Adjunctive strategies in the management of resistant, 'undilatable' coronary lesions after successfully crossing a CTO with a guidewire.

Successful revascularisation of chronic total occlusions (CTOs) remains one of the greatest challenges in the era of contemporary percutaneous coronary intervention (PCI). Such lesions are encountered with increasing frequency in current clinical practice. A predictable increase in the future burden of CTO management can be anticipated given the ageing population, increased rates of renal failure, graft failure and diabetes mellitus. Given recent advances and developments in CTO PCI management, successful recanalisation can be anticipated in the majority of procedures undertaken at high-volume centres when performed by expert operators. Despite advances in device technology, the management of resistant, calcific lesions remains one of the greatest challenges in successful CTO intervention. Established techniques to modify calcific lesions include the use of high-pressure non-compliant balloon dilation, cutting-balloons, anchor balloons and high speed rotational atherectomy (HSRA). Novel approaches have proven to be safe and technically feasible where standard approaches have failed. A step-wise progression of strategies is demonstrated, from well-recognised techniques to techniques that should only be considered when standard manoeuvres have proven unsuccessful. These methods will be described in the setting of clinical examples and include use of very high-pressure non-compliant balloon dilation, intentional balloon rupture with vessel dissection or balloon assisted micro-dissection (BAM), excimer coronary laser atherectomy (ECLA) and use of HSRA in various 'offlabel' settings

Molecular Interactions of the Min Protein System Reproduce Spatiotemporal Patterning in Growing and Dividing Escherichia coli Cells

© 2015 Walsh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Oscillations of the Min protein system are involved in the correct midcell placement of the divisome during Escherichia coli cell division. Based on molecular interactions of the Min system, we formulated a mathematical model that reproduces Min patterning during cell growth and division. Specifically, the increase in the residence time of MinD attached to the membrane as its own concentration increases, is accounted for by dimerisation of membrane- bound MinD and its interaction with MinE. Simulation of this system generates unparalleled correlation between the waveshape of experimental and theoretical MinD distributions, suggesting that the dominant interactions of the physical system have been successfully incorporated into the model. For cells where MinD is fully-labelled with GFP, the model reproduces the stationary localization of MinD-GFP for short cells, followed by oscillations from pole to pole in larger cells, and the transition to the symmetric distribution during cell filamentation. Cells containing a secondary, GFP-labelled MinD display a contrasting pattern. The model is able to account for these differences, including temporary midcell localization just prior to division, by increasing the rate constant controlling MinD ATPase and heterotetramer dissociation. For both experimental conditions, the model can explain how cell division results in an equal distribution of MinD and MinE in the two daughter cells, and accounts for the temperature dependence of the period of Min oscillations. Thus, we show that while other interactions may be present, they are not needed to reproduce the main characteristics of the Min system in vivo

A Technical Focus on Antegrade Dissection and Re-entry for Coronary Chronic Total Occlusions: a Practice Update for 2019.

Coronary chronic total occlusions (CTOs) are a commonly encountered lesion. These present in a diverse patient population with variable anatomy. Technical success rates of ~90% are achievable for CTO lesions in centers with appropriate expertise. Many lesions can be crossed with wire-based techniques. However, the most anatomically complex and technically challenging lesions will often require more advanced approaches such as retrograde access and/or the application of blunt dissection techniques in the vessel to safely navigate long and/or ambiguous CTO segments. Retrograde dissection and re-entry (RDR) and antegrade dissection and re-entry (ADR) strategies are often needed to treat such lesions. In many circumstances, ADR offers a safe and efficient means to successfully cross a CTO lesion. Therefore, operators must remain cognizant of the risks and benefits of differing technical approaches during CTO percutaneous coronary intervention, particularly when both ADR and RDR are feasible. This article provides an overview of the ADR technique in addition to updated approaches in contemporary clinical practice

Patterning of the MinD cell division protein in cells of arbitrary shape can be predicted using a heuristic dispersion relation

© 2016, Paul M. G. Curmi, et al. Many important cellular processes require the accurate positioning of subcellular structures. Underpinning many of these are protein systems that spontaneously generate spatiotemporal patterns. In some cases, these systems can be described by non-linear reaction-diffusion equations, however, a full description of such equations is rarely available. A well-studied patterning system is the Min protein system that underpins the positioning of the FtsZ contractile ring during cell division in Escherichia coli. Using a coordinate-free linear stability analysis, the reaction terms can be separated from the geometry of a cell. The reaction terms produce a dispersion relation that can be used to predict patterning on any cell shape and size. Applying linear stability analysis to an accurate mathematical model of the Min system shows that while it correctly predicts the onset of patterning, the dispersion relation fails to predict oscillations and quantitative mode transitions. However, we show that data from full solutions of the Min model can be used to generate a heuristic dispersion relation. We show that this heuristic dispersion relation can be used to approximate the Min protein patterning obtained by full simulations of the non-linear reaction-diffusion equations. Moreover, it also predicts Min patterning obtained from experiments where the shapes of E. coli cells have been deformed into rectangles or arbitrary shapes. Using this procedure, it should be possible to generate heuristic dispersion relations from protein patterning data or simulations for any patterning process and subsequently use these to predict patterning for arbitrary cell shapes

Disparities In Cancer Care And Costs At The End Of Life: Evidence From England's National Health Service

