Friedrich Reiterer

Sirolimus for the treatment of children with various complicated vascular anomalies

AbstractVascular anomalies include a heterogeneous group of disorders that are categorized as vascular tumors or vascular malformations. Treatment options include resection, embolization, laser therapy, and sclerotherapy or medical treatment such as propranolol, steroids, interferon, and cytostatic chemotherapy. Mammalian target of rapamycin seems to play a key role in the signal pathway of angiogenesis and subsequently in the development of vascular anomalies. Recently, the successful use of sirolimus has been reported in children with lymphatic malformations and kaposiform hemangioendotheliomas. We report on six patients with different vascular anomalies (kaposiform hemangioendothelioma nu2009=u20092, combined lymphatico-venous malformation nu2009=u20092, pulmonary lymphangiectasia nu2009=u20091, and orbital lymphatic malformation nu2009=u20091) who were treated with peroral sirolimus. Three of the children initially presented with a Kasabach-Merrit phenomenon. Median duration of treatment was 10xa0months; two children are still on treatment. Three children each achieved complete and partial remission. Kasabach-Merrit phenomenon resolved within 1xa0month in all patients. Treatment with sirolimus was tolerated well; only mild reversible leukopenia was observed.n Conclusion: Sirolimus proved to be effective in children with complicated lymphatic or lymphatico-venous malformations and kaposiform hemangioendotheliomas. Treatment was tolerated well with acceptable side effects. The optimum length of treatment and possible long-term side effects have to be evaluated.What is Known:• Vascular anomalies including vascular tumors and vascular malformations may lead to life-threatening conditions.• Some patients are refractory to established treatment and/or are not available for local invasive procedures.What is New:• We reviewed the literature focusing treatment of vascular anomalies in children and adolescents.• Our data support recent studies that sirolimus is an effective treatment option in patients with complicated vascular tumors and malformations.

Multi-modal approach to prophylaxis of necrotizing enterocolitis: clinical report and review of literature

For the first time a multimodal approach to NEC prophylaxis is reported, consisting of early trophic feeding with human breast milk, and enteral administration of an antibiotic, an antifungal agent, and probiotics. A retrospective analysis of local protocol of NEC prophylaxis is presented. Included were all VLBWI admitted to the NICU, including transfers within the first 28xa0days of life. These infants were divided into two groups, an “inborn group” (infants admitted within the first 24xa0h of life) and an “outborn group” (infants admitted after the onset of their second day of life). Prophylaxis of NEC according to protocol was started at the day of admission, and was continued until discharge. Between 1998 and 2004, 405 VLBWI were admitted, including all transfers within the first 28xa0days of life. A total of 334 (82%) infants were admitted within the first 24xa0h of life (inborn group), and 71 (18%) were admitted after 24xa0h of life (outborn group). Five infants developed clinical features of necrotizing enterocolitis. The inborn group showed a NEC incidence of 0.7% (two infants), whereas the outborn group showed a NEC incidence of 4.5% (three infants), respectively. This difference was significant (P=0.049, Fisher’s exact test). A surgical treatment with bowel resection was performed in two infants (both from the outborn group). The present study used a combination of different strategies, all having shown to have some beneficial effect, but not having brought a clinical breakthrough in single administration studies. Combinated were the beneficial effects of human breast milk feeding, oral antiobiotics, oral antifungal agents, and the administration of probiotics. In a homogenous group of preterm infants, using this protocol of multimodal NEC prophylaxis, there was a very low incidence of NEC, when started within the first 24xa0h of life.

Pancytopenia due to suppressed hematopoiesis in a case of fatal hemolytic disease of the newborn associated with anti-K supported by molecular K1 typing.

The authors report on a fatal case of hemolytic disease of the newborn (HDN) due to anti-K antibodies with subsequent trilineage pancytopenia in a preterm infant of 28 weeks gestational age, with pronounced leukopenia and neutropenia. In addition, molecular typing of the Kk polymorphism was necessary to confirm HDN. This case of HDN associated with anti-K provides additional evidence that trilineage pancytopenia due to suppressed hematopoiesis is part of the disease. Therefore, antibodies against antigens of the Kell blood group system should be considered as a potential cause of unexplained inhibition of myelopoiesis.

Congenital pulmonary lymphangiectasis.

Congenital pulmonary lymphangiectasis (CPL) is a rare vascular malformation causing dilated lymph vessels and disturbed drainage of lymph fluid. Based on the pathogenesis and clinical phenotype it can be classified as primary or secondary CPL. Associated genetic syndromes with or without lymphedema, familial occurrence and gene mutations have been described. In utero, it may present as non-immune hydrops with pleural effusions. At birth neonates may have respiratory failure due to chylothorax and pulmonary hypoplasia, causing very high short term mortality rates. Other cases may become symptomatic any time later in childhood or even during adult life. CPL is usually diagnosed based on the combination of clinical signs, imaging and histological findings. Open-lung biopsy is considered the gold standard for the diagnosis of CPL. Treatment is primarily supportive featuring aggressive mechanical ventilation and the management of problems associated with congenital chylothorax including chest-drainage, medium-chain triglycerides (MCT) diet, and octreotide.

