Robotic Assisted Percutaneous Coronary Intervention: Initial Australian Experience.

BACKGROUND & AIM: Robotic-assisted percutaneous coronary intervention (R-PCI) has been increasingly performed overseas. Initial observations have demonstrated its clinical efficacy and safety with additional potential benefits of more accurate lesion assessment and stent deployment, with reduced radiation exposure to operators and patients. However, data from randomised controlled trials or clinical experience from Australia are lacking. METHODS: This was a single-centre experience of all patients undergoing R-PCI as part of the run-in phase for an upcoming randomised clinical trial (ACTRN12623000480684). All R-PCI procedures were performed using the CorPath GRX robot (Corindus Vascular Robotics, Waltham, Massachusetts, USA). Key inclusion criteria included patients with obstructive coronary disease requiring percutaneous coronary intervention. Major exclusion criteria included ST-elevation myocardial infarction, cardiogenic shock or lesions deemed unsuitable for R-PCI by the operator. Clinical success was defined as residual stenosis <30% without in-hospital major adverse cardiovascular events (MACE). Technical success was defined as the completion of the R-PCI procedure without unplanned manual conversion. Procedural characteristics were compared between early (cases 1-3) and later (cases 4-21) cases. RESULTS: Twenty-one (21) patients with a total of 24 lesions were analysed. The mean age of patients was 66.5 years, and 66% of cases were male. Radial access was used in 18 cases (86%). Most lesions were American Heart Association/American College of Cardiology class B2/C (66%). Clinical success was achieved in 100% with manual conversion required in four cases (19%). No procedural complications or in-hospital MACE occurred. Compared to the early cases, later cases had a statistically significantly shorter fluoroscopy time (44.0mins vs 25.2mins, p<0.007), dose area product (967.3 dGy.cm2 vs 361.0dGy.cm2, p=0.01) and air kerma (2484.3mGy vs 797.4mGy, p=0.009) with no difference in contrast usage (136.7mL vs 131.4mL, p=0.88). CONCLUSIONS: We present the first clinical experience of R-PCI in Australia using the Corindus CorPath GRX robot. We achieved clinical success in all patients and technical success in the majority of cases with no procedural complications or in-hospital MACE. With increasing operator and staff experience, cases required shorter fluoroscopy time and less radiation exposure but similar contrast usage.

Historical evaluation of the in vivo adventitious virus test and its potential for replacement with next generation sequencing (NGS).

The Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB) collected historical data from 20 biopharmaceutical industry members on their experience with the in vivo adventitious virus test, the in vitro virus test, and the use of next generation sequencing (NGS) for viral safety. Over the past 20 years, only three positive in vivo adventitious virus test results were reported, and all were also detected in another concurrent assay. In more than three cases, data collected as a part of this study also found that the in vivo adventitious virus test had given a negative result for a sample that was later found to contain virus. Additionally, the in vivo adventitious virus test had experienced at least 21 false positives and had to be repeated an additional 21 times all while using more than 84,000 animals. These data support the consideration and need for alternative broad spectrum viral detection tests that are faster, more sensitive, more accurate, more specific, and more humane. NGS is one technology that may meet this need. Eighty one percent of survey respondents are either already actively using or exploring the use of NGS for viral safety. The risks and challenges of replacing in vivo adventitious virus testing with NGS are discussed. It is proposed to update the overall virus safety program for new biopharmaceutical products by replacing in vivo adventitious virus testing approaches with modern methodologies, such as NGS, that maintain or even improve the final safety of the product.

Improving Pediatric Readiness in General Emergency Departments: A Prospective Interventional Study.

OBJECTIVE: To describe the impact of a national interventional collaborative on pediatric readiness within general emergency departments (EDs). STUDY DESIGN: A prospective, multicenter, interventional study measured pediatric readiness in general EDs before and after participation in a pediatric readiness improvement intervention. Pediatric readiness was assessed using the weighted pediatric readiness score (WPRS) on a 100-point scale. The study protocol extended over 6 months and involved 3 phases: (1) a baseline on-site assessment of pediatric readiness and simulated quality of care; (2) pediatric readiness interventions; and (3) a follow-up on-site assessment of WPRS. The intervention phase included a benchmarking performance report, resources toolkits, and ongoing interactions between general EDs and academic medical centers. RESULTS: Thirty-six general EDs were enrolled, and 34 (94%) completed the study. Four EDs (11%) were located in Canada, and the rest were in the US. The mean improvement in WPRS was 16.3 (P < .001) from a baseline of 62.4 (SEM = 2.2) to 78.7 (SEM = 2.1), with significant improvement in the domains of administration/coordination of care; policies, protocol, and procedures; and quality improvement. Six EDs (17%) were fully adherent to the protocol timeline. CONCLUSIONS: Implementing a collaborative intervention model including simulation and quality improvement initiatives is associated with improvement in WPRS when disseminated to a diverse group of general EDs partnering with their regional pediatric academic medical centers. This work provides evidence that innovative collaboration facilitated by academic medical centers can serve as an effective strategy to improve pediatric readiness and processes of care.

