Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies

In today’s global economy and affordable vacation travel, it is increasingly important that visitors to another country and their physician be familiar with emerging infections, infections unique to a specific geographic region, and risks related to the process of travel. This is never more important than for patients with primary immunodeficiency disorders (PIDD). A recent review addressing common causes of fever in travelers provides important information for the general population Thwaites and Day (N Engl J Med 376:548-560, 2017). This review covers critical infectious and management concerns specifically related to travel for patients with PIDD. This review will discuss the context of the changing landscape of infections, highlight specific infections of concern, and profile distinct infection phenotypes in patients who are immune compromised. The organization of this review will address the environment driving emerging infections and several concerns unique to patients with PIDD. The first section addresses general considerations, the second section profiles specific infections organized according to mechanism of transmission, and the third section focuses on unique phenotypes and unique susceptibilities in patients with PIDDs. This review does not address most parasitic diseases. Reference tables provide easily accessible information on a broader range of infections than is described in the text.     

高海拔地区老年社区获得性肺炎患者体液免疫功能变化结果分析

目的 研究高海拔地区老年社区获得性肺炎(CAP)患者体液免疫功能变化及其关系.方法 CAP患者分别在发病后24h、4d、7d、10d、15d、18d、23d以内检测血清IgG、IgA、IgM水平并与215名健康对照者进行比对分析.方法 CAP患者发病早期24h内血清IgG、IgA、IgM水平与健康对照组比较差异无统计学意义(P＞0.05),4d后血清IgG、IgA水平明显减低,与健康对照组比较差异有统计学意义(P＜0.01),且持续下降至15d、18d后血清IgG、IgA水平开始回升,23d血清IgG、IgA水平基本恢复正常,与健康对照组比较差异无统计学意义(P＞0.05).结论 高海拔地区老年CAP患者以IgG、IgA水平降低为主,且持续时间长,老年CAP患者体液免疫功能变化与病情转归有比较密切的关系,调节免疫治疗,可能会缩短病程,改善预后和降低死亡率,对老年CAP的预防和治疗具有重要意义.     

High Susceptibility for Enterovirus Infection and Virus Excretion Features in Tunisian Patients with Primary Immunodeficiencies

To estimate the susceptibility to enterovirus infection and the frequency of long-term poliovirus excreters in Tunisian patients with primary immunodeficiencies (PIDs), enteroviruses were assessed in stool specimens of 82 patients with humoral, combined, and other PIDs. Isolated viruses were typed and intratyped by standard molecular techniques, and the whole VP1 region of poliovirus isolates was sequenced. Polioviruses were detected in 6 patients; all isolates were vaccine related. Five patients rapidly stopped excretion; one excreted a poliovirus type 1 isolate for several months, and the isolate accumulated up to 14 mutations in the VP1 region. Nonpolio enteroviruses were identified in 6 patients; 4 of them kept excreting the same strain for more than 6 months. The rate of enterovirus infection was 13.4% of the PID patients and 20.7% of those with an IgG defect; it greatly exceeded the rates generally found in Tunisian supposed-immunocompetent individuals (4.1% during the study period; P = 0.001 and P < 0.0001, respectively). Interestingly, patients with combined immunodeficiencies were at a higher risk for enterovirus infection than those with an exclusively B cell defect. A major histocompatibility complex (MHC) class II antigen expression defect was found in 54% of enterovirus-positive patients and in the unique long-term poliovirus excreter. The study results also suggest that substitutive immunoglobulin therapy may help clearance of a poliovirus infection and that most PID patients have the ability to stop poliovirus excretion within a limited period. However, the high susceptibility of these patients to enterovirus infection reinforces the need for enhanced surveillance of these patients until the use of oral poliovirus vaccine (OPV) is stopped.     

质子泵抑制剂和重度AECOPD患者的医院获得性肺炎之间关系

目的探讨应用质子泵抑制剂(PPI)是否是重度慢性阻塞性肺病急性加重期(AECOPD)患者发生医院获得性肺炎(HAP)的危险因素。方法收集我科2015年6月1日至2016年1月31日重度AECOPD患者198例,其中使用PPI患者96例,未使用PPI患者102例,使用Logistic回归分析PPI与HAP发生率的关系。结果使用PPI组HAP发生率较未使用PPI组高,特别是超过使用PPI药物7天患者。在不同多变量Logistic回归模型中,用APACHEII评分校正后,使用PPI及使用PPI的天数示重度ACOPD患者HAP的危险因素。结论长时间使用PPI可以增加重度AECOPD患者HAP发生率。     

The Treatment of Inflammatory Bowel Disease in Patients with Selected Primary Immunodeficiencies

