Awareness and diagnosis for intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) in neonatal (NICU) and pediatric intensive care units (PICU) - a follow-up multicenter survey.

BACKGROUND: Constantly elevated intra-abdominal pressure (IAH) can lead to abdominal compartment syndrome (ACS), which is associated with organ dysfunction and even multiorgan failure. Our 2010 survey revealed an inconsistent acceptance of definitions and guidelines among pediatric intensivists regarding the diagnosis and treatment of IAH and ACS in Germany. This is the first survey to assess the impact of the updated guidelines on neonatal/pediatric intensive care units (NICU/PICU) in German-speaking countries after WSACS published those in 2013. METHODS: We conducted a follow-up survey and sent 473 questionnaires to all 328 German-speaking pediatric hospitals. We compared our findings regarding awareness, diagnostics and therapy of IAH and ACS with the results of our 2010 survey. RESULTS: The response rate was 48% (n = 156). The majority of respondents was from Germany (86%) and working in PICUs with mostly neonatal patients (53%). The number of participants who stated that IAH and ACS play a role in their clinical practice rose from 44% in 2010 to 56% in 2016. Similar to the 2010 investigations, only a few neonatal/pediatric intensivists knew the correct WSACS definition of an IAH (4% vs 6%). Different from the previous study, the number of participants who correctly defined an ACS increased from 18 to 58% (p < 0,001). The number of respondents measuring intra-abdominal pressure (IAP) increased from 20 to 43% (p < 0,001). Decompressive laparotomies (DLs) were performed more frequently than in 2010 (36% vs. 19%, p < 0,001), and the reported survival rate was higher when a DL was used (85% ± 17% vs. 40 ± 34%). CONCLUSIONS: Our follow-up survey of neonatal/pediatric intensivists showed an improvement in the awareness and knowledge of valid definitions of ACS. Moreover, there has been an increase in the number of physicians measuring IAP in patients. However, a significant number has still never diagnosed IAH/ACS, and more than half of the respondents have never measured IAP. This reinforces the suspicion that IAH and ACS are only slowly coming into the focus of neonatal/pediatric intensivists in German-speaking pediatric hospitals. The goal should be to raise awareness of IAH and ACS through education and training and to establish diagnostic algorithms, especially for pediatric patients. The increased survival rate after conducting a prompt DL consolidates the impression that the probability of survival can be increased by timely surgical decompression in the case of full-blown ACS.

Incidence and prevalence of hamstring injuries in field-based team sports: a systematic review and meta-analysis of 5952 injuries from over 7 million exposure hours.

OBJECTIVE: This study aimed to systematically review and meta-analyse the incidence and prevalence of hamstring injuries in field-based team sports. A secondary aim was to determine the impact of other potential effect moderators (match vs training; sport; playing surface; cohort age, mass and stature; and year when data was collected) on the incidence of hamstring injury in field-based team sports. DESIGN: Systematic review and meta-analysis. DATA SOURCES: CINAHL, Cochrane Library, MEDLINE Complete (EBSCO), Embase, Web of Science and SPORTDiscus databases were searched from database inception to 5 August 2020. ELIGIBILITY CRITERIA: Prospective cohort studies that assessed the incidence of hamstring injuries in field-based team sports. METHOD: Following database search, article retrieval and title and abstract screening, articles were assessed for eligibility against predefined criteria then assessed for methodological quality using the Critical Appraisal Tool for prevalence studies. Meta-analysis was used to pool data across studies, with meta-regression used where possible. RESULTS: Sixty-three articles were included in the meta-analysis, encompassing 5952 injuries and 7 262 168 hours of exposure across six field-based team sports (soccer, rugby union, field hockey, Gaelic football, hurling and Australian football). Hamstring injury incidence was 0.81 per 1000 hours, representing 10% of all injuries. Prevalence for a 9-month period was 13%, increasing 1.13-fold for every additional month of observation (p=0.004). Hamstring injury incidence increased 6.4% for every 1 year of increased average cohort age, was 9.4-fold higher in match compared with training scenarios (p=0.003) and was 1.5-fold higher on grass compared with artificial turf surfaces (p<0.001). Hamstring injury incidence was not significantly moderated by average cohort mass (p=0.542) or stature (p=0.593), was not significantly different between sports (p=0.150) and has not significantly changed over the last 30 years (p=0.269). CONCLUSION: Hamstring injury represents 10% of all injuries in field-based team sports, with 13% of the athletes experiencing a hamstring injury over a 9-month period most commonly during matches. More work is needed to reduce the incidence of hamstring injury in field-based team sports. PROSPERO REGISTRATION NUMBER: CRD42020200022.

