Impact of intraosseous versus intravenous resuscitation during in-hospital cardiac arrest: A retrospective study.

AIM: To compare outcomes between Intraosseous (IO) and peripheral intravenous (PIV) injection during in-hospital cardiac arrest (IHCA) and examine its utility in individuals with obesity. METHODS: We performed a retrospective cohort analysis of adult, atraumatic IHCA at a single tertiary care center. Subjects were classified as either IO or PIV resuscitation. The primary outcome of interest was survival to hospital discharge. The secondary outcomes of interest were survival with favourable neurologic status, rates-of-ROSC (ROR) and time-to-ROSC (TTR). Subgroup analysis among patients with BMI ≥ 30 kg/m2 was performed. RESULTS: Complete data were available for 1852 subjects, 1039 of whom met eligibility criteria. A total of 832 were resuscitated via PIV route and 207 via IO route. Use of IO compared to PIV was associated with lower overall survival to hospital discharge (20.8% vs 28.4% p = 0.03), lower rates of survival with favourable neurologic status (18.4% vs 25.2% p = 0.04), lower ROR (72.2% vs 80.7%) and longer TTR (12:38 min vs 9:01 min). After multivariate adjustment there was no significant differences between IO and PIV in rates of survival to discharge (OR 0.71, 95% CI 0.47-1.06, p = 0.09) or rates of survival with favourable neurologic status (OR 0.74, 95% CI 0.49-1.13, p = 0.16). The ROR and TTR remained significantly worse in the IO group. Subgroup analysis of patients with BMI ≥ 30 kg/m2 identified no benefit or harm with use of IO compared to PIV. CONCLUSION: Intraosseous medication delivery is associated with inferior rates-of-ROSC and longer times-to-ROSC compared to PIV, but no differences in overall survival to hospital discharge or survival with favourable neurologic status during IHCA.

Molecular Analysis of Membrane Targeting by the C2 Domain of the E3 Ubiquitin Ligase Smurf1.

SMAD ubiquitination regulatory factor 1 (Smurf1) is a Nedd4 family E3 ubiquitin ligase that regulates cell motility, polarity and TGFß signaling. Smurf1 contains an N-terminal protein kinase C conserved 2 (C2) domain that targets cell membranes and is required for interactions with membrane-localized substrates such as RhoA. Here, we investigated the lipid-binding mechanism of Smurf1 C2, revealing a general affinity for anionic membranes in addition to a selective affinity for phosphoinositides (PIPs). We found that Smurf1 C2 localizes not only to the plasma membrane but also to negatively charged intracellular sites, acting as an anionic charge sensor and selective PIP-binding domain. Site-directed mutagenesis combined with docking/molecular dynamics simulations revealed that the Smurf1 C2 domain loop region primarily interacts with PIPs and cell membranes, as opposed to the ß-surface cationic patch employed by other C2 domains. By depleting PIPs from the inner leaflet of the plasma membrane, we found that PIP binding is necessary for plasma membrane localization. Finally, we used a Smurf1 cellular ubiquitination assay to show that the amount of ubiquitin at the plasma membrane interface depends on the lipid-binding properties of Smurf1. This study shows the mechanism by which Smurf1 C2 targets membrane-based substrates and reveals a novel interaction for non-calcium-dependent C2 domains and membrane lipids.

Risk Factors for Gastrostomy Tube Placement in Single Ventricle Patients Following The Norwood Procedure.

Neonates with single ventricle heart disease frequently experience poor oral feeding and inconsistent weight gain, often requiring gastrostomy tube (gtube) placement. We sought to identify risk factors for gtube placement in neonates following the Norwood procedure at our institution. We retrospectively reviewed multiple preoperative, operative, and postoperative variables in neonates <30 days with single ventricle heart disease following the Norwood procedure. Study outcomes included duration of mechanical ventilation, hospital length of stay (HLOS), and gtube requirement. Multivariable logistic regression was used to analyze for associated risk factors. Seventy-nine neonates were included in the study, of which 47 underwent gtube placement (59.5%). Multivariable regression analysis found vocal cord dysfunction (P = 0.001, odds ratio 1.1, 95% confidence interval 1.0-1.4) and longer duration of sedative or narcotic infusion (P = 0.01, odds ratio 1.1, 1.03-1.2) to be independently associated with the requirement for gtube among patients who underwent the Norwood procedure. There was a significant difference in HLOS (median 69 vs 33, P = 0.003) between the gtube and the no gtube groups. Univariate analysis comparing the era of surgery was performed and found a significant difference between the groups in terms of the number of gtubes placed (P = 0.02) and duration of sedative or narcotic infusion days (P = 0.038). Both were greater in the era from 2011 to 2015. In a single-institution analysis of neonates following the Norwood procedure, gtube requirement was independently associated with vocal cord dysfunction and longer duration of sedative or narcotic infusions. gtube placement was also associated with longer HLOS.

The Ebola virus matrix protein deeply penetrates the plasma membrane: an important step in viral egress.

Ebola virus, from the Filoviridae family has a high fatality rate in humans and nonhuman primates and to date, to the best of our knowledge, has no FDA approved vaccines or therapeutics. Viral protein 40 (VP40) is the major Ebola virus matrix protein that regulates assembly and egress of infectious Ebola virus particles. It is well established that VP40 assembles on the inner leaflet of the plasma membrane; however, the mechanistic details of VP40 membrane binding that are important for viral release remain to be elucidated. In this study, we used fluorescence quenching of a tryptophan on the membrane-binding interface with brominated lipids along with mutagenesis of VP40 to understand the depth of membrane penetration into lipid bilayers. Experimental results indicate that VP40 penetrates 8.1 Å into the hydrocarbon core of the plasma membrane bilayer. VP40 also induces substantial changes to membrane curvature as it tubulates liposomes and induces vesiculation into giant unilamellar vesicles, effects that are abrogated by hydrophobic mutations. This is a critical step in viral egress as cellular assays demonstrate that hydrophobic residues that penetrate deeply into the plasma membrane are essential for plasma membrane localization and virus-like particle formation and release from cells.