Therapeutic options for severe, refractory status asthmaticus: inhalational anaesthetic agents, extracorporeal membrane oxygenation and helium/oxygen ventilation

Despite improvements in supportive care, the mortality and morbidity of asthma remain constant. The risks and incidence of morbidity related to barotrauma remain high in patients that require mechanical ventilation. The authors present three alternative strategies including the inhalation of anaesthetic agents, helium/oxygen ventilation, and extracorporeal membrane oxygenation which may be beneficial when 'conventional therapies' fail in the intubated patient with status asthmaticus.     

A randomized controlled trial of sedation in the critically ill

A randomized controlled trial comparing: a) a combination of oral chloral hydrate and promethazine to b) a continuous intravenous midazolam infusion, for maintenance sedation in critically ill children, was carried out. The level of sedation was assessed four hourly using a specifically devized sedation scale. Forty-four children entered the study of whom two were subsequently excluded. The number of satisfactory assessments (desired and actual levels of sedation equal) was significantly greater in the chloral hydrate and promethazine group (Chi-squared P <0.01; confidence intervals of the difference 0.06 to 0.20). The number of assessments at level 5 on the sedation scale (patient restless/distressed) was significantly greater in the midazolam group (Chi-squared P <0.05). The total number of satisfactory assessments in the two groups were only 61 and 48% respectively, suggesting that sedation can be considerably improved. Chloral hydrate and promethazine are more effective than midazolam as maintenance sedation in critically ill children. It is possible to prospectively study the efficacy of sedative drugs in critically ill children.     

The Swedish childhood diabetes study — a multivariate analysis of risk determinants for diabetes in different age groups

Summary In a nationwide incident case-referent study stepwise univariate analysis has revealed several risk determinants for childhood diabetes mellitus. In a multivariate analysis we have determined the set of risk determinants that would independently predict childhood Type 1 (insulin-dependent) diabetes. Possible interactions between the risk determinants and differences in risk profiles with different ages at onset were also examined. Reported familial insulin-treated and non-insulin-treated diabetes were significant risk factors in all age groups, as was also a low frequency of milk intake. The frequency of infections and a high intake of foods rich in nitrosamine tended to interact (OR 11.8, p=0.053) indicating a synergistic effect. A Cox regression analysis revealed that stressful life events during the last year was the only variable that tended to affect the age at onset (p=0.055). This indicated that psychological stress may rather precipitate than induce Type 1 diabetes. A short breast-feeding duration (OR=3.81), and an increased body height (OR=3.82) contributed significantly to the predictive model in only the youngest age group (0–4 years). An increased frequency of infections in the year preceding onset (OR=2.15) and no vaccination against measles (OR=3.33) contributed significantly to the model only in the age group 5–9 years. Various nutrients had different impacts on the risk of developing Type 1 diabetes in different age groups. It is concluded that in the genetically susceptible child, risk factors which are associated with eating habits, frequency of infections, vaccination status, growth pattern and severe psychological stress affect the risk of developing diabetes independently of each other. The set of risk determinants varies with the age at onset. A high frequency of infections and a high frequency of nitrosamine-rich food intake seem to have a synergistic effect on the risk of developing diabetes in childhood.     

Glibenclamide treatment in a Cantú syndrome patient with a pathogenic ABCC9 gain‐of‐function variant: Initial experience

