实体器官移植后侵袭性肺曲菌病的CT表现

背景：实体器官移植后肺部感染的发病率和死亡率居高不下,尤其是作为机会感染的曲菌,早期诊断侵袭性肺曲霉菌病是困难的。 目的：总结实体器官移植后侵袭性曲菌性肺炎的CT表现。 方法：以“实体器官移植/肾移植/肝移植/肺移植/心脏移植,曲菌,真菌,霉菌,肺,侵袭性,体层摄影术,X线计算机”为中文捡索词,以“solid organ transplantation/renal transplantation/liver transplantation/lung transplantation/heart transplantation, aspergillosis,fungus,mold,pulmonary invasive, tomography computerized”为英文检索词,检索维普和中国知网(CNKI)期刊全文数据库、Medline,highwire和外文生物医学期刊全文数据库(Foreign Journals Integration System)2001年1月至2012年10月有关肺曲菌感染和真菌或霉菌肺感染报告中主要涉及曲菌的侵袭性曲菌肺炎CT表现的临床报道。然后二次人工检索实体器官移植后,纳入有关实体器官移植后侵袭性曲菌肺炎CT表现的文献,排除重复性研究和不典型报道。 结果与结论：实体器官移植后侵袭性肺曲霉菌病典型的胸部CT表现包括结节、肿块、实变以及磨玻璃影。随感染时间依次出现晕征、反晕征、空洞和空气半月征。这些征象的发生率的不同可能与CT检查时间和早期抗真菌治疗已经真菌预防性治疗有关。有意义的结果是侵袭性肺曲霉菌病征象与患者预后的关系。无实变或肿块和小腔空洞存在可能与更好预后相关。大结节、多发梗死性实变、肾脏替代治疗和持久性的血清半乳甘露聚糖阳性是90 d的死亡率独立的预测因子。而代表出血的晕征与90 d的死亡率无关。尽管报告较少,用CT肺血管造影诊断侵袭性真菌性肺炎是有前景的诊断手段,可以早期发现反映侵袭性血管受累的血管闭塞征,其敏感性和特异性优于晕征,与血清曲菌半乳甘露聚糖试验近似。     

Aspergillus endocarditis in a known case of allergic bronchopulmonary aspergillosis: an autopsy report

Invasive aspergillosis is an emerging infection mainly affecting immunocompromised patients. Aspergillus endocarditis remains a rare infection and usually occurs following cardiac surgery for prosthetic valves. This is an uncommon case of a 60-year-old asthmatic male who developed allergic bronchopulmonary aspergillosis during the course of his illness, and while receiving low dose oral steroids, he subsequently developed right-sided Aspergillus mural and native valvular endocarditis with extensive invasive pulmonary aspergillosis.     

Disseminated infection with Prototheca zopfii after unrelated stem cell transplantation for leukemia

Disseminated infection with Prototheca zopfii is a rare disease in immunosuppressed patients. We here report the first case of lethal infection with P. zopfii following unrelated stem cell transplantation for leukemia. Breakthrough protothecosis occurred during long-term administration of voriconazole in the case of pulmonary aspergillosis.     

Discordant rise in galactomannan antigenemia in a patient with resolving Aspergillosis, renal failure, and ongoing hemodialysis

We describe the case of a patient with improving invasive aspergillosis and paradoxically rising serum galactomannan levels in the presence of chronic renal failure and ongoing hemodialysis. Dialysate tested negative for galactomannan, demonstrating the inability of treatments such as hemodialysis to clear Aspergillus antigen from serum. In patients with renal failure and aspergillosis, rising serum galactomannan levels may not necessarily signify progressive infection.     

Performance characteristics of the platelia Aspergillus enzyme immunoassay for detection of Aspergillus galactomannan antigen in bronchoalveolar lavage fluid

We have evaluated the Platelia Aspergillus enzyme immunoassay for detection of galactomannan in bronchoalveolar lavage (BAL) specimens in solid organ transplant patients with aspergillosis. The precision and reproducibility in serum or BAL to which galactomannan was added were similar. Sensitivity was 81.8% in patients with aspergillosis, and specificity was 95.8% in lung transplant patients who underwent BAL for surveillance for infection or rejection. Among transplant controls, positive results were more common in patients (i) who underwent diagnostic BAL performed for evaluation of symptoms or chest computed tomographic abnormalities, (ii) who had undergone lung transplantation, or (iii) who were colonized with Aspergillus. Galactomannan testing in BAL is useful for diagnosis of aspergillosis in transplant patients. The significance of positive results in patients without confirmed aspergillosis requires further evaluation.     

