Das zyanotische Kind mit kardialer Erkrankung im Notfalldienst

Zusammenfassung: Im Gegensatz zu Erwachsenen mit vorwiegend pulmonalen Erkrankungen wie der chronisch obstruktiven Lungenerkrankung, entsteht bei Kindern eine zentrale Zyanose meist durch angeborene Herzfehler. Zyanotische Herzfehler kommen mit einer Häufigkeit von ca.13 pro 10.000Lebendgeburten vor. Dadurch, dass heutzutage auch komplexe Herzfehler erfolgreich palliiert werden, steigt die Wahrscheinlichkeit stetig an, im Rettungsdienst Kindern mit einer zentralen Zyanose zu begegnen. Ursachen für das untersättigte Blut in den großen Arterien können eine Minderperfusion der Lungen oder eine vermehrte Durchmischung von arteriellen mit venösem Blut über einen Rechts-Links-Shunt sein. Der beste Indikator einer zentralen Zyanose ist die Zunge, da sie reichlich vaskularisiert und frei von Pigmenten ist. Je nach Altersklasse ist eher eine primäre Volumentherapie oder eine großzügige Sauerstoffapplikation essenziell, oder aber auch keine Notfalltherapie notwendig. Nach der präklinischen Versorgung ist eine stationäre Einweisung unabdingbar, bevorzugt in ein Zentrum mit der Option der kinderintensivmedizinischen oder kinderkardiologischen Betreuun

A novel targeted/untargeted GC-Orbitrap metabolomics methodology applied to Candida albicans and Staphylococcus aureus biofilms

Introduction: Combined infections from Candida albicans and Staphylococcus aureus are a leading cause of death in the developed world. Evidence suggests that Candida enhances the virulence of Staphylococcus—hyphae penetrate through tissue barriers, while S. aureus tightly associates with the hyphae to obtain entry to the host organism. Indeed, in a biofilm state, C. albicans enhances the antimicrobial resistance characteristics of S. aureus. The association of these microorganisms is also associated with significantly increased morbidity and mortality. Due to this tight association we hypothesised that metabolic effects were also in evidence. Objectives: To explore the interaction, we used a novel GC-Orbitrap-based mass spectrometer, the Q Exactive GC, which combines the high peak capacity and chromatographic resolution of gas chromatography with the sub-ppm mass accuracy of an Orbitrap system. This allows the capability to leverage the widely available electron ionisation libraries for untargeted applications, along with expanding accurate mass libraries and targeted matches based around authentic standards. Methods: Optimised C. albicans and S. aureus mono- and co-cultured biofilms were analysed using the new instrument in addition to the fresh and spent bacterial growth media. Results: The targeted analysis experiment was based around 36 sugars and sugar phosphates, 22 amino acids and five organic acids. Untargeted analysis resulted in the detection of 465 features from fresh and spent medium and 405 from biofilm samples. Three significantly changing compounds that matched to high scoring library fragment patterns were chosen for validation. Conclusion: Evaluation of the results demonstrates that the Q Exactive GC is suitable for metabolomics analysis using a targeted/untargeted methodology. Many of the results were as expected: e.g. rapid consumption of glucose and fructose from the medium regardless of the cell type. Modulation of sugar-phosphate levels also suggest that the pentose phosphate pathway could be enhanced in the cells from co-cultured biofilms. Untargeted metabolomics results suggested significant production of cell-wall biosynthesis components and the consumption of non-proteinaceous amino-acids

Third-generation continuous-flow left ventricular assist devices: a comparative outcome analysis by device type.

