139 research outputs found
Scotland Registry for Ankylosing Spondylitis (SIRAS) â Protocol
Funding SIRAS was funded by unrestricted grants from Pfizer and AbbVie. The project was reviewed by both companies, during the award process, for Scientific merit, to ensure that the design did not compromise patient safety, and to assess the global regulatory implications and any impact on regulatory strategy.Publisher PD
Impact of proctoring on success rates for percutaneous revascularisation of coronary chronic total occlusions.
OBJECTIVE: To assess the impact of proctoring for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in six UK centres. METHODS: We retrospectively analysed 587 CTO procedures from six UK centres and compared success rates of operators who had received proctorship with success rates of the same operators before proctorship (pre-proctored) and operators in the same institutions who had not been proctored (non-proctored). There were 232 patients in the pre-proctored/non-proctored group and 355 patients in the post-proctored group. Complexity was assessed by calculating the Japanese CTO (JCTO) score for each case. RESULTS: CTO PCI success was greater in the post-proctored compared with the pre-proctored/non-proctored group (77.5% vs 62.1%, p<0.0001). In more complex cases where JCTOâ„2, the difference in success was greater (70.7% vs 49.5%, p=0.0003). After proctoring, there was an increase in CTO PCI activity in centres from 2.5% to 3.5%, p<0.0001 (as a proportion of total PCI), and the proportion of very difficult cases with JCTO score â„3 increased from 15.3% (35/229) to 29.7% (105/354), p<0.0001. CONCLUSIONS: Proctoring resulted in an increase in procedural success for CTO PCI, an increase in complex CTO PCI and an increase in total CTO PCI activity. Proctoring may be a valuable way to improve access to CTO PCI and the likelihood of procedural success
Comparison of Characteristics and Complications in Men Versus Women Undergoing Chronic Total Occlusion Percutaneous Intervention
Gender differences exist in clinical outcomes after routine percutaneous coronary intervention (PCI), but studies reporting such outcomes after chronic total occlusion (CTO) PCI are limited. We assessed the characteristics and outcomes of female patients undergoing CTO PCI. We retrospectively analyzed a dedicated national (United Kingdom) prospective CTO database from 2011 to 2015 for outcomes and characteristics of female patients undergoing CTO PCI (unmatched and propensity matched). Female patients constituted 20.5% (n = 260 of 1,271) of the unmatched cohort and 33.3% (n = 233 of 699) of the matched cohort and were more likely to be older (women aged >70 years, 48% in the unmatched and 45% in the matched cohort). An increased inhospital complication rate was observed in female patients (unmatched: 10% women vs 4.45% men, p = 0.0012, and matched 9.87% women vs 3.86% men, p = 0.0032). Coronary perforation, bleeding, and contrast-induced nephropathy were more frequently observed in female patients. Femoral access site with >6 French sheath was associated with an increased risk of bleeding. Presence of calcification in the CTO artery was associated with coronary perforation (grade III) in female patients in the matched cohort (p = 0.007). Female patients undergoing CTO PCI were older and experienced increased of inhospital complications. Increased awareness of these complications could influence the selection of access site and sheath size, the need for prehydration, judicious choice of balloon size, collateral selection, and wire placement in female patients undergoing CTO PCI
The effects of remote ischaemic preconditioning on coronary artery function in patients with stable coronary artery disease
Background: Remote ischaemic preconditioning (RIPC) is a cardioprotective intervention invoking intermittent
periods of ischaemia in a tissue or organ remote from the heart. The mechanisms of this effect are incompletely
understood. We hypothesised that RIPC might enhance coronary vasodilatation by an endothelium-dependent
mechanism.
Methods: We performed a prospective, randomised, sham-controlled, blinded clinical trial. Patients with stable
coronary artery disease (CAD) undergoing elective invasive management were prospectively enrolled,
and randomised to RIPC or sham (1:1) prior to angiography. Endothelial-dependent vasodilator function
was assessed in a non-target coronary artery with intracoronary infusion of incremental acetylcholine doses
(10â6
, 10â5
, 10â4 mol/l). Venous blood was sampled pre- and post-RIPC or sham, and analysed for circulating
markers of endothelial function. Coronary luminal diameter was assessed by quantitative coronary angiography.
The primary outcome was the between-group difference in the mean percentage change in coronary luminal diameter
following the maximal acetylcholine dose (Clinicaltrials.gov identifier: NCT02666235).