SUPERMAN regulates floral whorl boundaries through control of auxin biosynthesis.

Proper floral patterning, including the number and position of floral organs in most plant species, is tightly controlled by the precise regulation of the persistence and size of floral meristems (FMs). In Arabidopsis, two known feedback pathways, one composed of WUSCHEL (WUS) and CLAVATA3 (CLV3) and the other composed of AGAMOUS (AG) and WUS, spatially and temporally control floral stem cells, respectively. However, mounting evidence suggests that other factors, including phytohormones, are also involved in floral meristem regulation. Here, we show that the boundary gene SUPERMAN (SUP) bridges floral organogenesis and floral meristem determinacy in another pathway that involves auxin signaling. SUP interacts with components of polycomb repressive complex 2 (PRC2) and fine-tunes local auxin signaling by negatively regulating the expression of the auxin biosynthesis genes YUCCA1/4 (YUC1/4). In sup mutants, derepressed local YUC1/4 activity elevates auxin levels at the boundary between whorls 3 and 4, which leads to an increase in the number and the prolonged maintenance of floral stem cells, and consequently an increase in the number of reproductive organs. Our work presents a new floral meristem regulatory mechanism, in which SUP, a boundary gene, coordinates floral organogenesis and floral meristem size through fine-tuning auxin biosynthesis.

DBS emergency surgery for treatment of dystonic storm associated with rhabdomyolysis and acute colitis in DYT-GNAO1.

INTRODUCTION: Patients with variants in the GNAO1 gene may present with life-threatening dystonic storm. There is little experience using pallidal deep brain stimulation (DBS) as an emergency treatment in such cases. CASE DESCRIPTION: We report on a 16-year-old girl with a variant in the GNAO1 gene (c.626G > T; p.(Arg209Leu)) who was admitted to the intensive care unit with medically refractory dystonic storm with secondary complications inducing rhabdomyolysis and acute colitis. Emergency pallidal DBS resulted in rapid improvement of dystonic storm and the subsidence of rhabdomyolysis and colitis. There were no further episodes of dystonic storm during follow-up of 2 years. CONCLUSION: Pallidal DBS is a useful treatment option for GNAO1-related dystonic storm with secondary complications which can be performed as an emergency surgery.

