Martin Poryo

Differential expression of microRNAs following cardiopulmonary bypass in children with congenital heart diseases

BackgroundChildren with congenital heart defects (CHDs) are at high risk for myocardial failure after operative procedures with cardiopulmonary bypass (CPB). Recent studies suggest that microRNAs (miRNA) are involved in the development of CHDs and myocardial failure. Therefore, the aim of this study was to determine alterations in the miRNA profile in heart tissue after cardiac surgery using CPB.MethodsIn total, 14 tissue samples from right atrium were collected from patients before and after connection of the CPB. SurePrint™ 8xa0×xa060K Human v21 miRNA array and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) were employed to determine the miRNA expression profile from three patients before and after connection of the CPB. Enrichment analyses of altered miRNA expression were predicted using bioinformatic tools.ResultsAccording to miRNA array, a total of 90 miRNAs were significantly altered including 29 miRNAs with increased and 61 miRNAs with decreased expression after de-connection of CPB (nxa0=xa03) compared to before CPB (nxa0=xa03). Seven miRNAs had been validated using RT-qPCR in an independent cohort of 11 patients. Enrichment analyses applying the KEGG database displayed the highest correlation for signaling pathways, cellular community, cardiovascular disease and circulatory system.ConclusionOur result identified the overall changes of the miRNome in right atrium tissue of patients with CHDs after CPB. The differentially altered miRNAs lay a good foundation for further understanding of the molecular function of changed miRNAs in regulating CHDs and after CPB in particular.

Ante-, peri- and postnatal factors associated with intraventricular hemorrhage in very premature infants

BACKGROUNDnIntraventricular hemorrhage (IVH) is one of the most serious complications in preterm infants and is associated with neurological sequelae and mortality. Over the past few decades, the rate of IVH has decreased due to improved neonatal intensive care. However, up to 15-25% of very and extremely premature infants (<32 and <28weeks of pregnancy (WOP) respectively) still suffer from IVH.nnnSTUDY PURPOSEnThe aim of this study was to perform an updated, multicenter analysis to identify ante-, peri, and postnatal factors other than gestational age/birth weight associated with IVH of any grade in a large cohort of very and extremely premature infants.nnnMETHODSnWe performed a retrospective analysis in a prospectively conducted multicenter cohort study between 01/01/1998-31/12/2012 at 5 level 3 perinatal centers. All relevant ante-, peri- and neonatal data were collected and univariate as well as multivariate logistic regression analysis was performed.nnnRESULTSn765 inborn infants with a gestational age<32 WOP were enrolled into this study (369 (48.2%) female; 396 (51.8%) male). Birth weight ranged from 315g to 2200g (mean 1149.7g, SD 371.9g); 279 (36.5%) were born ≤27+6 WOP and 486 (63.5%)≥28+0 WOP. IVH was seen in 177 (23.1%) patients. Multivariate analysis revealed that in addition to higher gestational age (OR 0.7, CI [0.6-0.8]), antenatal steroid treatment (OR 0.3, CI [0.2-0.6]) and caesarian section without uterine contraction (OR 0.6, CI [0.4-0.9]) were associated with a lower rate of IVH while RDS (OR 5.6, CI [1.3-24.2]), pneumothorax (OR 2.8, CI [1.4-5.5]) and use of catecholamines (OR 2.7, CI [1.7-4.5]) were associated with an increased risk of IVH. After exclusion of gestational age and birth weight from multivariate analysis, early onset sepsis (OR 1.6, CI [1.01-2.7]) and patent ductus arteriosus (OR 1.9, CI [1.1-3.1]) were associated with a higher rate of IVH. In addition, univariate analysis revealed that Apgar scores at 5min (p<0.001), BDP/ROP/NEC (p<0.001), mechanical ventilation (p<0.001) and inhalative nitric oxide (p<0.001) were significantly associated with IVH.nnnCONCLUSIONSnOur comprehensive analysis demonstrated that the occurrence of IVH in very premature infants is significantly associated with ante-, peri- and postnatal factors being either related to the degree of immaturity or indicating a critical clinical course after birth. The analysis reiterates the necessity for a very close cooperation between obstetricians and neonatologists to reduce the incidence of IVH in this susceptible cohort.