Aspergillus mural endocarditis.

Infectious mural endocarditis is uncommon and not well documented. The clinical setting and pathologic features of five patients with Aspergillus mural endocarditis are described. Leukemia, carcinoma, renal transplantation, and hepatic failure were the primary diseases. Associated conditions include high-dose corticosteroids, cytotoxic therapy, renal failure, gram-negative sepsis, and endotracheal intubation. All patients received prolonged antibiotic therapy or treatment with three or more antibiotics. All had clinically undetected aspergillosis and severe fungal pneumonia. Fungal myocardial abscesses were present in each patient. Aspergillus mural endocarditis developed in more than 40% of patients with cardiac aspergillosis. Endocardial vegetations were contiguous with underlying myocardial infection; yet they may develop initially as a subendocardial focus rather than from a myocardial abscess. Aspergillus mural endocarditis progressed to destroy the mitral valve ring and served as a source of mycotic embolization to vital organs.     

Intensive care management of influenza-associated pulmonary aspergillosis

BackgroundSevere pulmonary infections are among the most common reasons for admission to intensive care units (ICU). Within the last decade, increasing reports of severe influenza pneumonia resulting in acute respiratory distress syndrome (ARDS) complicated by Aspergillus infection were published.ObjectivesTo provide a comprehensive review of management of influenza-associated pulmonary aspergillosis in patients with ARDS.SourcesReview of the literature pertaining to severe influenza-associated pulmonary aspergillosis. PubMed database was searched for publications from the database inception to January 2019.ContentIn patients with lower respiratory symptoms, development of respiratory insufficiency should trigger rapid and thorough clinical evaluation, in particular in cases of suspected ARDS, including electrocardiography and echocardiography to exclude cardiac dysfunction, arrhythmias and ischaemia. Bronchoalveolar lavage should obtain lower respiratory tract samples for galactomannan assay, direct microscopy, culture, and bacterial, fungal and viral PCR. In case of positive Aspergillus testing, chest CT is the imaging modality of choice. If influenza pneumonia is diagnosed, neuraminidase inhibitors are the preferred approved drugs. When invasive aspergillosis is confirmed, first-line therapy consists of isavuconazole or voriconazole. Isavuconazole is an alternative in case of intolerance to voriconazole, drug–drug interactions, renal impairment, or if a spectrum of activity including the majority of Mucorales is desired. Primary anti-mould prophylaxis with posaconazole is recommended in haematology patients at high-risk. It may be considered in newly diagnosed influenza and ARDS, but ideally in clinical trials.ImplicationsThe rising reports of influenza-associated pulmonary aspergillosis in patients with ARDS, who are otherwise not considered at risk for fungal pneumonia demands heightened clinical awareness. Tracheobronchitis and Aspergillus in respiratory tract samples should prompt suspicion of invasive fungal infection and further work-up. The management algorithm should comprise bronchoalveolar lavage, CT imaging, sophisticated ventilator-management, rescue extracorporeal membrane oxygenation, and antifungal and antiviral therapy. To decrease the burden of influenza-related illness, vaccination is of utmost importance, specifically in patients with co-morbidities.     

A systematic review of epidemiology,risk factors,diagnosis, antifungal resistance,and management of invasive aspergillosis in Africa

Invasive aspergillosis (IA) affects more than 300,000 people annually worldwide with a case fatality rate reaching 80%. However, in Africa despite the presence of risk factors for the development of IA, the burden of these fungal infections remained unknown. This systematic review aimed to update the available information on the epidemiology and the therapeutic management of IA in Africa. The published papers were systematically searched on major medical databases from September 20 to October 10, 2021. The list of references of eligible articles and the Google scholar database were also checked in order to search for possible eligible articles. Results were reported following the Preferred Reporting Items for Systematic and Meta-analyses (PRISMA) guidelines. The search yielded 1864 articles of which 29 met the inclusion criteria. This systematic review showed the existence of IA in Africa. The prevalence of IA can reach 27% with a fatality rate of more than 60%. The most common clinical form of IA found was invasive pulmonary aspergillosis. The main predisposing conditions identified were neutropenia, HIV/AIDS, renal transplant recipients, and renal failure. Aspergillus section Flavi and Nigri were the main Aspergillus species identified and Aspergillus section Fumigati was uncommon. The main management strategy for IA cases was to start antifungal therapy only after a failure of broad-spectrum antibiotic therapy. This review provided evidence of the existence of invasive aspergillosis in Africa and especially a high rate of undiagnosed invasive aspergillosis cases.     