AIMS Continuous-flow left ventricular assist devices (CF-LVADs) have become a standard of care in end-stage heart failure. Limited data exist comparing outcomes of HeartMate3 (HM3) and HeartWare HVAD (HW). We aimed to compare midterm outcomes of these devices. METHODS AND RESULTS Investigator-initiated retrospective-observational comparative analysis of all patients who underwent primary LVAD implantation of either HM3 or HW at our centre between January 2010 and December 2020. Data were derived from a prospective registry. Primary endpoints were all-cause mortality and heart transplantation. Secondary endpoints included device-related major adverse cardiac and cerebrovascular events, which included major bleeding, major neurological dysfunction (defined as persisting neurological impairment for ≥24 h), device-related major infection (excluding driveline infections), major device malfunctions leading to re-intervention or partial device exchange (pump failure, outflow-graft twist or failure, controller failure, battery failure, patient cable failure, but excluding pump thrombosis), and pump thrombosis. Further secondary endpoints included right heart failure, gastrointestinal bleeding, driveline infections, and surgical re-interventions. The secondary outcomes were analysed not only for the first event but also for recurrent events. The analysis included competing risks analysis and recurrent event regression analysis, with adjustment for confounders age, gender, body mass index (BMI), and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level. Out of 106 primary CF-LVAD implantations, 36 (34%) received HM3 and 70 (66%) received HW. Median follow-up was 1.48 years [interquartile range 0.67, 2.41]. HM3 was more often implanted in men (91.7% vs. 72.9%, P = 0.024); patients were older (median 61 years [54, 66.5] vs. 52.5 years [43, 60], P < 0.001), had a higher BMI (median 26.7 kg/m2 [23.4, 29.0] vs. 24.3 kg/m2 [20.7, 27.4], P = 0.013), had more comorbidities, and were more likely targeted for destination therapy (36.1% vs. 14.3%, P = 0.010). Death occurred in 33.3% of HM3 patients, compared with 22.9% of HW patients, P = 0.247 (probability of survival at 4 years, 54.7% vs. 74.1%, P = 0.296). After adjustment for confounders, we observed a significant six-fold risk increase in device malfunctions for HW [hazard ratio (HR) 6.49, 95% confidence interval (CI) [1.89, 22.32], P = 0.003], but no significant differences in pump thrombosis (P = 0.173) or overall survival (P = 0.801). CONCLUSIONS Comparing midterm outcomes between HM3 and HW for LVAD support from a prospective registry, HW patients had a significantly higher risk of device malfunctions. No significant differences were evident between devices in overall survival and in respect to most outcomes

Initial experience with minimally invasive extracorporeal circulation in coronary artery bypass graft reoperations

AIMS OF THE STUDY Minimally invasive extracorporeal circulation (MiECC) is an established alternative to conventional extracorporeal circulation (CECC) in coronary artery bypass graft surgery (CABG), but data on its use in cardiac reoperations are limited. We aimed to analyse perioperative morbidity and mortality in adult patients undergoing reoperations for isolated CABG using either CECC or MiECC circuits at our centre. METHODS AND RESULTS In a single centre retrospective observational study of all adult patients undergoing cardiac reoperations for isolated CABG between 2004 and 2016, we identified 310 patients, and excluded those who received concomitant cardiac procedures (n = 205). Of the remaining 105 patients, 47 received isolated redo-CABG using MiECC, and 58 received CECC. Propensity score modelling was performed, and inversed probability treatment analysis was used between the treatment groups. Primary endpoint was 30-day all-cause mortality. Secondary endpoints included major adverse cardiac or cerebrovascular events or need for conversion to CECC. Groups were comparable, apart from a higher incidence of NYHA class III or higher in CECC group (33.5% vs 8.6%, p= 0.004). Shorter times for operation, cardiopulmonary bypass and aortic cross-clamp were observed in the MiECC group. The incidence of postoperative atrial fibrillation was significantly lower with MiECC (22.1%, p = 0.012). No significant difference was observed in all-cause 30-day mortality between the MiECC and CECC groups (6.8% vs. 8.3%, p = 0.81). CONCLUSION We found no difference in overall mortality between CECC and MiECC in patients undergoing reoperation for isolated CABG. Furthermore, we found no indication of differences in most outcomes between extracorporeal circuit types. In the case of redo-CABG, MiECC could provide an alternative strategy

Single Low-Dose Targeted Bevacizumab Infusion in Adult Patients with Steroid-Refractory Radiation Necrosis of the Brain: A Phase II Open-Label Prospective Clinical Trial