Neonatal Ureaplasma urealyticum colonization increases pulmonary and cerebral morbidity despite treatment with macrolide antibiotics

ObjectiveTo evaluate the influence of Ureaplasma urealyticum (UU) colonization on neonatal pulmonary and cerebral morbidity.MethodsSingle-center case–control study including all preterm infants with positive UU tracheal colonization between 1990 and 2012. Cases were matched with controls by birth year, gestational age, birth weight, and sex. All cases had received macrolide antibiotics for UU infection starting at the time of first positive culture results from tracheal aspirates. Main outcome parameters included presence and severity of hyaline membrane disease (IRDS), duration of ventilation, bronchopulmonary dysplasia at 36 postmenstrual age and neurological morbidities (seizures, intra-/periventricular hemorrhages-I/PVH, periventricular leukomalacia-PVL).ResultsOf 74 cases identified 8 died and 4 had to be excluded; thus, 62 preterm infants were compared to 62 matched controls. UU was significantly associated with IRDS (79 vs. 61xa0%, pxa0=xa00.015), BPD (24 vs. 6xa0%, pxa0=xa00.003), seizures (23 vs. 5xa0%, pxa0=xa00.002) and I/PVH (45 vs. 24xa0%, pxa0=xa00.028). Cases had longer duration of mechanical ventilation and total duration of invasive and non-invasive ventilation (median 11 vs. 6xa0days pxa0=xa00.006 and 25 vs. 16.5xa0days pxa0=xa00.019, respectively).ConclusionUU was found to be significantly associated with pulmonary short- and long-term morbidity and mild cerebral impairment despite treatment with macrolide antibiotics.

Aortic Coarctation Associated with Alveolar Capillary Dysplasia and Misalignment of the Pulmonary Veins

Abstract After surgical repair of an aortic coarctation a term infant presented with severe pulmonary hypertension and cyanosis unresponsive to treatment including extracorporeal membrane oxygenation. The atypical clinical course became apparent once the accompanying diagnosis of congenital alveolar capillary dysplasia with misalignment of the pulmonary veins had been established at autopsy. In infants with congenital heart defects and with refractory pulmonary hypertension unexplainable on anatomic findings, a lung biopsy at the time of cardiac repair should be considered to avoid further therapies that would not alter the uniformly fatal course of this rare lung disorder.

Severe primary pulmonary lymphangiectasis in a premature infant: Management and follow up to early childhood

Primary pulmonary lymphangiectasis (PPL) is a rare congenital developmental abnormality of the lung with a generally poor prognosis. Only a limited number of patients with neonatal‐onset PPL have been reported to survive. We present the case of a male preterm infant (gestational age 34u2009weeks 6u2009days) with histologically confirmed PPL, complicated by hydrops fetalis, bilateral hydrothorax (treated in utero with pleuro‐amniotic shunts), and immediate respiratory distress at birth. He survived after extensive neonatal intensive care therapy and was discharged home at the age of 7u2009months. At last follow up he was 3u2009years 7u2009months old, still requiring assisted ventilation via tracheostomy, having recurrent episodes of wheezing and had mild global developmental delay. This case demonstrates that survival beyond the neonatal period is possible even with severe PPL but long‐term morbidity may be relevant, and multidisciplinary management and close follow up are essential.

Povidone-iodine pleurodesis for congenital chylothorax of the newborn.

Chemical pleurodesis with povidone-iodine (PVI) in neonates has been first described by Brissaud et al 1 in four cases of congenital chylothorax (CCT). Since this report, a few more cases of PVI pleurodesis have been reported in the literature.2–5 Adding our own experience of a fatal case of CCT with histologically proven pulmonary lymphangiectasis, we aimed to summarise the current evidence for PVI pleurodesis in case of CCT by means of a literature review.nnWe report the case of a preterm infant (29u2005weeks’ gestational age, birth weight 1530u2005g) born by caesarean section (antenatal steroids were given 17u2005days before birth; Apgar scores at 1/5/10u2005min were 4/7/7, respectively) with bilateral pleural effusions requiring chest …

Respiratory syncytial virus associated hospitalizations in children with congenital diaphragmatic hernia

BACKGROUNDnTo evaluate the risk of RSV infection in infants and children with congenital diaphragmatic hernia (CDH) over two consecutive RSV seasons.nnnMETHODSnRetrospective, single-center cohort study from southern Austria including infants with CDH born between 1993 and 2012. Infants were retrieved by searching via ICD-10 codes Q79.0 and Q79.1 and by using a local electronic database. Children were followed over 2 years of life including at least two consecutive RSV seasons (November to April). We also defined a group of hypothetical RSV infections with the following criteria: 70% of the admissions due to a respiratory infection (diagnosis of bronchiolitis and/or LRI score ≥3) during the RSV seasons over the first 2 years of life, when no test for RSV was performed.nnnRESULTSnTwenty-nine of 45 infants with CDH comprised the study population (6 were lost to follow-up and 10 died) of whom 9 (31%) exhibited 17 hospitalizations due to respiratory illness. Two hospitalized infants (6.9% of the study population) tested RSV positive, one during the first and the other during the second RSV season. Nine of 29 infants (31%) had documentation of palivizumab prophylaxis, none (0%) had proven RSV hospitalization compared to 1 of 20 (5%) without prophylaxis during the first RSV season (pxa0=xa00.256). Including the hypothetical cases, we calculated 0 of 9 (0%) in the palivizumab group and 4 of 20 (20%) in the group without prophylaxis (pxa0=xa00.079).nnnCONCLUSIONSnWe found a moderate rate of proven RSV hospitalizations in infants with CDH, and palivizumab prophylaxis led to a non-significant reduction of proven and hypothesized RSV hospitalizations.

Unchanged heart rate–respiratory frequency ratio in preterm infants during spontaneous arousals

Aim: To find out whether a correlation of heart rate (HR) and respiratory frequency (RF) defined as HR‐RF‐ratio (HRR) may be helpful to identify arousals in term and preterm infants.