肾移植及移植后的血管并发症

背景：尽管肾移植手术技术已相当成熟,但各移植中心难免会出现术中及术后的血管并发症。 目的：分析肾移植过程中及移植后血管并发症的诊断与处理。 方法：回顾性分析 11 例肾移植过程中、移植后血管并发症资料。移植过程中并发症：动脉吻合口狭窄2例,肾静脉横断1例,髂外动脉硬化斑块剥脱堵塞肾动脉3例,移植肾静脉扭曲1例;移植后并发症：肾外型假性动脉瘤2例,吻合口狭窄1例,移植肾动脉压迫梗阻1例。 结果与结论：肾移植中吻合口狭窄2例移植后恢复良好,分别于移植后6年及11年移植肾失功;肾静脉横断1例随访12年移植肾失功;髂外动脉硬化斑块剥脱堵塞肾动脉3例,1例移植肾当即失功,另2例分别随访6年及2年,现移植肾功能良好;移植肾静脉扭曲1例移植后出现移植肾功能延迟恢复,1个月后因重症肺部感染死亡。移植后发生的血管并发症中肾外型假性动脉瘤2例移植肾均失功;吻合口狭窄1例经置入支架后肾功能恢复正常,已随访18个月;移植肾动脉压迫梗阻1例移植后出现移植肾功能延迟恢复,3周后因重症肺部感染死亡。结果说明肾移植过程中及移植后发生血管并发症,只要诊断准确、处理及时,可取得比较满意的治疗效果。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

Refractory invasive pulmonary aspergillosis due to Aspergillus flavus detected with the combination of two in-house Aspergillus qPCR

We present a case of probable invasive pulmonary aspergillosis due to Aspergillus flavus, in a female patient treated for an acute myeloid leukemia. Two weeks after an allogenic stem cell transplantation a probable invasive pulmonary aspergillosis was diagnosed based on thoracic imaging combined with positive galactomannan antigen and positive in-house mitochondrial Aspergillus qPCR in serum. Although an antifungal treatment was initiated, Aspergillus qPCR and galactomannan antigen remained positive in serum and worsening of the thoracic lesions was observed. The discordance between the negativity of the in-house ribosomal Aspergillus qPCR (specific to A. fumigatus) and the positivity of the in-house mitochondrial Aspergillus qPCR (targeting A. fumigatus and some other Aspergillus) allowed the suspicion of a thermophilic Aspergillus species that was not A. fumigatus. No strain was obtained in culture but the involvement of A. flavus was confirmed using a specific A. flavus qPCR.This case illustrated the usefulness of our original strategy combining two different in-house Aspergillus qPCRs, in addition to galactomannan assay, to diagnose invasive aspergillosis in hematology patients.     

Late antibody-mediated rejection by de novo donor HLA-DP-specific antibody after renal transplantation: A case report

The role of donor HLA-DP-specific antibodies after renal transplantation is controversial, and only preformed HLA-DP-specific antibodies have been shown to mediate rejection. Here we present a case of late humoral rejection mediated by de novo donor HLA-DP-specific antibodies in a non-sensitized recipient. This unique case demonstrates the pathogenic role of de novo anti-DP antibodies and suggests that HLA-DP matching might be relevant for renal transplantation.     

Cerebral aspergillosis in liver transplantation.

Nine cases of cerebral aspergillosis were identified in a series of 44 brains obtained at necropsy from patients who had undergone liver transplantation. In two of these there was dual infection with Candida albicans. The primary focus of infection was invariably in the lungs. One case of pulmonary Aspergillus infection was found with no evidence of cerebral disease. Infection tended to occur in the period soon after transplantation, was associated with high dose steroids, retransplantation, and showed a significant seasonal incidence. Neurological findings were non-specific and only two cases were diagnosed before death. Aspergillus infection soon after transplantation indicates that this organism is a considerable nosocomial hazard, particularly in the winter and spring months. Positive cultures before death are rarely obtained and antifungal treatment should be started on clinical suspicion alone.     

