Immunocompromised patients

免疫功能低下患者
  • 文章类型: Journal Article
    免疫功能低下的患者对普通或机会性病毒感染的脆弱性特别高。临床标本中病毒载量的定量对于该患者人群的感染和再激活的诊断和管理很重要。特别是移植接受者。随着关于体外诊断方法的新法规“IVDR”即将在法国生效,诊断实验室必须实施与这一新法规兼容的方法和系统。AltoStar®腺病毒(AdV)的技术性能,巨细胞病毒(CMV)和人疱疹病毒-6(HHV-6)DNAPCR试剂盒1.5在AltoStar自动化系统AM16上使用146个临床样品中的参考试剂盒进行评估。临床标本的总体一致性为87.5%(28/32),96.8%(62/64),100%(22/22),ADV的100%(28/28)和92.8%(26/28),CMV(WB样本和其他矩阵),分别为HHV-6A和B。定量结果高度相关,估计在0.057至0.648对数差异内等效。我们发现AltoStarAM16系统上的altona试剂盒适用于AdV的临床监测,免疫受损宿主中的CMV和HHV-6。
    The vulnerability of immunocompromised patients to common or opportunistic viral infections is particularly high. The quantitation of viral load in clinical specimens is important for the diagnosis and management of the infection and reactivation in this patient population, particularly transplant recipients. As the new regulation \"IVDR\" regarding in vitro diagnosis methods is about to come into effect in France, diagnostic laboratories have to implement methods and systems compatible with this new regulation. Technical performance of the AltoStar® Adenovirus (AdV), Cytomegalovirus (CMV) and human Herpesvirus-6 (HHV-6) DNA PCR Kits 1.5 was assessed on the AltoStar Automation system AM16 using reference kits in 146 clinical samples. Overall agreement in clinical specimens was 87.5 % (28/32), 96.8 % (62/64), 100 % (22/22), 100 % (28/28) and 92.8 % (26/28) for AdV, CMV (WB samples and other matrices), HHV-6 A&B respectively. Quantitative results were highly correlated and estimated to be equivalent within a 0.057-0.648 log-amount difference.We found that altona kits on The AltoStar AM16 system are suitable for clinical monitoring of AdV, CMV and HHV-6 in immunocompromised hosts.
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  • 文章类型: Journal Article
    在高危患者中使用主动免疫和被动免疫来预防COVID-19的严重病程,但预防性中和抗体对mRNA疫苗免疫反应的影响仍然是个谜。在这里,我们显示CD4T和B细胞对Spikevax加强免疫的反应被治疗性抗体Casirivimab和Imdevimab抑制。B细胞和T细胞应答在对照中被显著诱导,但在抗体处理的患者中未被诱导。数据表明,体液免疫,即高水平的抗体,负面影响反应性免疫,导致增强时细胞反应减弱。这表明疫苗接种工作的时间分离;优选在预防性治疗性抗体治疗之前应用主动疫苗接种。
    Active and passive immunization is used in high-risk patients to prevent severe courses of COVID-19, but the impact of prophylactic neutralizing antibodies on the immune reaction to the mRNA vaccines has remained enigmatic. Here we show that CD4 T and B cell responses to Spikevax booster immunization are suppressed by the therapeutic antibodies Casirivimab and Imdevimab. B cell and T cell responses were significantly induced in controls but not in antibody-treated patients. The data indicates that humoral immunity, i. e. high levels of antibodies, negatively impacts reactive immunity, resulting in blunted cellular responses upon boosting. This argues for temporal separation of vaccination efforts; with active vaccination preferably applied before prophylactic therapeutic antibody treatment.
