极重度支气管肺发育不良气管切开/家庭机械通气治疗2例病例报告

背景：气管切开/家庭机械通气治疗极重度支气管肺发育不良（sBPD）在中国尚未见报道。 目的：介绍2例sBPD患儿气管切开/家庭机械通气治疗经验。 设计：病例报告。 方法：报告2例sBPD患儿的临床特征、气管切开前评估、气管切开后从医院过渡至家庭辅助通气前的准备及出院后管理。 结果：2例早产儿因生后长时间（例1胎龄27+5周,生后7月19 d;例2胎龄24+6周,生后6月24 d）不能脱离有创呼吸支持转入复旦大学附属儿科医院,入院后从肺实质病变、气道病变、肺动脉高压角度细致评估sBPD表型,明确患儿存在严重气管、支气管软化伴肺实质病变。经多学科讨论明确患儿存在气管切开、长期家庭机械通气支持指征。充分与家属沟通并告知气管切开/长期机械通气的必要性和风险性后行气管切开术。在护理人接受家庭护理培训、各类环境/硬件准备、病房过渡等充分出院准备后,2例sBPD患儿成功过渡至家庭机械通气。 结论：气管切开/长期机械通气治疗为国内sBPD患儿提供了可能有效的长期通气解决方案,但需要多学科医疗团队和家庭护理人员长时间共同配合,仍存在成本、风险高,出院后管理体系未健全等诸多难点。     

早产儿支气管肺发育不良相关肺动脉高压诊治研究进展

支气管肺发育不良(BPD)相关肺动脉高压(PH)是早产儿BPD最严重的并发症,是BPD患儿后期死亡的重要原因,近年日益受到关注。肺血管发育异常和重构是PH发生的病理基础。对中重度BPD患儿进行监测和筛查肺动脉压力,可早期诊断BPD相关PH,对BPD相关PH早期防治、改善预后具有重要意义。由于BPD相关PH为慢性过程,持续时间长,治疗仍然比较困难,主要药物是肺血管扩张剂,尚缺乏足够的证据支持,有待更多的研究进一步验证其有效性和安全性。     

早产儿支气管肺发育不良的表型演变

支气管肺发育不良(bronchopulmonary dysplasia,BPD)是早产儿最常见的慢性肺部疾病,与婴儿死亡率、呼吸系统发病率增加有关。随着新生儿重症医学取得进展的同时,BPD的表型已从主要影响晚期早产儿、肺纤维囊性变演变为主要影响胎龄小于28周的超早产儿、肺实质受损和血管生长失调。文章评估了BPD定义演变、病理生理演变、影像演变及临床表型的演变特点,以期寻找新的循证预防和管理策略,改善疾病表型分类,早期识别高危早产儿的临床特点,以改善其预后。     

糖皮质激素防治支气管肺发育不良的循证医学证据

支气管肺发育不良(bronchopulmonary dysplasia,BPD)又称慢性肺疾病(chronic lung disease,CLD),是早产儿最常见的长期并发症之一.随着新生儿重症监护技术的迅速发展,越来越多的早产儿和极低出生体重儿得以存活,BPD成为引起早产儿疾病和死亡的重要原因.在存活者中,BPD延长了患儿的住院时间,增加了再入院和神经系统发育障碍发生的风险.在BPD的防治上,肺表面活性物质替代治疗、新的机械通气策略、限制液体输入和利尿剂的使用、最优化的营养支持及对动脉导管未闭的积极处理均已取得共识,惟有糖皮质激素( glucocorticoids,GCs)的使用仍是目前最具争议的领域.     

