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Electrical impedance segmentography offers a new radiation-free possibility of continuous bedside ventilation monitoring. The aim of this study was to evaluate the efficacy and reproducibility of this bedside tool by comparing synchronized intermittent mandatory ventilation (SIMV) with neurally adjusted ventilatory assist (NAVA) in critically-ill children. In this prospective randomized case–control crossover trial in a pediatric intensive care unit of a tertiary center, including eight mechanically-ventilated children, four sequences of two different ventilation modes were consecutively applied. All children were randomized into two groups; starting on NAVA or SIMV. During ventilation, electric impedance segmentography measurements were recorded. The relative difference of vertical impedance between both ventilatory modes was measured (median 0.52, IQR 0–0.87). These differences in left apical lung segments were present during the first (median 0.58, IQR 0–0.89, p = 0.04) and second crossover (median 0.50, IQR 0–0.88, p = 0.05) as well as across total impedance (0.52 IQR 0–0.87; p = 0.002). During NAVA children showed a shift of impedance towards caudal lung segments, compared to SIMV. Electrical impedance segmentography enables dynamic monitoring of transthoracic impedance. The immediate benefit of personalized ventilatory strategies can be seen when using this simple-to-apply bedside tool for measuring lung impedance.

Summary Background Despite current progress in research of congenital diaphragmatic hernia, its management remains challenging, requiring an interdisciplinary team for optimal treatment. Objective Aim of the present study was to evaluate potential risk factors for mortality of infants with congenital diaphragmatic hernia. Methods A single-center chart review of all patients treated with congenital diaphragmatic hernia over a period of 16 years, at the Medical University of Vienna, was performed. A comparison of medical parameters between survivors and non-survivors, as well as to published literature was conducted. Results During the observational period 66 patients were diagnosed with congenital diaphragmatic hernia. Overall survival was 84.6%. Left-sided hernia occurred in 51 patients (78.5%) with a mortality of 7.8%. In comparison, right-sided hernia occurred less frequently (n = 12) but showed a higher mortality (33.3%, p = 0.000). Critically instable patients were provided with venoarterial extracorporeal membrane oxygenation (ECMO, 32.3%, n = 21). Survival rate among these patients was 66.7%. Right-sided hernia, treatment with inhaled nitric oxide (iNO) over 15 days and the use of ECMO over 10 days were significant risk factors for mortality. Conclusion The survival rate in this cohort is comparable to the current literature. Parameters such as the side of the diaphragmatic defect, duration of ECMO and inhaled nitric oxide were assessed as mortality risk factors. This analysis of patients with congenital diaphragmatic hernia enhances understanding of risk factors for mortality, helping to improve management and enabling further evaluation in prospective clinical trials.

Sepsis is, worldwide, one of the leading causes of death among infants and children. Over the past two decades, mortality rates have declined due to advanced treatment options; however, the incidence of sepsis and septic shock is still on the rise in many hospital settings. The objective of this study was to evaluate the course of this disease in pediatric intensive care patients.An evaluation of pediatric patients in the intensive care unit diagnosed with infections or sepsis between 2005 and 2015 was performed via a retrospective exploratory data analysis.During the observational period, 201 patients were diagnosed with infection or sepsis. The study population was divided into five age subgroups. The majority of patients were newborns, infants, and toddlers. Forty percent had sepsis; 6% had septic shock. Viral infection was the most prevalent (59%). The overall survival rate was 83%; newborns and adolescents had the lowest survival rates.With this registry, children divided into five age subgroups with infection or sepsis were evaluated and treatment strategies were examined. We have shown that our findings on children treated in our pediatric intensive care unit conform with current literature about pediatric sepsis. In addition to maintaining strict hygiene standards, optimal aspects of sepsis care should be stringently observed, such as the quick administration of empirical broad-spectrum antibiotics, initial adequate fluid resuscitation, and a reliable and frequent routine of source control.HINTERGRUND: Sepsis ist weltweit eine der häufigsten Todesursachen bei Säuglingen und Kindern. In den letzten 2 Jahrzehnten sank die Sterblichkeitsrate durch verbesserte Behandlungsoptionen, die Inzidenz der Sepsis und des septischen Schocks nimmt jedoch weiterhin zu. Ziel dieser Studie war es, den Krankheitsverlauf bei pädiatrischen IntensivpatientInnen mit Sepsis oder Infektion zu beurteilen.Es erfolgte eine retrospektive explorative Datenanalyse von pädiatrischen PatientInnen, die zwischen 2005 und 2015 aufgrund einer Infektion oder Sepsis auf der Intensivstation stationär aufgenommen worden waren.Während des Beobachtungszeitraums wurde bei 201 Patienten eine Infektion oder Sepsis diagnostiziert. Die Studienpopulation wurde in 5 Altersuntergruppen eingeteilt, die Mehrheit davon waren Neugeborene, Säuglinge und Kleinkinder. Eine Sepsis wurde bei 40 % und ein septischer Schock bei 6 % der PatientInnen diagnostiziert. Am häufigsten waren Virusinfektionen (59 %). Die Gesamtüberlebensrate betrug 83 %, dabei wiesen Neugeborene und Jugendliche die niedrigste Überlebensrate auf.Mit dieser Registeranalyse wurden die Daten von Kindern mit Infektion oder Sepsis evaluiert und Behandlungsstrategien untersucht. Es wurde dabei gezeigt, dass die vorliegenden Ergebnisse mit der aktuellen Literatur vergleichbar sind. Strenge Hygienestandards und optimale Sepsisversorgung sollten korrekt durchgeführt werden, wie z. B. rasche Verabreichung empirischer Breitbandantibiotika, entsprechendes Flüssigkeitsmanagement sowie zuverlässige und regelmäßige Laborkontrollen hinsichtlich der Infektionsquelle.