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  • 文章类型: Editorial
    每年进行的实体器官移植的数量正在增加,并且按以下顺序增加:肾脏,肝脏,心,肺,胰腺,小肠,和子宫移植。然而,移植的结果正在改善(第1年后器官存活率>90%).因此,普通外科医生很有可能会面临急腹症移植患者的治疗。免疫功能低下患者的手术问题可能不仅包括与移植物相关的问题,还包括与非移植物相关的问题。围手术期免疫抑制的调节,伴随的免疫抑制问题的治疗,皮质醇的管理,最重要的是,在这些患者中,了解迅速恶化的情况以及对临床表现的准确评估和解释尤为重要。围手术期评估和准备包括评估患者的心血管系统,确定患者是否患有高血压或下丘脑-垂体-肾上腺轴抑制,或患者是否有任何凝血机制异常或血栓栓塞发作。移植患者的免疫抑制与钙调磷酸酶抑制剂的使用有关,皮质类固醇,和抗增殖剂。很多时候,临床表现不典型,导致诊断和治疗的延误,并导致发病率和死亡率增加。多探测器计算机断层扫描对于早期诊断和管理至关重要。移植接受者容易感染,特别是由巨细胞病毒和艰难梭菌引起的特异性感染,并且他们容易发生术中或术后并发症,需要格外小心和警惕。有必要遵循循证治疗方案。因此,要求临床医生为患者选择正确的治疗计划(保守,紧急开放手术或微创手术,包括腹腔镜甚至机器人手术)。
    The number of solid organ transplantations performed annually is increasing and are increasing in the following order: Kidney, liver, heart, lung, pancreas, small bowel, and uterine transplants. However, the outcomes of transplants are improving (organ survival > 90% after the 1st year). Therefore, there is a high probability that a general surgeon will be faced with the management of a transplant patient with acute abdomen. Surgical problems in immunocompromised patients may not only include graft-related problems but also nongraft-related problems. The perioperative regulation of immunosuppression, the treatment of accompanying problems of immunosuppression, the administration of cortisol and, above all, the realization of a rapidly deteriorating situation and the accurate evaluation and interpretation of clinical manifestations are particularly important in these patients. The perioperative assessment and preparation includes evaluation of the patient\'s cardiovascular system and determining if the patient has hypertension or suppression of the hypothalamic-pituitary-adrenal axis, or if the patient has had any coagulation mechanism abnormalities or thromboembolic episodes. Immunosuppression in transplant patients is associated with the use of calcineurin inhibitors, corticosteroids, and antiproliferation agents. Many times, the clinical picture is atypical, resulting in delays in diagnosis and treatment and leading to increased morbidity and mortality. Multidetector computed tomography is of utmost importance for early diagnosis and management. Transplant recipients are prone to infections, especially specific infections caused by cytomegalovirus and Clostridium difficile, and they are predisposed to intraoperative or postoperative complications that require great care and vigilance. It is necessary to follow evidence-based therapeutic protocols. Thus, it is required that the clinician choose the correct therapeutic plan for the patient (conservative, emergency open surgery or minimally invasive surgery, including laparoscopic or even robotic surgery).
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  • 文章类型: Editorial
    在这篇社论中,我们讨论了一个令人信服的案例,重点是后部可逆性脑病综合征(PRES),这是接受肝移植并接受他克莫司治疗的患者的并发症。他克莫司(FK506),来自筑鹿链霉菌,是一种有效的免疫抑制大环内酯。它通过结合FK结合蛋白抑制T细胞转录,并能增强糖皮质激素和孕酮的作用。他克莫司可有效预防移植患者的同种异体移植排斥反应,但具有不利影响,例如他克莫司相关的PRES。PRES表现出各种神经症状以及血压升高,在神经影像学上主要表现为血管源性水肿。当计算机断层扫描检测到初始病变时,磁共振成像,尤其是流体衰减反转恢复序列,对诊断皮质和皮质下水肿具有优势。我们的讨论集中在实体器官移植受者中PRES的发生率,范围在0.5到5+ACU-之间,随着不同的介绍,从癫痫到视觉障碍。一名66岁男性肝移植后的病例强调了与他克莫司相关的PRES相关的诊断和管理挑战。在顶叶和枕叶放射学上明显,PRES强调需要提高医疗保健提供者的警惕。这篇社论强调了及早认识的重要性,准确诊断,和PRES的有效管理,以优化肝移植患者的预后。该病例进一步探讨了他克莫司免疫抑制疗效与其潜在神经系统风险之间的平衡,强调在这一患者人群中仔细监测和干预策略的必要性。
    In this editorial, we talk about a compelling case focusing on posterior reversible encephalopathy syndrome (PRES) as a complication in patients undergoing liver transplantation and treated with Tacrolimus. Tacrolimus (FK 506), derived from Streptomyces tsukubaensis, is a potent immunosuppressive macrolide. It inhibits T-cell transcription by binding to FK-binding protein, and is able to amplify glucocorticoid and progesterone effects. Tacrolimus effectively prevents allograft rejection in transplant patients but has adverse effects such as Tacrolimus-related PRES. PRES presents with various neurological symptoms alongside elevated blood pressure, and is primarily characterized by vasogenic edema on neuroimaging. While computed tomography detects initial lesions, magnetic resonance imaging, especially the Fluid-Attenuated Inversion Recovery sequence, is superior for diagnosing cortical and subcortical edema. Our discussion centers on the incidence of PRES in solid organ transplant recipients, which ranges between 0.5 to 5 +ACU-, with varying presentations, from seizures to visual disturbances. The case of a 66-year-old male status post liver transplantation highlights the diagnostic and management challenges associated with Tacrolimus-related PRES. Radiographically evident in the parietal and occipital lobes, PRES underlines the need for heightened vigilance among healthcare providers. This editorial emphasizes the importance of early recognition, accurate diagnosis, and effective management of PRES to optimize outcomes in liver transplant patients. The case further explores the balance between the efficacy of immunosuppression with Tacrolimus and its potential neurological risks, underlining the necessity for careful monitoring and intervention strategies in this patient population.
