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Background: Heart failure (HF) due to myocarditis might not respond in the same way to standard therapy as HF due to other aetiologies. The aim of this study was to investigate the value of endomyocardial biopsies (EMB) for clinical decision-making and its relation to the outcome of paediatric patients with myocarditis. Methods: Clinical and EMB data of children with myocarditis collected for the MYKKE-registry between 2013 and 2020 from 23 centres were analysed. EMB studies included histology, immunohistology, and molecular pathology. The occurrence of major adverse cardiac events (MACE) including mechanical circulatory support (MCS), heart transplantation, and/or death was defined as a combined endpoint. Results: Myocarditis was diagnosed in 209/260 patients: 64% healing/chronic lymphocytic myocarditis, 23% acute lymphocytic myocarditis (AM), 14% healed myocarditis, no giant cell myocarditis. The median age was 12.8 (1.4-15.9) years. Time from symptom-onset to EMB was 11.0 (4.0-29.0) days. Children with AM and high amounts of mononuclear cell infiltrates were significantly younger with signs of HF compared to those with healing/chronic or healed myocarditis. Myocardial viral DNA/RNA detection had no significant effect on outcome. The worst event-free survival was seen in patients with healing/chronic myocarditis (24%), followed by acute (31%) and healed myocarditis (58%, p=0.294). A weaning rate of 64% from MCS was found in AM. Conclusions: EMB provides important information on the type and stage of myocardial inflammation and supports further decision-making. Children with fulminant clinical presentation, high amounts of mononuclear cell infiltrates or healing/chronic inflammation and young age have the highest risk for MACE.

Background In critically ill children, detection of intra-abdominal hypertension (IAH > 10 mmHg) and abdominal compartment syndrome (ACS = IAH + organ dysfunction) is paramount and usually monitored through intra-vesical pressures (IVP) as current standard. IVP, however, carries important disadvantages, being time-consuming, discontinuous, with infection risk through observer-dependent manipulation, and ill-defined for catheter sizes. Therefore, we sought to validate air-capsule-based measurement of intra-gastric pressure (ACM-IGP). Methods We prospectively compared ACM-IGP with IVP both in vivo and in vitro (water column), according to Abdominal-Compartment-Society validation criteria. We controlled for patient age, admission diagnosis, gastric filling/propulsive medication, respiratory status, sedation levels and transurethral catheters, all influencing intra-abdominal pressure (IAP). Results In tertiary care PICU setting, finally, n = 97 children were enrolled (median age, 1.3 years [range 0 days–17 years], LOS-PICU 8.0 [1–332] days, PRISM-III-Score 13 [0–35]). In n = 2.770 measurements pairs, median IAP was 6.7 [0.9–23.0] mmHg, n = 38 (39%) children suffered from IAH > 10 mmHg, n = 4 from ACS. In vitro against water column, ACM-IGP correlated perfectly (r2 0.99, mean bias − 0.1 ± 0.5 mmHg, limits of agreement (LOA) − 1.1/+ 0.9, percentage error [PE] 12%) as compared with IVP (r2 0.98, bias + 0.7 ± 0.6 mmHg, LOA − 0.5/+ 1.9, PE 15%). With larger IVP catheters at higher pressure levels, IVP underestimated pressures against water column. In vivo, agreement between either technique was strong (r2 0.95, bias 0.3 ± 0.8 mmHg, LOA − 1.3/+ 1.9 mmHg, PE 23%). No impact of predefined control variables on measurement agreement was observed. Conclusions In a large PICU population with high IAH prevalence, ACM-IGP agreed favourably with IVP. More widespread usage of ACM-IGP may improve detection rates of ACS in critically ill children. Trial registration WHO-ICTRP-No. DRKS00006556 (German Clinical Trial Register). Registered 12th September 2014, URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00006556

Introduction: Liver transplantation (LT) in children has undergone significant changes over the last years. Especially the use of split and living donor transplants even for infants has led to new challenges in pre- and post-operative care. Systemic inflammatory response syndromes (SIRS, sepsis) as well-known complications after LT have not yet been systematically examined in the pediatric population. Methods: We analyzed clinical data of 39 pediatric liver transplant recipients regarding potential risk factors for post-transplant SIRS and sepsis. Secondly, the prognostic impact of SIRS and sepsis on post-transplant clinical course, patient and transplant-survival has been analyzed. Results: 64% of patients developed either SIRS (n = 16, 41%) or sepsis (n = 9, 23%) within 30 days after transplantation. No pre-transplant risk factors for increased susceptibility for SIRS or sepsis could be identified. Secondary closure of the abdomen (p = 0.045) and secondary biliary reconstruction (p = 0.043) were associated with a higher incidence of sepsis and were associated with significantly prolonged mechanical ventilation times in the presence of sepsis (p = 0.001). Patients with sepsis, but not SIRS, stayed significantly longer on PICU (p = 0.021) and suffered from higher mortality (n = 3 versus 0; p = 0.0006). All deaths within 30 days of transplantation were due to septic multiorgan failure. Neither early SIRS nor sepsis were associated with loss of transplant function. Conclusions: SIRS and sepsis are frequent events after pediatric liver transplantation. Sepsis increased length of PICU-stay and mortality significantly and prolonged duration of mechanical ventilation. Secondary biliary reconstruction and closure of the abdomen could be identified as potential risk factors for sepsis.

Additional file 1: Continuous Intra-Gastral Monitoring of Intra-Abdominal Pressure in Critically ill Children – A Validation Study.