Aim Since therapeutic hypothermia (TH) is known for its inhibitory effects on leucocyte migration and cytokine synthesis, our aim was to underline the necessity of early monitoring for potential immunomodulatory risks. Methods Using a 13‐year retrospective case‐control study at the paediatric intensive care unit (PICU) of the Medical University in Vienna, all newborn infants and children receiving TH were screened and compared with a diagnosis‐matched control group undergoing conventional normothermic treatment (NT). TH was accomplished by using a non‐invasive cooling device. Target temperature was 32‐34°C. Children with evident infections, a medical history of an immunodeficiency or undergoing immunosuppressive therapy, were excluded. Results During the observational period, 108 patients were screened, 27 of which underwent TH. Culture‐proven infections occurred in 22% of the TH group compared with 4% of the normothermic controls (P = .1). From the second day following PICU admission, median C‐reactive protein (CRP) values were higher in the TH group (day two P = .002, day three P = .0002, day six P = .008). Conclusion Children undergoing TH showed earlier and higher increases in CRP levels when compared to normothermic controls. These data underline the necessity of early and continuous monitoring for possible infectious complications.

Objectives:In critical care it is crucial to appropriately assess the risk of mortality for each patient. This is especially relevant in pediatrics, with its need for accurate and repeatable scoring. Aim of this study was to evaluate an age-adapted version of the expanded Simplified Acute Physiology Score II; (p-SAPS II), a repeatable, newly-designed scoring system compared to established scores (Pediatric Sequential Organ Failure Assessment Score/pSOFA, Pediatric Logistic Organ Dysfunction Score-2/PELOD-2 and Pediatric Index of Mortality 3/PIM3).Design:This retrospective cohort pilot study included data collected from patients admitted to the Pediatric Intensive Care Unit (PICU) at the Medical University of Vienna between July 2017 through December 2018.Patients:231 admissions were included, comprising neonates (gestational age of ≥ 37 weeks) and patients up to 18 years of age with a PICU stay longer than 48 h.Main Outcomes:Mortality risk prediction and discrimination between survivors and non-survivors were the main outcomes of this study. The primary statistical methods for evaluating the performance of each score were the area under the receiver operating characteristic curve (AUROC) and goodness-of-fit test.Results:Highest AUROC curve was calculated for p-SAPS II (AUC = 0.86; 95% CI: 0.77–0.96;p< 0.001). This was significantly higher than the AUROCs of PELOD-2/pSOFA but not of PIM3. However, in a logistic regression model including p-SAPS II and PIM3 as covariates, p-SAPS II had a significant effect on the accuracy of prediction (p= 0.003). Nevertheless, according to the goodness-of-fit test for p-SAPS II and PIM3, p-SAPS II overestimated the number of deaths, whereas PIM3 showed acceptable estimations. Repeatability testing showed increasing AUROC values for p-SAPS II throughout the clinical stay (0.96 at day 28) but still no significant difference to PIM 3. The prediction accuracy, although improved over the days and even exceeded PIM 3.Conclusions:The newly-created p-SAPS II performed better than the established PIM3 in terms of discriminating between survivors and non-survivors. Furthermore, p-SAPS II can be assessed repeatably throughout a patient's PICU stay what improves mortality prediction. However, there is still a need to optimize calibration of the score to accurately predict mortality sooner throughout the clinical stay.

