Pre-hospital ECPR in an Australian metropolitan setting: a single-arm feasibility assessment-The CPR, pre-hospital ECPR and early reperfusion (CHEER3) study.

INTRODUCTION: Survival from refractory out of hospital cardiac arrest (OHCA) without timely return of spontaneous circulation (ROSC) utilising conventional advanced cardiac life support (ACLS) therapies is dismal. CHEER3 was a safety and feasibility study of pre-hospital deployed extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (ECPR) for refractory OHCA in metropolitan Australia. METHODS: This was a single jurisdiction, single-arm feasibility study. Physicians, with pre-existing ECMO expertise, responded to witnessed OHCA, age < 65 yrs, within 30 min driving-time, using an ECMO equipped rapid response vehicle. If pre-hospital ECPR was undertaken, patients were transported to hospital for investigations and therapies including emergent coronary catheterisation, and standard intensive care (ICU) therapy until either cardiac and neurological recovery or palliation occurred. Analyses were descriptive. RESULTS: From February 2020 to May 2023, over 117 days, the team responded to 709 "potential cardiac arrest" emergency calls. 358 were confirmed OHCA. Time from emergency call to scene arrival was 27 min (15-37 min). 10 patients fulfilled the pre-defined inclusion criteria and all were successfully cannulated on scene. Time from emergency call to ECMO initiation was 50 min (35-62 min). Time from decision to ECMO support was 16 min (11-26 min). CPR duration was 46 min (32-62 min). All 10 patients were transferred to hospital for investigations and therapy. 4 patients (40%) survived to hospital discharge neurologically intact (CPC 1/2). CONCLUSION: Pre-hospital ECPR was feasible, using an experienced ECMO team from a single-centre. Overall survival was promising in this highly selected group. Further prospective studies are now warranted.

The aerosol box for intubation in coronavirus disease 2019 patients: an in-situ simulation crossover study.

The coronavirus disease 2019 pandemic has led to the manufacturing of novel devices to protect clinicians from the risk of transmission, including the aerosol box for use during tracheal intubation. We evaluated the impact of two aerosol boxes (an early-generation box and a latest-generation box) on intubations in patients with severe coronavirus disease 2019 with an in-situ simulation crossover study. The simulated process complied with the Safe Airway Society coronavirus disease 2019 airway management guidelines. The primary outcome was intubation time; secondary outcomes included first-pass success and breaches to personal protective equipment. All intubations were performed by specialist (consultant) anaesthetists and video recorded. Twelve anaesthetists performed 36 intubations. Intubation time with no aerosol box was significantly shorter than with the early-generation box (median (IQR [range]) 42.9 (32.9-46.9 [30.9-57.6])s vs. 82.1 (45.1-98.3 [30.8-180.0])s p = 0.002) and the latest-generation box (52.4 (43.1-70.3 [35.7-169.2])s, p = 0.008). No intubations without a box took more than 1 min, whereas 14 (58%) intubations with a box took over 1 min and 4 (17%) took over 2 min (including one failure). Without an aerosol box, all anaesthetists obtained first-pass success. With the early-generation and latest-generation boxes, 9 (75%) and 10 (83%) participants obtained first-pass success, respectively. One breach of personal protective equipment occurred using the early-generation box and seven breaches occurred using the latest-generation box. Aerosol boxes may increase intubation times and therefore expose patients to the risk of hypoxia. They may cause damage to conventional personal protective equipment and therefore place clinicians at risk of infection. Further research is required before these devices can be considered safe for clinical use.

Should ongoing airway education be a mandatory component of continuing professional development for College of Intensive Care Medicine Fellows?

