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Background Vein of Galen malformation (VGM) is a rare congenital intracerebral vascular malformation. The intention of this study was to gain reliable data about epidemiology, clinical manifestations and pre-, peri- and post-interventional treatment strategies in Germany. Methods This prospective epidemiological study was conducted by ESPED (Erhebungseinheit fur Seltene Padiatrische Erkrankungen in Deutschland), a hospital-based German nation-wide surveillance unit for rare pediatric diseases. Patients up to the age of 18 years with a new diagnosis of vein of Galen malformation (VGM) were prospectively included between January 1, 2014 to December 31, 2015. Results In the 2-year study period, 30 cases of newly diagnosed VGM were reported resulting in an estimated annual incidence rate of VGM in Germany of at least 1: 58100 live births. The main symptoms were age dependent. Neonates presented with mainly cardiac manifestations of high output failure, infants and older children mainly suffered from neurologic complications. Ninety-five % of all patients with endovascular treatment survived, but only 41% of these patients were discharged home without any complications. The Bicetre Neonatal Evaluation Score (BNES) was a good predictor for poor outcome but could have led to palliative care in some patients with good outcome. Conclusions The incidence of VGM in Germany is estimated to be 1:58100 live births. The majority of patients was eligible for endovascular treatment. Nevertheless, due to side effects and long-term sequelae in the majority of patients further improvement in care of children with VGM is required.

Near infrared spectroscopy (NIRS) calculates regional tissue oxygenation (rSO2) using the different absorption spectra of oxygenated and deoxygenated hemoglobin molecules. A probe placed on the skin emits light that is absorbed, scattered, and reflected by the underlying tissue. Detectors in the probe sense the amount of reflected light: this reflects the organ-specific ratio of oxygen supply and consumption - independent of pulsatile flow. Modern devices enable the simultaneous monitoring at different body sites. A rise or dip in the rSO2 curve visualizes changes in oxygen supply or demand before vital signs indicate them. The evolution of rSO2 values in relation to the starting point is more important for interpretation than are absolute values. A routine clinical application of NIRS is the surveillance of somatic and cerebral oxygenation during and after cardiac surgery. It is also administered in preterm infants at risk for necrotizing enterocolitis, newborns with hypoxic ischemic encephalopathy and a potential risk of impaired tissue oxygenation. In the future, NIRS could be increasingly used in multimodal neuromonitoring, or applied to monitor patients with other conditions (e.g., after resuscitation or traumatic brain injury).

Septischer und anaphylaktischer Schock sind seltene Notfalle im Kindesalter. Die rasche klinische Diagnose und Therapieeinleitung sind fur den Patienten uberlebenswichtig. In der folgenden Ubersicht soll auf Besonderheiten der Pathophysiologie und insbesondere auf Klinik und Therapie dieser beiden Formen eingegangen werden.

SummaryBackground In pediatric patients, invasive procedures such as the insertion of a central venous catheter or gastroscopy require deep sedation. It is unknown whether listening to parental voice during deep sedation in children can reduce sedative doses. Aim The aim of this prospective study was to determine the effect of listening to a parent's voice during deep sedation on consumption of sedatives in children. Methods Fifty children aged 2–14 years undergoing central line placement or gastroscopy under deep sedation with propofol were randomly assigned to two groups: (A) listening or (B) not listening their parents’ recorded voice reading a standardized text by the use of earphones. Depth of sedation was monitored by Comfort Score and by Bispectral Index. Results Mean sedative dose of propofol in both groups was equal (A 0.25 mg·kg−1·min−1; B 0.28 mg·kg−1·min−1; Δ −0.03 mg·kg−1·min−1 (CI 95% −0.08 to 0.01); P = 0.089). Furthermore, complication rate (P = 1.0) and recovery time (A 14.5 min; B 16.1 min; Δ = −1.6 min (CI 95% −6.98 to 3.81); P = 0.60) did not differ between the intervention and the control group. Conclusion Listening to parental voice during deep sedation does not result in a reduction of sedative dose in children undergoing short medical procedures.

BACKGROUND: Infectious complications after pediatric liver transplantation frequently occur and are potentially serious. Data concerning strictly defined bacterial infections and their associated risk factors are lacking. METHODS: For the pediatric liver transplant postoperative period we analyzed data from the nosocomial infection surveillance (2006-2015). RESULTS: A total of 235 bacterial infections in 162 transplantations (47%) occurred, including 32 bacterial pneumonia cases, 104 surgical site infections, 27 urinary tract infections and 40 bloodstream infections. Sepsis was diagnosed in 127 cases (54%), severe sepsis in 22 (9%) cases and septic shock in 41 (17%) cases. Thirty patients (9%) died, and septic shock was the leading cause of death. The carrier status of multi-drug resistant bacteria and a tacrolimus level \textgreater20 ng/ml were independent risk factors for surgical site infections and the occurrence of severe sepsis or septic shock. The length of mechanical ventilation was an independent risk factor for pneumonia and surgical site infection. CONCLUSION: Bacterial infections in the early postoperative period after pediatric liver transplantation are associated with high morbidity and mortality. Physicians involved in the medical care of these patients should be aware of the specific risk factors, and further development of prevention programs is highly recommended.