3D Echo in Routine Clinical Practice - State of the Art in 2019.

Three-dimensional (3D) echo has been around for almost five decades. Recent advances in ultrasound, electronic and computing technologies have moved 3D echo from the research environment to everyday clinical practice. Real time 3D echo and full volume acquisition are now possible with transthoracic as well as transoesophageal probes. The main advantages of 3D echo are the infinite cut planes possible, allowing direct, en face, and anatomical views of cardiac structures, avoiding foreshortening and circumventing the geometric assumptions of the cardiac chambers inherent in any 2D echo techniques. Three-dimensional echo is still dependent on image quality, subjected to ultrasound artifacts and faces the compromise between spatial and temporal resolution. In routine clinical practice in 2019, we recommend a focussed 3D examination after a full 2D echo study. The area where 3D echo has been consistently shown to have superior accuracy and reproducibility over 2D echo is in the assessment of left ventricular (LV) volumes and ejection fraction. We recommend obtaining a full volume 3D echo data set from the apical window, from which LV volumes and LV global longitudinal strain can be measured. Further 3D examination can be performed depending on the pathologies identified on 2D examination. Three-dimensional echo is superior to 2D echo in the assessment of mitral valve pathologies and atrial septal defects. Furthermore, real time 3D transoesophageal echo is a very useful technique in guiding structural cardiac intervention, both before, during and after the procedure. While 3D echo is not the holy grail of echocardiography, it does represent a useful technique in selected areas of cardiac imaging.

Emergency department ondansetron use in children with type 1 diabetes mellitus and vomiting.

OBJECTIVE: To assess the hypothesis that ondansetron administration to children with type 1 diabetes mellitus (T1DM) presenting for emergency department (ED) care with intercurrent illness and vomiting improves clinical outcomes by reducing hospitalization rates (primary), length of ED stay, intravenous fluid (IVF) administration, and revisits (secondary outcomes). STUDY DESIGN: We conducted a single-center, 10-year retrospective cohort study of 345 ED encounters of children aged 6 months-8 years with T1DM and vomiting. We compared outcomes among children receiving and not receiving ondansetron. To avoid selection bias related to ondansetron administration, we also investigated outcomes by conducting comparisons by ondansetron usage periods (ie, low [2002-2004] vs high [2009-2011]). RESULTS: Ondansetron usage increased from 0% to 67% of ED encounters between 2002 and 2011. Admission rates were similar among those administered [54% (58/107)] and not administered ondansetron [55% (131/238)]. Length of stay was longer in children receiving ondansetron (409 vs 315 minutes; P = .03). IVF administration (77% vs 77%) and revisits (5.6% vs 5.9%) were similar. Ondansetron administration was not associated with reduced admission in logistic regression modeling. Admission rate (62%; 56/91 vs 49%; 57/111) (-13%, 95% CI -23%, 3%), length of stay (395 vs 327 minutes [IQR 164 501]; P < .001), and IVF administration decreased (84% [77/91] to 70% [78/111]; P = .02] when comparing low and high ondansetron usage periods. CONCLUSIONS: Ondansetron administration was not independently associated with lower admission rates. Over time, along with increasing ondansetron use, there have been reductions in admissions, length of stay, and IVF administration in children with T1DM.

Rate-limiting step analysis of the microbial desulfurization of dibenzothiophene in a model oil system.

A mechanistic analysis of the various mass transport and kinetic steps in the microbial desulfurization of dibenzothiophene (DBT) by Rhodococcus erythropolis IGTS8 in a model biphasic (oil-water), small-scale system was performed. The biocatalyst was distributed into three populations, free cells in the aqueous phase, cell aggregates and oil-adhered cells, and the fraction of cells in each population was measured. The power input per volume (P/V) and the impeller tip speed (vtip ) were identified as key operating parameters in determining whether the system is mass transport controlled or kinetically controlled. Oil-water DBT mass transport was found to not be limiting under the conditions tested. Experimental results at both the 100 mL and 4 L (bioreactor) scales suggest that agitation leading to P/V greater than 10,000 W/ m(3) and/or vtip greater than 0.67 m/s is sufficient to overcome the major mass transport limitation in the system, which was the diffusion of DBT within the biocatalyst aggregates.

Stabilizing the heterologously expressed uric acid-xanthine transporter UapA from the lower eukaryote Aspergillus nidulans.

