重症肝病并发侵袭性真菌病的诊治

重症肝病并发侵袭性真菌病(IFD)是影响重症肝病患者预后的重要因素,其早期诊断仍是困扰临床医生的重要问题。临床最常见的4种IFDs是念珠菌病、曲菌病、隐球菌病以及肺孢子菌肺炎,在重症肝病患者临床诊疗过程中重视并发IFD的可能,尤其对存在高危因素的患者,及早发现、及时诊断、恰当治疗,对改善危重症肝病的预后至关重要。     

血液病患者继发侵袭性真菌病诊治的现状及进展

近年来,随着广谱抗生素、皮质类固醇、免疫抑制剂、抗肿瘤药物的大量应用及器官移植术的开展,侵袭性真菌病（invasive fungal disease,IFD）的发病率、病死率正逐年增加,IFD是血液系统疾病、特别是血液系统恶性肿瘤化疗过程中常见的并发症和死因之一。IFI）原称侵袭性真菌感染（invasive fungal infection,IFI）,是指疾病一开始即侵犯深部组织器官或病变从局部开始进一步发展,侵犯深部脏器、组织形成感染灶,甚至引起真菌性败血症。恶性血液病患者本身免疫力低下,加之大剂量化疗后出现粒细胞缺乏,化疗药物的不良反应及大剂量广谱抗生素的使用等高危因素的存在,使血液病患者更易继发IFD。近年来随着高危患者的增多,临床医师对IFD的认识不断提高,诊断方法越来越多,但早期诊断仍较为困难,从而影响早期治疗。IFD进展快,未及时治疗,导致病死率增高,使之成为临床上面临的一大难题。本文将从血液病患者继发IFD的流行病学、病原学、诊断及治疗进展做一综述。     

恶性肿瘤患者放疗后侵袭性真菌病的临床特点

目的探讨恶性肿瘤患者放疗后侵袭性真菌病(IFD)的发病率、发病时间及危险因素,为IFD临床诊治提供参考。方法采用回顾性调查方法,收集山东省医学科学院附属医院2017年11月-2019年4月期间行放疗的345例患者的性别、年龄、原发病诊断、合并良性基础疾病等一般资料及诊治情况,疑似出现侵袭性真菌病的患者进行影像学、血清学、微生物学检查及组织病理学检查并进行统计学分析。结果 345例恶性肿瘤患者放疗后发生IFD29例次,其中确诊6例次,临床诊断11例次,拟诊12例次,总体发生率为8.4%。平均IFD发生时间为放疗开始后(36.8±25.41)d。共真菌15例次(其中念珠菌10例次,曲霉菌5例次),标本分别来源于外周血或骨髓5例,痰或呼吸道灌洗液9例,活组织标本1例。在未明确病原体的病例中,有1例GM试验阳性,G试验阳性、GM试验阴性1例,未检出隐球菌及肺孢子菌感染者。肺癌、合并基础疾病、出现重度粒细胞缺乏、使用广谱抗菌药物是IFD发生高危因素(P值分别为0.039、0.005、0.001、0.047)。结论 IFD临床诊断困难,对于存在高危因素的恶性肿瘤放疗后疑似患者,应及时采取相应措施,降低感染发生率,保证患者治疗效果。     

肝衰竭并发侵袭性真菌病的诊治及预防

肝衰竭的并发症临床上表现复杂多样,极易并发局部或全身的侵袭性真菌病(IFD),继发其他脏器的损伤,从而导致肝损伤的进一步加重,使其形成"恶性循环"的病理进程,最终导致多脏器功能衰竭,病死率极高,成为临床处理中的"棘手问题"。介绍了肝衰竭并发IFD的原因、症状、诊断、治疗、预后、预防等方面的研究进展,探讨了近年来关于肝衰竭并发IFD的一些共识和争议,阐述其研究的意义及前景,旨在提高肝衰竭并发IFD的临床诊断和治疗水平。     

肝衰竭合并侵袭性肺曲霉病临床分析

目的探讨肝衰竭患者合并侵袭性肺曲霉病（IPA）的临床特点及治疗对策。方法对我中心341例肝功能衰竭合并肺部感染患者的临床资料进行回顾性分析。结果组织病理诊断明确的IPA11例,临床诊断病例3例。肺部IPA主要诱因为长期应用广谱抗生素和糖皮质激素;临床症状和影像学变化非特异性和不典型;及时诊断并及时使用卡泊芬净治疗,可以减少IPA患者的病死率。结论对肝衰竭患者需要提高早期诊断、治疗IPA的意识。     