In general anesthesia, cartoon watching and playing video games reduce anxiety in children. It is unknown whether watching a video in the intervention room has a similar effect, and therefore is able to reduce sedative doses in children undergoing small medical procedures. Aim of this prospective study was to determine the effect of watching a standardized cartoon immediately before and during sleep induction for deep sedation on consumption of propofol in children.50 children aged 2-14 years undergoing deep sedation were randomly assigned to 2 groups: (A) watching or (B) not watching a standardized videoclip during sleep induction with propofol. The achievement of predefined sedation depth was objectified by measuring Comfort Score (aim 10-14) and Bispectral Index (aim 50-60).The median sleep induction dose of propofol did not differ in both groups (A: 1.76 (0.62-4.37) mg/kg; B: 1.37 (0.66-5.26) mg/kgKG; p=0.65). Cartoon watching was associated with shorter sleep onset latency (A: 120 (60-480)s; B: 240 (40-600)s; p=0.043). Subgroup analysis reveals this especially for school children and girls. In both groups no complications occurred.Children watching a standard cartoon during sleep induction for deep sedation have a shorter sleep onset time but sedative dose is not reduced.Vor und während der Einleitung einer Vollnarkose reduziert das Ansehen eines Cartoons oder das Spielen von Videospielen bei Kindern Angst. Es ist nicht bekannt, ob das auch im Zusammenhang mit Sedierungen gilt und die notwendige Sedativadosis für kleine Eingriffe oder Prozeduren bei Kindern durch das Ansehen eines Films reduziert werden kann. Ziel dieser prospektiven Studie war es deswegen, den Effekt zu ermitteln, den das Ansehen eines standardisierten Videos unmittelbar vor und während Schlafinduktion für eine tiefe Sedierung auf den Propofolbedarf bei Kindern hat.50 Kinder zwischen 2 und 14 Jahren wurden in 2 Gruppen randomisiert, denen während medikamentöser Induktion mit Propofol für eine tiefe Sedierung entweder ein Standardfilm (Gruppe A) oder kein Film (Gruppe B) präsentiert wurde. Die gewünschte Schlaftiefe war definiert und wurde durch Erheben eines klinischen Scores (Comfort Score, Ziel 10–14) und den Einsatz von Bispektralem Index (Ziel 50–60) objektiviert.Die mediane Schlafinduktionsdosis für Propofol unterschied sich in beiden Gruppen nicht (A: 1,76 (0,62–4,37) mg/kg; B: 1,37 (0,66–5,26) mg/kgKG; p=0,65). Die Kinder, die einen Cartoon sahen, hatten eine kürzere Einschlafzeit (A: 120 (60–480)s; B: 240 (40–600)s; p=0,043). In der Subgruppenanalyse zeigt sich, dass dies insbesondere für Mädchen und Schulkinder gilt. In beiden Gruppen kam es zu keinerlei Komplikationen.Kinder, die während Sedierungseinleitung einen Film ansehen, haben eine kürzere Einschlafzeit, die Dosis der notwendigen Sedativa ist jedoch unbeeinflusst.

Introduction and aim. Procalcitonin is widely used as a biomarker to distinguish bacterial infections from other etiologies of systemic inflammation. Little is known about its value in acute liver injury resulting from intoxication with paracetamol.Material and methods. We performed a single-center retrospective analysis of the procalcitonin level, liver synthesis, liver cell damage and renal function of patients admitted with paracetamol-induced liver injury to a tertiary care children’s hospital. Children with acute liver failure due to other reasons without a bacterial or fungal infection served as the control group. Twelve patients with acute paracetamol intoxication and acute liver injury were compared with 29 patients with acute liver failure.Results. The procalcitonin levels were higher in children with paracetamol intoxication than in patients with acute liver failure without paracetamol intoxication (median 24.8 (0.01-55.57) ng/mL vs. 1.36 (0.1-44.18) ng/mL; p < 0.005), although their liver and kidney functions were better and the liver cell injury was similar in both groups. Outcome analysis showed a trend towards better survival without transplantation in patients with paracetamol intoxication (10/12 vs. 15/29). Within each group, procalcitonin was significantly correlated with alanine aminotransferase and aspartate aminotransferase but was not correlated with the International Normalized Ratio or paracetamol blood levels in the paracetamol group. In conclusion, paracetamol intoxication leads to a marked increase in procalcitonin serum levels, which are significantly higher than those seen in acute liver failure.Conclusion. The underlying mechanism is neither caused by infection nor fully explained by liver cell death alone and remains to be determined.

The use of Propofol and Remifentanil for analgosedation in children is common and safe. For sedation monitoring clinical scores as Comfort Score (CS) as well as bispectral index (BIS) are frequently applied. The impact of BIS for sedation monitoring in pediatric patients is still under debate. This prospective study aims to investigate whether dual sedation monitoring of CS and BIS compared with monitoring of CS alone during muscle biopsies in children can reduce sedative doses, reduce awakening time and prevent complications.50 pediatric patients requiring sedation for open muscle biopsy were prospectively enrolled. Analgosedation was performed with remifentanil and propofol. Patients were randomly assigned to 2 groups: In 25 patients, sedation was monitored using CS alone, and in 25 patients CS and BIS monitoring were simultaneously applied. The primary outcome was the propofol dose applied during muscle biopsy. Secondary outcome parameters were recovery time and the frequency of complications.The median CS during the intervention in both groups was equal (11, P=1.000). The median BIS in group 2 was 59. No complications occurred in either group. There was no difference in propofol dose in either group (8.4 vs. 7.2 mg/kg/h; P=0.58) and no difference in the duration until eye opening (9 vs. 11 min; P=0.081).For children undergoing minor surgical procedures under analgosedation, BIS monitoring does not affect the sedative dose, the time until eye opening or the frequency of complications.Zur Analgosedierung von Kindern hat sich eine Medikamentenkombination aus Propofol und Remifentanil bewährt. Zum Sedierungsmonitoring sind sowohl klinische Scores wie der Comfort Score (CS) als auch der bispektrale Index (BIS) üblich. Die Bedeutung von BIS zum Sedierungsmonitoring bei Kindern ist nach wie vor nicht eindeutig und Gegenstand wissenschaftlicher Diskussionen. Ziel der vorliegenden prospektiven Studie ist es zu untersuchen, ob bei pädiatrischen Patienten das kombinierte Sedierungsmonitoring mit CS und BIS verglichen mit einem alleinigen Monitoring mittels CS während offener Muskelbiopsien zu einer Reduktion der Sedativadosis, einer verkürzten Aufwachzeit und einer Reduktion der Häufigkeit von Komplikationen führt.50 pädiatrische Patienten, die während offener Muskelbiopsien Propofol und Remifentanil zur Analgosedierung erhielten, wurden untersucht und dazu in 2 Gruppen randomisiert: Bei 25 Patienten wurde die Analgosedierung mittels CS allein, bei 25 mittels CS und zusätzlichem BIS Monitoring überwacht. Primärer Outcome Parameter war die benötigte Propofoldosis während des Eingriffs. Sekundäre outcome parameter waren Aufwachzeit und Häufigkeit von Komplikationen.Der mediane CS während des Eingriffs war in beiden Gruppen gleich (11, P=1,000). Der mediane BIS in Gruppe 2 war 59. In beiden Gruppen kam es zu keinerlei Komplikationen. Es gab keinen Unterschied in der applizierten Propofoldosis (8,4 vs. 7,2 mg/kg/h; P=0,081) und in der Aufwachzeit zwischen beiden Gruppen (9 vs. 11 min; P=0,081).Für die Analgosedierung während kleiner chirurgischer Eingriffe bei pädiatrischen Patienten hat das zusätzliche Sedierungsmonitoring mittels BIS keinen Einfluss auf die verwendete Sedativadosis, die Aufwachzeit oder die Häufigkeit von Komplikationen.