Results: 75 patients were enrolled. Following angiography, 60 patients (mean ± SD age 57.5 ± 8.5 years; 80%
male) were eligible and completed the protocol (n = 30 RIPC, n = 30 sham). The mean percentage change in
coronary luminal diameter was â13.3 ± 22.3% and â2.0 ± 17.2% in the sham and RIPC groups respectively
(difference 11.32%, 95%CI: 1.2â 21.4, p = 0.032). This remained significant when age and sex were included as
covariates (difference 11.01%, 95%CI: 1.01â 21.0, p = 0.035). There were no between-group differences in
endothelial-independent vasodilation, ECG parameters or circulating markers of endothelial function.
Conclusions: RIPC attenuates the extent of vasoconstriction induced by intracoronary acetylcholine infusion. This
endothelium-dependent mechanism may contribute to the cardioprotective effects of RIP
Single vs. multiple operators for chronic total occlusion percutaneous coronary interventions: From the PROGRESSâCTO Registry
Risk assessment for the spread of Serratia marcescens within dental-unit waterline systems using Vermamoeba vermiformis
Vermamoeba vermiformis is associated with the biofilm ecology of dental-unit waterlines (DUWLs). This study investigated whether V. vermiformis is able to act as a vector for potentially pathogenic bacteria and so aid their dispersal within DUWL systems. Clinical dental water was initially examined for Legionella species by inoculating it onto Legionella selective-medium plates. The molecular identity/profile of the glassy colonies obtained indicated none of these isolates were Legionella species. During this work bacterial colonies were identified as a non-pigmented Serratia marcescens. As the water was from a clinical DUWL which had been treated with Alpronâą this prompted the question as to whether S. marcescens had developed resistance to the biocide. Exposure to Alpronâą indicated that this dental biocide was effective, under laboratory conditions, against S. marcescens at up to 1x108 colony forming units/millilitre (cfu/ml). V. vermiformis was cultured for eight weeks on cells of S. marcescens and Escherichia coli. Subsequent electron microscopy showed that V. vermiformis grew equally well on S. marcescens and E. coli (p = 0.0001). Failure to detect the presence of S. marcescens within the encysted amoebae suggests that V. vermiformis is unlikely to act as a vector supporting the growth of this newly isolated, nosocomial bacterium
Predictors of segmental myocardial functional recovery in patients after an acute ST-elevation myocardial infarction
Objective:
We hypothesized that Displacement Encoding with Stimulated Echoes (DENSE) and feature-tracking derived circumferential strain would provide incremental prognostic value over the extent of infarction for recovery of segmental myocardial function.
Methods:
Two hundred and sixty-one patients (mean age 59 years, 73% male) underwent MRI 2 days post-ST elevation myocardial infarction (STEMI) and 241 (92%) underwent repeat imaging 6 months later.
The MRI protocol included cine, 2D-cine DENSE, T2 mapping and late enhancement.
Wall motion scoring was assessed by 2-blinded observers and adjudicated by a third. (WMS: 1=normal, 2=hypokinetic, 3=akinetic, 4=dyskinetic). WMS improvement was defined as a decrease in WMSââ„â1, and normalization where WMSâ=â1 on follow-up. Segmental circumferential strain was derived utilizing DENSE and feature-tracking.
A generalized linear mixed model with random effect of subject was constructed and used to account for repeated sampling when investigating predictors of segmental myocardial improvement or normalization
Results:
At baseline and follow-up, 1416 segments had evaluable data for all parameters. Circumferential strain by DENSE (pâ<â0.001) and feature-tracking (pâ<â0.001), extent of oedema (pâ<â0.001), infarct size (pâ<â0.001), and microvascular obstruction (pâ<â0.001) were associates of both improvement and normalization of WMS. Circumferential strain provided incremental predictive value even after accounting for infarct size, extent of oedema and microvascular obstruction, for segmental improvement (DENSE: odds ratio, 95% confidence intervals: 1.08 per â1% peak strain, 1.05â1.12, pâ<â0.001, feature-tracking: odds ratio, 95% confidence intervals: 1.05 per â1% peak strain, 1.03â1.07, pâ<â0.001) and segmental normalization (DENSE: 1.08 per â1% peak strain, 1.04â1.12, pâ<â0.001, feature-tracking: 1.06 per â1% peak strain, 1.04â1.08, pâ<â0.001).
Conclusions:
Circumferential strain provides incremental prognostic value over segmental infarct size in patients post STEMI for predicting segmental improvement or normalization by wall-motion scoring
Intravascular Lithotripsy for Calcium Modification in Chronic Total Occlusion Percutaneous Coronary Intervention.