肝衰竭合并侵袭性肺曲霉菌病的临床特点及危险因素分析

目的探讨肝衰竭合并侵袭性肺曲霉菌病(IPA)患者的临床特点和危险因素,为临床诊治提供参考。方法收集2010年1月-2014年12月河南省人民医院诊治的肝衰竭患者447例,回顾性分析其中合并IPA患者的临床特征、实验室指标及影像学检查结果。另随机选取同期住院且年龄相近未合并肺部感染的肝衰竭患者49例作为对照。计量资料组间比较采用独立样本t检验;计数资料组间比较采用χ~2检验或Fisher's精确概率法。采用多因素Logistic回归分析肝衰竭合并IPA的危险因素。结果 447例肝衰竭患者发生IPA 43例(9.6%)。年龄(P=0.023)、合并肝性脑病(P=0.021)、长期广谱抗菌药物使用(P=0.007)、激素的应用(P=0.016)和深静脉置管(P0.001)是IPA发生的独立危险因素。肝衰竭合并IPA患者的临床表现缺乏特异性,肺部CT改变以双肺多发结节、肿块影和近胸膜楔形实变较常见,典型的晕轮征和空气新月征较少见。35例接受抗真菌治疗的患者中30例好转或治愈,3例死于消化道出血,2例死于肺部感染,其余未接受治疗的患者全部死亡。结论肝衰竭患者存在诸多发生IPA的危险因素,且临床表现不典型,发病率和病死率高;早发现、早治疗是提高生存率的关键。     

慢加急性肝衰竭合并肺部感染危险因素及预后分析

摘要 目的：探讨慢加急性肝衰竭(ACLF)患者发生肺部感染的危险因素及其对预后的影响，并建立预后预测模型。方法：回顾性分析310例ACLF患者的临床资料，通过Logistic回归分析ACLF患者发生肺部感染的危险因素，并利用Nomogram方法建立预后预测模型。结果：ACLF患者感染发生率65.5%，其中肺部感染发生率为38.7%。ACLF合并肺部感染患者较无感染及肺外感染患者的短期病死率更高。Logistic回归多因素分析显示肺部感染的独立危险因素包括侵入性操作、使用激素治疗及高敏C反应蛋白；而年龄、总胆红素、国际标准化比率（INR）以及合适的抗生素治疗是影响肺部感染患者30d病死率的独立危险因素。纳入相应的危险因素，建立名为TAIST的Nomogram预测模型，其受试者工作特征曲线下面积为0.844(95%CI 0.741～0.946)，具有比其他预后模型更高的判别性能。结论：ACLF合并肺部感染患者预后差，TAIST模型有助于早期识别其危险因素并优化治疗策略。     

冠心病合并抑郁焦虑障碍常用量表评价

随着医学模式向社会-心理-生物综合医学模式转变,心理、社会因素在心血管疾病的发生、发展、预后和治疗中的作用越来越受到人们的关注。抑郁焦虑可能是冠心病的危险因素之一,可加速其进程,并且是患者预后不良的危险因素。然而,非精神科医务人员对冠心病合并抑郁焦虑的识别率很低,此类患者往往未能得到及时的诊断和治疗,甚至由于过度的检查和治疗,进一步加重了患者的心理障碍和经济负担。及早正确识别冠心病合并抑郁焦虑并对其进行干预是有待解决的问题。文章就如何识别冠心病患者合并抑郁焦虑障碍以及目前常用抑郁焦虑量表的应用及评价方面的研究现状做一综述。     

慢性肝衰竭患者预后的影响因素

目的:探讨影响慢性肝衰竭患者预后的独立危险因素,并建立预测模型.方法:选择天津市第三中心医院2002-05/2007-03行人工肝治疗的慢性肝功能衰竭,且病例资料完整的患者228例,对其临床资料进行回顾性分析.使用Logistic回归分析筛选影响预后的独立危险因素,根据筛选出的独立危险因素建立适合我国慢性肝衰竭患者的预测模型.结果:影响慢性肝衰竭患者预后的独立危险因素有Child-Pugh评分、血钠值、酪氨酸、是否有胆酶分离、是否合并肝癌、间接胆红素及白细胞.228例慢性肝衰竭患者中大于9.5分者的病死率72.18%,小于9.5分者的病死率13.68%,两组比较有显著性差异(P＜0.05).患者早期的病死率为13.68%,中期的病死率68.91%,晚期的病死率为100%,三组比较有显著性差异(P＜0.05).结论:本研究建立的LOG模型对慢性肝衰竭患者的预后有很好的预测性.     