Clinical evaluation of an interoperable clinical decision-support system for the detection of systemic inflammatory response syndrome in critically ill children.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) is defined as a non-specific inflammatory process in the absence of infection. SIRS increases susceptibility for organ dysfunction, and frequently affects the clinical outcome of affected patients. We evaluated a knowledge-based, interoperable clinical decision-support system (CDSS) for SIRS detection on a pediatric intensive care unit (PICU). METHODS: The CDSS developed retrieves routine data, previously transformed into an interoperable format, by using model-based queries and guideline- and knowledge-based rules. We evaluated the CDSS in a prospective diagnostic study from 08/2018-03/2019. 168 patients from a pediatric intensive care unit of a tertiary university hospital, aged 0 to 18 years, were assessed for SIRS by the CDSS and by physicians during clinical routine. Sensitivity and specificity (when compared to the reference standard) with 95% Wald confidence intervals (CI) were estimated on the level of patients and patient-days. RESULTS: Sensitivity and specificity was 91.7% (95% CI 85.5-95.4%) and 54.1% (95% CI 45.4-62.5%) on patient level, and 97.5% (95% CI 95.1-98.7%) and 91.5% (95% CI 89.3-93.3%) on the level of patient-days. Physicians' SIRS recognition during clinical routine was considerably less accurate (sensitivity of 62.0% (95% CI 56.8-66.9%)/specificity of 83.3% (95% CI 80.4-85.9%)) when measurd on the level of patient-days. Evaluation revealed valuable insights for the general design of the CDSS as well as specific rule modifications. Despite a lower than expected specificity, diagnostic accuracy was higher than the one in daily routine ratings, thus, demonstrating high potentials of using our CDSS to help to detect SIRS in clinical routine. CONCLUSIONS: We successfully evaluated an interoperable CDSS for SIRS detection in PICU. Our study demonstrated the general feasibility and potentials of the implemented algorithms but also some limitations. In the next step, the CDSS will be optimized to overcome these limitations and will be evaluated in a multi-center study. TRIAL REGISTRATION: NCT03661450 (ClinicalTrials.gov); registered September 7, 2018.

SUPERMAN prevents class B gene expression and promotes stem cell termination in the fourth whorl of Arabidopsis thaliana flowers.

The molecular and genetic networks underlying the determination of floral organ identity are well studied, but much less is known about how the flower is partitioned into four developmentally distinct whorls. The SUPERMAN gene is required for proper specification of the boundary between stamens in whorl 3 and carpels in whorl 4, as superman mutants exhibit supernumerary stamens but usually lack carpels. However, it has remained unclear whether extra stamens in superman mutants originate from an organ identity change in whorl 4 or the overproliferation of whorl 3. Using live confocal imaging, we show that the extra stamens in superman mutants arise from cells in whorl 4, which change their fate from female to male, while floral stem cells proliferate longer, allowing for the production of additional stamens.

Development and validation of a diagnostic model for early differentiation of sepsis and non-infectious SIRS in critically ill children - a data-driven approach using machine-learning algorithms.

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.

Live confocal imaging of Arabidopsis flower buds.

Recent advances in confocal microscopy, coupled with the development of numerous fluorescent reporters, provide us with a powerful tool to study the development of plants. Live confocal imaging has been used extensively to further our understanding of the mechanisms underlying the formation of roots, shoots and leaves. However, it has not been widely applied to flowers, partly because of specific challenges associated with the imaging of flower buds. Here, we describe how to prepare and grow shoot apices of Arabidopsis in vitro, to perform both single-point and time-lapse imaging of live, developing flower buds with either an upright or an inverted confocal microscope.

Systemic inflammatory response syndrome after pediatric congenital heart surgery: Incidence, risk factors, and clinical outcome.

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.

Development and virucidal activity of a novel alcohol-based hand disinfectant supplemented with urea and citric acid.

BACKGROUND: Hand disinfectants are important for the prevention of virus transmission in the health care system and environment. The development of broad antiviral spectrum hand disinfectants with activity against enveloped and non-enveloped viruses is limited due to a small number of permissible active ingredients able to inactivate viruses. METHODS: A new hand disinfectant was developed based upon 69.39 % w/w ethanol and 3.69 % w/w 2-propanol. Different amounts of citric acid and urea were added in order to create a virucidal claim against poliovirus (PV), adenovirus type 5 (AdV) and polyomavirus SV40 (SV40) as non-enveloped test viruses in the presence of fetal calf serum (FCS) as soil load. The exposure time was fixed to 60 s. RESULTS: With the addition of 2.0 % citric acid and 2.0 % urea an activity against the three test viruses was achieved demonstrating a four log10 reduction of viral titers. Furthermore, this formulation was able to inactivate PV, AdV, SV40 and murine norovirus (MNV) in quantitative suspension assays according to German and European Guidelines within 60 s creating a virucidal claim. For inactivation of vaccinia virus and bovine viral diarrhea virus 15 s exposure time were needed to demonstrate a 4 log10 reduction resulting in a claim against enveloped viruses. Additionally, it is the first hand disinfectant passing a carrier test with AdV and MNV. CONCLUSIONS: In conclusion, this new formulation with a low alcohol content, citric acid and urea is capable of inactivating all enveloped and non-enveloped viruses as indicated in current guidelines and thereby contributing as valuable addition to the hand disinfection portfolio.