This study aimed to determine whether airway education should be introduced to the continuing professional development (CPD) program for College of Intensive Care Medicine (CICM) Fellows. A random representative sample of 11 tertiary intensive care units (ICUs) was chosen from the list of 56 units accredited for 12 or 24 months of CICM training. All specialist intensive care Fellows (n=140) currently practising at the eleven ICUs were sent the questionnaire via email. Questionnaire data collection and post-collection data analysis was used to determine basic respondent demographics, frequency of certain airway procedures in the past 12 months, confidence with advanced airway practices in ICU, participation in airway education in the past three years, knowledge of can't intubate, can't oxygenate (CICO) algorithms, preference for certain airway equipment/techniques, and support for required airway education as a component of the CICM CPD program. All responses were tabled for comparison. Data was analysed to establish any significant effect of another specialty qualification and current co-practice in anaesthesia on volume of practice, confidence with multiple airway procedures, use of airway equipment, and support for airway education. In total, 112 responses (response rate 80%) to the questionnaire were received within four weeks; 107 were completed in full (compliance 96%). All results were tabled. There is currently widespread support amongst CICM Fellows for airway skills education as a CPD requirement for CICM Fellows. Volumes of practice and confidence levels with different airway procedures vary amongst Fellows and further support the need for education.

Optimization of propagation-based x-ray phase-contrast tomography for breast cancer imaging.

The aim of this study was to optimise the experimental protocol and data analysis for in-vivo breast cancer x-ray imaging. Results are presented of the experiment at the SYRMEP beamline of Elettra Synchrotron using the propagation-based phase-contrast mammographic tomography method, which incorporates not only absorption, but also x-ray phase information. In this study the images of breast tissue samples, of a size corresponding to a full human breast, with radiologically acceptable x-ray doses were obtained, and the degree of improvement of the image quality (from the diagnostic point of view) achievable using propagation-based phase-contrast image acquisition protocols with proper incorporation of x-ray phase retrieval into the reconstruction pipeline was investigated. Parameters such as the x-ray energy, sample-to-detector distance and data processing methods were tested, evaluated and optimized with respect to the estimated diagnostic value using a mastectomy sample with a malignant lesion. The results of quantitative evaluation of images were obtained by means of radiological assessment carried out by 13 experienced specialists. A comparative analysis was performed between the x-ray and the histological images of the specimen. The results of the analysis indicate that, within the investigated range of parameters, both the objective image quality characteristics and the subjective radiological scores of propagation-based phase-contrast images of breast tissues monotonically increase with the strength of phase contrast which in turn is directly proportional to the product of the radiation wavelength and the sample-to-detector distance. The outcomes of this study serve to define the practical imaging conditions and the CT reconstruction procedures appropriate for low-dose phase-contrast mammographic imaging of live patients at specially designed synchrotron beamlines.

Novel polymeric coatings with the potential to control in-stent restenosis--an in vitro study.

Restenosis following percutaneous coronary intervention (PCI) is a considerable problem in long-term performance of cardiovascular stents, with a functional endothelial cell monolayer being important in its prevention. This study evaluates the influence of polymer coatings on human aortic endothelial cells (HAEC) and coronary artery smooth muscle cells (HCASMC) in vitro, in terms of morphology, cell number, and phenotype. It was demonstrated that the polymer coatings can be tailored to enhance adhesion and growth of HAECs whilst suppressing that of HCASMCs. It is concluded that one of the polymer coatings (BTL 01015) shows potential as a stent coating to enhance re-endothelialization.

Invasive breast cancers detected by screening mammography: a detailed comparison of computer-aided detection-assisted single reading and double reading.