Bacillus cereus is a spore-forming, gram-positive bacterium that causes food poisoning presenting with either emesis or diarrhea. Diarrhea is caused by proteinaceous enterotoxin complexes, mainly hemolysin BL, non-hemolytic enterotoxin (NHE), and cytotoxin K. In contrast, emesis is caused by the ingestion of the depsipeptide toxin cereulide, which is produced in B. cereus contaminated food, particularly in pasta or rice. In general, the illness is mild and self-limiting. However, due to cereulide intoxication, nine severe cases with rhabdomyolysis and/or liver failure, five of them lethal, are reported in literature. Here we report the first case of life-threatening liver failure and severe rhabdomyolysis in this context that could not be survived without emergency hepatectomy and consecutive liver transplantation.

OBJECTIVES To assess the influence of an infusion of clonidine 1 μg/kg/hr on fentanyl and midazolam requirement in ventilated newborns and infants. DESIGN Prospective, double-blind, randomized controlled multicenter trial. Controlled trials.com/ISRCTN77772144. SETTING Twenty-eight level 3 German PICUs/neonatal ICUs. PATIENTS Ventilated newborns and infants: stratum I (1-28 d), stratum II, (29-120 d), and stratum III (121 d to 2 yr). INTERVENTIONS Patients received clonidine 1 μg/kg/hr or placebo on day 4 after intubation. Fentanyl and midazolam were adjusted to achieve a defined level of analgesia and sedation according to Hartwig score. MEASUREMENTS AND MAIN RESULTS Two hundred nineteen infants were randomized; 212 received study medication, 69.7% were ventilated in the postoperative care and 30.3% for other reasons. Primary endpoint: consumption of fentanyl and midazolam in the 72 hours following the onset of study medication (main observation period) in the overall study population. The confirmatory analysis of the overall population showed no difference in the consumption of fentanyl and midazolam. Explorative age-stratified analysis demonstrated that in stratum I (n = 112) the clonidine group had a significantly lower consumption of fentanyl (clonidine: 2.1 ± 1.8 μg/kg/hr, placebo: 3.2 ± 3.1 μg/kg/hr; p = 0.032) and midazolam (clonidine: 113.0 ± 100.1 μg/kg/hr, placebo: 180.2 ± 204.0 μg/kg/hr; p = 0.030). Strata II (n = 43) and III (n = 46) showed no statistical difference. Sedation and withdrawal-scores were significantly lower in the clonidine group of stratum I (p < 0.001). Frequency of severe adverse events did not differ between groups. CONCLUSIONS Clonidine 1 μg/kg/hr in ventilated newborns reduced fentanyl and midazolam demand with deeper levels of analgesia and sedation without substantial side effects. This was not demonstrated in older infants, possibly due to lower clonidine serum levels.

Background CD59 is a cell surface glycoprotein of approximately 20 kDa limiting the lytic activity of the terminal complement complex C5b-9. Although CD59 is known as a red blood cell (RBC) antigen defined by monoclonal antibodies, it so far has not been identified as a blood group antigen, since the description of a human alloantibody was missing. In this study we show the presence of an anti-CD59 in a patient affected by a homozygous CD59 deficiency. Study Design and Methods RBC CD59 and CD55 were determined by flow cytometry or by the column agglutination technique using monoclonal antisera. Commercially available His-tagged recombinant soluble CD59 protein was used to inhibit anti-CD59. Results Seven cases of an isolated CD59 deficiency due to three distinct null alleles of the CD59 gene have been published so far. Recently we described the CD59-null allele c.146delA in a young child of heterozygous parents. Her plasma contained an alloantibody directed against the high-prevalence RBC antigen CD59. The antibody specificity was identified using soluble recombinant human CD59 protein, which blocked the reactivity of the patient's antibody and of monoclonal anti-CD59 but not of monoclonal anti-CD55. In addition, RBC alloantibodies such as anti-K, anti-C, anti-c, or anti-Fya remained unaffected. Therefore, inhibition by recombinant CD59 is a useful diagnostic tool to detect alloantibodies in the presence of anti-CD59. Conclusion This is the first demonstration of a human anti-CD59 alloantibody, which defines CD59 as an RBC blood group antigen. CD59 represents a candidate for a new blood group system.

In the developed countries septic shock has a favorable outcome for the majority of previously healthy children but also in children with comorbidities if all available medical resources were used. However, septic shock remains a rare disease in children, and caregivers might not always recognize it at early stages. The resulting delay of appropriate treatment prevents lower mortality rates. The current review gives an overview of the pathophysiology of septic shock and the early clinical signs as well as new and future diagnostic approaches such as "point-of-care" laboratory tests for an early diagnosis.

Kindernotfalle sind immer heikel, ganz besonders aber respiratorische Notfalle mit ihrer oft dramatischen Symptomatik. Aus der kindlichen Anatomie und Physiologie der Atmung ergeben sich einige Besonderheiten fur das praktische Vorgehen im Einsatz.

This study reports the first cases of neurogenic stunned myocardium in two children with vein of Galen aneurysmal malformation after interventional treatment. Two newborns with vein of Galen aneurysmal malformation and high output cardiac failure developed a severe reversible left ventricular dysfunction shortly after embolization, concurrently with acute hydrocephalus. There was a resolution of the cardiac symptoms of left ventricular dysfunction within a few days under treatment with milrinone and dobutamine. Reversible left ventricular dysfunction is observed in adult patients mainly after subarachnoid hemorrhage and is called neurogenic stunned myocardium (NSM). Other forms of brain injuries have also been identified accounting for this condition in adults. In pediatric population especially with specific cerebral diseases, NSM may be underdiagnosed.