Cantú syndrome (CS), characterized by hypertrichosis, distinctive facial features, and complex cardiovascular abnormalities, is caused by pathogenic variants in ABCC9 and KCNJ8 genes. These genes encode gain‐of‐function mutations in the regulatory (SUR2) and pore‐forming (Kir6.1) subunits of K_ATP channels, respectively, suggesting that channel‐blocking sulfonylureas could be a viable therapy. Here we report a neonate with CS, carrying a heterozygous ABCC9 variant (c.3347G>A, p.Arg1116His), born prematurely at 32 weeks gestation. Initial echocardiogram revealed a large patent ductus arteriosus (PDA), and high pulmonary pressures with enlarged right ventricle. He initially received surfactant and continuous positive airway pressure ventilation and was invasively ventilated for 4 weeks, until PDA ligation. After surgery, he still had ongoing bilevel positive airway pressure (BiPAP) requirement, but was subsequently weaned to nocturnal BiPAP. He was treated for pulmonary hypertension with Sildenafil, but failed to make further clinical improvement. A therapeutic glibenclamide trial was commenced in week 11 (initial dose of 0.05 mg^–1 kg^–1 day^–1 in two divided doses). After 1 week of treatment, he began to tolerate time off BiPAP when awake, and edema improved. Glibenclamide was well tolerated, and the dose was slowly increased to 0.15 mg^?1 kg^?1day^?1 over the next 12 weeks. Mild transient hypoglycemia was observed, but there was no cardiovascular dysfunction. Confirmation of therapeutic benefit will require studies of more CS patients but, based on this limited experience, consideration should be given to glibenclamide as CS therapy, although problems associated with prematurity, and complications of hypoglycemia, might limit outcome in critically ill neonates with CS.     

Co‐occurring medical conditions in adults with Down syndrome: A systematic review toward the development of health care guidelines. Part II

Adults with Down syndrome (DS) represent a unique population who are in need of clinical guidelines to address their medical care. Many of these conditions are of public health importance with the potential to develop screening recommendations to improve clinical care for this population. Our workgroup previously identified and prioritized co‐occurring medical conditions in adults with DS. In this study, we again performed detailed literature searches on an additional six medical conditions of clinical importance. A series of key questions (KQ) were formulated a priori to guide the literature search strategy. Our KQs focused on disease prevalence, severity, risk‐factors, methodologies for screening/evaluation, impact on morbidity, and potential costs/benefits. The available evidence was extracted, evaluated and graded on quality. The number of participants and the design of clinical studies varied by condition and were often inadequate for answering most of the KQ. Based upon our review, we provide a summary of the findings on hip dysplasia, menopause, acquired cardiac valve disease, type 2 diabetes mellitus, hematologic disorders, and dysphagia. Minimal evidence demonstrates significant gaps in our clinical knowledge that compromises clinical decision‐making and management of these medically complex individuals. The creation of evidence‐based clinical guidance for this population will not be possible until these gaps are addressed.     

A study on facial features of children with Williams syndrome in China based on three‐dimensional anthropometric measurement technology

To describe special facial features of children with Williams syndrome in China by using method of three‐dimensional craniofacial anthropometry. Using three‐dimensional stereo photogrammetric device, 14 craniofacial anthropometric measurements were performed and five indices were calculated in 52 children with Williams syndrome and 208 age and sex matched controls of Han Chinese ethnicity. Except intercanthal width, mouth breadth, morphological face height, nasal height‐breadth index, nasal breadth‐depth index, morphological ear index, the Williams syndrome group under 3 years old were smaller than the control group in the other 12 variables. Compared with the control group, the Williams syndrome group aged 3–5 years old had smaller biocular breadth, nasal length, nasorostral angle, bitragal breadth, ear width, morphological ear index and face depth. The Williams syndrome group aged above 6 years old had smaller biocular breadth, nasal breadth, bitragal breadth, ear width, ear length and face depth than the control group. The craniofacial variability index of the Williams syndrome group was greater than the control group. Greater variation was found among children with Williams syndrome than normal in China, specifically at eye, nose, ear and face shape, which demonstrate the usefulness of three‐dimensional stereo photogrammetric analysis in supporting accurate diagnose of the patient with Williams syndrome.     

A patient with novel MBOAT7 variant: The cerebellar atrophy is progressive and displays a peculiar neurometabolic profile