SQUINT promotes stem cell homeostasis and floral meristem termination in Arabidopsis through APETALA2 and CLAVATA signalling.

Plant meristems harbour stem cells, which allow for the continuous production of new organs. Here, an analysis of the role of SQUINT (SQN) in stem cell dynamics in Arabidopsis is reported. A close examination of sqn mutants reveals defects that are very similar to that of weak clavata (clv) mutants, both in the flower meristem (increased number of floral organs, occasional delay in stem cell termination) and in the shoot apical meristem (meristem and central zone enlargement, occasional fasciation). sqn has a very mild effect in a clv mutant background, suggesting that SQN and the CLV genes act in the same genetic pathway. Accordingly, a loss-of-function allele of SQN strongly rescues the meristem abortion phenotype of plants that overexpress CLV3. Altogether, these data suggest that SQN is necessary for proper CLV signalling. SQN was shown to be required for normal accumulation of various miRNAs, including miR172. One of the targets of miR172, APETALA2 (AP2), antagonizes CLV signalling. The ap2-2 mutation strongly suppresses the meristem phenotypes of sqn, indicating that the effect of SQN on stem cell dynamics is largely, but not fully, mediated by the miR172/AP2 tandem. This study refines understanding of the intricate genetic networks that control both stem cell homeostasis and floral stem cell termination, two processes that are critical for the proper development and fertility of the plant.

Dialysis-dependent acute kidney injury in children with end-stage liver disease: prevalence, dialysis modalities and outcome.

BACKGROUND: Acute kidney injury (AKI) is a major complication in children with hepatic failure which leads to increased morbidity and mortality. The aim of this study was to provide paediatric data on the prevalence of dialysis-dependent AKI (dAKI), the feasibility and efficacy of dialysis methods and outcome. METHODS: We conducted a retrospective analysis of 367 children listed for orthotopic liver transplantation (OLT) in our centre during the past decade. RESULTS: Data on 30 children (15 boys, 15 girls) were compiled for retrospective analysis, and data on dialysis feasibility and efficacy were available for 26 of these. Median age was 3.5 (range 0.4-17.7) years. Median MELD (Model For End-Stage Liver Disease) score was 33. dAKI was caused by hepato-renal syndrome in 16 of the 30 children. Twenty-one patients were treated with continuous veno-venous haemofiltration (CVVH), and nine patients received peritoneal dialysis (PD). Overall mortality was 77%. Mortality within the PD-group was 100 % versus 67% in the CVVH-group (p = 0.039). Urea reduction rate within the first 24 h of treatment was 12.9% in the PD group and 23.5% in the CVVH group (p = 0.019). CONCLUSIONS: Children with end-stage liver disease have a high risk for dAKI associated with high mortality. CVVH is associated with better efficacy and less mortality than PD.

In-line Filtration Decreases Systemic Inflammatory Response Syndrome, Renal and Hematologic Dysfunction in Pediatric Cardiac Intensive Care Patients.

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.

Neonatal aortic arch thrombosis: analysis of thrombophilic risk factors and prognosis.

UNLABELLED: 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.

Synthesis and characterization of photoaffinity probes that target the 5-HT3 receptor.

The 5-HT3 receptor is one of several ion channels responsible for the transmission of nerve impulses in the peripheral and central nervous systems. Until now, it has been difficult to characterize transmembrane receptors with classical structural biology approaches like X-ray crystallography. The use of photoaffinity probes is an alternative approach to identify regions in the protein where small molecules bind. To this end, we present two photoaffinity probes based on granisetron, a well known antagonist of the 5-HT3 receptor. These new probes show nanomolar binding affinity for the orthosteric binding site. In addition, we investigated their reactivity using irradiation experiments.