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  • 文章类型: Journal Article
    由于HCMV感染或再激活引起的并发症仍然是免疫功能低下患者的一个具有挑战性的临床问题。主要是由于T细胞功能不足或缺失。病毒靶标的知识对于改善高危患者的监测和优化抗病毒T细胞治疗至关重要。为了扩大表位谱,设计基因工程树突状细胞(DC)和成纤维细胞以分泌可溶性HLA-A*11:01,并感染缺乏免疫逃避分子的HCMV突变体(US2-6+11)。超过700个HLA-A*11:01限制性表位,包括来自广泛的HCMV开放阅读框(ORFs)的50多个表位通过质谱鉴定,并使用已建立的预测工具筛选HLA-A*11:01结合。在健康HLA-A*11:01+/HCMV+供体中体外评估24个得分最高的新候选物的免疫原性。因此,四个亚优势表位和一个免疫优势表位,来自抗凋亡蛋白UL36和ORFL101C(A11SAL),已确定。体外验证了其HLA-A*11:01复合物的稳定性。深入分析揭示了针对A11SAL的高度增殖和细胞毒性记忆T细胞反应,具有与免疫显性HLA-A*02:01限制性HCMVpp65NLV表位相当的T细胞应答。A11SAL特异性T细胞在免疫抑制移植患者体内也可检测到,并在体外HCMV感染模型中显示出有效。表明它们在抑制病毒复制和改善患者预后方面的关键作用。开发的体外管道是第一个利用基因工程改造的DC来鉴定天然呈递的免疫显性HCMV来源的表位。因此,它提供了优于计算机预测的优势,可转移到其他HLA等位基因,并将显着扩大病毒靶标库,以改善治疗选择。
    Complications due to HCMV infection or reactivation remain a challenging clinical problem in immunocompromised patients, mainly due to insufficient or absent T-cell functionality. Knowledge of viral targets is crucial to improve monitoring of high-risk patients and optimise antiviral T-cell therapy. To expand the epitope spectrum, genetically-engineered dendritic cells (DCs) and fibroblasts were designed to secrete soluble (s)HLA-A*11:01 and infected with an HCMV mutant lacking immune evasion molecules (US2-6 + 11). More than 700 HLA-A*11:01-restricted epitopes, including more than 50 epitopes derived from a broad range of HCMV open-reading-frames (ORFs) were identified by mass spectrometry and screened for HLA-A*11:01-binding using established prediction tools. The immunogenicity of the 24 highest scoring new candidates was evaluated in vitro in healthy HLA-A*11:01+/HCMV+ donors. Thus, four subdominant epitopes and one immunodominant epitope, derived from the anti-apoptotic protein UL36 and ORFL101C (A11SAL), were identified. Their HLA-A*11:01 complex stability was verified in vitro. In depth analyses revealed highly proliferative and cytotoxic memory T-cell responses against A11SAL, with T-cell responses comparable to the immunodominant HLA-A*02:01-restricted HCMVpp65NLV epitope. A11SAL-specific T cells were also detectable in vivo in immunosuppressed transplant patients and shown to be effective in an in vitro HCMV-infection model, suggesting their crucial role in inhibiting viral replication and improvement of patient\'s outcome. The developed in vitro pipeline is the first to utilise genetically-engineered DCs to identify naturally presented immunodominant HCMV-derived epitopes. It therefore offers advantages over in silico predictions, is transferable to other HLA alleles, and will significantly expand the repertoire of viral targets to improve therapeutic options.