A case of myocardial bridging as a rare cause of chest pain in children

Asymptomatic myocardial bridging is a frequently seen pathology in adult patients, often in association with hypertrophic cardiomyopathy. Left anterior descending coronary artery is mostly affected. We report on a 14-year-old boy with repeated angina-like pain, disturbances of repolarization in the ECG and elevated values for Troponin T. After exclusion of a myocarditis in the MRI, myocardial bridging was detectable in coronary angiography and confirmed by myocardial perfusion imaging with 430xa0MBq 99mTc-Tetrofosmin at rest and under physical stress. After surgical myotomy, improvement of the cardiac symptoms could be noted and myocardial perfusion imaging studies at rest and under stress demonstrated reversal of the myocardial ischemia. Myocardial bridging is a rare and important differential diagnosis for angina-like pain in childhood without hypertrophic cardiomyopathy.

Optimized care in Patients with Rare Diseases: TSC at the Center for Rare Diseases (ZSEUKS) at Saarland University Medical Center, Germany

Providing comprehensive medical care for patients with rare diseases is both challenging and rewarding. We will give a short summary of the most relevant medical issues pertinent to this subject, and will illustrate some of these issues by sharing our experience in the care of patients with TSC disease.

Reference values for nucleated red blood cells and serum lactate in very and extremely low birth weight infants in the first week of life

STUDY PURPOSEnTo provide reference values for nucleated red blood cells and serum lactate concentrations in very and extremely low birth weight (VLBW/ELBW) infants in the first week of life.nnnPATIENTS AND METHODSnRetrospective data analysis of serial, daily measurements of NRBC counts and serum lactate during the first 6days of life in VLBW and ELBW infants.nnnRESULTSnIn total, 250 infants<1500g were included in this study. Intrauterine growth retardation (IUGR) was seen in 87 (34.8%) patients. Gestational age (GA) ranged from 23 to 35weeks (mean 29.0weeks) and birth weight (BW) was 320-1499g (mean 1047.9g). During hospital stay, 55 (22%) patients developed IVH and 55 children (22%) BPD. PVL was seen in 12 (4.8%) cases, ROP in 93 (37.2%) and NEC in only 1 (0.4%) patient. NRBC counts as well as serum lactate concentrations depended significantly on birth weight (p<0.01) and presence respectively absence of IUGR (p<0.01). Both NRBC counts and serum lactate concentrations declined constantly during the 6-day period (p<0.01), and both were highly inter-correlated (p<0.01).nnnCONCLUSIONSnThis is one of only a very few studies that systematically and serially evaluated both NRBC counts and serum lactate concentration in VLBW and ELBW infants in the first 6days of life. Both parameters were significantly dependent on birth weight and the presence of IUGR. Moreover, a significant correlation between NRBC counts and serum lactate concentrations in this early period of life could be demonstrated. In future studies, the role of these readily available biomarkers in predicting important neonatal outcome parameters needs to be evaluated in a prospective manner.

Ventriculoperitoneal Shunt Tip as a Rare Cause for Recurrent Pain Episodes in a Child: Think Irritable Peritoneum

Ventriculoperitoneal (VP) shunting is an established treatment to regulate the drainage of cerebrospinal fluid (CSF) in posthaemorrhagic hydrocephalus. Several complications (e.g. blockage of CSF shunting, overdrainage, but also catheter-related perforation of abdominal organs, etc.) may occur and may lead to painful episodes, mostly headache, in these children. Here, we report on a 7-year-old child with recurrent painful episodes after revision of a VP shunt that subsided only after repositioning of the abdominal tip of the VP shunt. Visceral irritation by a malpositioned VP shunt should be considered as a cause for recurrent pain in non-verbal children without other relevant clinical findings.

The role and limitations of Cochrane reviews at the bedside: a systematic synopsis of five pediatric subspecialties