Intravascular lithotripsy (IVL) has been shown to be safe and effective for calcium modification in nonocclusive coronary artery disease (CAD), but there are only case reports of its use in calcified chronic total occlusions (CTO). We report data from an international multicenter registry of IVL use during CTO percutaneous coronary intervention (PCI) and provide provisional data regarding its efficacy and safety. During the study period, IVL was used in 55 of 1053 (5.2%) CTO PCI procedures. IVL was used within the occluded segment after successful CTO crossing in 53 procedures and during incomplete CTO crossing in 2 cases. The mean J-CTO score was 3.1. CTO PCI technical and procedural success was achieved in 53 (96%) and 51 (93%) cases. Six patients had a procedural complication, with 3 main vessel perforations (5%). Two had covered stent implantation, one required pericardiocentesis, and one was managed conservatively. All had combination therapy with another calcium modification device. Two patients had a procedural myocardial infarction (PMI) (4%), and two others had a major adverse cardiovascular event (MACE) (4%) at a median follow-up of 13 (4-21) months. IVL can effectively facilitate calcium modification during CTO PCI. More data are required to establish the efficacy and safety of IVL and other calcium modification devices when used extraplaque or in combination during CTO PCI
Effects of Intracoronary Alteplase on Microvascular Function in Acute Myocardial Infarction
BackgroundâImpaired microcirculatory reperfusion worsens prognosis following acute STâsegmentâelevation myocardial infarction. In the TâTIME (A Trial of LowâDose Adjunctive Alteplase During Primary PCI) trial, microvascular obstruction on cardiovascular magnetic resonance imaging did not differ with adjunctive, lowâdose, intracoronary alteplase (10 or 20 mg) versus placebo during primary percutaneous coronary intervention. We evaluated the effects of intracoronary alteplase, during primary percutaneous coronary intervention, on the index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio.
Methods and ResultsâA prespecified physiology substudy of the TâTIME trial. From 2016 to 2017, patients with STâsegmentâelevation myocardial infarction â€6 hours from symptom onset were randomized in a doubleâblind study to receive alteplase 20 mg, alteplase 10 mg, or placebo infused into the culprit artery postreperfusion, but prestenting. Index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio were measured after percutaneous coronary intervention. Cardiovascular magnetic resonance was performed at 2 to 7 days and 3 months. Analyses in relation to ischemic time (<2, 2â4, and â„4 hours) were prespecified. One hundred fortyâfour patients (mean age, 59±11 years; 80% male) were prospectively enrolled, representing 33% of the overall population (n=440). Overall, index of microcirculatory resistance (median, 29.5; interquartile range, 17.0â55.0), coronary flow reserve(1.4 [1.1â2.0]), and resistive reserve ratio (1.7 [1.3â2.3]) at the end of percutaneous coronary intervention did not differ between treatment groups. Interactions were observed between ischemic time and alteplase for coronary flow reserve (P=0.013), resistive reserve ratio (P=0.026), and microvascular obstruction (P=0.022), but not index of microcirculatory resistance.
ConclusionsâIn STâsegmentâelevation myocardial infarction with ischemic time â€6 hours, there was overall no difference in microvascular function with alteplase versus placebo
Targeting endothelin receptor signalling overcomes heterogeneity driven therapy failure
Approaches to prolong responses to BRAF targeting drugs in melanoma patients are challenged by phenotype heterogeneity. Melanomas of a âMITFâhighâ phenotype usually respond well to BRAF inhibitor therapy, but these melanomas also contain subpopulations of the de novo resistance âAXLâhighâ phenotype. > 50% of melanomas progress with enriched âAXLâhighâ populations, and because AXL is linked to deâdifferentiation and invasiveness avoiding an âAXLâhigh relapseâ is desirable. We discovered that phenotype heterogeneity is supported during the response phase of BRAF inhibitor therapy due to MITFâinduced expression of endothelin 1 (EDN1). EDN1 expression is enhanced in tumours of patients on treatment and confers drug resistance through ERK reâactivation in a paracrine manner. Most importantly, EDN1 not only supports MITFâhigh populations through the endothelin receptor B (EDNRB), but also AXLâhigh populations through EDNRA, making it a master regulator of phenotype heterogeneity. Endothelin receptor antagonists suppress AXLâhighâexpressing cells and sensitize to BRAF inhibition, suggesting that targeting EDN1 signalling could improve BRAF inhibitor responses without selecting for AXLâhigh cells
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