Dose adjustment of unfractionated heparin (UFH) anticoagulation is an important factor to reduce hemorrhagic events. High doses of heparin can be monitored by Activated Clotting Time (ACT). Because of limited information about the monitoring of low-dose heparin we assessed monitoring by ACT, aPTT and anti-Xa. Blood samples from healthy volunteers (n = 54) were treated ex vivo with increasing UFH doses (0-0.4 IU/ml). Samples from ICU-patients (n = 60), were drawn during continuous UFH infusion. Simultaneous ACT measurements were performed using iSTAT and Hemochron. In UFH treated blood, iSTAT and Hemochron showed a significant change of ACT at ≥0.075 IU/ml and ≥0.1 IU/ml UFH, respectively. In ICU-patients no relationship between ACT and either UFH dose, aPTT and anti-Xa was observed. Hemochron was affected by antithrombin and platelet count. iSTAT was sensitive to CRP and hematocrit. A moderate correlation was identified between UFH dose and aPTT (R2 = 0.196) or anti-Xa (R2 = 0.162). In heparin-spiked blood, ACT is sensitive to heparin at levels of ≥0.1 IU/ml heparin. In ICU-patients, ACT did not correlate with UFH dose or other established methods. Both systems were differently influenced by certain parameters.

Background: During cardiopulmonary bypass (CPB) in children, anesthesia maintained by sevoflurane administered via the oxygenator is increasingly common. Anesthetic uptake and requirement may be influenced by the non-physiological conditions during hypothermic CPB. Narcotrend-processed EEG monitoring may, therefore, be useful to guide the administration of sevoflurane during this phase. Objective: The objective of this prospective, clinical, observational study was to assess the correlation between body temperature, Narcotrend Index (NI) and administered sevoflurane in children during CPB. Methods: Forty-four children aged 0 to 10 years undergoing hypothermic cardiac surgery were studied. On bypass, anesthesia was maintained with sevoflurane administered via the oxygenator of the heart-lung machine. Nasopharyngeal temperature, NI and minimum alveolar concentration (MAC) of sevoflurane were recorded in intervals of 10 minutes. Expiratory gas was sampled from the oxygenator’s sole expiratory port via a separate connecting line and the MAC was measured by the agent analyzer of the anesthesia machine. Results: Raw (r = 0.74) and corrected (r = 0.73) r-values show that narcosis depth (as indicated by NI) can primarily be explained by the interaction of MAC and temperature. The analysis of variance (without the interaction term) confirms the significant and independent association of both factors, MAC (pConclusion: Perfusionists and anesthetists should be aware of the results of processed electroencephalograph (EEG) monitoring during CPB. Sevoflurane requirements differ inter-individually; they may decrease during cooling and increase during rewarming. Therefore, it seems reasonable to include the results of processed EEG monitoring when administering sevoflurane during CPB in children, but further studies are necessary to confirm this thesis.

BACKGROUND Sevoflurane induction followed by intravenous anesthesia is a widely used technique to combine the benefits of an easier and less traumatic venipuncture after sevoflurane inhalation with a recovery with less agitation, nausea, and vomiting after total intravenous anesthesia (TIVA). Combination of two different anesthetics may lead to unwanted burst suppression in the electroencephalogram (EEG) during the transition phase. OBJECTIVE The objective of this prospective clinical observational study was to identify the optimal initial propofol bolus dose for a smooth transition from sevoflurane induction to TIVA using the EEG Narcotrend Index (NI). METHODS Fifty children aged 1-8 years scheduled for elective pediatric surgery were studied. After sevoflurane induction and establishing of an intravenous access, a propofol bolus dose range 0-5 mg·kg-1 was administered at the attending anesthetist's discretion to maintain a NI between 20 and 64, and sevoflurane was stopped. Anesthesia was continued as TIVA with a propofol infusion dose of 15 mg·kg-1 ·h-1 for the first 15 min, followed by stepwise reduction according to McFarlan's pediatric infusion regime, and remifentanil 0.25 μg·kg-1 ·min-1 . Endtidal concentration of sevoflurane, NI, and hemodynamic data were recorded during the whole study period using a standardized case report form. Propofol plasma concentrations were calculated using the paedfusor dataset and a TIVA simulation program. RESULTS Median endtidal concentration of sevoflurane at the time of administration of the propofol bolus was 5.1 [IQR 4.7-5.9] Vol%. The median propofol bolus dose was 1.2 [IQR 0.9-2.5] mg·kg-1 and median NI thereafter was 33 [IQR 23-40]. Nine children presented with a NI 13-20 and three children with burst suppression in the EEG (NI 0-12); all of them received an initial propofol bolus dose >2 mg·kg-1 . Regression equation demonstrated that NI 20-64 was achieved with a 95% probability when using a propofol bolus dose of 1 mg·kg-1 after sevoflurane induction. Decrease in mean arterial blood pressure correlated significantly with propofol bolus dose (P = 0.038). After 25 min of TIVA, children younger than 2 years had a higher NI (median difference 14.0, 95%CI: 6.0-20.0, P = 0.001), higher deviations from the expected Narcotend Index (median difference 4.1, 95%CI: 3.9-4.2, P < 0.001) and lower calculated propofol plasma concentrations (median difference 0.2 μg·ml-1 , 95% CI: 0.1-0.3 μg·ml-1 , P < 0.001) than older children. CONCLUSION After sevoflurane induction, a reduced propofol bolus dose of 1 mg·kg-1 followed by TIVA according to McFarlan's regime resulted in a NI within the recommended range in children aged 1-8 years. During the course of TIVA, children younger than 2 years displayed higher NI values and more pronounced interindividual variation. Processed EEG monitoring is recommended to find adequate individual age-dependent doses.