Despite detailed genetic and mutagenic analysis and a recent high-resolution structure of a bacterial member of the nucleobase-ascorbate transporter (NAT) family, understanding of the mechanism of action of eukaryotic NATs is limited. Preliminary studies successfully expressed and purified wild-type UapA to high homogeneity; however, the protein was extremely unstable, degrading almost completely after 48 h at 4°C. In an attempt to increase UapA stability we generated a number of single point mutants (E356D, E356Q, N409A, N409D, Q408E and G411V) previously shown to have reduced or no transport activity, but correct targeting to the membrane. The mutant UapA constructs expressed well as GFP fusions in Saccharomyces cerevisiae and exhibited similar fluorescent size exclusion chromatography (FSEC) profiles to the wild-type protein, following solubilization in 1% DDM, LDAO or OM + 1 mM xanthine. In order to assess the relative stabilities of the mutants, solubilized fractions prepared in 1% DDM + 1 mM xanthine were heated at 45°C for 10 min prior to FSEC. The Q408E and G411V mutants gave markedly better profiles than either wild-type or the other mutants. Further FSEC analysis following solubilization of the mutants in 1% NG ± xanthine confirmed that G411V is more stable than the other mutants, but showed that Q408E is unstable under these conditions. G411V and an N-terminally truncated construct G411VΔ1-11 were submitted to large-scale expression and purification. Long-term stability analysis revealed that G411VΔ1-11 was the most stable construct and the most suited to downstream structural studies.

S-nitrosoglutathione reductase deficiency increases mutagenesis from alkylation in mouse liver.

In human hepatocellular carcinoma (HCC) and many other cancers, somatic point mutations are highly prevalent, yet the mechanisms critical in their generation remain poorly understood. S-nitrosoglutathione reductase (GSNOR), a key regulator of protein S-nitrosylation, is frequently deficient in human HCC. Targeted deletion of the GSNOR gene in mice can reduce the activity of the DNA repair protein O (6)-alkylguanine-DNA alkyltransferase (AGT) and promote both carcinogen-induced and spontaneous HCC. In this study, we report that following exposure to the environmental carcinogen diethylnitrosamine, the mutation frequency of a transgenic reporter in the liver of GSNOR-deficient mice (GSNOR(-/-)) is significantly higher than that in wild-type control. In wild-type mice, diethylnitrosamine treatment does not significantly increase the frequency of the transition from G:C to A:T, a mutation deriving from diethylnitrosamine-induced O (6)-ethylguanines that are normally repaired by AGT. In contrast, the frequency of this transition from diethylnitrosamine is increased ~20 times in GSNOR(-/-) mice. GSNOR deficiency also significantly increases the frequency of the transversion from A:T to T:A, a mutation not affected by AGT. GSNOR deficiency in our experiments does not significantly affect either the frequencies of the other diethylnitrosamine-induced point mutations or hepatocyte proliferation. Thus, GSNOR deficiency, through both AGT-dependent and AGT-independent pathways, significantly raises the rates of specific types of DNA mutations. Our results demonstrate a critical role for GSNOR in maintaining genomic integrity in mice and support the hypothesis that GSNOR deficiency is an important cause of the widespread mutations in human HCC.

Implementation of a North American pediatric emergency medicine simulation curriculum using the virtual resuscitation room.

Background: Simulation provides consistent opportunities for residents to practice high-stakes, low-frequency events such as pediatric resuscitations. To increase standardization across North American residency programs, the Emergency Medicine Resident Simulation Curriculum for Pediatrics (EM ReSCu Peds) was developed. However, access to high-quality simulation/pediatric expertise is not uniform. As the concurrent COVID-19 pandemic necessitated new virtual simulation methods, we adapted the Virtual Resus Room (VRR) to teach EM ReSCu Peds. VRR is an award-winning, low-resource, open-access distance telesimulation platform we hypothesize will be effective and scalable for teaching this curriculum. Methods: EM residents completed six VRR EM ReSCu Peds simulation cases and received immediate facilitator-led teledebriefing. Learners completed retrospective pre-post surveys after each case. Learners and facilitators completed end-of-day surveys. Primary outcomes were learning effectiveness measured by a composite of the Simulation Effectiveness in Teaching Modified (SET-M) tool and self-reported changes in learner comfort with case objectives. Secondary outcome was VRR scalability to teach EM ReSCu Peds using a composite outcome of net promoter scores (NPS), resource utilization, open-text feedback, and technical issues. Results: Learners reported significantly increased comfort with 95% (54/57) of EM ReSCu Peds-defined case objectives (91% cognitive, 9% psychomotor), with moderate (Cohen's d 0.71, 95% CI 0.67-0.76) overall effect size. SET-M responses indicated simulation effectiveness, particularly with debriefing. Ninety EM residents from three North American residency programs were taught by 59 pediatric faculty from six programs over 4 days-more than possible if simulations were conducted in person. Learners (39) and faculty (68) NPS were above software industry benchmarks (13). Minor, quickly resolved, technical issues were reported by 18% and 29% of learners and facilitators, respectively. Conclusions: Learners and facilitators report that the VRR is an effective and scalable platform to teach EM ReSCu Peds. This low-cost, accessible distance simulation intervention could increase equitable, global access to high-quality pediatric emergency education.