肝癌肝切除术后肝衰竭危险因素的Meta分析

目的探讨我国肝癌肝切除术后肝衰竭(PHLF)发生的危险因素,为预测和预防术后肝衰竭的发生提供理论依据。方法检索中国生物医学文献服务系统、维普、中国知网、万方等数据库,并辅以手工检阅相关论文及其参考文献,收集我国自1990年1月至2013年6月期间公开发表的有关PHLF危险因素的相关文献,运用Meta分析方法进行合并分析。结果共纳入11项研究,2859例肝癌手术切除患者。Meta分析结果显示术前Child-Pugh A级PHLF发生率明显低于对照组(合并OR值为6.28,95%CI:4.55~8.65);术前前白蛋白水平低于170 mg/dl组患者术后肝衰竭发生率增高(合并OR值为4.96,95%CI:3.03~8.10);合并肝硬化组术后肝衰竭发生率高于未合并肝硬化组(合并OR值为4.14,95%CI:2.46~6.98);术中失血量1000 ml组术后肝衰竭发生率较对照组低(合并OR值为5.62,95%CI:3.46~9.11);肿瘤直径10 cm组(合并OR值为2.69,95%CI:1.58~4.57)及切肝范围半肝组(合并OR值为1.64,95%CI:1.12~2.40)肝衰竭发生率均低于对照组;年龄≥60岁(合并OR值为1.73,95%CI:1.25~2.39)、术中输血(合并OR值为3.79,95%CI:2.20~6.51)增加术后肝衰竭发生率。性别、术中是否阻断入肝血流与术后肝衰竭发生无相关性(P0.05)。结论年龄、术前Child-Pugh分级、前白蛋白水平、术中失血量、肿瘤直径、切肝范围、合并肝硬化、术中输血等是影响PHLF发生的危险因素。     

Invasive fungal infection before and after liver transplantation

Invasive infections are a major complication before liver transplantation (LT) and in the early phase after surgery. There has been an increasing prevalence of invasive fungal disease (IFD), especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure, who suffer from a profound state of immune dysfunction and receive intensive care management. In such patients, who are listed for LT, development of an IFD often worsens hepatic and extra-hepatic organ dysfunction, requiring a careful evaluation before surgery. In the post-transplant setting, the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis, even if several major issues still remain, such as duration, target population and drug type(s). Nevertheless, the development of IFD in the early phase after surgery significantly impairs graft and patient survival. This review outlines presentation, prophylactic and therapeutic strategies, and outcomes of IFD in LT candidates and recipients, providing specific considerations for clinical practice.     

A comprehensive diagnostic approach using galactomannan,targeted β‐d‐glucan,baseline computerized tomography and biopsy yields a significant burden of invasive fungal disease in at risk haematology patients

Invasive fungal disease (IFD) is difficult to diagnose. We investigated the incidence of IFD and risk factors using the revised European Organization for Research and Treatment of Cancer (EORTC) and the Mycoses Study Group (MSG) definitions. Patients (N = 203) undergoing intensive therapy with expected neutropenia ≥10 d were recruited prospectively and followed for a median (range) of 556 (12–730) d. Baseline chest computerized tomography (CT) was performed pre‐therapy. Twice‐weekly surveillance with galactomannan (GM) was combined with targeted β‐d ‐glucan (BDG) testing on patients with possible IFD or who were GM‐positive. Tissue diagnosis was obtained whenever possible. The cumulative incidence of proven/probable IFD among the 202 evaluable cases after 2 years follow‐up was 21%, including 14 proven and 30 probable IFDs. Using either GM or BDG as the sole biomarker (plus host and clinical evidence) the apparent overall incidence of proven/probable IFD was 11% and 16%, respectively. Combined GM/BDG detected all biopsy‐proven mould IFD. Baseline CT abnormalities were found in 76/202 (38%) patients. Baseline CT abnormalities and Karnofsky score <90, monocytopenia >10 d and bacteraemia were independent risk factors associated with greater than twofold increased IFD risk. This combined diagnostic approach identified a high incidence of IFD and important risk factors in this cohort.     