In universal health care systems such as the English National Health Service, equality of access is a core principle, and health care is free at the point of delivery. However, even within a universal system, disparities in care and costs exist along a socioeconomic gradient. Little is known about socioeconomic disparities at the end of life and how they affect health care costs. This study examines disparities in end-of-life treatment costs for cancer patients in England. Analyzing data on over 250,000 colorectal, breast, prostate, and lung cancer patients from multiple national databases, we found evidence illustrating that disparities are driven largely by the greater use of emergency inpatient care among patients of lower socioeconomic status. Even within a system with free health care, differences in the use of care create disparities in cancer costs. While further studies of these barriers is required, our research suggests that disparities may be reduced through better management of needs through the use of less expensive and more effective health care settings and treatments

Evaluating the design and reporting of pragmatic trials in osteoarthritis research

Objectives. Among the challenges in health research is translating interventions from controlled experimental settings to clinical and community settings where chronic disease is managed daily. Pragmatic trials offer a method for testing interventions in real-world settings but are seldom used in OA research. The aim of this study was to evaluate the literature on pragmatic trials in OA research up to August 2016 in order to identify strengths and weaknesses in the design and reporting of these trials. Methods. We used established guidelines to assess the degree to which 61 OA studies complied with pragmatic trial design and reporting. We assessed design according to the pragmatic–explanatory continuum indicator summary and reporting according to the pragmatic trials extension of the CONsolidated Standards of Reporting Trials guidelines. Results. None of the pragmatic trials met all 11 criteria evaluated and most of the trials met between 5 and 8 of the criteria. Criteria most often unmet pertained to practitioner expertise (by requiring specialists) and criteria most often met pertained to primary outcome analysis (by using intention-to-treat analysis). Conclusion. Our results suggest a lack of highly pragmatic trials in OA research. We identify this as a point of opportunity to improve research translation, since optimizing the design and reporting of pragmatic trials can facilitate implementation of evidence-based interventions for OA care

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 JCTO≥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 ≥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

Are bisphosphonates effective in the treatment of osteoarthritis pain? A meta-analysis and systematic review.

Osteoarthritis (OA) is the most common form of arthritis worldwide. Pain and reduced function are the main symptoms in this prevalent disease. There are currently no treatments for OA that modify disease progression; therefore analgesic drugs and joint replacement for larger joints are the standard of care. In light of several recent studies reporting the use of bisphosphonates for OA treatment, our work aimed to evaluate published literature to assess the effectiveness of bisphosphonates in OA treatment

Developing a genetic manipulation system for the Antarctic archaeon, Halorubrum lacusprofundi: Investigating acetamidase gene function

© 2016 The Author(s). No systems have been reported for genetic manipulation of cold-adapted Archaea. Halorubrum lacusprofundi is an important member of Deep Lake, Antarctica (∼10% of the population), and is amendable to laboratory cultivation. Here we report the development of a shuttle-vector and targeted gene-knockout system for this species. To investigate the function of acetamidase/formamidase genes, a class of genes not experimentally studied in Archaea, the acetamidase gene, amd3, was disrupted. The wild-type grew on acetamide as a sole source of carbon and nitrogen, but the mutant did not. Acetamidase/formamidase genes were found to form three distinct clades within a broad distribution of Archaea and Bacteria. Genes were present within lineages characterized by aerobic growth in low nutrient environments (e.g. haloarchaea, Starkeya) but absent from lineages containing anaerobes or facultative anaerobes (e.g. methanogens, Epsilonproteobacteria) or parasites of animals and plants (e.g. Chlamydiae). While acetamide is not a well characterized natural substrate, the build-up of plastic pollutants in the environment provides a potential source of introduced acetamide. In view of the extent and pattern of distribution of acetamidase/formamidase sequences within Archaea and Bacteria, we speculate that acetamide from plastics may promote the selection of amd/fmd genes in an increasing number of environmental microorganisms

Safety and efficacy of the hybrid approach in coronary chronic total occlusion percutaneous coronary intervention: The Hybrid Video Registry

Objectives The aim of the Hybrid Video Registry (HVR) is to assess the acute safety and efficacy of the Hybrid Approach in comparison to other contemporary methods of CTO‐PCI. Background: Recently, multiple techniques in Percutaneous Coronary Intervention (PCI) for coronary Chronic Total Occlusions (CTO) have been synthesized into a method referred to as the “Hybrid Approach”. Methods About 194 video‐taped timed live cases from CTO‐PCI training workshops were analyzed by independent data abstractors and compared to three contemporary CTO‐PCI registries stratified by case complexity based on the J‐CTO score. Results Overall procedural success was 95% of all cases attempted with an excellent safety profile. In the most complex lesion subset, which made up 45% of all HVR cases, success was 92.8%, which was significantly higher than either the Royal Bromptom (78.9%), or Japanese‐CTO (73.3%) registries, P = 0.04 Hybrid vs. Royal Brompton, P = 0.006 Hybrid vs. Japanese‐CTO). The Hybrid Approach was also associated with shorter procedure times and lower contrast utilization. Conclusions In a real world angiographic registry of complex CTOs, the Hybrid Approach to CTO‐PCI is safe, and may be superior to other contemporary approaches to CTO intervention with respect to procedural success and efficiency among a diverse group of operators and lesion complexity