早产儿支气管肺发育不良的药物治疗研究进展

支气管肺发育不良（BPD）是存活极早产儿最常见的远期并发症，并且可能导致肺动脉高压，增加新生儿晚期死亡率，以及神经系统发育异常。目前关于早产儿支气管肺发育不良药物治疗的有效性及利弊仍然存在争议。本文综述了BPD的药物治疗研究进展。     

维甲酸对新生大鼠高氧肺损伤的保护作用

新生儿支气管肺发育不良 (bronchopumonarydysplasia ,BPD)是与早产、感染及长期吸入高浓氧有关的严重慢性肺疾病。目前临床多采用地塞米松预防和治疗BPD ,该药虽有助于患儿早日脱离气管插管 ,但由于其可引起血压升高、消化道出血、脑及肺发育受阻等副作用 ,而限制了其在临床的应用[1 ] 。近年研究发现 ,极低出生体重儿BPD的病理改变以肺发育受阻为主 ,表现为肺泡隔形成受阻和肺泡化降低[2 ] 。维甲酸 (retinoicacid ,RA)可降低维生素A缺乏的早产儿BPD的发病率 ,显著提高新生大鼠由于使用地塞米松而降低了的肺泡化水平[3] 。本实验通…     

支气管肺发育不良的肺血管发育与肺动脉高压的诊断和治疗相关问题

肺动脉高压( PH)是支气管肺发育不良( BPD)的严重并发症,伴随着高病死率,肺血管发育的异常、肺血管的高反应性及结构的重建是导致PH的病理生理基础,本病临床症状隐匿,与本身肺部疾病难以鉴别,出现症状后诊断往往不可逆,建议具有高危因素的BPD患儿应常规进行筛查。心脏超声是无创、动态监测最常用的检查手段,对治疗效果不佳者行心导管或CT检查排除心血管异常,治疗包括急性阶段的综合治疗和降低肺动脉压力的药物选择,早期诊断、治疗将改善其预后。     

支气管肺发育不良定义和命名的演变与治疗进展

支气管肺发育不良( bronchopulmonary dysplasia,BPD)又称慢性肺疾病( chronic lung disease,CLD),是早产儿常见的呼吸系统疾病;1967年由Northway等首次报道并命名,具有独特的病因、病理及临床特征。 Northway等报道的BPD又称“旧”BPD或“经典型”BPD。由于产前糖皮质激素和出生后外源性肺表面活性物质的应用,以及保护性通气策略的实施,显著地改变了早产儿呼吸系统疾病的表现形式和预后。 Northway描述的严重 BPD已很少见,更为常见的是轻型 BPD (又称为“新”BPD)。自从1967年首次提出BPD以来,BPD的定义或命名一直存在争议。本文系统介绍了BPD定义的历史变迁和治疗进展。     

吸入和微吸入——早产儿支气管肺发育不良防治中不可忽略的问题

胃食管反流(GER)是早产儿常见的临床表现,反流引起的吸入和微吸入,通过引发气道与喉痉挛、气道阻塞、肺部炎症等多种方式,诱发或加重早产儿支气管肺发育不良(BPD)的肺部损伤。故临床治疗上应尽量避免吸入与微吸入,必要时可采取适当干预措施,对防治BPD有一定的作用。     

超声监测下管理肺疾病：或使早产儿支气管肺发育不良成为可避免的疾病

支气管肺发育不良（bronchopulmonary dysplasia, BPD）是早产儿最常见的慢性肺部疾病,虽然对其病因、机制、预防和治疗的研究取得了重要进展,但预后并没有明显改善。BPD患儿不仅病死率高,对存活者也造成呼吸、神经、心脏等多方面的持久性损害。作者团队在肺脏超声监测下管理新生儿肺疾病,在过去近7年的时间里避免了BPD的发生,为BPD的预防开辟了新途径。该文对此予以简介,以期加强相关研究,为预防或最大程度减少BPD的发生提供更加科学的管理方案。[中国当代儿科杂志,2024,26 (1):14-18]     

Bibliometric data: a disaster for many non-American biomedical journals

Bibliometric data published by the Institute of Scientific Information in Philadelphia (ISI), and which was previously discussed in Acta Paediatrica , has increasingly been used despite all the relevant and severe criticism that has been raised against this method of evaluating individual research results and grading scientific journals. It is obvious that the present trend regarding the use of bibliometric data as a basis for priorities and funding of research and for the promotion of individual scientists favours American-oriented research projects at the expense of those that are based on concepts of predominantly European relevance.