Reduction in Mortality after Umbilical Cord Blood Transplantation in Children Over a 20-Year Period (1995-2014)

Infections and graft-versus-host disease (GVHD) have historically resulted in high mortality among children undergoing umbilical cord blood transplantation (UCBT). However, recent advances in clinical practice have likely improved outcomes of these patients. We conducted a retrospective cohort study of children (<18years of age) undergoing UCBT at Duke University between January 1, 1995 and December 31, 2014. We compared 2-year all-cause and cause-specific mortality during 3 time periods based on year of transplantation (1995 to 2001, 2002 to 2007, and 2008 to 2014). We used multivariable Cox regression to identify demographic and UCBT characteristics that were associated with all-cause mortality, transplantation-related mortality, and death from invasive aspergillosis after adjustment for time period. During the 20-year study period 824 children underwent UCBT. Two-year all-cause mortality declined from 48% in 1995 to 2001 to 30% in 2008 to 2014 (P?=?.0002). White race and nonmalignant UCBT indications were associated with lower mortality. Black children tended to have a higher risk of death for which GVHD (18% versus 11%; P?=?.06) or graft failure (9% versus 3%; P?=?.01) were contributory than white children. Comparing 2008 to 2014 with 1995 to 2001, more than half (59%) of the reduced mortality was attributable to a reduction in infectious mortality, with 45% specifically related to reduced mortality from invasive aspergillosis. Antifungal prophylaxis with voriconazole was associated with lower mortality from invasive aspergillosis than low-dose amphotericin B lipid complex (hazard ratio, .09; 95% confidence interval, .01 to .76). With the decline in mortality from invasive aspergillosis, adenovirus and cytomegalovirus have become the most frequentinfectious causes of death in children after UCBT. Advances in clinical practice over the past 20years improved survival of children after UCBT. Reduced mortality from infections, particularly invasive aspergillosis, accounted for the largest improvement in survival and was associated with use of voriconazole for antifungal prophylaxis.     

Amyloidosis secondary to chronic pulmonary aspergillosis: Case report and a systematic review of literature

Secondary amyloidosis results from the deposition of abnormally folded proteins in body organs due to chronic inflammatory disorders. Kidneys are the most commonly affected organ and manifest as nephrotic syndrome with or without renal failure. Chronic pulmonary aspergillosis (CPA) is a chronic infection of lung parenchyma affecting those with an underlying structural lung disease. Herein, we present a case of CPA where the initial manifestation was that of nephrotic syndrome due to renal amyloidosis. We also perform a systematic review for studies describing secondary amyloidosis due to CPA.     

Use of recombinant nucleocapsid proteins of the hantaan and nephropathia epidemica serotypes of Hantaviruses as immunodiagnostic antigens

Cytomegalovirus-specific in vitro antibody production (CMV-IVAP) by peripheral blood lymphocytes (PBL) was investigated in 12 renal transplant recipients. CMV-IVAP, CMV-serology, and viral cultures were carried out weekly during at least 8 weeks after transplantation. Nine episodes of CMV infection occurred in eight patients. CMV-IVAP was positive in eight episodes; IgG and/or IgA and/or IgM antibodies reacting with several CMV polypeptides were secreted by PBL. In two patients with primary CMV infection, only IgA antibodies were detected. Cytomegalovirus cultures were positive in eight episodes and serological evidence of CMV infection was obtained in five episodes. In one case, CMV-IVAP was observed before CMV isolation and in another case, before serological evidence of CMV infection. Our study indicates that CMV-IVAP could represent an additional tool for the diagnosis of CMV infection. Our study indicates that CMV-IVAP could represent an additional tool for the diagnosis of CMV infection in renal transplant recipients. © 1993 Wiley-Liss, Inc.     