The gastrointestinal tract is heavily populated with innate and adaptive immune cells that have an active role in preservation of mucosal homeostasis and prevention of inflammation. Inflammatory bowel diseases are thought to result from dysregulated immune function that is influenced by genetic background, environmental triggers, and microbiome changes. While most inflammatory bowel disease patients present in adolescent years or adulthood, in a minority of cases, the disease develops early in life, and in some of these young patients, a monogenic disease causing intestinal inflammation can be identified. Many of these conditions result from mutations in immune-mediated genes and can present with or without concomitant recurrent infections. In this review, we will discuss the treatment of patients with selected primary immunodeficiencies and inflammatory bowel diseases. We will focus on five conditions resulting from mutations in IL10/IL10 receptor, NADPH oxidase complex, XIAP, LRBA, and CTLA-4.     

Molecular and Clinical Characteristics of Hospital and Community Onset Methicillin-Resistant Staphylococcus aureus Strains Associated with Bloodstream Infections

Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are classified epidemiologically as health care-associated hospital onset (HAHO)-, health care-associated community onset (HACO)-, or community-associated (CA)-MRSA. Clinical and molecular differences between HAHO- and HACO-MRSA BSI are not well known. Thus, we evaluated clinical and molecular characteristics of MRSA BSI to determine if distinct features are associated with HAHO- or HACO-MRSA strains. Molecular genotyping and medical record reviews were conducted on 282 MRSA BSI isolates from January 2007 to December 2009. MRSA classifications were 38% HAHO-, 54% HACO-, and 8% CA-MRSA. Comparing patients with HAHO-MRSA to those with HACO-MRSA, HAHO-MRSA patients had significantly higher rates of malignancy, surgery, recent invasive devices, and mortality and longer hospital stays. Patients with HACO-MRSA were more likely to have a history of renal failure, hemodialysis, residence in a long-term-care facility, long-term invasive devices, and higher rate of MRSA relapse. Distinct MRSA molecular strain differences also were seen between HAHO-MRSA (60% staphylococcal cassette chromosome mec type II [SCCmec II], 30% SCCmec III, and 9% SCCmec IV) and HACO-MRSA (47% SCCmec II, 35% SCCmec III, and 16% SCCmec IV) (P < 0.001). In summary, our study reveals significant clinical and molecular differences between patients with HAHO- and HACO-MRSA BSI. In order to decrease rates of MRSA infection, preventive efforts need to be directed toward patients in the community with health care-associated risk factors in addition to inpatient infection control.     

Delay in Administering the First Dose of Antibiotics in Patients Admitted to Hospital with Serious Infections

 The interval from the time of admission to the emergency room until the administration of antibiotics in patients presenting with a serious infectious disease was analysed. Fifty patients presumptively diagnosed in the emergency room as having a serious infection (respiratory tract, urinary tract, erysipelas, fever with neutropenia or bacteremia) needing immediate empirical antibiotic treatment were enrolled in the study. A median interval from time of admission to administration of antibiotics of 5 hours was determined (range 0.6–13.3 h). The interval was significantly shorter in patients admitted at night than in patients admitted during office hours (3.7 vs. 6.0 h, P<0.05). There was no difference with respect to the presenting features, body temperature, laboratory values at presentation or number of cultures performed. In 41 of the 50 patients blood samples were taken for culture. More than 80% of the patients received an antibiotic chosen in accordance with hospital guidelines. The analysis revealed that the median delay of 5 hours before patients received their initial dose of antibiotic depended on several factors. Attempts to provide optimal antimicrobial therapy should thus concentrate not only on the correct choice and dosage of a drug but also on prompt institution of therapy.     

