Variation in emergency percutaneous coronary intervention in ventilated patients in the UK: insights from a national database

Aims Pre-procedural ventilation is a marker of high risk in PCI patients. Causes include out-of-hospital cardiac arrest (OHCA) and cardiogenic shock. OHCA occurs in approximately 60,000 patients in the UK per annum. No consensus exists regarding the need/timing of coronary angiography ± revascularization without ST elevation. The aim was to describe the national variation in the rate of emergency PCI in ventilated patients. Methods and Results Using the UK national database for PCI in 2013, we identified all procedures performed as ‘emergency’ or ‘salvage’ for whom ventilation had been initiated before the PCI. Of the 92,589 patients who underwent PCI, 1342 (5.5%) fulfilled those criteria. There was wide variation in practice. There was no demonstrable relationship between the number of emergency PCI patients with pre-procedure ventilation per annum and (i) total number of PPCIs in a unit (r = −0.186), and (ii) availability of 24 h PCI, (iii) on-site surgical cover. Conclusion We demonstrated a wide variation in practice across the UK in rates of pre-procedural ventilation in emergency PCI. The majority of individuals will have suffered an OHCA. In the absence of a plausible explanation for this discrepant practice, it is possible that (a) some patients presenting with OHCA that may benefit from revascularization are being denied treatment and (b) procedures may be being undertaken that are futile. Further prospective data are needed to aid in production of guidelines aiming at standardized care in OHCA

Comparison of denitrification induced by various organic substances - reaction rates, microbiology and temperature effect

Widespread groundwater pollution with nitrate (NO3−) and the finite and decreasing geogenic NO3− degradation capacity in aquifers require a better understanding of potential treatment methods. This project aimed at exploring and comparing the efficiency of four organic substances as electron donors for heterotrophic denitrification. Circulation column experiments using sediment without NO3− degradation capacity and high agricultural NO3− groundwater were conducted. Acetate, glucose, ascorbic acid, and ethanol were added to these columns in three concentration steps to induce biological denitrification, whereby also temperature dependence of denitrification rates (room temperature and typical groundwater temperature of 10°C) was taken into account. Results show denitrification with all four carbon (C) sources with intensities varying considerably between electron donors. Comparison of the two temperature approaches shows substantial differences between applied organic substances and indicates T as an important variable for denitrification. Ethanol is clearly the most effective electron donor for biodenitrification in groundwater investigated in this study, with a stronger and more effective NO3− degradation at 10°C than at room temperature. In contrast, much higher reaction rates are achieved with glucose at room temperature, compared to 10°C. Denitrification with ascorbic acid is very low at both temperatures; its addition produces biomass which repeatedly led to column clogging. In the entire test series, nitrite (NO2−) accumulation occurred more frequently and in higher concentrations at 10°C. Analysis of microorganisms shows a strong modification in microbial community in reaction to the addition of different organic C as well as between the two temperature approaches

The influence of Karst Aquifer mineralogy and geochemistry on groundwater characteristics: West Bank, Palestine

This work reports, for the first time, the mineralogical and geochemical characteristics of karst aquifers in the Central West Bank (CWB) catchment in Palestine. It provides an integrated study approach by correlating the geochemistry of the lithology and hydrochemical data of groundwater samples. Mineralogical analysis showed that all of the samples were dominantly composed of either calcite CaCO3 (5–100 wt. %) or dolomite CaMg(CO3)2 (4–100 wt. %), with minor amounts of quartz and feldspar, which is supported by the inorganic carbon content (9–13 wt. %) and hydrochemical composition of the spring water samples. The whole-rock geochemical data indicated that the samples have low contents of trace elements and transition metals. In contrast, the concentrations of alkaline earth elements (Mg, Ca, Sr, Ba) and Mn were high in the rock and groundwater samples. Generally, the trace elements of rock samples with concentrations >10 ppm included Sr (17–330 ppm), Mn (17–367 ppm), Ba (2–32 ppm), W (5–37 ppm), Cr (3–23 ppm), Zn (1.7–28 ppm), V (4–23 ppm), and Zr (1–22 ppm), while the concentrations of all the other trace elements was below 10 ppm. Ionic ratios and hierarchical cluster analysis (HCA) suggested that the chemical evolution of groundwater was mainly related to the geogenic (rock–water) interaction in the study area. This is clear in the alkaline earth elements (Mg, Ca, Sr, Ba) ratios, especially regarding the Sr values. The calcite rock samples had higher Sr (mean 160 ppm, n = 11) than those of the dolomite rocks (mean 76 ppm, n = 9)

Hyper-acute cardiovascular magnetic resonance T1 mapping predicts infarct characteristics in patients with ST elevation myocardial infarction