Conclusion: For the future of non-American research, it is important that no single super-power, i.e. the USA, should dominate scientific priorities. The condition for efficient European competition is that European Centres with high levels of competence for creative research and training of scientists from all over the world are established. In addition, it is important that the results of European research are published in prestigious European journals, as was the situation before World War II.     

The importance of different immunosuppressive regimens in the development of posttransplant diabetes mellitus

Solid-organ transplantation is the optimal long-term treatment for most patients with end-stage organ failure. After solid-organ transplantation, short-term graft survival significantly improved (1). However, due to chronic allograft nephropathy and death with functioning graft, long-term survival has not prolonged remarkably (2). Posttransplant immunosuppressive medications consist of one of the calcineurin inhibitors in combination with mycophenolate mofetil (MMF) or azathioprine (Aza) and steroids. All of them have different adverse effects, among which posttransplant diabetes mellitus (PTDM) is an independent risk factor for cardiovascular (CV) events and infections causing the death of many transplant patients and it may directly contribute to graft failure (3). According to the criteria of the American Diabetes Association (4), diabetes mellitus (DM) is defined by symptoms of diabetes (polyuria and polydipsia and weight loss) plus casual plasma glucose concentration ≥ 11.1 mmol/L or fasting plasma glucose (FPG) ≥ 7.0 mmol/L or 2-h plasma glucose level ≥ 11.1 mmol/L following oral glucose tolerance test (OGTT). This metabolic disorder occurring as a complication of organ transplantation has been recognized for many years. PTDM, which is a combination of decreased insulin secretion and increased insulin resistance, develops in 4.9/15.9% of liver transplant patients, in 4.7/11.5% of kidney recipients, and in 15/17.5% of heart and lung transplants [cyclosporine A (CyA)/tacrolimus (Tac)-based regimen, respectively] (5). Risk factors of PTDM can be divided into non-modifiable and modifiable ones (6), among which the most prominent is the immunosuppressive therapy being responsible for 74% of PTDM development (7). Emphasizing the importance of the PTDM, numerous studies have determined the long-term outcome. On the basis of these studies, graft and patient survival is tendentiously (8) or significantly (9, 10) decreased for those developing PTDM.     

alpha -SMOOTH MUSCLE ACTIN DISTRIBUTION IN THE PULMONARY VASCULATURE COMPARING HYPOPLASTIC AND NORMAL FETAL LUNGS

We investigated the intra-acinar pulmonary vascular muscularization in the developing human fetal lung between the 17th and 24th gestational weeks, that is, during the canalicular phase of lung development. Fifteen hypoplastic and 25 normal developed lungs were included in this study using monoclonal alpha -smooth muscle (sm) actin antibodies for smooth muscle detection. Computer-aided image analysis was performed for morphometrical measurements and statistical evaluation. Alphasm-actin-immunoreactive intra-acinar vessels down to a luminal diameter of less than 10 mu m were detected in hypoplastic as well as in normally developed lungs. Crucial differences presented as follows: significantly higher density of intra-acinar vessels, especially due to alpha -sm-actin-negative vessels less than 30 mu m in luminal diameter, in the control group; significantly higher alpha -sm-actin immunoreactivity per section unit as well as per vessel in the hypoplastic lung group. As suggested by others, alpha-sm-actin-positive cells of the intra-acinar vessel wall in the developing human lung were demonstrated to be smooth muscle cells, their immediate precursors, and pericytes. We conclude that the increased alpha -sm-actin immunoreactivity represents muscularization of the vessel wall in functional terms and may be regarded as one structural cause among others for the establishment of persistent fetal circulation in hypoplastic lungs.     

Whole-body mineral measurements in Swedish adolescents at 17 years compared to 15 years of age

Aim: To provide reference data for bone mineral variables in 15- and 17-y-old adolescents and to analyse the relationships between these variables and measures of bone and body size, gender, puberty, growth, various lifestyle and environmental factors and socioeconomic background.

Methods: In the same 321 randomly selected adolescents (147 boys and 174 girls) living in two different regions of Sweden, the total bone mineral content (TBMC), bone area (BA) and total bone mineral density (TBMD) were assessed by dual-energy X-ray absorptiometry at ages 15 and 17 y. The effects of bone and body size, gender, growth, sexual maturity, physical activity, region of domicile, social conditions, food habits, smoking and alcohol intake on TBMC and TBMD were examined in multivariate analyses.