Transpulmonary ultrasound dilution (TPUD) method, a novel indicator dilution (ID) technique for cardiac output measurement, detects and quantifies shunts, both in children and adults. However, its accuracy and reproducibility in cardiac right-to-left-shunt (RLS) detection have not been investigated. In a prospective observational study, we assessed the validity of TPUD algorithm for RLS detection in children with congenital heart disease (CHD) and proven RLS in comparison with controls without shunts between February 2010 and October 2011. As TPUD algorithm was unknown, we tested ID curve morphology, appearance time (AT) and central blood volume index (CBVI) as diagnostic criteria. TPUD identified RLS correctly in all 16 RLS subjects [median age (range): 18 months (1 month–15 years 6 months)] and excluded RLS in all 26 controls [74 months (8 months to 17 years 4 months)]. AT was significantly shorter in RLS (P

Background Since early antimicrobial therapy is mandatory in septic patients, immediate diagnosis and distinction from non-infectious SIRS is essential but hampered by the similarity of symptoms between both entities. We aimed to develop a diagnostic model for differentiation of sepsis and non-infectious SIRS in critically ill children based on routinely available parameters (baseline characteristics, clinical/laboratory parameters, technical/medical support). Methods This is a secondary analysis of a randomized controlled trial conducted at a German tertiary-care pediatric intensive care unit (PICU). Two hundred thirty-eight cases of non-infectious SIRS and 58 cases of sepsis (as defined by IPSCC criteria) were included. We applied a Random Forest approach to identify the best set of predictors out of 44 variables measured at the day of onset of the disease. The developed diagnostic model was validated in a temporal split-sample approach. Results A model including four clinical (length of PICU stay until onset of non-infectious SIRS/sepsis, central line, core temperature, number of non-infectious SIRS/sepsis episodes prior to diagnosis) and four laboratory parameters (interleukin-6, platelet count, procalcitonin, CRP) was identified in the training dataset. Validation in the test dataset revealed an AUC of 0.78 (95% CI: 0.70–0.87). Our model was superior to previously proposed biomarkers such as CRP, interleukin-6, procalcitonin or a combination of CRP and procalcitonin (maximum AUC = 0.63; 95% CI: 0.52–0.74). When aiming at a complete identification of sepsis cases (100%; 95% CI: 87–100%), 28% (95% CI: 20–38%) of non-infectious SIRS cases were assorted correctly. Conclusions Our approach allows early recognition of sepsis with an accuracy superior to previously described biomarkers, and could potentially reduce antibiotic use by 30% in non-infectious SIRS cases. External validation studies are necessary to confirm the generalizability of our approach across populations and treatment practices. Trial registration ClinicalTrials.gov number: NCT00209768; registration date: September 21, 2005. Electronic supplementary material The online version of this article (10.1186/s12887-018-1082-2) contains supplementary material, which is available to authorized users.

BACKGROUND Systemic inflammatory response syndrome (SIRS) is frequent after cardiac surgery, but data on its incidence and perioperative risk factors are scarce for children with congenital heart disease. METHODS SIRS incidence within 72 hours following cardiac surgery was evaluated in a secondary analysis of children enrolled to a treatment-free control group of a randomized controlled trial. Intraoperative parameters were investigated for their association with SIRS using multivariable fractional polynomial logistic regression models. Effects of SIRS on various organ functions and length of stay were evaluated using time-varying Cox regression models. RESULTS In 116 children after cardiac surgery (median age [range]: 7.4 month [1 day-16.2 years]) SIRS occurred in n = 39/102 with and n = 1/14 without cardiopulmonary bypass (CPB). Duration of CPB (hazard ratio [HR]: 2.28 per hour; 95% confidence interval [CI] 1.17; 4.42) and amount of fresh frozen plasma (HR: 1.23 per 10 mL/kg; 95%CI 1.06; 1.42) were identified as predictors for SIRS; neonates seemed to be less susceptible for SIRS development (HR: 0.86; 95%CI 0.79; 0.95). SIRS was associated with organ dysfunction (HR: 2.69; 95%CI 1.41; 5.12) and extended stay in the pediatric intensive care unit (PICU) (median: 168 vs. 96 hours; p = 0.007). CONCLUSIONS SIRS is a frequent complication after pediatric congenital heart surgery; it affects nearly one third of children and prolongs PICU stay significantly. Duration of CPB and amount of fresh frozen plasma were identified as important risk factors. Neonates seem to be less susceptible to SIRS development.

Arterial thrombosis in neonates and children is a rare event and is often associated with external risk factors such as asphyxia or sepsis. We report our experiences with two neonates with spontaneous aortic arch thrombosis mimicking aortic coarctation. Despite single case reports until now, no data exist for the underlying thrombophilic risk factors and prognosis of this rare event. Both patients were carriers of a heterozygous factor V Leiden mutation, which has been reported once before as a risk factor for aortic arch thrombosis. One of our patients was operated upon successfully and is alive. The second patient suffered a large infarction of the right medial cerebral artery and had a thrombotic occlusion of the inferior caval vein. The patient obtained palliative care and died at the age of 6 days. In the literature, we identified 19 patients with neonatal aortic arch thrombosis. Of the 19 patients, 11 (58%) died. Including the two reported patients, the mortality rate of patients with multiple thromboses was 80% (8/10) compared with 18% (2/11) for patients with isolated aortic arch thrombosis; this difference reached statistical significance (p = 0.009). The analysis of thrombophilic disorders revealed that factor V Leiden mutation and protein C deficiency seem to be the most common risk factors for aortic arch thrombosis.Conclusion:Neonatal aortic arch thrombosis is a very rare but life-threatening event, with a high rate of mortality, especially if additional thrombotic complications are present. Factor V Leiden mutation seems to be one important risk factor in the pathogenesis of this fatal disease.

