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血液病患者毛霉菌病的临床特征、预后因素和宏基因组下一代测序诊断。

Clinical Characteristics, Prognosis Factors and Metagenomic Next-Generation Sequencing Diagnosis of Mucormycosis in patients With Hematologic Diseases.

机构信息

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

Tianjin Institutes of Health Science, Tianjin, China.

出版信息

Mycopathologia. 2024 Aug 1;189(4):71. doi: 10.1007/s11046-024-00875-w.

Abstract

INTRODUCTION

New diagnostic methods and antifungal strategies may improve prognosis of mucormycosis. We describe the diagnostic value of metagenomic next⁃generation sequencing (mNGS) and identify the prognostic factors of mucormycosis.

METHODS

We conducted a retrospective study of hematologic patients suffered from mucormycosis and treated with monotherapy [amphotericin B (AmB) or posaconazole] or combination therapy (AmB and posaconazole). The primary outcome was 84-day all-cause mortality after diagnosis.

RESULTS

Ninety-five patients were included, with "proven" (n = 27), "probable" (n = 16) mucormycosis confirmed by traditional diagnostic methods, and "possible" (n = 52) mucormycosis with positive mNGS results. The mortality rate at 84 days was 44.2%. Possible + mNGS patients and probable patients had similar diagnosis processes, overall survival rates (44.2% vs 50.0%, p = 0.685) and overall response rates to effective drugs (44.0% vs 37.5%, p = 0.647). Furthermore, the median diagnostic time was shorter in possible + mNGS patients than proven and probable patients (14 vs 26 days, p < 0.001). Combination therapy was associated with better survival compared to monotherapy at six weeks after treatment (78.8% vs 53.1%, p = 0.0075). Multivariate analysis showed that combination therapy was the protective factor (HR = 0.338, 95% CI: 0.162-0.703, p = 0.004), though diabetes (HR = 3.864, 95% CI: 1.897-7.874, p < 0.001) and hypoxemia (HR = 3.536, 95% CI: 1.874-6.673, p < 0.001) were risk factors for mortality.

CONCLUSIONS

Mucormycosis is a life-threatening infection. Early management of diabetes and hypoxemia may improve the prognosis. Exploring effective diagnostic and treatment methods is important, and combination antifungal therapy seems to hold potential benefits.

摘要

介绍

新的诊断方法和抗真菌策略可能改善毛霉菌病的预后。我们描述了宏基因组下一代测序(mNGS)的诊断价值,并确定了毛霉菌病的预后因素。

方法

我们对接受单药治疗(两性霉素 B [AmB]或泊沙康唑)或联合治疗(AmB 和泊沙康唑)的血液病患者进行了回顾性研究。主要结局是诊断后 84 天的全因死亡率。

结果

共纳入 95 例患者,其中“确诊”(n=27)、“疑似”(n=16)毛霉菌病采用传统诊断方法确诊,“可能”(n=52)毛霉菌病采用 mNGS 阳性结果确诊。84 天死亡率为 44.2%。可能+ mNGS 患者和疑似患者的诊断过程、总生存率(44.2% vs 50.0%,p=0.685)和有效药物的总反应率(44.0% vs 37.5%,p=0.647)相似。此外,可能+ mNGS 患者的中位诊断时间短于确诊和疑似患者(14 天 vs 26 天,p<0.001)。与单药治疗相比,治疗 6 周后联合治疗的生存率更高(78.8% vs 53.1%,p=0.0075)。多变量分析显示,联合治疗是保护因素(HR=0.338,95%CI:0.162-0.703,p=0.004),而糖尿病(HR=3.864,95%CI:1.897-7.874,p<0.001)和低氧血症(HR=3.536,95%CI:1.874-6.673,p<0.001)是死亡的危险因素。

结论

毛霉菌病是一种危及生命的感染。早期管理糖尿病和低氧血症可能改善预后。探索有效的诊断和治疗方法很重要,联合抗真菌治疗似乎有潜在益处。

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