Results: In the 15-y-old adolescents, BA, height, gender, physical activity, maturity and weight explained 91% and 48%, of the variance in TBMC and TBMD, respectively. In similar analyses in the 17-y-olds, the corresponding figures were 92% and 62%, respectively, when BA, height, growth, physical activity, gender and region emerged as significant in the model. In all these analyses, BA explained most of the variance in TBMC and TBMD. No significant reduction of variance was found when different measures of social conditions, smoking, food habits, alcohol or dietary intakes of energy, calcium or vitamin D were included in the models. The reason why region of domicile had a significant impact on TBMC in the 17-y-olds is not known. The fact that the normal fluoride concentration in drinking water (1.1 mg/L) is 10 times higher in the region where TBMC was higher than in the other region is an interesting observation.

Conclusion: Almost 90% of the variance in TBMC and 50% of that in TBMD was explained by measures of bone and body size and only a few percent by gender, physical activity, Tanner stage, growth and region of domicile.     

VARICELLA ZOSTER VIRUS INFECTIONS IN THE PEDIATRIC STEM CELL TRANSPLANT PATIENT

Varicella zoster virus (VZV), a member of the human herpesvirus family, causes the clinical syndromes of chickenpox during primary infection and shingles on later reactivation. In immunocompromised patients, including those undergoing hematopoietic stem cell transplantation, VZV can produce life-threatening infections. The most serious forms of VZV infection involve hematogenous dissemination of the virus to vital organs, such as the lung, brain, and liver. Advances in immunoprophylaxis, antiviral chemotherapy, and vaccine development have provided effective tools to limit the morbidity and mortality previously associated with VZV infection in hematopoietic stem cell transplant patients. In this review, we discuss virologic aspects of VZV, pathogenesis of VZV infection, methods of viral diagnosis, clinical manifestations of infection in both normal and immunocompromised patients, and available preventative and therapeutic measures.     

The potential role of rapamycin in pediatric transplantation as observed from adult studies

Although pediatric patient and renal graft survival rates have shown marked improvements during the past decade, the persistent toxicities of immunosuppressive drugs and chronic allograft attrition remain major obstacles in transplant therapy. Results in adult patients suggest that complete steroid withdrawal is possible in the majority of recipients under treatment with a cyclosporin A-rapamycin (CsA RAPA) regimen. Furthermore, preliminary studies suggest that a marked reduction in the dose of CsA may be possible under the umbrella of RAPA coverage. The gain in immunosuppressive efficacy afforded by RAPA has not only been obtained without an increased morbidity owing to infectious or neoplastic causes, but also with the potential for reducing the incidence and/or progression of chronic rejection.     

GENETICS OF CARNEY COMPLEX AND RELATED FAMILIAL LENTIGINOSES, AND OTHER MULTIPLE TUMOR SYNDROMES

Carney complex is a multiple endocrine neoplasia (MEN) syndrome that affects the adrenal cortex, the pituitary and thyroid glands, and the gonads. The complex is also associated with skin and mucosa pigmentation abnormalities and myxoid and other neoplasms of mesenchymal and neural crest origin. Thus, this syndrome also belongs to another group of genetic disorders, the lentiginoses (or lentigenoses), which include the Peutz-Jeghers, LEOPARD, arterial dissections and lentiginosis, and Laugier-Hunziker syndromes, Cowden disease and Ruvalcaba-Myhre-Smith (Bannayan-Zonana) syndrome and the centrofacial, benign patterned and segmental lentiginoses, all of which can be associated with a variety of developmental defects. The inheritance of Carney complex, just like that of the other MENs and the lentiginoses, is autosomal dominant. Genetic loci or genes have been identified for Carney complex, Peutz-Jeghers and Ruvalcaba-Myhre-Smith syndromes, but not for other lentiginoses. Elucidation of the molecular defects responsible for these disorders is expected to shed light on aspects of early neural crest differentiation, the regulation of pigmentation, the development of autonomous endocrine function, and endocrine and nonendocrine tumorigenesis.     