胰岛素不同给药方式治疗2型糖尿病合并社区获得性肺炎研究

目的观察应用双C和MSII治疗2型糖尿病（type 2 diabetes mellitus,T2DM）合并社区获得性肺炎（community acquired pneumonia,CAP）患者强化血糖控制的有效性和安全性。方法将2004年10月至2009年10月在我院住院的未使用过胰岛素治疗的T2DM合并CAP患者99例随机分为双C组（50例）和MSII组（49例）,分别给予双C和MSII。双C是应用持续皮下胰岛素输注（CSII）结合动态血糖监测系统（CGMS）一即“双C”方案。MSII是每日多次皮下注射胰岛素（MSII）结合每日八次指尖血糖监测。两组患者应用胰岛素和抗生素治疗后,观察CAP主要症状缓解时间、血糖达标时间、胰岛素用量、低血糖发生频率及肺炎控制时间的差异。结果双C组和MSII组患者治疗后空腹血糖分别为（6．3±0．2）mmol／L和（6．8±1．2）mmol／L,餐后2h血糖分别为（8．7±0．4）mmol／L和（9．3±1．2）mmol／L,均能达标。治疗后双C组患者果糖胺（7．2±0．13）mmol／L与MSII组（9．0±0．11）mmol／L比较,差异有统计学意义（P〈0．01）。双C组患者肺炎主要症状（发热、胸痛、咳黄痰、剧烈咳嗽、呼吸困难和湿啰音）缓解时间分别为（4．2±1．8）d、（3．7±1．2）d、（d．7±1．8）d、（8．2±1．3）d、（8．3±1．1）d和（9．2±2．6）d,血糖达标时间为（3．7±0．6）d、肺炎控制时间（12．8±4．5）d、胰岛素用量（37．6±6．5）次／d及低血糖发生频率（0．6±0．4）次／例;MSII组分别为（6．2±1．7）d、（4．3±1．4）d、（8．4±2．5）d、（9．6±3．5）d、（9．6±3．4）d、（12．4±4．1）d、（7．2±1．2）d、（18．2±6．8）d、（57．2±10．3）U／d和（4．3±0．7）次／例,两组比较差异均有统计学意义（P〈0．05）。结论在配合抗生素的前提下,“双C”方案治疗能及时、有效地控制T2DM合并CAP患者的血糖水平．肺炎症状缓解时间及治愈肺炎的时间均较MSII组短,而且胰岛素用量少,低血糖发生率低,是理想的治疗方法。     

老年社区获得性肺炎并脓毒症患者sCD14和CD14+/HLA-DR表达及意义

目的 探讨老年社区获得性肺炎（CAP）并脓毒症患者血清sCD14和外周血单核细胞CD14+/HLA-DR表达水平及临床意义。方法 选取2015年1月~2018年12月我院呼吸内科及ICU收治的老年CAP患者126例,根据是否并发脓毒症将老年CAP患者分为脓毒症组56例,非脓毒症组70例,另选择老年健康体检者45例为对照组,脓毒症组根据是否存活分为死亡组30例及存活组26例。采用ELISA法和流式细胞术检测并比较各组血清sCD14及外周血单核细胞CD14+/HLA-DR+表达水平,脓毒症组及非脓毒症组48 h CURB-65评分、28 d死亡率。结果 脓毒症组血清sCD14水平高于非脓毒症组和对照组,而CD14+/HLA-DR+表达水平则低于非脓毒症组和对照组,差异均有统计学意义（P＜0.05）。死亡组血清sCD14水平高于存活组,CD14+/HLA-DR表达水平低于死亡组,差异有统计学意义（P＜0.05）;相关分析显示,血清sCD14水平与CURB-65评分和28 d死亡率呈正相关（r=0.750、0.712,P＜0.05）,而与CD14+/HLA-DR呈负相关（r=-0.692,P＜0.05）,CD14+/HLA-DR与CURB-65评分和28 d死亡率呈负相关（r=-0.653、-0.721,P＜0.05）。结论 老年社区获得性肺炎并脓毒症患者存在免疫失衡,血清sCD14和CD14+/HLA-DR表达水平与CURB-65评分和28 d死亡率密切相关,可作为早期预测感染性疾病病情严重程度和预后的免疫学指标。     

Patients with Primary Immunodeficiencies in Pediatric Intensive Care Unit: Outcomes and Mortality-Related Risk Factors

Purposes

The aims of this study were to review the frequency, characteristics, and the clinical course of primary immunodeficiency (PID) patients admitted to pediatric intensive care unit (PICU) and attempt to identify factors related with mortality that might predict a poor outcome.

Methods

We performed a retrospective review of children with PID aged 1 month to 18 years and admitted to PICU from January 2002 to January 2012 in our tertiary teaching children’s hospital.

Results

There were a total of 51 patients accounting for 71 admissions to the PICU. The most common diagnosis was severe combined immunodeficiency. Respiratory problems were the leading cause for admission. A total of 20 patients received hematopoietic stem cell transplantation. Immune reconstitution was achieved in 9 (45 %) patients and eight of them did survive. In all 56 % of all admission episodes resulted in survival. Risk factors for mortality included requirement of mechanical ventilation (P?<?.001), number of organ system failure (P?=?.013), need for renal replacement therapy (P?<?.001), use of inotropes (P?<?.001), higher Pediatric Logistic Organ Dysfunction (PELOD) score (P?=?.005), and length of PICU stay (P?<?.001).