Background There is only sparse data on the use of non-invasive ventilation (NIV) in acute respiratory failure (ARF) in infants and children. For this setting we investigated feasibility and efficacy of NIV and aimed to identify early predictors for treatment failure. Patients and Methods Retrospective chart review was performed for all patients treated with NIV for ARF from 2003 to 2010 on an 8-bed pediatric intensive care unit of a tertiary university hospital. Results Seventy-four patients were treated with NIV. One patient did not tolerate mask ventilation and needed immediate invasive ventilation. Intubation rate of the remaining patients was 23% and mortality 15%. Institution of NIV led to significant improvement of both respiratory and heart rate in all patients within the first hour and to further stabilization within the next 8–10 hr. In patients with NIV success blood gases improved significantly 1–2 hr after starting NIV. Multivariate analysis identified low pH after 1–2 hr to be an individual risk factor for NIV failure. Other factors tested were age, underlying disease, acute respiratory insufficiency versus post-extubation failure (PEF), and 1–2 hr after starting NIV oxygen saturation, respiratory rate, PCO2, and FiO2. Patients with PEF tended to show better outcomes compared to those with acute respiratory insufficiency. Conclusion NIV can be effective in infants and children with ARF. Low pH 1–2 hr after start of NIV is associated with NIV failure. It may therefore be useful in the decision to continue or stop mask ventilation. Pediatr. Pulmonol. 2011; 46:1114–1120. © 2011 Wiley Periodicals, Inc.

ZusammenfassungIm letzten Jahrzehnt wurden große Fortschritte in der Diagnostik und Therapie neuromuskulärer Erkrankungen gemacht. Insbesondere die Therapie des chronischen Atemmuskelversagens mit der nicht-invasiven Beatmung konnte Morbidität und Mortalität senken und die Lebensqualität verbessern. Rezidivierende Atemweginfekte und Atelektasen komplizieren den Verlauf bei Patienten mit fortgeschrittenen Erkrankungen und sind Folgen eines insuffizienten Hustens. Ein wichtiger, aber noch nicht ausreichend angewandter Bestandteil der Therapie ist die Technik des assistierten Hustens. Mit steigender Lebenserwartung rückt die Herzbeteiligung als lebenslimitierender Faktor weiter in den Vordergrund. In dieser Übersichtsarbeit wird die aktuelle Datenlage zum Atemmuskelversagen und der Herzbeteiligung bei neuromuskulären Erkrankungen diskutiert.

Background In pediatric neuromuscular disorders (NMD), respiratory muscle weakness parallels respiratory failure. The objectives of this study are (1) to evaluate respiratory muscle capacity in neuromuscular children and (2) to assess the relationship between vital capacity, respiratory muscle performance, and alveolar ventilation during sleep and wakefulness. Methods Inspiratory vital capacity (IVC), peak inspiratory pressure (PIP), mouth occlusion pressure (P 0.1 ), and noninvasive tension-time index of the respiratory muscles (TTImus) were studied in 80 NMD subjects (12.1 ± 3.3 years) and 80 healthy children (11.1 ± 2.2 years). Subjects' results were compared with arterial blood gases and polysomnography. Results In 15 NMD subjects with normal ventilation IVC and PIP were reduced to 70% predicted but TTImus was normal. In 50 NMD subjects with nocturnal hypoventilation IVC and PIP were lower than 50% predicted, TTImus was doubled compared with the control group. In 15 NMD subjects with diurnal and nocturnal hypoventilation IVC and PIP were below 30% predicted, TTImus was increased fourfold, and thus the main determinant of respiratory failure. Conclusions In NMD children, reduced IVC and PIP result in increased respiratory muscle load and disturbed ventilation. TTImus is an important noninvasive determinant of disturbed ventilation in children with NMD.

Background Antimicrobially pre-treated children with systemic inflammation often pose a diagnostic challenge to the physician. We aimed to evaluate the additional use of SeptiFast multiplex polymerase chain reaction (PCR) to identify causative pathogens in children with suspected systemic bacterial or fungal infection. Methods Prospective observational study in 39 children with systemic inflammatory response syndrome (SIRS) under empiric antibiotic treatment. Primary outcome was the rate of positive blood cultures (BC), compared to the rate of positive SeptiFast (SF) results. Results In total, 14 SF-samples yielded positive results, compared to 4 positive BC (p

Chest infections are serious complications in neuromuscular disorders. The predictive values of lung and respiratory muscle function including peak cough flow still remain unclear. We performed retrospective analysis of 46 children and adolescents (12.7+/-3.7 years) in whom lung function, respiratory muscle function and peak cough flows had been obtained. Data were related to: (1). number of chest infections and days of antibiotic treatment the year prior to the study and (2). history of severe chest infection requiring hospital admission. The number of chest infections and the number of days treated with antibiotics correlated with Inspiratory Vital Capacity IVC, peak cough flow PCF and Peak Expiratory Pressure PEP. Twenty-two patients were hospitalized at least once due to severe chest infection. IVC (0.65 vs. 1.44 l; P

Adenoviruses (AdV) are opportunistic pathogens that can lead to severe infections and respiratory failure (acute respiratory distress syndrome, ARDS) with high mortality in immunosuppressed patients. Cidofovir (CDV) has been used in adenoviral disease in bone marrow transplant recipients. Two pediatric liver transplant recipients with disseminated adenoviral disease and ARDS were treated with reduction of immunosuppression, CDV, and inhaled nitric oxide (iNO). CDV 1 mg/kg was given three times per week intravenously with intravenous hydration and oral probenecid. Viral suppression and clinical improvement was achieved. AdV hepatitis did not occur, and graft function was preserved, although acute rejection occurred in both patients. Adverse effects were mild and transient not requiring dose modification. Severe hypoxemia was reversed with iNO 10-20 p.p.m. CDV treatment of AdV infections in organ transplant recipients and other immunocompromised patients should be further investigated in prospective studies.

Patients with CD59 deficiency have progressive neurologic dysfunction and episodes of hemolytic anemia. Eculizumab, a complement inhibitor, was administered to reverse hemolytic anemia in a patient. After the anemia improved, neurologic improvement was also noted.