All you ever wanted to know about infant formulas (but were afraid to ask)

The World Health organisation recommends breast feeding infants for the first six months of life. When this breast feeding does not occur either through parental choice or medical need, infant formulas will be required. There is a bewildering array of formulas on the UK market for many different requirements. When faced with an unsettled infant many parents (and health care professionals) will experiment with the infant formula available and often attend the paediatric clinic looking for help and advice. It is therefore essential that paediatricians understand what milks are available and what the key differences between different products are. This review attempts to provide a simple guide through many of the formulations currently available in the UK; and offers advice for the dietary management of the child with extra calorie requirements, infants with cow's milk protein allergy, gastro oesophageal reflux disease, apparent unresolved hunger and infantile colic. Whatever the underlying condition, there is likely to be an infant formula that is suitable in this generation of ever expanding formulations.     

Génétique des schizophrénies : mise en perspective des schizophrénies à début précoce et autres pathologies du développement

Schizophrenia (SCZ) is a severe brain disorder characterized by hallucinations, delusions, flat and/or inappropriate affect and cognitive impairment. The lifetime risk is about 0.5% with heritability of 65–85%. The prevalence of early-onset schizophrenia (defined here as before 15 years of age) has not been well studied, but is likely to be 5–10% of all cases. The rarity of early-onset SCZ has made it difficult to study. We focus on genetic studies of adults with schizophrenia, highlighting results for early-onset schizophrenia where available. Prior to the past 5 years, studies failed to find replicable association or linkage between SCZ and specific genes when appropriate statistical corrections for multiple testing were used. Many false positive results were probably reported using the candidate gene approach. Recently, the development of single nucleotide polymorphism (SNP) “chips” has permitted large genome-wide association study (GWAS) analyses that suggest that across all age groups, a proportion of genetic risk can be attributed to a large number of common SNP, each with a very small effect on risk (odds ratios of 1.1 or less). The greatest known genetic effect is conferred by the 1.5–3 Mb 22q.11.2 deletions, which occurs in ∼ 1/4000–1/6000 births with SCZ developing in 20–30% of carriers. Large SNP and aCGH microarray studies have now identified associations between SCZ and other rare, large copy number variations (CNV, insertions and deletions) with high odds ratios (5–10), including deletions of 1q21, 2p16.3 (neurexin-1 gene), 3q29 and 15q13.3, and duplications of 16p11.2. Some of these CNV are also associated with autism or other developmental disorders as well as epilepsy or intellectual deficiency, suggesting some overlap in the mechanisms that contribute to risks of these disorders. Based on preliminary data from larger-scale analyses in progress, approximately 1–2% of cases carry a CNV that has been clearly associated with SCZ (ORs 4–12). Whole exome and genome sequencing studies of large adult samples will be the next steps to identify rarer SCZ-associated mutations, including point mutations and smaller as well as rarer CNV. Genetic findings are beginning to contribute to an understanding of biological mechanisms of SCZ risk and may lead to new approaches to treatment.     

INACTIVATION OF PULMONARY SURFACTANT AND THE TREATMENT OF ACUTE LUNG INJURIES

Inactivation of pulmonary surfactant may be important in acute lung injury and acute respiratory distress syndrome. Treatment of surfactant dysfunction by instilling exogenous surfactants may improve gas exchange and pulmonary mechanics. Surfactants used for treatment vary in their attributes and effects, so when various surfactants are considered for therapy, resistance to inactivation is an important consideration. Animal models of acute lung injury exist in which the relative merits of surfactants can be compared. We hypothesize that the surfactants most resistant to inactivation in vitro will be the ones that are most effective in treatment of animal models of acute lung injury. Surfactants with higher concentrations of surfactant proteins (specifically A, B, and C) are more resistant to inactivation. Nonionic polymers mimic surfactant proteins in preventing surfactant inactivation under some conditions. Adding nonionic polymers to surfactant containing minimal amounts of SP-B and SP-C markedly improves lung function of animals with lung injury. Making surfactants more "inactivation-proof" may improve surfactant therapy of acute lung injuries.