JNNP: HIV阴性免疫活性隐球菌性脑膜炎感染后炎症反应综合征的预测因子

2020-12-20 MedSci原创 MedSci原创

隐球菌病作为一种深部真菌病,主要侵犯中枢神经系统,约占隐球菌感染的80%,预后严重,死亡率高。隐球菌属包括17种和8个变种,在真菌分类学上归入半知菌亚门、芽孢菌纲、隐球酵母目、隐球酵母科。致病菌主要是

隐球菌病作为一种深部真菌病,主要侵犯中枢神经系统,约占隐球菌感染的80%,预后严重,死亡率高。隐球菌属包括17种和8个变种,在真菌分类学上归入半知菌亚门、芽孢菌纲、隐球酵母目、隐球酵母科。致病菌主要是新生隐球菌,已报道可引起人类疾病的还有浅黄隐球菌、浅白隐球菌和罗伦隐球菌等,但很少见。新生隐球菌有3个变种,即新生变种(var neoformans)、格特变种(var gattii)和上海变种(shanghaiensis)。按血清学分类可分为A、B、C、D及AD型5型,此外尚有少量不确定型。在高活性抗逆转录病毒治疗(HAART)开始后,大约10%-20%的HIV-CM患者出现了反常的隐球菌免疫重建综合征(IRIS)。然而,目前尚不清楚哪些因素可以预测CM-PIIRS的发生。、本研究旨在填补这一研究空白主要探讨HIV阴性免疫活性CM-PIIRS的预测指标。

2011年1月至2019年12月,在中国广州中山大学第三附属医院接受CM评估和治疗的113名患者。对人口统计学特征(年龄性别)、临床症状(头痛、发热、视力和听力障碍、精神状态、恶心呕吐)和治疗史、血液和脑脊液(CSF)样本测试、改良Rankin量表(mRS)评分和腰椎穿刺进行在线分析。使用随机森林来选择有用的预测变量并预测PIIRS的发展。首先使用选定的变量将随机森林拟合到训练集中(75%,n=84),然后用它来预测测试集的PIIRS状态(25%,n=29)。通过使用所有患者和最有用的预测变量拟合决策树,证明了一个简洁的预测规则。进一步分析了从开始杀菌治疗到PIIRS出现或随访结束的时间,以及脑脊液真菌计数减少率与后来PIIRS的关系。

比较了41例PIIRS患者和72例没有PIIRS患者的基线特征。头痛、发热、精神状态改变、呕吐、癫痫、共病和初始mRS评分均无差异。然而,CM-PIIRS患者的视觉和听觉症状、VPS、更高的CSF开放压力和更多的CSF真菌计数高于没有PIIRS的CM患者。选择听力受损、脑脊液真菌计数、脑脊液压力和总胆固醇进行预测,随机森林的准确度为0.749(95%CI为0.571至0.893),曲线下面积为0.799(95%CI为0.631-0.939)。基于脑脊液真菌计数和TC的分裂并不显著。低脑脊液真菌计数(≤338/mL)组发生PIIRS的时间比高脑脊液真菌计数(>338/mL)组快,差异为28.6天(95%CI 10.2-47.1,p=0.005)。线性回归得到PIIRS与治疗后天数的相互作用系数为0.002(p=0.941),表明治疗后(log)脑脊液真菌计数的减少率与PIIRS的发生无关,在脑脊液葡萄糖、蛋白质和氯化物中也可以发现类似的结果。

决策树的发现将听力受损和脑脊液高压(>230mmH2O)的CM患者确定为PIIRS的高危患者。从开始杀菌治疗到出现PIIRS的天数的进一步生存分析显示其与听力损失、脑脊液压力和脑脊液真菌计数有关。 首次在HIV阴性免疫功能正常的CM患者中显示了PIIRS发展的预测指标。现脑脊液压力高于230mmH2O是PIIRS的有力预测因子。颅内压增高的患者可能有更严重的炎症反应。此外,本文发现患有CM-PIIRS的患者比没有CM-PIIRS的患者更多(39.0%比4.1%)。听力损伤也是CM-PIIRS的一个强有力的预测因子。除了颅内压升高外,隐球菌感染本身也会导致听力损失。炎症机制可能在CM患者的听力损害中起作用。CM发病时伴随的听力损害可能表明有强烈的炎症反应。

36.3%的未感染HIV-CM的患者出现PIIRS,且发病中位数为开始抗真菌治疗后50天。这与在HAART上感染CM的HIV感染者相似,虹膜发生率为31.7%,发病中位数为60天。5例CM-PIIRS患者的脑脊液真菌计数高于未感染CM的患者,从治疗开始到出现PIIRS的天数的进一步生存分析也揭示了其与脑脊液真菌计数的关系。低脑脊液真菌计数(≤338/mL)组PIIRS较高真菌计数(>338/mL)组发生PIIRS的时间早,差异有显著性(28.6天)。这一结果表明,脑脊液真菌计数低的患者发生PIIRS的风险较低,但如果PIIRS发生在这些患者中,则会更早发生PIIRS。此外,多元logistic回归和基于树的分析表明脑脊液真菌计数不能作为CM-PIIRS的预测因子,这与CM-IRIS不一致。此外,脑脊液真菌计数减少的比率没有发现与PIIRS事件相关。

总之,基线听力损伤和高脑脊液压力(230mmH2O)是评估HIV阴性免疫活性CM患者PIIRS发生的潜在危险因素。

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    2020-12-22 xugc
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    2020-12-21 ms6000000156981277

    0

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    2020-12-21 飞翔的乌龟

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    2020-12-21 慎独

    研究探索 医学发展

    0

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对于HIV-1感染者,每8周1次卡博特韦联合利匹韦林治疗效果与每4周1次相当,研究支持每2个月1次的长效卡博特韦-利匹韦林治疗方案用于HIV-1感染者

Lancet Gastroen Hepatol:男男性行为人群的HCV风险研究

HIV阳性的男男性行为人群的HCV感染风险大大增加,而艾滋病暴露前预防使用频率的增加,相应的HCV感染风险也显著增加

ViiV两月一次长效注射剂cabotegravir用于预防HIV,获得FDA的突破性疗法称号

与每日口服FTC/TDF片剂相比,cabotegravir预防HIV的效率提高了66%。