SummaryBackgroundCochrane meta-analyses provide the physician at the bedside with the most relevant, up-to-date clinical information. However, implementation of evidence-based medicine (EBM) at the bedside may be difficult for axa0variety of reasons. The aim of this study was to assess relevant issues and obstacles related to implementing EBM in pediatrics in real life at the bedside/cotside.MethodsWe performed five systematic literature reviews of all published Cochrane reviews in neonatology (1996–2010), pediatric neurology (1996–2010), pediatric gastroenterology (1993–2012), pediatric cardiology (2001–2015), and complementary and alternative medicine (1996–2012; CAM) in children and neonates. In all five analyses, the main outcome variables were percentage of reviews concluding that axa0certain intervention provides axa0benefit, percentage of reviews concluding that axa0certain intervention should not be performed, and percentage of studies concluding that the current level of evidence is inconclusive.ResultsIn all five areas of pediatrics, axa0substantial number of Cochrane reviews yielded inconclusive data (neonatology: 46.6%; neuropediatrics: 26.8%; pediatric gastroenterology: 27.9%; pediatric cardiology: 42.9%; complementary and alternative medicine: 66.9%).ConclusionsOur up-dated systematic synopsis reiterates the need for high-quality, sophisticated research to reduce the number of inconclusive meta-analyses in the field of pediatrics—most importantly in the field of complementary and alternative medicine (CAM), neonatology, and pediatric cardiology. The realization of high-quality, clinically driven research will in turn yield more systematic reviews with axa0clear conclusion (e.u2009g., in favor or against axa0certain intervention, or treatment modality), thus, substantively decreasing the proportion of inconclusive reviews.

Nucleated red blood cells and serum lactate values on days 2 and 5 are associated with mortality and morbidity in VLBW infants

SummaryAimTo correlate nucleated red blood cell counts and serum lactate concentrations on dayxa02 andxa05 of life with morbidity and mortality in very low birth weight infants and to determine corresponding cutoff values.MethodsRetrospective analysis in axa0cohort of very low birth weight infants.Results250 very low birth weight infants were included in this study. Gestational age ranged from 23 to 35xa0weeks (mean 29.04) and birth weight was 320–1500u202fg (mean 1047.9). 55 (22%) patients developed intraventricular hemorrhage, 55 (22%) bronchopulmonary dysplasia, 12 (4.8%) periventricular leukomalacia, 93 (37.2%) retinopathy of prematurity, and 1 (0.4%) necrotizing enterocolitis. Mortality rate was 25/250 (10%). Nucleated red blood cells and serum lactate on dayxa02 of life were associated with mortality (pu202f<u20090.001). Serum lactate on dayxa05 of life demonstrated an association with retinopathy of prematurity (pu202f=u20090.017), bronchopulmonary dysplasia (pu202f=u20090.044), and intraventricular hemorrhage (pu202f<u20090.001). Cutoff values predicting mortality were >89.5 nucleated red blood cells/100 leucocytes (sensitivity 68.2%, specificity 89.0%) and serum lactate concentrations >8.5u202fmmol/l (sensitivity 69.6%, specificity 93.5%) on dayxa02 of life.ConclusionWe conclude that both nucleated red blood cell count and serum lactate concentration are valuable biomarkers in predicting important outcome parameters in very low birth weight infants.ZusammenfassungZielZiel der Untersuchung war es die Normoblastenzahl und Serumlaktatkonzentration an Lebenstag 2 und 5 mit der Morbidität und Mortalität von very low birth weight-Neonaten zu korrelieren und Cut-off-Werte zu bestimmen.MethodikRetrospektive Analyse in einer Gruppe von very low birth weight-Neonaten.ErgebnisseInsgesamt 250 very low birth weight-Neonaten wurden in die Studie eingeschlossen. Das Gestationsalter reichte von 23 bis 35 Schwangerschaftswochen (Mittelwert 29,04) und das Geburtsgewicht von 320 bis 1500xa0g (Mittelwert 1047,9). 55 (22xa0%) Patienten entwickelten eine intraventrikuläre Blutung, 55 (22xa0%) eine bronchopulmonale Dysplasie, 12 (4,8xa0%) eine periventrikuläre Leukomalazie, 93 (37,2xa0%) eine Frühgeborenen-Retinopathie und ein Patient (0,4xa0%) eine nekrotisierende Enterokolitis. Die Mortalität betrug 25/250 (10xa0%). Die Normoblasten und Serumlaktatkonzentrationen an Lebenstag 2 waren mit einer erhöhten Mortalität assoziiert (pxa0<xa00,001). Die Serumlaktatkonzentrationen an Lebenstagxa05 war mit einer erhöhten Rate an Frühgeborenen-Retinopathie (pxa0=xa00,017), bronchopulmonaler Dysplasie (pxa0=xa00,044) und intraventrikulärer Blutung (pxa0<xa00,001) assoziiert. Cut-off-Werte >xa089,5 Normoblasten/100 Leukozyten (Sensitivität 68,2xa0%, Spezifität 89,0xa0%) und Serumlaktatkonzentrationen >xa08,5xa0mmol/l (Sensitivität 69,6xa0%, Spezifität 93,5xa0%) an Lebenstag 2 wiesen auf eine erhöhte Mortalität hin.SchlussfolgerungWir schließen daraus, dass beide, die Normoblastenzahl als auch die Serumlaktatkonzentration, wertvolle Biomarker sind, die wichtige Outcome-Parameter von very low birth weight-Neonaten vorhersagen können.

