Cardiac neural crest

Neural crest cells (NCCs) contribute to many organs and tissues during embryonic development. Amongst these, the cardiovascular system represents a fascinating example. In this review, recent advances in our understanding of the developmental biology and molecular genetics regulating cardiac NCC maturation will be summarized. While the existence of a significant neural crest (NC) contribution to the developing heart has been appreciated for more than 20 years, only in the last few years have molecular pathways regulating this process been elucidated and the significant contribution of these mechanisms to the etiology of congenital heart disease in man become apparent. Emerging data suggest that ongoing studies will reveal complex inductive interactions between cardiac NC and a series of other cell types contributing to the developing cardiovascular system.     

Dog as a model in studies on human hereditary diseases and their gene therapy

During the last 15 years spectacular progress has been achieved in knowledge on the dog genome organization and the molecular background of hereditary diseases in this species. A majority of canine genetic diseases have their counterparts in humans and thus dogs are considered as a very important large animal model in human biomedicine. Among canine monogenic diseases with known causative gene mutations there are two large groups classified as retinal dystrophies and lysosomal storage diseases. Specific types of these diseases are usually diagnosed in a single or several breeds. A well known disorder, restricted to a single breed, is congenital stationary night blindness described in Briards. This disease is a counterpart of Leber amaurosis in children. On the other hand, one of the most common monogenic human diseases (Duchenne muscular dystrophy), has its canine counterparts in several breeds (e.g., the Golden retriever, Beagle and German short-haired pointer). For some of the canine diseases gene therapy strategy was successfully applied, e.g., for congenital stationary night blindness, rod-cone dystrophy and muccopolysaccharydoses type I, IIIB and VII. Since phenotypic variability between the breeds is exceptionally high, the dog is an interesting model to study the molecular background of congenital malformations (e.g., dwarfism and osteoporosis imperfecta). Also disorders of sexual development (DSD), especially testicular or ovotesticular DSD (78,XX; SRY-negative), which is widely distributed across dozens of breeds, are of particular interest. Studies on the genetic background of canine cancers, a major health problem in this species, are also quite advanced. On the other hand, genetic studies on canine counterparts of major human complex diseases (e.g., obesity, the metabolic syndrome and diabetes mellitus) are still in their infancy.     

Low-dose paediatric cardiac and thoracic computed tomography with prospective triggering: Is it possible at any heart rate?

ObjectiveTo demonstrate that the use of step-and-shoot (SAS) mode in paediatric cardiac CT angiography (CCTA) is possible at heart rates (HR) greater than 65 bpm, allowing low-dose acquisition with single-source 64-slices CT.MethodsWe retrospectively included 125 paediatric patients (0–6 years). CCTA was performed with SAS at diastolic phase in 31 patients (group D, HR < 65 bpm), at systolic phase in 45 patients (group S, HR ≥ 65 bpm) and with non-gated mode in 49 patients (group NG). Effective dose (ED) and image quality using a 3-grade scoring scale (1, excellent; 2, moderate; 3, insufficient) of group S were compared with group D for coronary examinations and group NG for entire thorax vascular anatomy.ResultsFor coronary indications, median ED was 0.6 mSv in group D versus 0.9 mSv in group S (p < 0.01). For whole thorax indications, median ED was 2.7 mSv in group NG versus 1.1 mSv in group S (p < 0.001). The mean image quality score was (1.4 ± 0.6) points in group D, (1.4 ± 0.7) in group S for coronary indications (p = 0.9), (1.3 ± 0.6) in group S for whole thorax indications and (2.0 ± 0.0) in group NG (p < 0.001).ConclusionSAS mode is feasible in children with HR greater than 65 bpm allowing low-dose CCTA. It provided comparable image quality in systole, compared to diastole. SAS at the systolic phase provided better image quality with less radiation dose compared to non-gated scans for whole thorax examinations.     

A modified multiplex ligation-dependent probe amplification method for the detection of 22q11.2 copy number variations in patients with congenital heart disease

Background

Copy number variations (CNVs) of chromosomal region 22q11.2 are associated with a subset of patients with congenital heart disease (CHD). Accurate and efficient detection of CNV is important for genetic analysis of CHD. The aim of the study was to introduce a novel approach named CNVplex®, a high-throughput analysis technique designed for efficient detection of chromosomal CNVs, and to explore the prevalence of sub-chromosomal imbalances in 22q11.2 loci in patients with CHD from a single institute.