To compare double reading plus arbitration for discordance, (currently best practice, (BP)) with computer-aided-detection (CAD)-assisted single reading (CAD-R) for detection of invasive cancers detected within BreastScreen Australia. Secondarily, to examine characteristics of cancers detected/rejected using each method. Mammograms of 157 randomly selected double-read invasive cancers were mixed 1:9 with normal cancers (total 1569), all detected in a BreastScreen service. Cancers were detected by two readers or one reader (C2 and C1 cancers, ratio 70:30%) in the program. The 1569 film-screen mammograms were read by two radiologists (reader A (RA) and reader B(RB)), with findings recorded before and after CAD. Discordant findings with BP were resolved by arbitration. We compared CAD-assisted reading (CAD-RA, CAD-RB) with BP, and CAD and arbitration contribution to findings. We correlated cancer size, sensitivity and mammographic density with detection methods. BP sensitivity 90.4% compared with CAD-RA sensitivity 86.6% (P = 0.12) and CAD-RB 94.3% (P = 0.14). CAD-RB specificity was less than BP (P = 0.01). CAD sensitivity was 93%, but readers rejected most positive CAD prompts. After CAD, reader's sensitivity increased 1.9% and specificity dropped 0.2% and 0.8%. Arbitration decreased specificity 4.7%. Receiving operator curves analysis demonstrated BP accuracy better than CAD-RA, borderline significance (P = 0.07), but not CAD-RB. Secondarily, cancer size was similar for BP and CAD-R. Cancers recalled after arbitration (P = 0.01) and CAD-R (P = 0.10) were smaller. No difference in cancer size or sensitivity between reading methods was found with increasing breast density. CAD-R and BP sensitivity and cancer detection size were not significantly different. CAD-R specificity was significantly lower for one reader.

How accurate are antenatal weight measurements? A survey of hospital and community clinics in a South Thames Region NHS Trust.

The accuracy of antenatal weight data recorded in obstetric notes was investigated in the 45 hospital and community antenatal clinics within a South Thames Region NHS Trust. In order to assess the reliability and validity of all 60 clinic scales triplicate measurements of body weight for low- and high-weight subjects were recorded on each clinical scale and on a calibrated standard scale. The quality of weighing practice during antenatal care was investigated by means of semi-structured interviews conducted with all 33 midwives who currently provide antenatal care within the Trust. Beam balances had the highest reliability and validity, whereas scales with spring mechanisms were the least accurate. Only 40% of the clinics surveyed had access to beam balances, yet most of the maternal weight measurements recorded during antenatal care are likely to be out by no more than 1-1.5% of body weight. Weighing practice was generally inconsistent, and serial measurements of maternal body weight collected during pregnancy are probably too imprecise to provide a sensitive screen for conditions associated with unusual weight gain and too inaccurate to assess compliance with guidelines for weight gain.

Nucleoside analogues previously found to be inactive against HIV may be activated by simple chemical phosphorylation.

Nucleoside analogues previously found to be inactive against the human immunodeficiency virus (HIV) may be activated by simple chemical derivatisation. As part of our effort to deliver masked phosphates inside living cells we have discovered that certain phosphate triester derivatives of inactive nucleoside analogues become inhibitors of HIV replication. This discovery underlies the importance of the masked phosphate approach, and has significant implications for the future design of chemotherapeutic nucleoside analogues. If highly modified nucleoside analogues may be active without the intervention of nucleoside kinase enzymes, major advantage may accrue in terms of low toxicity and enhanced selectivity. Moreover, the increased structural freedom may have implications for dealing with the emergence of resistance. The concept herein described as 'kinase bypass' may thus stimulate the discovery of a new generation of antiviral agents.

Phosphate derivatives of AZT display enhanced selectivity of action against HIV 1 by comparison to the parent nucleoside.

Novel phosphate derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. In particular, phosphates carrying ester-containing side-chains are described. These materials are designed to act as membrane-soluble pro-drugs of the bio-active free nucleotides. In vitro evaluation revealed the compounds to have a pronounced, selective antiviral activity. In several cases the phosphate derivatives are more selective in their action than the parent nucleoside AZT. In particular, this arises from the low toxicity of the phosphate pro-drugs by comparison to AZT. These data support the suggestion that the phosphate derivatives exert their biological effects via intracellular release of the nucleotide forms, and suggests that such pro-drug forms may be worthy of further study.

Synthesis and anti-HIV activity of some novel lactyl and glycolyl phosphate derivatives.

Novel phosphate triester derivatives of 3'-acetylthymidine, and of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. These materials are designed to act as membrane-soluble pro-drugs of the bio-active free nucleotides. In particular, novel glycolate and lactate phosphate derivatives have been prepared. In vitro evaluation revealed the AZT compounds to have a pronounced and selective antiviral effect, the magnitude of which varied considerably with the nature of the phosphate blocking group.