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  • 文章类型: Journal Article
    背景:血液系统恶性肿瘤患者发生侵袭性真菌感染(FI)的风险很高,因为他们经历了几个周期的治疗,导致中性粒细胞减少症发作。此外,他们在住院和在家期间交替。因此,当他们在住院期间被诊断出有助于预防感染时,确定真菌污染的来源非常具有挑战性。这项研究的目的是通过在其住所中采集空气和水样本来分析20名白血病患者在家中的真菌暴露情况。
    方法:使用便携式空气系统冲击器在每个家庭的3个房间中采样空气。在每个家庭的3个水分配点收集自来水。对于阳性样本,真菌通过质谱或根据其形态特征进行鉴定。
    结果:85%的家庭显示空气中存在曲霉属。属于Fumigati部分的那些人表现出最高的浓度和最大的隔离频率。关于粘膜,根霉属。和Mucorspp。被隔离在20%和5%住宅的空气中,分别。在4家,在空气中鉴定出的真菌物种中有70%以上是潜在的机会主义者;这些主要是曲霉属。浓度大于20cfu/m3。水样显示3所住宅中存在镰刀菌,浓度高达80cfu/L最后,一个病人,住院期间分离出的真菌种类在表型上与在家中采集的样本中分离出的真菌种类相似.对于第二个病人来说,PCRMucorale对支气管肺泡液样本呈阳性,而在其家中采集的空气样本也显示存在粘膜。
    结论:所有探索家庭的空气中都存在机会性真菌物种,这表明需要在免疫功能低下患者的家中加强预防措施。通过基因分型研究比较(从患者和他们的环境中)分离的真菌将是有趣的,该研究旨在指定患者家中存在的真菌物种与同一患者中负责FI的真菌物种之间存在的对应关系。
    BACKGROUND: Patients with hematological malignancies are at a high risk of developing invasive fungal infections (IFI) because they undergo several cycles of treatment leading to episodes of neutropenia. In addition, they alternate between hospital stays and periods spent at home. Thus, when an IFI is diagnosed during their hospital stays, it is highly challenging to identify the origin of the fungal contamination. The objective of this study was to analyze at home fungal exposure of 20 patients with leukemia by taking air and water samples in their living residence.
    METHODS: Air was sampled in 3 rooms of each home with a portable air system impactor. Tap water was collected at 3 water distribution points of each home. For positive samples, fungi were identified by mass spectrometry or on the basis of their morphological features.
    RESULTS: 85 % of homes revealed the presence in air of Aspergillus spp. and those belonging to the section Fumigati presented the highest concentrations and the greatest frequency of isolation. Concerning mucorales, Rhizopus spp. and Mucor spp. were isolated in air of 20 % and 5 % of dwellings, respectively. In 4 homes, more than 70 % of the fungal species identified in air were potential opportunists; these were mainly Aspergillus spp. with concentrations greater than 20 cfu/m3. The water samples revealed the presence of Fusarium in 3 dwellings, with concentrations up to 80 cfu/L. Finally, for one patient, fungal species isolated during a period of hospitalization were phenotypically similar to those isolated in samples taken at home. For a second patient, a PCR Mucorale was positive on a sample of bronchoalveolar fluid while air samples taken at his home also revealed also the presence of mucorales.
    CONCLUSIONS: The presence of opportunistic fungal species in the air of all the explored homes suggests the need for strengthened preventive measures in the home of immunocompromised patients. It would be interesting to compare the fungi isolated (from patients and from their environment) by genotyping studies aimed at specifying the correspondence existing between fungal species present in the patients\' homes and those responsible for IFI in the same patients.
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  • 文章类型: Journal Article
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  • 文章类型: Case Reports
    对于HIV阳性的发热患者,必须考虑非结核分枝杆菌,腹痛,减肥,脾肿大.
    genavense分枝杆菌是免疫受损背景患者的机会性缓慢生长的非结核分枝杆菌,尤其是HIV阳性患者。在这项研究中,我们介绍了2例HIV阳性患者的基因分枝杆菌感染病例,对准确治疗有良好的临床反应.
    UNASSIGNED: It is essential to consider non-tuberculosis mycobacterium in HIV-positive patients with fever, abdominal pain, weight loss, and splenomegaly.
    UNASSIGNED: Mycobacterium genavense is an opportunistic slow-growing nontuberculous mycobacterium in patients with immunocompromised backgrounds, especially HIV-positive patients. In this study, we present two cases of Mycobacterium genovese infection in HIV-positive patients with a good clinical response to accurate treatment.