Background Myocardial recovery after primary percutaneous coronary intervention in acute myocardial infarction is variable and the extent and severity of injury are difficult to predict. We sought to investigate the role of cardiovascular magnetic resonance T1 mapping in the determination of myocardial injury very early after treatment of ST-segment elevation myocardial infarction (STEMI). Methods STEMI patients underwent 3 T cardiovascular magnetic resonance (CMR), within 3 h of primary percutaneous intervention (PPCI). T1 mapping determined the extent (area-at-risk as %left ventricle, AAR) and severity (average T1 values of AAR) of acute myocardial injury, and related these to late gadolinium enhancement (LGE), and microvascular obstruction (MVO). The characteristics of myocardial injury within 3 h was compared with changes at 24-h to predict final infarct size. Results Forty patients were included in this study. Patients with average T1 values of AAR ≥1400 ms within 3 h of PPCI had larger LGE at 24-h (33% ±14 vs. 18% ±10, P = 0.003) and at 6-months (27% ±9 vs. 12% ±9; P  9.5%) with 100% positive predictive value at the optimal cut-off of 1400 ms (area-under-the-curve, AUC 0.88, P = 0.006). Conclusion Hyper-acute T1 values of the AAR (within 3 h post PPCI, but not 24 h) predict a larger extent of MVO and infarct size at both 24 h and 6 months follow-up. Delayed CMR scanning for 24 h could not substitute the significant value of hyper-acute average T1 in determining infarct characteristics

The coordination of cell growth during fission yeast mating requires Ras1-GTP hydrolysis

The spatial and temporal control of polarity is fundamental to the survival of all organisms. Cells define their polarity using highly conserved mechanisms that frequently rely upon the action of small GTPases, such as Ras and Cdc42. Schizosaccharomyces pombe is an ideal system with which to study the control of cell polarity since it grows from defined tips using Cdc42-mediated actin remodeling. Here we have investigated the importance of Ras1-GTPase activity for the coordination of polarized cell growth during fission yeast mating. Following pheromone stimulation, Ras1 regulates both a MAPK cascade and the activity of Cdc42 to enable uni-directional cell growth towards a potential mating partner. Like all GTPases, when bound to GTP, Ras1 adopts an active conformation returning to an inactive state upon GTP-hydrolysis, a process accelerated through interaction with negative regulators such as GAPs. Here we show that, at low levels of pheromone stimulation, loss of negative regulation of Ras1 increases signal transduction via the MAPK cascade. However, at the higher concentrations observed during mating, hyperactive Ras1 mutations promote cell death. We demonstrate that these cells die due to their failure to coordinate active Cdc42 into a single growth zone resulting in disorganized actin deposition and unsustainable elongation from multiple tips. These results provide a striking demonstration that the deactivation stage of Ras signaling is fundamentally important in modulating cell polarity

Very early invasive angiography versus standard of care in higher-risk non-ST elevation myocardial infarction: study protocol for the prospective multicentre randomised controlled RAPID N-STEMI trial

Background: There are a paucity of randomised data on the optimal timing of invasive coronary angiography (ICA) in higher-risk patients with non-ST elevation myocardial infarction (N-STEMI). International guideline recommendations for early ICA are primarily based on retrospective subgroup analyses of neutral trials. Aims: The RAPID N-STEMI trial aims to determine whether very early percutaneous revascularisation improves clinical outcomes as compared with a standard of care strategy in higher-risk N-STEMI patients. Methods and analysis: RAPID N-STEMI is a prospective, multicentre, open-label, randomised-controlled, pragmatic strategy trial. Higher-risk N-STEMI patients, as defined by Global Registry of Acute Coronary Events 2.0 score ≥118, or >90 with at least one additional high-risk feature, were randomised to either: very early ICA±revascularisation or standard of care timing of ICA±revascularisation. The primary outcome is the proportion of participants with at least one of the following events (all-cause mortality, non-fatal myocardial infarction and hospital admission for heart failure) at 12 months. Key secondary outcomes include major bleeding and stroke. A hypothesis generating cardiac magnetic resonance (CMR) substudy will provide mechanistic data on infarct size, myocardial salvage and residual ischaemia post percutaneous coronary intervention. On 7 April 2021, the sponsor discontinued enrolment due to the impact of the COVID-19 pandemic and lower than expected event rates. 425 patients were enrolled, and 61 patients underwent CMR. Ethics and dissemination: The trial has been reviewed and approved by the East of England Cambridge East Research Ethics Committee (18/EE/0222). The study results will be submitted for publication within 6 months of completion. Trial registration number: NCT03707314; Pre-results

Histamine receptor activation by unsaturated (allyl and propargyl) homologs of histamine

The spectrum of agonist activity for three new homologs of histamine (cis- and trans-imidazolylallylamine and imidazolylpropargylamine) was evaluated in the isolated guinea pig ileum and right atrium. The homologs were about three log units less potent than histamine in stimulating contractions of the longitudinal muscles of the ileum, but they were histamine-like, pharmacologically, because they were sensitive to blockade by pyrilamine and resistant to blockade by atropine. In the right atrium, these weak agonists were partially sensitive to blockade by cimetidine. The agonist activity of the cis-isomer in particular was completely blocked by a combination of cimetidine and propranolol, but resistant to reserpine treatment (neuronal catecholamine depletion). Therefore, these homologs of histamine have the ability to stimulate H 1 - and H 2 -histamine receptors and beta -adrenoreceptors in vitro .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44880/1/11_2005_Article_BF01966582.pd