Summary Background In pediatric anesthesia, preoperative fasting guidelines are still often exceeded. Objective The objective of this noninterventional clinical observational cohort study was to evaluate the effect of an optimized preoperative fasting management (OPT) on glucose concentration, ketone bodies, acid–base balance, and change in mean arterial blood pressure (MAP) during induction of anesthesia in children. Methods Children aged 0–36 months scheduled for elective surgery with OPT (n = 50) were compared with peers studied before optimizing preoperative fasting time (OLD) (n = 50) who were matched for weight, age, and height. Results In children with OPT (n = 50), mean fasting time (6.0 ± 1.9 h vs 8.5 ± 3.5 h, P 2 h 8% vs 70%), ketone bodies (0.2 ± 0.2 mmol·l−1 vs 0.6 ± 0.6 mmol·l−1, P < 0.001), and incidence of hypotension (MAP

Purpose Particulate contamination due to infusion therapy carries a potential health risk for intensive care patients. Methods This single-centre, prospective, randomized controlled trial assessed the effects of filtration of intravenous fluids on the reduction of complications in critically ill children admitted to a pediatric intensive care unit (PICU). A total of 807 subjects were randomly assigned to either a control (n = 406) or filter group (n = 401), with the latter receiving in-line filtration. The primary endpoint was reduction in the rate of overall complications, which included the occurrence of systemic inflammatory response syndrome (SIRS), sepsis, organ failure (circulation, lung, liver, kidney) and thrombosis. Secondary objectives were a reduction in the length of stay on the PICU and overall hospital stay. Duration of mechanical ventilation and mortality were also analyzed. Findings Analysis demonstrated a significant reduction in the overall complication rate (n = 166 [40.9 %] vs. n = 124 [30.9 %]; P = 0.003) for the filter group. In particular, the incidence of SIRS was significantly lower (n = 123 [30.3 %] vs. n = 90 [22.4 %]; P = 0.01). Moreover the length of stay on PICU (3.89 [95 % confidence interval 2.97−4.82] vs. 2.98 [2.33−3.64]; P = 0.025) and duration of mechanical ventilation (14.0 [5.6−22.4] vs. 11.0 [7.1−14.9] h; P = 0.028) were significantly reduced. Conclusion In-line filtration is able to avert severe complications in critically ill patients. The overall complication rate during the PICU stay among the filter group was significantly reduced. In-line filtration was effective in reducing the occurrence of SIRS. We therefore conclude that in-line filtration improves the safety of intensive care therapy and represents a preventive strategy that results in a significant reduction of the length of stay in the PICU and duration of mechanical ventilation (ClinicalTrials.gov number: NCT00209768). Electronic supplementary material The online version of this article (doi:10.1007/s00134-012-2539-7) contains supplementary material, which is available to authorized users.

Especially in critically ill children with cardiac diseases, fluid management and monitoring of cardiovascular function are essential. Ultrasound dilution technique (UDT) was recently introduced to measure cardiac output (CO) and volumetric parameters, such as intrathoracic and end-diastolic blood volume. We compared UDT with the well-established transpulmonary thermodilution (TPTD) method (PiCCO) for determining CO measurements and derived volumes in a juvenile animal model. Experiments were performed in 18 ventilated, anesthetized piglets during normovolemia and after isovolemic hemodilution. At baseline and 20 min after each step of isovolemic hemodilution, 3 independent measurements of CO and volumetric parameters were conducted with TPTD and UDT, consecutively, under hemodynamically stable conditions. We observed comparable results for CO measurements with both methods (mean 1.98 l/min; range 1.12-2.87) with a percentage error of 17.3% (r = 0.92, mean bias = 0.28 l/min). Global end-diastolic volume (GEDV) and intrathoracic blood volume (ITBV) by TPTD were almost two times greater than analogous volumes [central blood volume (CBV); total end-diastolic volume (TEDV)] quantified by UDT (CBV = 0.58 × ITBV + 27.1 ml; TEDV = 0.48 × GEDV + 23.1 ml). CO measurements by UDT were found to be equivalent and hence interchangeable with TPTD. Discrepancies in volumetric parameters could either be due to the underlying algorithm or different types of indicators (diffusible vs. nondiffusible). Compared with the anatomically defined heart volume, TPTD seems to overestimate end-diastolic volumes. Future studies will be necessary to assign these results to critically ill children and to validate volumetric parameters with reference techniques.