OBJECTIVE There is an unmet need for safe and rapidly effective therapies for refractory brain radiation necrosis (RN). The aim of this prospective single-arm phase II trial was to evaluate the safety and efficacy of a single low-dose targeted bevacizumab infusion after blood-brain barrier disruption (BBBD) in adult patients with steroid-refractory brain RN. METHODS Ten adults with steroid-refractory, imaging-confirmed brain RN were enrolled between November 2016 and January 2018 and followed for 12 months after treatment. Bevacizumab 2.5 mg/kg was administered as a one-time targeted intra-arterial infusion immediately after BBBD. Primary outcomes included safety and \u3e 25% decrease in lesion volume. Images were analyzed by a board-certified neuroradiologist blinded to pretrial diagnosis and treatment status. Secondary outcomes included changes in headache, steroid use, and functional status and absence of neurocognitive sequelae. Comparisons were analyzed using the Fisher exact test, Mann-Whitney U-test, linear mixed models, Wilcoxon signed-rank test, and repeated-measures 1-way ANOVA. RESULTS Ten adults (mean ± SD [range] age 35 ± 15 [22-62] years) participated in this study. No patients died or exhibited serious adverse effects of systemic bevacizumab. At 3 months, 80% (95% CI 44%-98%) and 90% (95% CI 56%-100%) of patients demonstrated \u3e 25% decrease in RN and vasogenic edema volume, respectively. At 12 months, RN volume decreased by 74% (median [range] 76% [53%-96%], p = 0.012), edema volume decreased by 50% (median [range] 70% [-11% to 83%], p = 0.086), and headache decreased by 84% (median [range] 92% [58%-100%], p = 0.022) among the 8 patients without RN recurrence. Only 1 (10%) patient was steroid dependent at the end of the trial. Scores on 12 of 16 (75%) neurocognitive indices increased, thereby supporting a pattern of cerebral white matter recovery. Two (20%) patients exhibited RN recurrence that required further treatment at 10 and 11 months, respectively, after bevacizumab infusion. CONCLUSIONS For the first time, to the authors\u27 knowledge, the authors demonstrated that a single low-dose targeted bevacizumab infusion resulted in durable clinical and imaging improvements in 80% of patients at 12 months after treatment without adverse events attributed to bevacizumab alone. These findings highlight that targeted bevacizumab may be an efficient one-time treatment for adults with brain RN. Further confirmation with a randomized controlled trial is needed to compare the intra-arterial approach with the conventional multicycle intravenous regimen

Contegra conduit for reconstruction of the right ventricular outflow tract: a review of published early and mid-time results

<p>Abstract</p> <p>Objective</p> <p>The valved conduit Contegra (bovine jugular vein) has being implanted for more than 7 years in the right ventricular outflow tract and it is noted that the available reports have been mixed. The aim of this study is to review the reported evidence in the literature.</p> <p>Methods</p> <p>Search of the relevant literature for the primary endpoints of operative mortality and morbidity and secondary endpoints of follow-up haemodynamic performance including severe stenosis, regurgitation and need for reintervention are presented.</p> <p>Results</p> <p>We selected and analysed 17 series including 767 patients. Commonest indication was Fallot's tetralogy. Operative mortality was 2.6%. Operative morbidity was 13.9%. In follow-up, the incidence of intraconduit stenosis was 10.9% (incidence of stenosis for the 12 millimetre conduit was 83.3% in one series) and that of at least moderate regurgitation was 6.3%.</p> <p>The aspirin users had a stenosis incidence of 10.5% compared to the non-users had a stenosis incidence of 9.6%.</p> <p>Conclusion</p> <p>A dissent on the performance of the Contegra is discussed, while results are satisfactory in the majority of studies apart for the smallest conduits (12 and 14 millimetre), suggesting an association to compromised run-off. The role of aspirin as antithrombotic modulator remains controversial.</p

Quantitative Metabolomics Reveals an Epigenetic Blueprint for Iron Acquisition in Uropathogenic Escherichia coli

Bacterial pathogens are frequently distinguished by the presence of acquired genes associated with iron acquisition. The presence of specific siderophore receptor genes, however, does not reliably predict activity of the complex protein assemblies involved in synthesis and transport of these secondary metabolites. Here, we have developed a novel quantitative metabolomic approach based on stable isotope dilution to compare the complement of siderophores produced by Escherichia coli strains associated with intestinal colonization or urinary tract disease. Because uropathogenic E. coli are believed to reside in the gut microbiome prior to infection, we compared siderophore production between urinary and rectal isolates within individual patients with recurrent UTI. While all strains produced enterobactin, strong preferential expression of the siderophores yersiniabactin and salmochelin was observed among urinary strains. Conventional PCR genotyping of siderophore receptors was often insensitive to these differences. A linearized enterobactin siderophore was also identified as a product of strains with an active salmochelin gene cluster. These findings argue that qualitative and quantitative epi-genetic optimization occurs in the E. coli secondary metabolome among human uropathogens. Because the virulence-associated biosynthetic pathways are distinct from those associated with rectal colonization, these results suggest strategies for virulence-targeted therapies