Catheter-related cutaneous aspergillosis complicated by fungemia and fatal pulmonary infection in an HIV-positive patient with acute lymphocytic leukemia

A case of intravenous catheter-related cutaneous aspergillosis andAspergillus fumigatus fungemia in an HIV-positive patient with Burkitt-cell acute lymphocytic leukemia is reported. The patient developed pulmonary aspergillosis with a rapidly fatal outcome despite recovery from neutropenia and improvement of the underlying malignancy. The unusual severity and rapid spread of the infection, despite normal neutrophil count and prompt antifungal therapy, suggest that HIV-related immunocompromise might play a role in the impairment of host defences againstAspergillus infection. Thus catheter-related cutaneous aspergillosis could lead to a severe deep-seated infection in HIV-positive patients.     

肾移植后排斥与感染中细胞免疫功能的监测

背景：Cylex ImmuKnow检测方法是惟一得到FDA认可的检测移植受者细胞免疫功能的方法, 它直接反映细胞免疫的功能,具有灵敏度高、特异性强,结果量化等优点。 目的：通过对肾移植后患者监测细胞免疫功能iATP值(intracellular adenosine triphosphatei),分析细胞免疫功能与肾移植术后排斥或感染的关系。 方法：140例肾移植受者采用ImmuKnowTM-Cylex®方法检测细胞免疫功能,收集数据结合患者临床状态分为排斥组18例,感染组35例与稳定组87例,同时收集61份健康人群血样检测细胞免疫功能数据作对照。分析细胞免疫功能与肾移植患者移植后发生排斥与感染的关系。 结果与结论：细胞免疫功能iATP值检测结果显示,感染组患者有71.4%(n=25)分布在低免疫区,同比对照组、稳定组与排斥组比例明显增高(P < 0.05)。感染组iATP值显著低于其他3组。说明感染与细胞免疫功能低下两者具有明显的相关性,细胞免疫功能测定对监测肾移植后感染具有显著意义。提示ImmuKnowTM-Cylex®方法测定细胞免疫功能为肾移植后并发感染的诊断与治疗提供可靠客观依据,但与肾移植后排斥反应的发生未见明显的相关性,有待于大样本的实验证实。     

Invasive pulmonary aspergillosis in an ICU patient with Legionnaires’ disease: A diagnostic challenge

Aspergillus fumigatus can cause a wide range of diseases, from hypersensitivity to invasive infection. Invasive disease usually occurs in severely immunocompromised patients with deep and prolonged neutropenia. It is a less well-recognized complication in critically ill patients without traditional risk factors. We describe a case of early invasive pulmonary aspergillosis (IPA) secondary to Legionella pneumophila serogroup 1 pneumonia in a patient on an intensive care unit (ICU). In addition to commonly accepted risk factors for IPA in ICU patients, we hypothesis that L. pneumophilia pneumonia could enhance this type of infection. We also reviewed all published cases of coinfection with L. pneumophila and A. fumigatus to assess whether Legionnaires’ disease could be a risk factor for IPA.     

COVID-19-associated mixed mold infection: A case report of aspergillosis and mucormycosis and a literature review

COVID-19-associated mold infections have been increasingly reported, and the main entity is COVID-19-associated aspergillosis (CAPA). Similarly, COVID-19-associated mucormycosis has been reported in hematology, and its prevalence is high and has been increasing in the diabetic population in India during the third COVID-19 pandemic wave. Simultaneous infection with Mucorales and Aspergillus is rare and even rarer during COVID-19. Here, we report the case of a previously immunocompetent patient with severe SARS-CoV-2 infection complicated with probable CAPA and mucormycosis co-infection. Specific diagnostic tools for mucormycosis are lacking, and this case highlights the advantages of analyzing blood and respiratory samples using the quantitative polymerase chain reaction to detect these fungi. We further reviewed the literature on mixed Aspergillus/Mucorales invasive fungal diseases to provide an overview of patients presenting with both fungi and to identify characteristics of this rare infection.     

Disseminated Scopulariopsis brevicaulis infection in an allogeneic stem cell recipient: case report and review of the literature

A fatal case of disseminated Scopulariopsis brevicaulis infection in an allogeneic stem cell transplant recipient is described. The patient was initially thought to have pulmonary aspergillosis, on the basis of clinical signs and antigenaemia, but Aspergillus was not isolated by culture. Scopulariopsis brevicaulis was subsequently isolated from skin and then from sputum and stool. Further investigation revealed that the infection had spread from a primary pulmonary site to the skin. A review of the literature underscores the difficulty of diagnosing infections caused by such emerging fungal pathogens and the poor outcome of immunocompromised patients with non-Aspergillus mould infections.