Conclusions

This is the first study regarding the outcome and mortality-related risk factors for PID patients requiring PICU admission. We suggest that PICU management is as important as early diagnosis and treatment for these patients. Prediction of those at risk for poorer outcome might be beneficial for accurate intensive care management and survival.     

痰热清联合抗菌药物对社区获得性肺炎患者CRP、PCT的影响及疗效分析

目的 探讨联合抗菌药物对社区获得性肺炎患者CRP、PCT的影响及疗效.方法 180例社区获得性肺炎患者随机分为治疗组和对照组,对照组予抗菌药物加常规对症治疗,治疗组在此几乎上予痰热清治疗,比较两组临床疗效,细菌清除率,以及PCT、CRP水平的变化情况和不良反应发生情况.结果 治疗组总有效84例,有效率达93.3％,明显高于对照组(81.1％)(P＜0.05).治疗组细菌清除率为94.0％,高于对照组(82.3％)(P＜0.05).与治疗前比较,治疗后两组CRP、PCT均降低(P＜0.05).而治疗后治疗组CRP、PCT水平均低于对照组(P＜0.05).两组不良反应发生率差异无统计学意义(P＞0.05).结论 痰热清联合抗菌药物对CAP具有较高的疗效和安全性,并且可以降低CAP患者CRP、PCT水平.     

Consanguinity Rate and Delay in Diagnosis in Turkish Patients with Combined Immunodeficiencies: a Single-Center Study

Combined immunodeficiency diseases comprise a group of disorders with different molecular basis. Clinical and immunological phenotypes for each group are extremely heterogenous. The frequency of combined immunodeficiencies may vary in different countries. The most frequent forms of combined immunodeficiency show inherited defects in development of T and/or B lymphocytes. These defects are classified according to immunologic phenotype and are categorized into T−B+ or T−B− including forms with or without natural killer lymphocytes. We report here twenty-three patients (female/male: 12/11) with combined immunodeficiency showing different immunological and clinical phenotypes, majority of whom were admitted because of severe upper and lower respiratory tract infections. Mean age of the study group, mean age at onset of the symptoms, and diagnosis were 47.5 ± 42.2, 11.2 ± 17.3, and 19.5 ± 23.8 months, respectively. There was nearly 8 months time delay between beginning of symptoms and diagnosis. Within the combined immunodeficiency phenotypes, T−B−NK+ category was the most frequent phenotype. Consanguinity was positive in 73.9% (n = 17) of patients while it was about 80.0% (n = 8) in deceased ten children. Bone marrow or umblical cord stem cell transplantation was applied to 11 of them. Three patients deceased after transplantation and seven patients deceased without transplantation. Twelve patients are being followed by prophylactic treatment. In conclusion; combined immunodeficiencies are frequent in our country because of high rate of consanguinity. T−B− combined immunodeficiencies are more often observed, and infants presenting severe infections beginning in the first 3 months of life have to be examined for combined immunodeficiencies. Shortening of time delay in diagnosis will increase success of life-saving treatment.     

高原红细胞增多症的骨髓细胞形态和活检病理组织的系列观察

目的:对高原红细胞增多症(HAPC)70例,经髓后上棘取材,观察骨髓形态、组织病理、超级结构,以揭示在高原低氧环境下,骨髓红细胞系统过度异常增生,是HAPC发病的重要因素.方法:骨髓涂片用瑞氏染色、形态学计数和分类.其中12例行骨髓活检,取出10～15mm活组织,分成两块,观察骨髓病理和骨髓超微结构.结果:骨髓形态学、组织病理、超微结构共同改变,即红系列增生极活跃,均有核浆发育不平衡的表现,有核红细胞的分裂指数、细胞分裂象在骨髓分裂中、红与粒细胞的比例均明显高于正常值.形态上红系以间接丝状分裂为主,骨髓组织病理可见,造血组织容积增加,含铁血黄素减少或消失.超微结构红系统的内质网、溶媒体、线粒体减少,线粒体排列紊乱,可见巨大线粒体.结论:HAPC的骨髓红系统过度增生,聚集在增多扩张的静脉窦中,并迅速进入血循环中,以改善低氧情况,但红系的核浆发育不平衡,细胞器的异常改变,所致的病态造血和红细胞的释放失控,可能是HAPC发病的组织结构基础.     

营养风险指数评估老年重症社区获得性肺炎患者预后的临床价值

目的 分析营养风险指数(geriatric nutritional risk index,GNRI)评估重症社区获得性肺炎(severe community-acquired pneumonia,SCAP)患者预后的临床价值.方法 以2015年8月至2018年12月我院收治的126例老年SCAP患者、60例非SCAP患...