Invasive fungal disease in patients treated for newly diagnosed acute leukemia

Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in patients undergoing treatment for acute leukemia (AL). Antifungal prophylactic strategies are associated with significant toxicities and cost. We performed a retrospective study of the incidence and risk factors for IFD among patients newly diagnosed with and treated for AL between January 1, 2004 and July 1, 2006. Patient follow up concluded January 1, 2007. Among 231 patients with newly diagnosed AL, 31 (13.4%) developed IFD by the end of follow up, 24 (10.4%) of whom developed IFD within the first 100 days after diagnosis of AL. The cumulative probability of developing IFD was 5.9% by 30 days and 11.1% at 100 days after AL diagnosis. Patients who had persistent leukemia after an initial course of induction chemotherapy were significantly more likely to develop IFD than those who did not have evidence of persistent leukemia (14/65 (21.5%) vs. 15/148 (10.1%), P = 0.03). In a time‐dependent Cox model, the adjusted hazard ratio for developing IFD within the first 100 days of AL diagnosis based on the number of days of neutropenia in that period was 4.85 (95% confidence interval: 1.52, 15.4). Those patients with more days of neutropenia in the first 100 days after AL diagnosis, such as those who did not achieve remission after a first course of induction chemotherapy, were more likely to develop IFD. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.     

药物性肝损害的危险因素、诊断规范及停药标准

药物性肝损害是指药物本身或其代谢产物引起的肝损害,是引起肝衰竭的重要原因之一。目前还缺乏有效的预测指标及诊疗手段。从易感因素、诊断和评价标准等方面对药物性肝损害进行介绍。了解药物性肝损害的最新进展,有利于及时发现药物性肝损害的易感患者;合理运用各种评价标准,有助于药物性肝损害的规范化诊疗。     

Fungal infections in children with haematologic malignancies and stem cell transplant recipients

Children with haematologic malignancies and haematopoietic stem cell transplant recipients are at high risk for invasive fungal diseases (IFD). There has been an increased number of at-risk children over the past two decades due to improvements in cancer therapies resulting in improved survival of children with high-risk and refractory malignancies. The predominant organisms that cause IFD include Candida spp., Aspergillus spp. and the Mucorales molds. Clinical presentations of IFD vary based on host immune status and the causative organism. Though serum biomarkers such as the galactomannan assay and beta-D-glucan assay have been validated in adults, there are limited data regarding their diagnostic value in children. Thus, the gold standard for IFD diagnosis remains tissue biopsy with histopathological and microbiological evaluation. Treatment of IFD is multimodal and involves antifungal drugs, correction of immune dysfunction and surgical resection when feasible. Paediatric practice regarding IFD is largely extrapolated from data generated in adult patients; in this review, we evaluate both primary paediatric studies and guidelines intended for adult patients that are applied to paediatric patients. There remain significant knowledge gaps with respect to the prevention, diagnosis and treatment of IFD in immunocompromised children, and further research is needed to help guide management decisions.     

重型肝炎患者并发医院真菌感染相关因素的研究

目的 了解重型肝炎(简称重肝)患者并发医院真菌感染的相关因素。方法 对1997年2月～2002年6月住院重肝并发真菌感染患者进行前瞻性研究。结果 115例重肝并发真菌感染患者平均(37.2±21.5)岁;其中男49例,女66例。主要感染部位为腹腔(40.9％),呼吸道(26.9％),消化道(21.8％)。感染菌种以白色念珠菌为主,占67.6％。其感染因素为使用广谱抗生素和激素、白细胞减少、疾病严重程度、侵袭性诊疗操作。研究组与同期无真菌感染的重肝患者(对照组)比较:病死率分别为59.1％(68/115)和34.8％(40/115),两组治疗无效的病例(恶化和死亡病例)比较差异有显著性,x~2=36.0,P<0.001。多变最分析发现白细胞减少、感染播散和疾病严重程度是影响预后的因素。结论 重肝并发真菌感染的相关因素和影响预后的因素对其预防、诊断、治疗、改进预后和生存质量有重要的临床意义。     