Sleep disordered breathing is a common but under-diagnosed complication causing sleep disturbance and daytime symptoms in children with spinal muscular atrophy. Non-invasive (positive pressure) ventilation is an established treatment of respiratory failure; its role in treatment of sleep disordered breathing though remains controversial. Aim of this study was to verify the hypothesis that nocturnal non-invasive ventilation has beneficial impact on breathing during sleep, sleep quality and daytime complaints in children with spinal muscular atrophy. Twelve children with spinal muscular atrophy type I or II (7.8+/-1.9 years) underwent polysomnography and were asked to fill out a symptom questionnaire. Seven patients (six with spinal muscular atrophy I and one with spinal muscular atrophy II) had sleep disordered breathing and received non-invasive ventilation during sleep. Five less severely affected patients (one with spinal muscular atrophy I and four with spinal muscular atrophy II) had no sleep disordered breathing and served as reference group. Patients were restudied after 6-12 months. In patients with sleep disordered breathing both sleep architecture and disease related symptoms were significantly worse than in the reference-group. Non-invasive ventilation during sleep completely eliminated disordered breathing, normalized sleep architecture and improved symptoms (P

Aim A series study mainly from Asia suggests that ABO-incompatible (ABOi) living-related liver transplantation (LRLT) for pediatric recipients is associated with excellent short- and long-term graft and patient survival. Until now, ABOi LRLT has been rarely performed in Europe. The aim of this study was to analyze the safety and early results of an ABOi LRLT in a German high-volume pediatric liver transplant center. Methods Six consecutive pediatric patients (four males and two females) were included in this prospective study from January, 2010 to January, 2013 with a median age of 13 months (range, 6–30 months) receiving ABOi LRLT and were matched with six patients receiving ABO-compatible LRLT in the same period. In the ABOi group, titers of IgG and IgM isoagglutinins against the donor's blood group were determined at day 14 before the transplantation and from day 1 to 14 after the transplantation, and then twice a week for another 8 weeks. The titer results were determined as the reciprocal number of the highest serum dilution that caused macroscopical reaction. Results The patients receiving ABOi and those receiving ABO-compatible LRLT were comparable regarding the recipient's preoperative pediatric end-stage liver disease (PELD), age, gender, and technical aspects of transplantation. The median follow-up was 2.6 years (range, 1–4.5 years). At the time of operation, the mean body weight was 7.7 kg (range, 5.7–16 kg) in ABO-compatible LRLT recipients and 8.8 kg (range, 5.5–18 kg) in ABOi LRLT recipients. In each group, the median PELD score was 28 (range, 28–35), respectively. All recipients received tacrolimus plus mycophenolate mofetil-based standard immunosuppression and four ABOi transplanted patients received intravenous immunoglobulins at days 1, 3, and 5 after liver transplantation. Patient and graft survival in this group was 83%. One female patient died within 24 hours due to fulminant gram-negative sepsis. Another patient developed acute cellular rejection at the 8th postoperative day, which responded to steroid treatment. No further complications occurred. In the ABO-compatible group, patient survival was 100% and graft survival was 83%; one patient in this group received retransplantation after 4 days. During follow-up, two patients of the ABOi group had maximum alloantibody titers of four against the donor's blood group; all other patients had titers below four. Conclusion ABOi LRLT seems to be safe without an escalation of immunosuppression and should be considered as an additional option to timely facilitate the transplantation.

Advanced stages of Duchenne muscular dystrophy (DMD) result in severe lung volume decline and are associated with high respiratory morbidity and mortality. The aim of this study was to investigate whether lung volume decline in subjects with DMD is associated with ventilation inhomogeneity measured with the multiple-breath washout technique.This cross-sectional study of lung function included 45 subjects with DMD and 16 healthy controls using multiple-breath washout, spirometry, and cough peak flow.Subjects with DMD exhibited an elevated lung clearance index (> 7.0) defined as the cumulative exhaled volume divided by the functional residual capacity to lower the sulfur hexafluoride concentration below 2.5% compared with controls (8.16 ± 2.55 vs 6.23 ± 0.46, P < .001). Lung clearance index elevation was negatively correlated with vital capacity (% predicted: r = -0.79, P < .001) and cough peak flow (L/min: r = -0.41, P = .005). Furthermore, dead-space ventilation (dead-space-to-tidal-volume ratio) and functional residual capacity showed a positive correlation with lung clearance index elevation (r = 0.81 and 0.48, P < .001). An FVC of < 24% predicted lung clearance index elevation with a sensitivity of 96% and a specificity of 80%.Moderate-to-severe lung volume decline in subjects with DMD is associated with ventilation inhomogeneity. Lung clearance index elevation may be the result of altered ventilation geometry or retention of airway secretions in the infection-free DMD subject. OA embargo

Only sparse data exist about children with septic shock in Europe. The present study aimed to evaluate demographics, treatment, outcome and risk factors for mortality in Western Germany.Children with septic shock aged 2 months to 17 years.In a multi-center retrospective study of 20 children's hospitals data were obtained and analyzed by chart review. Risk factors for mortality were identified and assessed by multivariate regression analysis.Overall mortality in 83 cases with septic shock was 25% (21 patients). Significant risk factors were high PRISM III score, low pH, low arterial systolic blood pressure, presence of disseminated intravascular coagulation and extent of multi-organ failure, but not lactate (p=0.05) and base excess (p=0.065). Mortality in hospitals which treated 10 or more patients (category 1) was 17% and increased to 22% in hospitals which treated 3-6 patients (category 2). In hospitals with only 1 or 2 patients (category 3) mortality rate was 61% (p0.01 when compared to category 1 or 2). A stepwise increase was also seen in the severely sick patients according to PRISM III (19): category 1: 23%, category 2: 40%, category 3: 62.5% (p0.05 for comparison of category 1 and 3). Multivariate analysis of significant risk factors revealed low number of treated patients as the only individual risk factor for mortality.Mortality from pediatric septic shock in an urban area in Western Germany is high. Disease severity and treatment in a department with few cases were associated with increased mortality.