Summary Objectives: Artificial colloids, frequently used to prevent hemorrhagic shock in children, impair blood coagulation. To determine the impact of acute isovolaemic hemodilution with artificial colloids on clot formation, we conducted an experimental study in a pediatric animal model. Methods: Fifteen piglets underwent hemorrhage by withdrawing 40 ml·kg−1 of blood volume in steps of 10 ml·kg−1 each within 1 hour. After each withdrawal, the blood loss was randomly compensated by administering 4% gelatin (GEL) or hydroxylethyl starch 130/0.42 (HES) in a ratio of 1 : 1, or isotonic crystalloid solution (ICS) in a ratio of 1 : 4 for isovolaemic hemodilution. Quality of clot formation and platelet function was measured using Thrombelastometry (ROTEM®) and Multiple electrode impedance aggregometry (Multiplate®) after 10, 20, and 40 ml·kg−1 blood replacement. Results: Moderate hemodilution (10–20 ml·kg−1 blood replacement) caused no significant differences among groups (e.g. INTEM®-MCF after 20 ml·kg−1 blood replacement (ICS vs GEL vs HES, P > 0.05). Profound hemodilution with 40 ml·kg−1 blood replacement showed a significant difference between ICS and both colloids (P

Acute respiratory distress syndrome, with the need for invasive mechanical ventilation (MV) remains a major cause of neonatal mortality and morbidity. Although venovenous extracorporeal lung support (VV-ECLS) has become a standard of care procedure in neonatal patients with acute pulmonary failure there are no reports regarding the use of a double-lumen cannula for extracorporeal minimal invasive lung support via the umbilical vein. A neonatal lamb model was used (n = 3). Umbilical vein was cannulated with a double-lumen catheter allowing venovenous extracorporeal gas exchange. Cannula was positioned with its tip in the right atrium. VV-ECLS was started and ventilation was stopped. Providing oxygenation and CO2 removal solely through VV-ECLS hemodynamics, blood gases were measured. Total VV-ECLS without MV was applied to all three neonatal lambs. Time on venovenous ECLS was 60, 120 and 120 min. Initial pCO2 was 60, 56 and 65 mmHg compared to 31, 32 and 32 mmHg at the end of VV-ECLS. Initial pO2 was 30, 27 and 26 mmHg compared to 22, 19 and 23 mmHg. Initial lactate was 5, 10 and 3.7 mmol/l compared to 13.3, 12.6 and 11.3 mmol/l at the end of VV-ECLS. MAP at baseline was 51, 52 and 65 mmHg compared to 36, 38 and 41 mmHg at the end of VV-ECLS. In all three lambs inotropes were admitted to maintain MAD >35 mmHg. Even without mechanical ventilation we were able to sufficiently remove pCO2 with our new minimal invasive VV-ECLS using a double-lumen catheter via the umbilical vein, supporting the idea of a lung protective strategy in neonatal acute respiratory failure. pO2 was measured 22, 19 and 23 mmHg, respectively, at the end of VV-ECLS, at least partially caused by recirculation phenomenon, which could possibly be improved by different cannula design. Inotropic support was necessary during VV-ECLS to achieve targeted MAD > 35 mmHg. While technically feasible, this new approach might allow further research in the field of extracorporeal lung support and therefore will follow the concept of a lung protective strategy in acute neonatal respiratory failure.

Albuminuria in diabetic nephropathy is due to endothelial dysfunction, a loss of negative charges in the basement membrane, and changes a of the slit-membrane diaphragm composition. We have recently shown that protein kinase C alpha (PKCalpha)-deficient mice are protected against the development of albuminuria under diabetic conditions. We here tested the hypothesis that PKCalpha mediates the hyperglycemia-induced downregulation of the slit-diaphragm protein nephrin. After 8 weeks of streptozotocin (STZ)-induced hyperglycemia the expression of glomerular nephrin was significantly reduced. In contrast, other slit-diaphragm proteins such as podocin and CD2AP were unaltered in diabetic state. In PKCalpha-/- mice, hyperglycemia-induced downregulation of nephrin was prevented. Podocin and CD2AP remained unchanged. In addition, the nephrin messenger RNA expression was also reduced in hyperglycemic wild-type mice but remained unaltered in PKCalpha-/- mice. We postulate that the underlying mechanism of the hyperglycemia-induced regulation of various proteins of the glomerular filtration barrier is a PKCalpha-dependent regulation of the Wilms' Tumor Suppressor (WT1) which previously has been shown to act as a direct transcription factor on the nephrin promoter. Our data suggest that PKCalpha activation may be an important intracellular signaling pathway in the regulation of nephrin expression and glomerular albumin permeability in the diabetic state.

Cardiac surgery with cardiopulmonary bypass (CPB) frequently leads to systemic inflammatory response syndrome (SIRS) with concomitant organ malfunction. Infused particles may exacerbate inflammatory syndromes since they activate the coagulation cascade and alter inflammatory response or microvascular perfusion. In a randomized, controlled, prospective trial, we have previously shown that particle-retentive in-line filtration prevented major complications in critically ill children. Now, we investigated the effect of in-line filtration on major complications in the subgroup of cardiac patients. Children admitted to tertiary pediatric intensive care unit were randomized to either control or filter group obtaining in-line filtration throughout complete infusion therapy. Risk differences and 95 % confidence intervals (CI) of several complications such as SIRS, sepsis, mortality, various organ failure and dysfunction were compared between both groups using the Wald method. 305 children (n = 150 control, n = 155 filter group) with cardiac diseases were finally analyzed. The majority was admitted after cardiac surgery with CPB. Risk of SIRS (−11.3 %; 95 % CI −21.8 to −0.5 %), renal (−10.0 %; 95 % CI −17.0 to −3.0 %) and hematologic (−8.1 %; 95 % CI −14.2 to −0.2 %) dysfunction were significantly decreased within the filter group. No risk differences were demonstrated for occurrence of sepsis, any other organ failure or dysfunctions between both groups. Infused particles might aggravate a systemic hypercoagulability and inflammation with subsequent organ malfunction in pediatric cardiac intensive care patients. Particle-retentive in-line filtration might be effective in preventing SIRS and maintaining renal and hematologic function. In-line filtration offers a novel therapeutic option to decrease morbidity in cardiac intensive care. Electronic supplementary material The online version of this article (doi:10.1007/s00246-015-1157-x) contains supplementary material, which is available to authorized users.

