Extracorporeal Cardiopulmonary Resuscitation

ECMO, or extracorporeal membrane oxygenation, is an advanced life support technique that provides cardiac and pulmonary support similar to cardiopulmonary bypass. ECPR (extracorporeal cardiopulmonary resuscitation) is the rapid deployment of VA-ECMO when conventional cardiopulmonary resuscitation fails to provide return of spontaneous circulation. Evidence in the literature is sparse, but with expanding reported applications, ECPR has shown promise to improve outcomes of cardiac arrest. ECPR is superior to conventional CPR for both survival and neurologic outcomes. ECPR has been successfully used to manage arrests secondary to cardiac and non-cardiac causes. Arrests secondary to primary cardiac causes have the best overall outcome. Other determinants of outcomes of ECPR include duration of low flow state and on-ECMO complications. A narrow list of ECPR contraindications exists, and includes severe neurologic injury and irreversible primary disease process. Various complications can occur with ECPR, and include mechanical, cardiovascular, pulmonary, hematologic, renal, and neurologic complications. Neurologic complications are the most serious, and significantly affect mortality or quality of life. ECPR is a nascent field, and substantial work remains to be done to optimize its application. Given the small number of patients at each institutional level, this is a field ripe for collaborative work and rewarding results

Ursolic acid inhibits colistin efflux and curtails colistin resistant Enterobacteriaceae

Abstract Colistin resistance in Enterobacteriaceae especially Klebsiella pneumoniae and Escherichia coli is driving the evolution of pan drug resistant strains. Screening a library of 13 plant nutraceuticals led to the identification of acetyl shikonin and ursolic acid, which exhibited synergy with colistin against extremely drug resistant (XDR) clinical strains of E. coli (U3790) and K. pneumoniae (BC936). Ursolic acid caused a significant colistin MIC reversal of 16-fold in U3790 and 4-fold in BC936 strains. Ursolic acid also potentiated the bactericidal effect of colistin against both U3790 and BC936 by causing ~ 4 to 4.5 log fold decline in CFU of both clinical isolates in a time kill assay. At 2× minimum effective concentration, ursolic acid was non-toxic to zebrafish as evidenced by brain and liver enzyme profiles and by histopathology studies. In combination with colistin, ursolic acid reduced bacterial bioburden of U3790/BC936 by 1–1.58 log fold from the infected muscle tissue of zebrafish. Mechanistic explorations via studies on real time efflux, membrane potential and intracellular accumulation of dansyl chloride tagged colistin revealed that colistin efflux is inhibited by ursolic acid. In addition, ursolic acid also enhanced outer membrane permeability which probably facilitates colistin’s attack on outer and inner membranes. Our study shows that ursolic acid synergizes with colistin by inhibiting colistin efflux in Enterobacteriaceae that helps to curtail colistin resistant Enterobacteriaceae.https://deepblue.lib.umich.edu/bitstream/2027.42/148135/1/13568_2019_Article_750.pd

Neural networks to predict radiographic brain injury in pediatric patients treated with Extracorporeal Membrane Oxygenation

Brain injury is a significant source of morbidity and mortality for pediatric patients treated with Extracorporeal Membrane Oxygenation (ECMO). Our objective was to utilize neural networks to predict radiographic evidence of brain injury in pediatric ECMO-supported patients and identify specific variables that can be explored for future research. Data from 174 ECMO-supported patients were collected up to 24 h prior to, and for the duration of, the ECMO course. Thirty-five variables were collected, including physiological data, markers of end-organ perfusion, acid-base homeostasis, vasoactive infusions, markers of coagulation, and ECMO-machine factors. The primary outcome was the presence of radiologic evidence of moderate to severe brain injury as established by brain CT or MRI. This information was analyzed by a neural network, and results were compared to a logistic regression model as well as clinician judgement. The neural network model was able to predict brain injury with an Area Under the Curve (AUC) of 0.76, 73% sensitivity, and 80% specificity. Logistic regression had 62% sensitivity and 61% specificity. Clinician judgment had 39% sensitivity and 69% specificity. Sequential feature group masking demonstrated a relatively greater contribution of physiological data and minor contribution of coagulation factors to the model\u27s performance. These findings lay the foundation for further areas of research directions

Extracorporeal Life Support Organization (ELSO): guidelines for pediatric cardiac failure

These guidelines are applicable to neonates and children with cardiac failure as indication for extracorporeal life support. These guidelines address patient selection, management during extracorporeal membrane oxygenation, and pathways for weaning support or bridging to other therapies. Equally important issues, such as personnel, training, credentialing, resources, follow-up, reporting, and quality assurance, are addressed in other Extracorporeal Life Support Organization documents or are center-specific.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

The effect of probiotics and zinc supplementation on the immune response to oral rotavirus vaccine: A randomized, factorial design, placebo-controlled study among Indian infants.

BACKGROUND: Strategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function. METHODS: Infants 5weeks old living in urban Vellore, India were enrolled in a randomized, double-blind, placebo-controlled trial with a 4-arm factorial design to assess the effects of daily zinc (5mg), probiotic (1010Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix®, GlaxoSmithKline Biologicals) given at 6 and 10weeks of age. Infants were eligible for participation if healthy, available for the study duration and without prior receipt of RV or oral poliovirus vaccine other than the birth dose. The primary outcome was seroconversion to rotavirus at 14weeks of age based on detection of VP6-specific IgA at ?20U/ml in previously seronegative infants or a fourfold rise in concentration. RESULTS: The study took place during July 2012 to February 2013. 620 infants were randomized equally between study arms and 551 (88.9%) completed per protocol. Seroconversion was recorded in 54/137 (39.4%), 42/136 (30.9%), 40/143 (28.0%), and 37/135 (27.4%) infants receiving (1) probiotic and zinc, (2) probiotic and placebo, (3) placebo and zinc, (4) two placebos. Seroconversion showed a modest improvement among infants receiving probiotic (difference between groups 1, 2 and 3, 4 was 7.5% (97.5% Confidence Interval (CI): -1.4%, 16.2%), p=0.066) but not zinc (difference between groups 1, 3 and 2, 4 was 4.4% (97.5% CI: -4.4%, 13.2%), p=0.272). 16 serious adverse events were recorded, none related to study interventions. CONCLUSIONS: Zinc or probiotic supplementation did not significantly improve the low immunogenicity of rotavirus vaccine given to infants in a poor urban community in India. A modest effect of combined supplementation deserves further investigation. TRIAL REGISTRATION: The trial was registered in India (CTRI/2012/05/002677)

Brain Deletion of Insulin Receptor Substrate 2 Disrupts Hippocampal Synaptic Plasticity and Metaplasticity

Diabetes mellitus is associated with cognitive deficits and an increased risk of dementia, particularly in the elderly. These deficits and the corresponding neurophysiological structural and functional alterations are linked to both metabolic and vascular changes, related to chronic hyperglycaemia, but probably also defects in insulin action in the brain. To elucidate the specific role of brain insulin signalling in neuronal functions that are relevant for cognitive processes we have investigated the behaviour of neurons and synaptic plasticity in the hippocampus of mice lacking the insulin receptor substrate protein 2 (IRS-2)

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio