In comparison to the conventional-dose regimen, the high-dose vancomycin regimen was associated with significantly more favorable clinical response without increase in the incidence of nephrotoxicity in patients with acute bacterial meningitis.     

Mondini dysplasia with recurrent bacterial meningitis caused by three different pathogens

Mondini dysplasia is rare, but has an important association with recurrent bacterial meningitis. We herein describe the case of a 3‐year‐old girl with unilateral sensorineural hearing loss who presented with three independent episodes of bacterial meningitis within 8 months. Temporal bone computed tomography indicated the characteristic features of Mondini dysplasia in the right inner ear. This was treated by surgical closure of the inner ear defect via oval window and additional vaccination was administered. Appropriate vaccination might prevent the recurrent bacterial meningitis associated with Mondini dysplasia.     

大肠杆菌K1穿越血脑屏障机制研究进展

新生儿化脓性脑膜炎是一种危重的中枢神经系统感染性疾病.大肠杆菌K1菌株(Escherichia coli K1,Ecoli K1)是常见的导致新生儿化脓性脑膜炎的革兰阴性菌,大部分大肠杆菌脑膜炎是血源性传播所导致,其穿过血脑屏障(blood-brain barrier,BBB)的机制一直是研究的重点.相关研究表明,Ecoli K1穿越BBB与高水平菌血症、对脑微血管内皮细胞的侵袭、受体介导的胞吞转运、活菌穿越BBB密切相关.该文从上述四个方面对E.coli K1穿过BBB进入大脑引起新生儿化脓性脑膜炎的发病机制进行综述.