Syncytial skeletal muscle cells contain hundreds of nuclei in a shared cytoplasm. We investigated nuclear heterogeneity and transcriptional dynamics in the uninjured and regenerating muscle using single-nucleus RNA-sequencing (snRNAseq) of isolated nuclei from muscle fibers. This revealed distinct nuclear subtypes unrelated to fiber type diversity, previously unknown subtypes as well as the expected ones at the neuromuscular and myotendinous junctions. In fibers of the Mdx dystrophy mouse model, distinct subtypes emerged, among them nuclei expressing a repair signature that were also abundant in the muscle of dystrophy patients, and a nuclear population associated with necrotic fibers. Finally, modifications of our approach revealed the compartmentalization in the rare and specialized muscle spindle. Our data identifies nuclear compartments of the myofiber and defines a molecular roadmap for their functional analyses; the data can be freely explored on the MyoExplorer server (https://shiny.mdc-berlin.de/MyoExplorer/)., The transcriptional programs of nuclei in the muscle syncytium were assumed to be homogenous except at the neuromuscular and myotendinous junctions. Here, using single-nucleus transcriptomics, the authors reveal a previously unrecognized diversity and dynamics of myonuclear transcriptional programs.

Zusammenfassung Hintergrund Hausarzte zahlen zu den Facharztgruppen mit den haufigsten Medikamenten-verordnungen. Die Vertiefung pharmakologischer Kenntnisse ist deshalb ein wichtiger Bestandteil der hausarztlichen Fort- und Weiterbildung. Das hausarztliche Selbstverstandnis, als erster Ansprechpartner bei allen Gesundheitsproblemen zu helfen, macht es zu einer Herausforderung, Weiterbildungsinhalte zu definieren und zu erwerben. Wahrend das von der Deutschen Gesellschaft fur Allgemeinmedizin entwickelte „Kompetenzbasierte Curriculum Allgemeinmedizin" essentielle Diagnosen, Beratungsanlasse und Kompetenzen fur die hausarztliche Tatigkeit definiert, fehlt eine solche Orientierung fur den pharmakologischen Bereich. Ziel dieser Arbeit ist, Wirkstoffe zu identifizieren und zu charakterisieren, die jeder Hausarzt so gut beherrschen sollte, dass er dazu beraten und Monitoringmasnahmen einleiten und durchfuhren kann. Methodik Es wurden die Verordnungen von Privat- und Kassenrezepten aller am CONTENT-Projekt teilnehmenden Praxen des Zeitraums 2009 bis 2014 analysiert. Die Analyse wurde auf oral applizierbare Wirkstoffe beschrankt, die von mindestens 25% (n=11) der Hausarztpraxen mindestens einmal verordnet wurden. Wahrend die hundert am haufigsten verordneten Wirkstoffe, die bereits uber 80% der Gesamtverordnungen ausmachten, aufgrund ihrer Verordnungshaufigkeit eingeschlossen wurden, wurden die weniger haufig verordneten Wirkstoffe in einem Rating-Verfahren zusatzlich nach ihrem Risikopotential und der hausarztlichen Relevanz beurteilt. Die auf dieser Basis eingeschlossenen Wirkstoffe wurden nach Beratungsanlassen/Diagnosen klassifiziert dargestellt. Ergebnisse Es wurden 1.912.896 Einzelverordnungen auf Basis der anatomisch-therapeutisch-chemischen Klassifikation (ATC) aus 44 Hausarztpraxen von 112.535 Patienten analysiert. Nach Anwendung der Einschlusskriterien verblieben 453 Wirkstoffe, von denen 302 Wirkstoffe als hausarztlich-relevant eingeschatzt wurden. Diese konnten 45 Beratungsanlassen/Diagnosen zugeordnet werden. Schlussfolgerung Das Ergebnis dieser Arbeit kann als Entwicklungsversion eines hausarztlich-pharmakologischen Curriculums gesehen werden und perspektivisch das kompetenzbasierte Curriculum Allgemeinmedizin sinnvoll erganzen.