Assessment of inspiratory muscle function (IMF) is limited in children with neuromuscular disorders, because respiratory muscle tests are poorly standardized and valid normative data are unavailable. We investigated maximum inspiratory pressure after exhalation to residual volume (MIP), mouth occlusion pressure (P0.1) and time of inspiration during quiet breathing and derived inspiratory muscle load (P0.1/MIP), and tension time index (TTI) in 301 healthy schoolchildren 6-16 years old. Gender-specific and age-dependent percentile curves for MIP were drawn with the median, 5%, 10%, 25%, 75% and 95% percentile. P0.1 was equal in boys and girls (0.23 ± 0.11 kPa), while MIP was significantly higher in boys (6.8 ± 2.2 versus 5.8 ± 2.4 kPa). Consequently, P0.1/MIP (4.8% ± 3.2% versus 4.0% ± 3.1%) and TTI (0.2 ± 0.14 versus 0.16 ± 0.14) were significantly higher in girls. MIP was 2.90 + 0.36 × age (kPa) and 3.19 + 0.24 × age (kPa) in boys and girls, respectively. The 95% confidence intervals for boys and girls, respectively, were MIP, 6.3-7.3 kPA and 5.4-6.2 kPa; P0.1/MIP, 3.5%-4.5% and 4.3%-5.3%; TTI, 0.14-0.18 and 0.18-0.22; and P0.1, 0.20-0.24 kPa for both. IMF in children has a wide interindividual variability; however percentile curves facilitate a longitudinal assessment of individual patients. Furthermore, narrow confidence intervals allow for comparisons of study populations, making IMF an appropriate endpoint for clinical trials.

SummaryBackground Open muscle biopsies in children are generally performed under general anesthesia. Alternatively, deep sedation and analgesia may be required. Objectives The aim of our study was to compare the Bispectral Index (BIS) and Comfort Score (CS) with respect to their clinical significance for sedation/analgesia in children undergoing open muscle biopsy. Methods Thirty pediatric patients subjected to open muscle biopsy for diagnosis of their underlying disease were prospectively enrolled. Sedation/analgesia was performed in all patients using remifentanil and propofol. The patients were simultaneously monitored using the CS and BIS. Results All sedations and muscle biopsies were performed uneventfully. The CS and BIS were significantly correlated (R = 0.589; P

Hintergrund Sepsis und septischer Schock sind Ursachen einer signifikanten Mortalitat und Morbiditat im Kindesalter. Fruhzeitiges Erkennen des kritischen Zustands und sofortige aggressive Therapie sind fur das Uberleben und die Organprotektion entscheidend.

CD59 is a cell surface glycoprotein of approximately 20 kDa limiting the lytic activity of the terminal complement complex C5b-9. Although CD59 is known as a red blood cell (RBC) antigen defined by monoclonal antibodies, it so far has not been identified as a blood group antigen, since the description of a human alloantibody was missing. In this study we show the presence of an anti-CD59 in a patient affected by a homozygous CD59 deficiency.RBC CD59 and CD55 were determined by flow cytometry or by the column agglutination technique using monoclonal antisera. Commercially available His-tagged recombinant soluble CD59 protein was used to inhibit anti-CD59.Seven cases of an isolated CD59 deficiency due to three distinct null alleles of the CD59 gene have been published so far. Recently we described the CD59-null allele c.146delA in a young child of heterozygous parents. Her plasma contained an alloantibody directed against the high-prevalence RBC antigen CD59. The antibody specificity was identified using soluble recombinant human CD59 protein, which blocked the reactivity of the patient's antibody and of monoclonal anti-CD59 but not of monoclonal anti-CD55. In addition, RBC alloantibodies such as anti-K, anti-C, anti-c, or anti-Fy(a) remained unaffected. Therefore, inhibition by recombinant CD59 is a useful diagnostic tool to detect alloantibodies in the presence of anti-CD59.This is the first demonstration of a human anti-CD59 alloantibody, which defines CD59 as an RBC blood group antigen. CD59 represents a candidate for a new blood group system.

„Lasst uns eine Oase sein, wo man begeistert ist vom Leben, von jedem Leben, auch von dem Leben, das sehr viel Muhe kostet.“ (Phil Bosmans; http://www.daszitat.de/)

Background Sepsis is a common cause of death in children. Early detection of bloodstream pathogens is crucial for the appropriate antibio­tic treatment. Blood cultures (BC) are the gold standard test used for detection. Recently, additional molecular detection methods of microbial DNA by multiplex PCR (SeptiFast, SF) have become available. Aim Our retrospective study was aimed to compare results of BC to those of SF regarding results and therapeutic relevance. Method We identified a total of 110 SF samples in 75 patients with suspected systemic infection by retrospective chart review. Each patient underwent SF and BC testing simultaneously. Results The initial analysis displayed no statistical significant difference in positive SF results compared to BC (p=0.19): in 26 of 110 samples (24%) microbial DNA was found. 19 BC (17%) showed microbial growth. 14 samples were positive in SF but negative in BC (13%). In patients who were pretreated with antibiotics (n=97) pathogens were identified in 24 samples by SF (25%) but only in 11 samples by BC (11%). Based on the clinical presentation and the spectrum of bacterial isolates 3 BC were considered contaminated. Considering this, SF yielded pathogens significantly more often than BC in the overall study population (p=0.04). SF results were available at least 31 h before BC results. Based on SF result antibiotic therapy was adjusted in 14 patients (13%). Conclusion Molecular detection of pathogens by SF was faster and more frequently positive than BC. We have therefore demonstrated that SF might be superior to BC in testing for bloodstream pathogens. Prospective multicentric studies are required to determine whether this hypothesis can be maintained.

The purpose of this investigation was to describe the use of linezolid in pediatric inpatient facilities. A retrospective multicenter survey including data from nine participating tertiary care pediatric inpatient facilities in Germany and Austria was undertaken. Data on 126 off-label linezolid treatment courses administered to 108 patients were documented. The survey comprises linezolid treatment in a broad spectrum of clinical indications to children of all age groups; the median age was 6.8 years (interquartile range 0.6-15.5 years; range 0.1-21.2 years; ten patients were older than 18 years of age but were treated in pediatric inpatient units). Of the 126 treatment courses, 27 (21%) were administered to preterm infants, 64 (51%) to pediatric oncology patients, and 5% to patients soon after liver transplantation. In 25%, the infection was related to a medical device. Linezolid iv treatment was started after intensive pre-treatment (up to 11 other antibiotics for a median duration of 14 days) and changed to enteral administration in only 4% of all iv courses. In 39 (53%) of 74 courses administered to children older than 1 week and younger than 12 years of age, the dose was not adjusted to age-related pharmacokinetic parameters. In only 17 courses (13%) was a pediatric infectious disease consultant involved in the clinical decision algorithm. Linezolid seemed to have contributed to a favorable outcome in 70% of all treatment courses in this survey. Although retrospective, this survey generates interesting data on the off-label use of linezolid and highlights several important clinical aspects in which the use of this rescue antibiotic in children might be improved.