Continuous monitoring of physiological data using the patient vital status fusion score in septic critical care patients.

Accurate and standardized methods for assessing the vital status of patients are crucial for patient care and scientific research. This study introduces the Patient Vital Status (PVS), which quantifies and contextualizes a patient's physical status based on continuous variables such as vital signs and deviations from age-dependent normative values. The vital signs, heart rate, oxygen saturation, respiratory rate, mean arterial blood pressure, and temperature were selected as input to the PVS pipeline. The method was applied to 70 pediatric patients in the intensive care unit (ICU), and its efficacy was evaluated by matching high values with septic events at different time points in patient care. Septic events included systemic inflammatory response syndrome (SIRS) and suspected or proven sepsis. The comparison of maximum PVS values between the presence and absence of a septic event showed significant differences (SIRS/No SIRS: p < 0.0001, η2 = 0.54; Suspected Sepsis/No Suspected Sepsis: p = 0.00047, η2 = 0.43; Proven Sepsis/No Proven Sepsis: p = 0.0055, η2 = 0.34). A further comparison between the most severe PVS in septic patients with the PVS at ICU discharge showed even higher effect sizes (SIRS: p < 0.0001, η2 = 0.8; Suspected Sepsis: p < 0.0001, η2 = 0.8; Proven Sepsis: p = 0.002, η2 = 0.84). The PVS is emerging as a data-driven tool with the potential to assess a patient's vital status in the ICU objectively. Despite real-world data challenges and potential annotation biases, it shows promise for monitoring disease progression and treatment responses. Its adaptability to different disease markers and reliance on age-dependent reference values further broaden its application possibilities. Real-time implementation of PVS in personalized patient monitoring may be a promising way to improve critical care. However, PVS requires further research and external validation to realize its true potential.

Metagenomics of hydrocarbon resource environments indicates aerobic taxa and genes to be unexpectedly common.

Oil in subsurface reservoirs is biodegraded by resident microbial communities. Water-mediated, anaerobic conversion of hydrocarbons to methane and CO2, catalyzed by syntrophic bacteria and methanogenic archaea, is thought to be one of the dominant processes. We compared 160 microbial community compositions in ten hydrocarbon resource environments (HREs) and sequenced twelve metagenomes to characterize their metabolic potential. Although anaerobic communities were common, cores from oil sands and coal beds had unexpectedly high proportions of aerobic hydrocarbon-degrading bacteria. Likewise, most metagenomes had high proportions of genes for enzymes involved in aerobic hydrocarbon metabolism. Hence, although HREs may have been strictly anaerobic and typically methanogenic for much of their history, this may not hold today for coal beds and for the Alberta oil sands, one of the largest remaining oil reservoirs in the world. This finding may influence strategies to recover energy or chemicals from these HREs by in situ microbial processes.

In-line filtration minimizes organ dysfunction: new aspects from a prospective, randomized, controlled trial.

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.

Achieving Interoperable Datasets in Pediatrics: A Data Integration Approach.

Despite their increased secondary value for developing applications and knowledge gain, routine, harmonized and standardized datasets are often not available in Pediatrics. We propose a data integration pipeline towards an interoperable routine dataset in pediatric intensive care medicine. Our three-level approach involves identifying relevant data from primary source systems, developing local data integration processes, and converting data into a standardized, interoperable format using openEHR. We modeled 15 openEHR templates and established 31 interoperable ETL processes, resulting in anonymized, standardized data of about 4,200 pediatric patients that were loaded into a harmonized database. Based on our pipeline and templates, we successfully integrated the first part of this data in our openEHR data repository. We seek to inspire other pediatric intensive care units to adopt similar approaches, with the aim of breaking down heterogenous data silos and promoting secondary use of routine data.