Assessing Responses to Treatment of Opportunistic Mycoses and Salvage Strategies

Invasive fungal disease (IFD) in immunocompromised patients remains a major cause of morbidity and mortality and there is a pressing need for studies of novel antifungal agents and strategies to improve outcomes. Trial design details often determine not only the appropriate interpretation of the results, but also their translation into clinical practice. However, the conduct of IFD clinical trials remains challenging due to the rarity of IFD, heterogeneity of underlying diseases, and the lack of clear and standardized response criteria. Response assessments are influenced by host, underlying disease and treatment factors as well as eligibility criteria. In addition, the criteria used to assess response, when response is assessed and the type of antifungal therapy under study can impact response evaluations. This article will discuss recent trials of primary, salvage, empiric, and prophylactic antifungal therapy with specific attention to the design of these antifungal therapy trials and how their designs influence their interpretation. The potential role of surrogate markers, such as the galactomannan index, fungal deoxyribonucleic acid polymerase chain reaction assay, and (18F) fluorodeoxyglucose positron emission tomography scans in establishing the early diagnosis of IFD, as well as enhancing the ability to assess outcomes to antifungal therapy, and thereby the optimal duration of antifungal therapy, will be discussed.     

伴肺部侵袭性真菌病史的血液病患者行异基因造血干细胞移植的临床分析

目的探讨血液病伴肺部侵袭性真菌病(IFD)病史患者行异基因造血干细胞移植(allo-HSCT)后其肺部IFD的复发、疗效及影响因素。方法2005年3月至2006年10月南方医科大学南方医院14例肺部IFD病史的血液病患者接受allo-HSCT,移植前经抗真菌治疗10例完全缓解(CR),4例部分缓解(PR),移植中均给予预防性抗真菌治疗。调查移植后肺部IFD的复发、疗效,IFD相关病死率,Logistic回归模型分析移植方式、移植前IFD状态、预处理方案、移植物抗宿主病(GVHD)预防方案[含抗胸腺球蛋白(ATG)和不含ATG]、供受关系、急性GVHD(aGVHD)及WBC重建对移植后肺部IFD转归的影响。结果移植后肺部IFD的复发率为71.4%(10/14),移植前10例CR患者6例复发,4例PR患者全部复发;其复发时间分别为移植后3个月内7例,4~6个月内3例;10例复发患者中9例接受抗真菌治疗后4例获CR,2例PR,3例无效(NR),总有效率为6/9;移植后IFD相关病死率为35.7%(5/14);二性霉素B、伊曲康唑及伏立康唑预防肺部IFD的复发率差异无显著性意义(P=0.122);经Logisitic回归分析未发现与移植后肺部IFD复发相关的危险因素及影响其转归的危险因素。结论肺部IFD病史不是allo-HSCT的绝对禁忌证;有肺部IFD病史的患者,其移植后IFD复发率及相关病死率高。     

侵袭性真菌病实验室诊断方法临床应用专家共识

侵袭性真菌病的诊断引起临床多学科关注,早期确切诊断是改善患者预后的关键。其方法主要包括真菌直接镜检、真菌培养和鉴定、真菌血清学检查、分子生物学检测和组织病理学检查。为了促进临床医师深入了解并合理应用这些方法,提高侵袭性真菌病诊断水平,我们邀请多学科专家共同编写了此共识。本共识对侵袭性真菌病诊断方法的应用人群、送检要求、结果解读及临床意义进行了介绍并提出建议,强调对于侵袭性真菌病高危患者,应综合应用多种诊断方法、正确取材送检、提高结果解读能力、了解不同方法的临床意义,以便合理应用,更好地服务于患者。     

侵袭性真菌病实验室诊断方法临床应用专家共识

侵袭性真菌病的诊断引起临床多学科关注,早期确切诊断是改善患者预后的关键。其方法主要包括真菌直接镜检、真菌培养和鉴定、真菌血清学检查、分子生物学检测和组织病理学检查。为了促进临床医师深入了解并合理应用这些方法,提高侵袭性真菌病诊断水平,我们邀请多学科专家共同编写了此共识。本共识对侵袭性真菌病诊断方法的应用人群、送检要求、结果解读及临床意义进行了介绍并提出建议,强调对于侵袭性真菌病高危患者,应综合应用多种诊断方法、正确取材送检、提高结果解读能力、了解不同方法的临床意义,以便合理应用,更好地服务于患者。