Incidence of tuberous sclerosis and age at first diagnosis: new data and emerging trends from a national, prospective surveillance study

BackgroundTuberous Sclerosis Complex (TSC) is a rare multisystem disorder. In 2012 diagnostic criteria for TSC were revised. However, data on the incidence of TSC are limited.MethodsProspective, national surveillance study in Germany over a 2-year-period (03/2015–02/2017) using current revised criteria for TSC. Patients up to the age of 18xa0years with a new diagnosis of definite or possible TSC (clinical and/or genetic) were included. The aims of this study were 1) to generate up-to-date data on the incidence of definite or possible TSC, 2) to assess age at first diagnosis, and 3) to compare these data with previous epidemiologic data.ResultsIn total, 86 patients met inclusion criteria (definite or possible TSC) with a median age at diagnosis of 6xa0months (range: 5xa0months before birth – 197xa0months of age). Among patients identified with features of TSC, 73.3% met criteria for definite diagnosis (median age: 7xa0months) and 26.7% met criteria for a possible diagnosis (median age: 3xa0months). 55.8% of patients were male. When excluding prenatally diagnosed patients, median age at diagnosis was 11xa0months with a range of 0 to 197xa0months. The 3 most common clinical features at diagnosis of TSC were central nervous system involvement in 73.3% patients (of these 95.2% experienced seizures), cutaneous involvement in 58.1% patients (with the most common lesion being hypomelanotic macules in 92%) and cardiac rhabdomyoma in half of the patients. Cardiac rhabdomyoma were detected by prenatal ultrasonography in 22.1% of patients. The presence of cardiac rhabdomyoma was associated with cardiac arrhythmias in 25.6% (about 13% of all diagnosed patients) in our cohort. The overall prevalence of seizure disorders was 69.8%. The annual incidence rate of TSC is estimated at a minimum of 1:17.785 live births. However correcting for underreporting, the estimated incidence rate of definite or possible TSC is approximately 1:6.760–1:13.520 live births in Germany.ConclusionsThis is the first study that assessed prospectively the incidence rate of TSC in children and adolescents using the updated diagnostic criteria of 2012. This prospective surveillance study demonstrates a low age at first diagnosis (median: 6xa0months), likely due to antenatal detection of cardiac rhabdomyoma. Early diagnosis bears the potential for implementing effective therapies at an earlier stage.

Diagnosis and Treatment of Tuberous Sclerosis Manifestations in Children: A Multicenter Study

Abstract Tuberous sclerosis complex (TSC) is a genetic disease with a significant morbidity and mortality. We conducted a retrospective analysis of two cohorts (Vall d’Hebron University Hospital [HVH], Barcelona, Spain, 1982‐2015, and at Saarland University Medical Center [UKS], Homburg, Germany, 1998‐2015) to assess prevalence and treatment of TSC associated manifestations and to evaluate if the follow‐up was in line with published recommendations. This was considered if more than 15% of patients did not receive adequate examination with regard to potential organ involvement. A definite diagnosis was made in 52 patients (96%), and a possible diagnosis was made in 2 patients (4%). Thirty‐four (63%) patients were from HVH and 20 (37%) from UKS. Median age at first presentation was 6 months (interquartile range: 0‐38 months), and median time of follow‐up was 6 years (interquartile range: 2‐13 years). Clinical symptoms that led to a diagnosis of TSC were cardiac rhabdomyoma (22/54), epilepsy (20/54), and cutaneous manifestations (4/54). Assessment of neuropsychiatric, renal, and ocular manifestations was inadequate in both hospitals, whereas cutaneous manifestation was inadequate at UKS only. Our data demonstrate insufficient examinations in a substantial number of TSC patients with regard to neuropsychiatric, renal, ocular, and cutaneous manifestations. The recently published guidelines may prove valuable in establishing a more comprehensive approach.