In critically ill children, monitoring of cardiac output (CO) is essential to guide haemodynamic management and facilitate cardiovascular therapy. The ultrasound dilution technique (UDT), a novel minimally invasive indicator method, was recently introduced to determine CO. We validated UDT against the 'gold standard' reference technique, the direct Fick principle, in infants and children.Twenty-six children (median age: 6 yr 2 months; median weight: 19.2 kg) underwent diagnostic heart catheterization. In each child, CO was determined by the Fick principle using direct measurement of oxygen consumption and invasive oximetry. Consecutively, haemodynamically stable conditions provided; three independent measurements of CO were conducted with UDT. CO values were compared using bias and limits of agreement calculated using the Bland-Altman approach and linear regression analysis for the complete study group and for a subgroup with body weight20 kg (n=14).The mean (standard deviation) CO values were 3.76 (1.73) litre min(-1) (range 1.38-6.97) for the direct Fick principle and 3.49 (1.72) litre min(-1) (range 1.31-7.00) for UDT. An excellent correlation (r=0.96) was found between both methods (P0.0001). The Bland-Altman analysis demonstrated good clinical agreement with a mean bias of 0.26 litre min(-1), limits of agreement of -0.66 and 1.19 litre min(-1), and percentage error of 25.9%. Comparable results were obtained for patients20 kg (mean bias=0.19 litre min(-1), percentage error=25.5%).CO measurements by UDT agree favourably with Fick-derived CO data and both techniques were found to be equivalent and interchangeable. UDT represents a valid and applicable method for repetitive CO determinations in infants and children.

The primary purpose of this research was to subject Conlon and Garland's (1993; Garland & Conlon, 1998) project completion hypothesis to a stronger test than it has faced in the past. We conducted an experiment in which we manipulated the degree of completion, sunk-cost amount, and anticipated sales price for a hypothetical real estate development project. The sales price information allowed participants to calculate the economic value of the project. Participants were also held "accountable" in the sense that they had to explain the reasoning behind their decisions to the experimenter. Together, the sales price information and accountability stipulation created an inducement to engage in an economically rational decision process. In spite of this inducement, participants were unduly affected by the project's closeness to completion. In fact, when the project was close to being finished, they often recommended completing the project even when it was economically unwise to do so. While the effects of the project completion manipulation were surprisingly strong, the sunk-cost manipulation had virtually no effect. Implications of these results and directions for future research are discussed. Copyright 2000 Academic Press.

Objectives: In pediatric patients with cardiogenic shock (CS)/or acute cardiac failure (ACF) extracorporeal membrane oxygenation (ECMO) is often used as a bridging procedure to recovery or further implantation of a ventricular assist device (VAD). Although ECMO has been established as a routine procedure in pediatric tertiary care centers, the clinical path guiding these patients to fully recovery or further VAD implantation is one of the most challenging for pediatric intensivists. Methods: The authors describe the use of venoarterial ECMO (VA-ECMO) as a treatment strategy for ACF in spontaneously breathing and conscious pediatric patients. It presents their experiences with the first five children treated using this new concept. The mean age of the patients was 86 months (range 0 – 226 mo). Mean amount of time on ECMO was 35 days (range 7 – 94 d). Results: Three patients fully recovered with their cardiac function while being treated on “Awake-VA-ECMO,” one was bridged to LVAD and one was successfully bridged to transplantation. Four of the five patients are alive without any recurrences. One patient died before a further heart transplantation while being on intracardiac rotation pump. Although reintubation was necessary in three of our five patients (due to interventional heart catheter) total time breathing spontaneously and being conscious while on ECMO was > 70%. Conclusion: The authors conclude that the concept of “Awake VA-ECMO” is feasible and safe for the treatment of ACF and can be used as a “bridging therapy” to recovery or further VAD implantation in pediatric patients.

Background Infused particles induce thrombogenesis, impair microcirculation and modulate immune response. We have previously shown in critically ill children, that particle-retentive in-line filtration reduced the overall complication rate of severe events, length of stay and duration of mechanical ventilation. We now evaluated the influence of in-line filtration on different organ function and thereby elucidated the potential underlying pathophysiological effects of particle infusion. Methods In this single-centre, prospective, randomized controlled trial 807 critically ill children were assigned to either control (n = 406) or filter group (n = 401), the latter receiving in-line filtration for complete infusion therapy. Both groups were compared regarding the differences of incidence rates and its 95% confidence interval (CI) of different organ dysfunction as defined by the International Pediatric Sepsis Consensus Conference 2005. Results The incidence rates of respiratory (−5.06%; 95% CI, −9.52 to −0.59%), renal (−3.87%; 95% CI, −7.58 to −0.15%) and hematologic (−3.89%; 95% CI, −7.26 to −0.51%) dysfunction were decreased in the filter group. No difference was demonstrated for the occurrence rates of cardiovascular, hepatic, or neurologic dysfunction between both groups. Conclusions In-line filtration has beneficial effects on the preservation of hematologic, renal and respiratory function in critically ill patients. The presented clinical data further support our hypothesis regarding potential harmful effects of particles. In critically ill patients infused particles may lead to further deterioration of the microcirculation, induce a systemic hypercoagulability and inflammation with consecutive negative effects on organ function. Trial registration ClinicalTrials.gov number; NCT00209768