Mutations in the MBOAT7 gene have been described in 43 patients, belonging to 18 families, showing nonspecific clinical features (intellectual disability [ID], seizures, microcephaly or macrocephaly, and mild to moderate cerebellar atrophy) that make the clinical diagnosis difficult. Here we report the first Italian patient, a 22.5‐year‐old female, one of the oldest reported, born to apparently consanguineous parents. She shows severe ID, macrocephaly, seizures, aggressive outbursts, hyperphagia. We also documented progressive atrophy of the cerebellar vermis, that appeared not before the age of 7. The whole‐exome sequencing of the trio identified a novel homozygous variant c.1057_1058delGCinsCA (p.Ala353His) in the MBOAT7 gene. The variant is considered to be likely pathogenic, since it is absent from population database and it lies in a highly conserved amino acid residue. This disorder has a neurometabolic pathogenesis, implicating a phospholipid remodeling abnormalities. A brain hydrogen‐magnetic resonance spectroscopy (H‐MRS) examination in our patient disclosed a peculiar neurometabolic profile in the cerebellar hemispheric region. This new finding could address the clinical suspicion of MBOAT7‐related disorder, among the wide range of genetic conditions associated with ID and cerebellar atrophy. Moreover, the documented progression of cerebellar atrophy and the worsening of the disease only after some years open to the possibility of a therapeutic window after birth.     

Congenital clubfoot in Europe: A population‐based study

We aimed to assess prevalence, birth outcome, associated anomalies and prenatal diagnosis of congenital clubfoot in Europe using data from the EUROCAT network, and to validate the recording of congenital clubfoot as a major congenital anomaly by EUROCAT registries. Cases of congenital clubfoot were included from 18 EUROCAT registries covering more than 4.8 million births in 1995–2011. Cases without chromosomal anomalies born during 2005–2009, were randomly selected for validation using a questionnaire on diagnostic details and treatment. There was 5,458 congenital clubfoot cases of which 5,056 (93%) were liveborn infants. Total prevalence of congenital clubfoot was 1.13 per 1,000 births (95% CI 1.10–1.16). Prevalence of congenital clubfoot without chromosomal anomaly was 1.08 per 1,000 births (95% CI 1.05–1.11) and prevalence of isolated congenital clubfoot was 0.92 per 1,000 births (95% CI 0.90–0.95), both with decreasing trends over time and large variations in prevalence by registry. The majority of cases were isolated congenital clubfoot (82%) and 11% had associated major congenital anomalies. Prenatal detection rate of isolated congenital clubfoot was 22% and increased over time. Among 301 validated congenital clubfoot cases, diagnosis was confirmed for 286 (95%). In conclusion, this large population‐based study found a decreasing trend of congenital clubfoot in Europe after 1999–2002, an increasing prenatal detection rate, and a high standard of coding of congenital clubfoot in EUROCAT.     

基于眼动技术的高危孤独症谱系障碍幼儿限制性兴趣研究

目的 分析高危孤独症谱系障碍(HR-ASD)幼儿的局限兴趣眼动特征及行为指标间相关性,为ASD的亚型分类早期识别及干预提供依据。方法 选取2018年6月—2020年6月就诊于南方医科大学附属深圳妇幼保健院符合入组标准的年龄相匹配的ASD幼儿39例、HR-ASD幼儿49例及正常发育幼儿44例,采用SMI RED250便携式眼动仪、孤独症观察量表(ADOS)及盖塞尔发育量表(GDS)对患儿进行测试,比较三组幼儿关注兴趣物的眼动特征与行为指标的结果,并分析其相关性。结果 1)ASD幼儿与HR-ASD组幼儿首次注视的兴趣物分别为轮船、台灯,注视轨迹均无规律性,正常发育幼儿首次注视物为气球,注视物轨迹有规律;ASD组与HR-ASD幼儿组的兴趣物倾向相似,且较正常幼儿对各种玩具车、转椅等异常注视,差异有统计学意义(F=123.01、89.32,P＜0.01)。2)ASD组与HR-ASD组幼儿较正常发育幼儿的适应性、精细动作、语言及个人社交能力水平均差(F＝47.05、23.70、32.30、50.19,P＜0.01),但ASD幼儿与HR-ASD组幼儿一般行为能力差异无统计学意义(P＞0.05)。3)ASD幼儿、HR-ASD幼儿对动车的眼动注视时间与语言能力均呈负相关(r=-0.22,-0.43,P＜0.05);正常幼儿的语言能力与其对动车及转椅的注视均呈负相关(r=-0.17,r=-0.17,P＜0.05),对蛋糕的眼动注视时间与个人-社交能力呈正相关(r=0.43,P＜0.01)。结论 早期识别高危孤独症谱系障碍幼儿局限兴趣,对ASD的早期亚型分类及早期辅助诊断与干预有重要指导意义。