Results

We developed a novel technique, CNVplex®, for high-throughput detection of sub-chromosomal copy number aberrations. Modified from the multiplex ligation-dependent probe amplification (MLPA) method, it introduced a lengthening ligation system and four universal primer sets, which simplified the synthesis of probes and significantly improved the flexibility of the experiment. We used 110 samples, which were extensively characterized with chromosomal microarray analysis and MLPA, to validate the performance of the newly developed method. Furthermore, CNVplex® was used to screen for sub-chromosomal imbalances in 22q11.2 loci in 818 CHD patients consecutively enrolled from Shanghai Children’s Medical Center. In the methodology development phase, CNVplex® detected all copy number aberrations that were previously identified with both chromosomal microarray analysis and MLPA, demonstrating 100% sensitivity and specificity. In the validation phase, 22q11.2 deletion and 22q11.2 duplication were detected in 39 and 1 of 818 patients with CHD by CNVplex®, respectively. Our data demonstrated that the frequency of 22q11.2 deletion varied among sub-groups of CHD patients. Notably, 22q11.2 deletion was more commonly observed in cases with conotruncal defect (CTD) than in cases with non-CTD (P < 0.001). With higher resolution and more probes against selected chromosomal loci, CNVplex® also identified several individuals with small CNVs and alterations in other chromosomes.

Conclusions

CNVplex® is sensitive and specific in its detection of CNVs, and it is an alternative to MLPA for batch screening of pathogenetic CNVs in known genomic loci.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1590-5) contains supplementary material, which is available to authorized users.     

Decrease in quality of life predicts mortality in adult patients with pulmonary arterial hypertension due to congenital heart disease

Background

Decrease in quality of life (QoL) in left-sided heart failure precedes poor survival, which can be reversed with exercise training. We investigated whether QoL is associated with mortality in pulmonary arterial hypertension due to congenital heart disease (PAH-CHD) patients.

Methods

In this observational study, PAH-CHD adults referred for PAH-specific therapy were included. QoL surveys (SF36) were recorded during 2 years of therapy. Based on shift in SF36 scores during this period, patients had either decreased or non-decreased QoL. Subsequently, the patients were followed for mortality.

Results

Thirty-nine PAH-CHD patients (mean age 42, 44 % male, 49 % Down’s syndrome) were analysed. Following PAH-specific therapy, SF36 physical component summary (PCS) decreased in 13 (35–31 points, p = 0.001) and showed no decrease in 26 patients (34–43 points, mean values, p < 0.001). Post-initiation phase, median follow-up was 4.5 years, during which 12 deaths occurred (31 %), 10 (56 %) in the decreased and 2 (10 %) in the non-decreased group (p = 0.002). Cox regression showed a decrease in SF36 PCS predicted mortality (HR 3.4, 95 % CI 1.03–11, p = 0.045).

Conclusions

In PAH-CHD patients, decrease in SF36 PCS following initiation of PAH-specific therapy is a determinant of mortality.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-015-0666-9) contains supplementary material, which is available to authorized users.     

Coronary artery-bronchial artery fistulas: report of two Dutch cases with a review of the literature

Background

Coronary bronchial artery fistulas (CBFs) are rare anomalies, which may be isolated or associated with other disorders.

Materials and methods

Two adult patients with CBFs are described and a PubMed search was performed using the keywords “coronary bronchial artery fistulas” in the period from 2008 to 2013.

Results

Twenty-seven reviewed subjects resulting in a total of 31 fistulas were collected. Asymptomatic presentation was reported in 5 subjects (19 %), chest pain (n = 17) was frequently present followed by haemoptysis (n = 7) and dyspnoea (n = 5). Concomitant disorders were bronchiectasis (44 %), diabetes (33 %) and hypertension (28 %). Multimodality and single-modality diagnostic strategies were applied in 56 % and 44 %, respectively. The origin of the CBFs was the left circumflex artery in 61 %, the right coronary artery in 36 % and the left anterior descending artery in 3 %. Management was conservative (22 %), surgical ligation (11 %), percutaneous transcatheter embolisation (30 %), awaiting lung transplantation (7 %) or not reported (30 %).

Conclusions

CBFs may remain clinically silent, or present with chest pain or haemoptysis. CBFs are commonly associated with bronchiectasis and usually require a multimodality approach to be diagnosed. Several treatment strategies are available. This report presents two adult cases with CBFs and a review of the literature.     