There is only sparse data on the use of non-invasive ventilation (NIV) in acute respiratory failure (ARF) in infants and children. For this setting we investigated feasibility and efficacy of NIV and aimed to identify early predictors for treatment failure.Retrospective chart review was performed for all patients treated with NIV for ARF from 2003 to 2010 on an 8-bed pediatric intensive care unit of a tertiary university hospital.Seventy-four patients were treated with NIV. One patient did not tolerate mask ventilation and needed immediate invasive ventilation. Intubation rate of the remaining patients was 23% and mortality 15%. Institution of NIV led to significant improvement of both respiratory and heart rate in all patients within the first hour and to further stabilization within the next 8-10 hr. In patients with NIV success blood gases improved significantly 1-2 hr after starting NIV. Multivariate analysis identified low pH after 1-2 hr to be an individual risk factor for NIV failure. Other factors tested were age, underlying disease, acute respiratory insufficiency versus post-extubation failure (PEF), and 1-2 hr after starting NIV oxygen saturation, respiratory rate, PCO(2) , and FiO(2) . Patients with PEF tended to show better outcomes compared to those with acute respiratory insufficiency.NIV can be effective in infants and children with ARF. Low pH 1-2 hr after start of NIV is associated with NIV failure. It may therefore be useful in the decision to continue or stop mask ventilation.

HHV type 6 has been reported with enhanced pathogenicity in immunocompromised patients. Herein, we report about a two-yr-old girl who experienced primary HHV 6 infection after liver transplantation. She clinically presented with graft rejection and necrotic hepatitis as well as high fever, pneumonitis with respiratory failure and a rash. Therapy with cidofovir of 5 mg/kg per wk did not show improvement, so that a full pharmacokinetic profile of cidofovir was performed. It demonstrated enhanced body weight normalized clearance of cidofovir and cidofovir dosage was augmented to 12 mg/kg per wk to reach adequate drug exposure. With additional reduction of immunosuppression, the patient dramatically improved and liver function stabilized.

Newborns with inborn errors of metabolism often present with hyperammonaemic coma, requiring prompt diagnosis and specific medical therapy, nutritional support and efficient toxin removal. Little information regarding the efficacy and safety of continuous venovenous haemodialysis (CVVHD) as an option for extracorporal ammonia detoxification in children is available.Twenty-one patients with hyperammonaemia [19 neonates (mean age 4.1 +/- 2.4 days) and two children 1 and 7 years of age, respectively] were admitted to our hospital for dialysis between 1996 and 2008. Seventeen children (15 neonates), received CVVHD. Four neonates received continuous peritoneal dialysis (CPD). All started medical treatment with sodium benzoate, l-arginine hydrochloride and carnitine as well as protein-restricted parenteral diets with high caloric intake before dialysis.Plasma ammonia levels (range 464-7267 microg/dl before dialysis and 27-3317 microg/dl after dialysis) were significantly reduced by 50% within 4.7 +/- 2.5 h with CVVHD compared with 13.5 +/- 6.2 h with CPD (P0.0001). Plasma ammonia levels200 microg/dl critical range were achieved within 22.4 +/- 18.1 h in CVVHD patients compared with 35.0 +/- 24.1 h with CPD. Depending on the weight and blood pressure stability of the patients, mean blood flow velocities of 9.8 +/- 3.4 ml/kg/min and mean dialysate flow rates of 3925 +/- 2398 ml/min/1.73 m(2) were employed. Blood and dialysate flows significantly correlated with ammonia clearance and decay of ammonia in vivo. Because of the severe underlying disease, 18% of CVVHD patients died compared with 50% undergoing CPD. In total, 82% of CVVHD patients survived the first 6 months after dialysis. Among these, 43% were without sequelae, 43% developed moderate mental retardation, and two (14%) developed severe mental retardation.CVVHD effectively and quickly eliminates plasma ammonia. To optimize long-term mental outcome, rapid identification and appropriate treatment of the underlying disease as well as starting dialysis early are of enormous therapeutic value.

Ein 8 Monate altes komatoses Kind mit Fieber und zerebralen Krampfanfallen seit 1 Tag wurde in unser Zentrum uberwiesen. Die Liquoruntersuchung zeigte eine Pleozytose. Ein Erregernachweis gelang nicht. In der cMRT (kranielle Magnetresonanztomographie) zeigten sich progressive symmetrische nekrotische Lasionen in den Basalganglien und im Hirnstamm, die charakteristisch fur eine akute nekrotisierende Enzephalopathie sind. Trotz breiter antiinfektioser Behandlung, der sich eine antiinflammatorische Therapie anschloss, blieb eine klinische Besserung aus. Bei der Patientin und bei ihrem Vater wurde eine Mutation im RANBP2-Gen nachgewiesen, die eine Schlusselrolle bei autosomal-dominanten Formen einer ANE (akute nekrotisierende Enzephalopathie) spielt.

Instable upper cervical spine injuries (CSI) in very young children are rare and consecutively only few data on the treatment and operative approaches exist in the literature. Hence, we suggest an operative strategy in the case of a 15-month-old infant treated for an instable CSI at the level of C2/3 at our department. Detailed steps of the operation with special consideration to the challenging anatomy of the immature spine are presented. A toddler suffered a CSI without neurological deficits after a stair fall. Computer tomography (CT) and magnetic resonance imaging (MRI) of the cervical spine revealed an instable luxation fracture of C2/3. As repositioning in the halo vest immobilization failed, surgical fusion was indicated. Via a posterior midline approach, the lamina of C2 and C3 was conflated in a modified sublaminar wiring technique using non-resorbable sutures, sparing the ossification zones of the vertebral arches. Postoperative immobilization in a halo vest facilitated bony fusion of the laminae at C2/3 without lordotic displacement of the cervical spine. We consider the instable CSI of the immature cervical in the very young a challenging situation for every treating physician. The particular features of the growing spine require special attention to avoid damage to the growth centers of the vertebrae. To our knowledge, this is the first technical report giving detailed information of an operative approach to the severely injured immature cervical spine and postoperative management.