In patients awaiting LuTx, MV and ECMO are often the last ways to create a bridge to LuTx. Both interventions are associated with a poor posttransplant outcome and survival rate. To improve the results of these patients, new "bridging-strategies" are necessary. Recent reports demonstrate promising results for the concept of "awake ECMO" in adult patients. To date, no data on this approach in pediatric patients have been available. We therefore describe the use of VV-ECMO as a treatment strategy for RF in awake pediatric patients. It presents our experiences with the first three children treated using this new concept. Mean amount of time on ECMO was 44 days (range, 11.5-109 days). Two patients were successfully bridged to their LuTx. Both are still alive without any recurrences (24 and three months following LuTx). One patient died before a further LuTx after 109 days on ECMO due to adenoviral infection. Although reintubation was necessary in two patients, and total time being awake while on ECMO was

Expectancy-valence (EV) theory has often been used as a model for understanding goal setting. The authors attempt to further distinguish within-person from across-persons uses of EV theory concepts in the goal-setting literature and present a within-person empirical test. The key element of the approach examined here is that an assigned goal's initial effect is on the patterns formed across levels of potential task performance by a person's judgments of expectancy, valence, and motivational force (i.e., performance-expectancy, performance-valence, and performance-motivational force functions). By examining these functions, the authors make available more detailed information regarding the motivational effects of assigned goals

Purpose To examine the physical properties and chemical composition of particles captured by in-line microfilters in critically ill children, and to investigate the inflammatory and cytotoxic effects of particles on endothelial cells (HUVEC) and macrophages in vitro. Methods Prospective, observational study of microfilters following their use in the pediatric intensive care unit. In vitro model utilizing cytokine assays to investigate the effects of particles on human endothelial cells and murine macrophages. Results Twenty filter membranes from nine patients and five controls were examined by electron microscopy (EM) and energy dispersion spectroscopy (EDX). The average number of particles found on the surface of the used membranes was 550 cm2. EDX analysis confirmed silicon as a major particle constituent. Half of the filter membranes showed conglomerates containing an uncountable number of smaller particles. In vitro, glass particles were used to mimic the high silicon content particles. HUVEC and murine macrophages were exposed to different contents of particles, and cytokine levels were assayed to assess their immune response. Levels of interleukin-1beta, interleukin-6, interleukin-8, and tumor necrosis factor alpha were suppressed. Conclusions Particle contamination of infusion solutions exists despite a stringent infusion regiment. The number and composition of particles depends on the complexity of the applied admixtures. Beyond possible physical effects, the suppression of macrophage and endothelial cell cytokine secretion in vitro suggests that microparticle infusion in vivo may have immune-modulating effects. Further clinical trials are necessary to determine whether particle retention by in-line filtration has an influence on the outcome of intensive care patients. Electronic supplementary material The online version of this article (doi:10.1007/s00134-010-1775-y) contains supplementary material, which is available to authorized users.

The construct validity of valence measures based on anticipated satisfaction, attractiveness, and importance was examined in three studies. Results indicated that only the satisfaction measure consistently fit the validity criteria. The importance and, to a lesser extent, the attractiveness measures appear to be less appropriate as assessments of valence, perhaps due to the influence of expectancy on those judgments.

Three-dimensional (3D) imaging, a recent technical innovation in laparoscopic surgery, has been postulated to enhance depth perception and facilitate operations. However, it has never been evaluated in conditions where the focus is close to the optical system. Thus, it is unclear whether 3D cameras can improve laparoscopic surgical performance in neonates and infants. We tested 3D versus two-dimensional (2D) vision during laparoscopic surgery in rabbits, mimicking the size of a neonatal patient. Cadaver New Zealand white rabbits (mean weight 2,755 g) were operated by two surgeons experienced in 2D laparoscopic surgery and two surgical residents (with basic skills in 2D laparoscopy). All surgeons had never performed 3D laparoscopic surgery. Animals underwent six operations: Nissen fundoplication, small bowel anastomosis, and closure of a diaphragmatic defect using either 2D or 3D. Primary endpoint was cumulative operating time and operating time of each operation. Secondary endpoints included the hemodynamic response and psychomental stress level of the surgeons. Finally, subjective data on depth perception were assessed by questionnaires. Cumulative operating time of all three types of operations was significantly shorter with 3D laparoscopy in experts (3D: 23.01 ± 5.65 min vs 2D: 29.51 ± 7.51 min, p

Background Some paediatricians seem to take Intra-abdominal Hypertension (IAH) and Abdominal Compartment Syndrome (ACS) for epiphenomenons of disorders which exclusively accompany illnesses that are treated only in specialised centres. Since the majority of ACS results from inflammation and capillary leakage, also disorders can lead to IAH/ACS, which superficially seem to be harmless paediatric entities. Thereby, the majority of IAH/ACS might be overseen and not be treated adequately. Aims The present study looks at the recognition and knowledge of IAH/ACS among paediatric intensivists of different sizes of ICU´s and number of cases per year. Methods In June 2010, a questionnaire was mailed to the heads of ICU´s of 265 German, Austrian and Swiss paediatric hospitals. Results Response rate was 59%. The more specialised departments are, the more often IAH/ACS is diagnosed. Predominantly, small ICU (s-ICU; 700 pat./a) at least diagnosed one case of IAH; >40% at least one ACS (s-ICU: 16% and 13%). Prevalence of IAH/ACS at intermediate ICU´s (i-ICU; 350–700 pat./a) and l-ICU´s was stated to be more than twice as high. Stated underlying risk factors only marginally varied between s-ICU´s, i-ICU´s and l-ICU´s. Regular IAP-measurements are performed by 13% of s-ICU´s in contrast to 20% and 35% of larger ones. Main reason is the lack of equipment. At least one decompressive laparotomy was performed by 41% of l-ICU´s in contrast to 7% of s-ICU´s. Conclusions Definitions and guidelines regarding diagnosis and management of IAH/ACS are not applied uniformly. This variability could express an ever present lack of awareness and solid prospective data.