先天性心脏病患儿术后并发医院感染的危险因素及其病原菌分布和药敏实验分析

目的:统计先天性心脏病(CHD)患儿术后医院感染的病原菌分布及细菌耐药性情况,分析影响CHD患儿术后医院感染的危险因素。方法:回顾性选取2010年3月-2017年10月我院行CHD手术治疗的患儿3800例,收集临床标本进行致病菌培养并进行药敏试验,统计CHD术后医院感染患儿病原菌种类及主要致病菌的耐药情况,分析影响CHD患儿术后医院感染的危险因素。结果:3800例CHD患儿术后医院感染率为3.13%(119/3800),共分离出菌株172株,G^-菌、G⁺菌、真菌分别占55.81%(96/172)、26.74%(46/172)、17.44%(30/172)。肺炎克伯雷菌、大肠杆菌对头孢类抗生素高度耐药,鲍曼不动杆菌检出率逐年增高,且仅对多黏菌素B保持敏感;肺炎链球菌、凝固酶阴性葡萄球菌、金黄色葡萄球菌对大环内脂类抗生素、克林霉素、青霉素高度耐药,对万古霉素和替加环素保持敏感。术后医院感染与年龄、体重、病程、手术时间、体外循环时间、机械通气时间、ICU停留时间、住院时间、合并肺动脉高压、吸痰次数、静脉营养、应用丙种球蛋白或白蛋白有关(P<0.05),且合并肺动脉高压、体外循环时间≥100 min、机械通气时间≥120 h、吸痰次数≥5次/d是CHD患儿术后医院感染的危险因素(P<0.05)。结论:G^-菌、G⁺菌是CHD患儿术后医院感染的主要致病菌,且对常用抗生素高度耐药,此外鲍曼不动杆菌的检出率和耐药性上升极为明显,合并肺动脉高压、体外循环时间及机械通气时间过长、吸痰次数多的CHD患儿医院感染风险升高。     

200例先天性尿道下裂患儿的临床特征及其危险因素分析

目的:研究200例先天性尿道下裂患儿的临床特征及其危险因素。方法:选择2016年1月~2019年12月我院收治的先天性尿道下裂患儿200例进行研究,记作观察组,另取同期于我院接受体检的健康儿童200例作为对照组,分析观察组患儿的临床分型情况,比较两组儿童父母的一般情况、儿童出生情况,并采用多因素Logistic回归分析先天性尿道下裂的影响因素。结果:200例先天性尿道下裂患儿临床分型按照占比从高到低的顺序依次为阴茎体型46.50%(93/200)、阴茎阴囊型28.00%(56/200)、冠状沟型17.00%(34/200)、阴囊型4.50%(9/200)、阴茎头型3.00%(6/200)、会阴型1.00%(2/200)。观察组父亲生活性接触化学物、母亲流产史、母亲孕期饮食缺乏肉类、母亲孕期饮食缺乏鱼类、母亲孕期应用保胎药、母亲孕期吸烟或被动吸烟人数占比均高于对照组(均P<0.05)。观察组早产、低出生体重人数占比高于对照组(均P<0.05)。经多因素Logistic回归分析显示,父亲生活性接触化学物、母亲流产史、母亲孕期饮食缺乏肉类、母亲孕期饮食缺乏鱼类、母亲孕期应用保胎药、母亲孕期吸烟或被动吸烟、早产、低出生体重均是先天性尿道下裂的危险因素(均P<0.05)。结论:先天性尿道下裂患儿临床分型以阴茎体型为主,双亲不良生活习惯、化学物接触史以及早产、低出生体重均是先天性尿道下裂的危险因素,值得临床重点关注。     

右美托咪定复合七氟醚对先天性心脏病介入封堵术患儿血流动力学、氧化应激反应和心肌损伤的影响

摘要 目的：观察右美托咪定复合七氟醚对先天性心脏病（CHD）介入封堵术患儿血流动力学、心肌损伤和氧化应激反应的影响。方法：选择2016年1月-2020年12月期间在我院择期行介入封堵术的CHD患儿 106例。按照住院号奇偶顺序将患儿分为对照组（七氟醚麻醉）和观察组（右美托咪定复合七氟醚麻醉）,各53例。观察两组围术期间的血流动力学、氧化应激反应和心肌损伤指标变化情况,记录两组患儿苏醒即刻的躁动评分和镇静评分、苏醒时间和围术期间的不良反应发生率。结果：两组T0~T4时间点心率（HR）均呈先升高后降低趋势,平均动脉压（MAP）均呈先降低后升高趋势（P<0.05）。术后24 h,观察组血清超氧化物歧化酶(SOD)水平高于对照组,丙二醛(MDA)水平低于对照组（P<0.05）。术后24 h,观察组血清肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白 I(cTnI)、心脏型脂肪酸结合蛋白(H-FABP)水平均低于对照组（P<0.05）。观察组苏醒即刻的躁动评分低于对照组（P<0.05）。两组患儿不良反应总发生率对比无差异（P>0.05）。结论：右美托咪定复合七氟醚应用于行介入封堵术的CHD患儿,可减少躁动发生情况,同时不影响患儿血流动力学和苏醒情况,在减轻氧化应激、心肌损伤方面亦有一定的积极意义。