Congestive heart failure as a cause of acute liver failure is rarely documented with only a few cases. Although the pathophysiology is poorly understood, there is rising evidence, that low cardiac output with consecutive reduction in hepatic blood flow is a main causing factor, rather than hypotension. In the setting of acute liver failure due to congestive heart failure, clinical signs of the latter can be absent, which requires an appropriate diagnostic approach. As a reference center for acute liver failure and liver transplantation we recorded from May 2003 to December 2007 202 admissions with the primary diagnoses acute liver failure. 13/202 was due to congestive heart failure, which was associated with a mortality rate of 54%. Leading cause of death was the underlying heart failure. Asparagine transaminase (AST), bilirubin, and international normalized ratio (INR) did not differ significantly in surviving and deceased patients at admission. Despite both groups had signs of cardiogenic shock, the cardiac index (CI) was significantly higher in the survival group on admission as compared with non-survivors (2.1 L/min/m2 vs. 1.6 L/min/m2, p = 0.04). Central venous - and pulmonary wedge pressure did not differ significantly. Remarkable improvement of liver function was recorded in the group, who recovered from cardiogenic shock. In conclusion, patients with acute liver failure require an appropriate diagnostic approach. Congestive heart failure should always be considered as a possible cause of acute liver failure.

Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). However, we identified a 7 Mb interval containing a susceptibility locus (ANE1) in a family segregating recurrent ANE as an incompletely penetrant, autosomal-dominant trait. We now report that all affected individuals and obligate carriers in this family are heterozygous for a missense mutation (c.1880C-->T, p.Thr585Met) in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2). To determine whether this mutation is the susceptibility allele, we screened controls and other patients with ANE who are unrelated to the index family. Patients from 9 of 15 additional kindreds with familial or recurrent ANE had the identical mutation. It arose de novo in two families and independently in several other families. Two other patients with familial ANE had different RANBP2 missense mutations that altered conserved residues. None of the three RANBP2 missense mutations were found in 19 patients with isolated ANE or in unaffected controls. We conclude that missense mutations in RANBP2 are susceptibility alleles for familial and recurrent cases of ANE.

Summary. Non-invasive ventilation (NIV) has been shown to improve gas exchange and survival in patients with chronic neuromuscular disorders. Little is known about its influence on respiratory tractinfections(RTIs).Twenty-fourpatientswithregularuseofNIVand11patientswithoutNIVwith neuromuscular disorders answered a questionnaire concerning the use of NIV and assisted coughing techniques, the status of influenza and pneumococcus vaccination, and the frequency andseverityofRTIs.Additionally,weperformedaretrospectivechartreviewoftwelvepatientswho were ventilated over a period of at least 5 years. In the first year of NIV consultations of a general practitioner due to RTI decreased from 9.2 � 20.8 to 3.2 � 5.3 per year (P

In neuromuscular disorders, reduced peak cough flows (PCFs) are considered to increase the risk of respiratory complications such as pneumonia or chronic atelectasis. Different methods were described to improve PCF. However, these studies were primarily carried out in adults, and there is limited information regarding the use and efficacy of these methods in children with respiratory muscle weakness. The aim of this study was to investigate whether hyperinsufflation with an intermittent positive-pressure breathing (IPPB) device is effective in cough augmentation in pediatric patients. Spirometry (forced inspiratory vital capacity, FIVC; forced expiratory volume in 1 sec, FEV1), respiratory muscle pressures (peak inspiratory pressure, PIP; peak expiratory pressure, PEP), and PCF were measured in 29 schoolchildren with various neuromuscular disorders. IPPB-assisted hyperinsufflation was taught individually to increase lung volumes (maximum insufflation capacity, MIC) above FIVC. The impact of hyperinsufflation on peak cough flow was documented. In 28/29 patients, IPPB-assisted hyperinsufflation enhanced FIVC from 0.68 +/- 0.40 l to an MIC of 1.05 +/- 0.47 l (P0.001). Unassisted PCF was 119.0 +/- 57.7 l/min, and increased to 194.5 +/- 74.9 l/min (P0.001) in 27/29 patients. This effect was similar in young patients (ages 6-10 years) and older patients (aged10 years). Augmentation of lung volumes from FIVC to MIC correlated with an increase of PCF (R = 0.42, P0.05). IPPB-assisted hyperinsufflation improves PCF in pediatric neuromuscular disorders. The results suggest that this technique can be used to improve clearance of airway secretions and therefore reduce respiratory morbidity in children with NMD.

Purpose of review Published research on neuromuscular respiratory failure has increased rapidly over the past decade. Progress in the management of respiratory complications and preventive care have improved outcomes and quality of life for many. In particular, noninvasive positive pressure ventilation (NIPPV) is effective in resolving respiratory failure and has dramatically changed the management of these patients. In this review we discuss recent studies assessing the course of respiratory failure, with a focus on non-Duchenne muscular dystrophy; investigating the impact NIPPV has when it is introduced before diurnal respiratory failure develops; and evaluating a device to treat insufficient cough--the mechanical insufflator--exsufflator (MI-E). Recent findings Studies in children with congenital muscular dystrophies and spinal muscular atrophies detected a high prevalence of respiratory complications and confirmed that respiratory failure can be predicted by measurement of vital capacity. NIPPV is an established treatment that is effective in the long-term management of end-stage diurnal respiratory failure. Additionally, recent studies showed improvement in symptoms, quality of life and prevention of respiratory complications when it is introduced for nocturnal hypoventilation before the development of diurnal respiratory failure. However, data on the efficiency of the MI-E are limited, and studies comparing it with other techniques of assisted coughing are needed. Summary Recent findings stress the importance of regular respiratory assessment in neuromuscular disease, including sleep studies; strongly support the introduction of NIPPV for management of symptomatic nocturnal hypoventilation; and suggest that prospective randomized trials are required to verify the usefulness of the MI-E.

In this study, noninvasive ventilation (NIV) was prospectively applied to eight patients (35.8 +/- 11.4 years) with late-onset Pompe disease and respiratory failure apparent from severe restrictive lung disease, nocturnal hypoxemia (83 +/- 8%), and daytime hypercapnia (66.7 +/- 17.9 mm Hg). The impact of NIV on respiratory function was followed for 34 +/- 17 months. Despite further decrease of vital capacity and inspiratory muscle strength, NIV normalized oxygen saturation during sleep (96 +/- 1%), daytime carbon dioxide tensions (44.1 +/- 3.6 mm Hg), and symptoms.