Fulminant arterial thrombosis leading to amputation of forearm in a 16-year-old girl – Disastrous combination of diabetes mellitus, factor V Leiden mutation and oral contraception

Objectives: Sepsis, systemic inflammatory response syndrome (SIRS) or organ failure often complicate the clinical course on intensive care units. Particulate contamination of infusion solution may contribute to clinical deterioration of these patients. Particles have been shown to induce thrombogenesis, deterioration of microcirculation and modulation of immunoresponse. In-line filtration almost completely prevents particulate infusion. We assessed the effect of in-line filtration on reduction of major complications in critically ill children (Clinical Trials.gov ID NCT 00209768). Patients and Methods: In a randomised, prospective trial children admitted to interdisciplinary PICU of tertiary university hospital were assigned to either control or interventional group, the latter receiving in-line filtration (infusion filter Pall ELD96LLCE/NOE96E, Braun Intrapur Lipid/ Intrapur Neonat Lipid) throughout infusion therapy. Prior to this study, infusion regiment was optimised to prevent precipitation and incompatibilities of solutions and drugs. Primary objectives included a reduction in incidence of sepsis, thrombosis, systemic inflammatory response syndrome (SIRS), organ failure (liver, lung, kidney, circulation) and mortality. Results: 807 children (343 female, 464 male) with heterogeneous background of underlying diagnoses and Gaussian distribution to either control or in-line filtration group were included. According to study criteria a significant reduction in incidence of SIRS for interventional group (95% CI, 145 versus 200 patients, P< 0.001) was evident. No differences were demonstrated for occurrence of sepsis, thrombosis, organ failure (liver, lung, kidney, circulation) or mortality between both groups. Conclusion: SIRS often complicates treatment in intensive care medicine. Inline-filtration is most effective reducing the incidence of SIRS and offers a novel therapeutic option.

Objectives: Recently introduced paediatric cardiac output monitor (COstatus, Transonic Systems Inc. Ithaca, NY) also measures blood volumes and detects cardiac shunts. The current study assessed its ability to identify left-to-right shunts and measured associated blood volumes during cardiac catheterisation in children. Patients and Methods: Cardiac catheterisation was performed in 20 children and adolescents (3.5 kg- 102 kg). Shunts and pulmonary (Qp) versus systemic blood flow (Qs) ratio were determined by routine oximetry. Subsequently three measurements with COstatus were performed while the monitor software announces the recognition of left-to-right shunt. Dilutions curves were recorded and validated. Results: Left-to-right shunts due to various types of cardiac defects were detected in 6 patients by oximetry. Applying COstatus diagnostic accuracy was very convincing, with a sensitivity of 100% (6/6) and a specificity of 92.8% (13/14). The threshold for determination a left-to-right shunt was an Qp/Qs ratio of 1.3. In one case of a hypertrophic obstructive cardiomyopathy the distortion of the dilution curve led to a false positive result. A significant difference was detected for means of central blood volume index between patients with left-to-right shunts and controls with no cardiac shunts (95% CI; 24.9 versus 18.2 ml/kg; P< 0.05). Conclusion: Novel ultrasound dilution technique identifies left-to-right shunts in children with a high sensitivity and detects even small shunts with an Qp/Qs ratio of 1.3. Raised central blood volume index corresponds well with clinical features in patients with left-to-right shunts and may become helpful a diagnostic parameter in the future.

Sepsis, systemic inflammatory response syndrome (SIRS) or organ failure often complicate the clinical course on an ICU. Particulate contamination of the infusion solution may contribute to the clinical deterioration of these patients. Particles have been shown to induce thrombogenesis, deterioration of microcirculation and modulation of immunoresponse. The use of inline filtration with microfilters almost completely prevents particulate infusion. We assessed the effect of inline filtration on the reduction of major complications in critically ill children (Clinical Trials.gov ID {"type":"clinical-trial","attrs":{"text":"NCT 00209768","term_id":"NCT00209768"}}NCT 00209768).

Particulate contamination of infusion solution implies a potential health risk for intensive care patients with a background of debilitation and impaired host responses. Particles have been shown to induce thrombogenesis, deterioration of microcirculation and modulation of immunoresponse. We assessed the effect of inline filtration on the reduction of major complications in critically ill children (Clinical Trials.gov ID {"type":"clinical-trial","attrs":{"text":"NCT 00209768","term_id":"NCT00209768"}}NCT 00209768).

As a part of a clinical trial to evaluate the potential benefits of inline filtration on reducing major complications of paediatric ICU (PICU) patients (Clinical Trials.gov ID {"type":"clinical-trial","attrs":{"text":"NCT 00209768","term_id":"NCT00209768"}}NCT 00209768), we examined the physical aspects and chemical composition of particles captured by inline microfilters. Additionally we investigated the inflammatory and cytotoxic effects of particles on human endothelial cells and macrophages in vitro.