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  • 文章类型: Journal Article
    本系统评价和荟萃分析旨在比较在两个剂量的主要系列mRNA疫苗后,非血清转化的免疫受损患者中另一种异源(病毒载体)与同源(mRNA)COVID-19疫苗剂量的免疫原性和安全性。我们搜索了截至2023年6月21日在PubMed上发表的研究,Scopus,和Embase。进行meta分析,以比较基于抗SARS-CoV-2刺突蛋白IgG(抗SIgG)和SARS-CoV-2特异性T细胞免疫应答率的血清阳性率,在4周时通过干扰素-γ释放试验评估,以及两种疫苗方案之间28天内严重不良事件(SAE)的发生率。在四项纳入的随机对照试验(RCT)中,异源和同源方案之间抗SIgG血清阳性率(风险比[RR]:0.79,95%CI:0.48-1.29)和SARS-CoV-2干扰素-γ浓度(RR:1.19,95%CI:0.96-1.48)无统计学差异.异源治疗方案显示注射疼痛的发生率显着降低(RR:0.55,95%CI:0.45-0.69),但与同源方案相比,头痛的发生率更高(RR:1.44,95%CI:1.02-2.02)。疫苗接种后28天内未报告疫苗相关的SAE。额外的异源或同源COVID-19疫苗剂量耐受性良好,并在最初接种两剂COVID-19mRNA疫苗的未血清转化的免疫受损患者中证明了相当的疫苗免疫原性。这一发现支持了在免疫功能低下的人群中扩大COVID-19疫苗接种主要系列的建议。
    This systematic review and meta-analysis aimed to compare the immunogenicity and safety of an additional heterologous (viral vector) versus homologous (mRNA) COVID-19 vaccine dose among non-seroconverted immunocompromised patients after a two-dose primary series of mRNA vaccine. We searched studies published up to 21 June 2023 in PubMed, Scopus, and Embase. The meta-analysis was conducted to compare the seropositivity rates based on anti-SARS-CoV-2 spike protein IgG (anti-S IgG) and SARS-CoV-2-specific T-cell immune response rates, assessed by interferon-γ release assay at 4 weeks, and the incidences of serious adverse events (SAEs) within 28 days between the two vaccine regimens. In four included randomized controlled trials (RCTs), there were no statistically significant differences in the seropositive rate of anti-S IgG (risk ratio [RR]: 0.79, 95% CI: 0.48-1.29) and the concentration of SARS-CoV-2 interferon-γ (RR: 1.19, 95% CI: 0.96-1.48) between heterologous and homologous regimens. The heterologous regimen exhibited a significantly lower incidence of injection pain (RR: 0.55, 95% CI: 0.45-0.69), but a higher incidence of headache (RR: 1.44, 95% CI: 1.02-2.02) compared with the homologous regimen. No vaccine-related SAEs were reported within 28 days following vaccination. An additional heterologous or homologous COVID-19 vaccine dose was well tolerated and demonstrated a comparable vaccine immunogenicity among non-seroconverted immunocompromised patients who were initially vaccinated with a two-dose COVID-19 mRNA vaccine. This finding supports the recommendations of an extended primary series of COVID-19 vaccination in immunocompromised persons.
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  • 文章类型: Journal Article
    Bowen病代表皮肤鳞状细胞癌的原位形式;虽然它有良好的预后,3-5%的病变进展为侵袭性皮肤鳞状细胞癌,免疫功能低下患者的风险较高。因此,治疗总是必要的,而传统的光动力疗法是一线选择。这篇综述的目的是提供临床反应的概述,复发率,安全,和美容结果的光动力疗法在治疗鲍恩病,考虑到光敏剂方面的不同方案,光源,和组合治疗。对于伤口愈合不良/延迟的部位的肿瘤,光动力疗法是一种有价值的选择。在多发性和/或大型肿瘤的情况下,以及手术困难或侵入性的地方。皮肤镜检查和反射共聚焦显微镜可以用作监测治疗反应的有价值的工具。治疗通常耐受性良好,有轻微的副作用,并与良好/出色的美容效果相关。由于复发和进展为cSCC的风险,光动力疗法后的定期随访是必不可少的。随着角质形成细胞肿瘤发病率的增加,光动力疗法的治疗空间将进一步增加。
    Bowen\'s disease represents the in situ form of cutaneous squamous cell carcinoma; although it has an excellent prognosis, 3-5% of lesions progress to invasive cutaneous squamous cell carcinoma, with a higher risk in immunocompromised patients. Treatment is therefore always necessary, and conventional photodynamic therapy is a first-line option. The aim of this review is to provide an overview of the clinical response, recurrence rates, safety, and cosmetic outcome of photodynamic therapy in the treatment of Bowen\'s disease, considering different protocols in terms of photosensitizers, light source, and combination treatments. Photodynamic therapy is a valuable option for tumors at sites where wound healing is poor/delayed, in the case of multiple and/or large tumors, and where surgery would be difficult or invasive. Dermoscopy and reflectance confocal microscopy can be used as valuable tools for monitoring the therapeutic response. The treatment is generally well tolerated, with mild side effects, and is associated with a good/excellent cosmetic outcome. Periodic follow-up after photodynamic therapy is essential because of the risk of recurrence and progression to cSCC. As the incidence of keratinocyte tumors increases, the therapeutic space for photodynamic therapy will further increase.
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