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Post-harvest treatments of pre-packaged salad leaves potentially cause l-ascorbate loss, but the mechanisms of ascorbate degradation remain incompletely understood, especially in planta. We explored the extent and pathways of ascorbate loss in variously washed and stored salad leaves. Ascorbate was assayed by 2,6-dichlorophenolindophenol titration, and pathways were monitored by 14C-radiolabelling followed by high-voltage electrophoresis. All leaves tested showed ascorbate loss during storage: lettuce showed the greatest percentage loss, wild rocket the least. Spinach leaves were particularly prone to losing ascorbate during washing, especially with simultaneous mechanical agitation; however, washing in the presence of hypochlorite did not significantly increase ascorbate loss. In spinach, [14C]oxalate was the major product of [14C]ascorbate degradation, suggesting that commercial washing causes oxidative stress. This study highlights that ascorbate/dehydroascorbic acid are lost via the oxidative pathway during washing and post-harvest storage of salad leaves. Thus changes to washing procedures could potentially increase the post-harvest retention of ascorbate.

BackgroundConsuming watercress is thought to provide health benefits as a consequence of its phytonutrient composition. However, for watercress there are currently limited genetic resources underpinning breeding efforts for either yield or phytonutritional traits. In this paper, we use RNASeq data from twelve watercress accessions to characterize the transcriptome, perform candidate gene mining and conduct differential expression analysis for two key phytonutritional traits: antioxidant (AO) capacity and glucosinolate (GLS) content.ResultsThe watercress transcriptome was assembled to 80,800 transcripts (48,732 unigenes); 71 % of which were annotated based on orthology to Arabidopsis. Differential expression analysis comparing watercress accessions with 'high' and 'low' AO and GLS resulted in 145 and 94 differentially expressed loci for AO capacity and GLS respectively. Differentially expressed loci between high and low AO watercress were significantly enriched for genes involved in plant defence and response to stimuli, in line with the observation that AO are involved in plant stress-response. Differential expression between the high and low GLS watercress identified links to GLS regulation and also novel transcripts warranting further investigation. Additionally, we successfully identified watercress orthologs for Arabidopsis phenylpropanoid, GLS and shikimate biosynthesis pathway genes, and compiled a catalogue of polymorphic markers for future applications.ConclusionsOur work describes the first transcriptome of watercress and establishes the foundation for further molecular study by providing valuable resources, including sequence data, annotated transcripts, candidate genes and markers.

Watercress (Nasturtium officinale R. Br.) is a nutrient intense, leafy crop that is consumed raw or in soups across the globe, but for which, currently no genomic resources or breeding programme exists. Promising morphological, biochemical and functional genomic variation was identified for the first time in a newly established watercress germplasm collection, consisting of 48 watercress accessions sourced from contrasting global locations. Stem length, stem diameter and anti-oxidant (AO) potential varied across the accessions. This variation was used to identify three extreme contrasting accessions for further analysis. Variation in global gene expression was investigated using an Affymetrix Arabidopsis ATH1 microarray gene chip, using the commercial control (C), an accession selected for dwarf phenotype with a high AO potential (dwarfAO, called 'Boldrewood') and one with high AO potential alone. A set of transcripts significantly differentially expressed between these three accessions, were identified, including transcripts involved in the regulation of growth and development and those involved in secondary metabolism. In particular, when differential gene expression was compared between C and dwarfAO, the dwarfAO was characterised by increased expression of genes encoding glucosinolates, which are known precursors of phenethyl isothiocyanate, linked to the anti-carcinogenic effects well-documented in watercress. This study provides the first analysis of natural variation across the watercress genome and has identified important underpinning information for future breeding for enhanced anti-carcinogenic properties and morphology traits in this nutrient-intense crop.

A diet rich in phytonutrients from fruit and vegetables has been acknowledged to afford protection against a range of human diseases, but many of the most popular vegetables are low in phytonutrients. Wild relatives of crops may contain allelic variation for genes determining the concentrations of these beneficial phytonutrients, and therefore understanding the genetic basis of this variation is important for breeding efforts to enhance nutritional quality. In this study, lettuce recombinant inbred lines, generated from a cross between wild and cultivated lettuce (Lactuca serriola and Lactuca sativa, respectively), were analysed for antioxidant (AO) potential and important phytonutrients including carotenoids, chlorophyll and phenolic compounds. When grown in two environments, 96 quantitative trait loci (QTL) were identified for these nutritional traits: 4 for AO potential, 2 for carotenoid content, 3 for total chlorophyll content and 87 for individual phenolic compounds (two per compound on average). Most often, the L. serriola alleles conferred an increase in total AOs and metabolites. Candidate genes underlying these QTL were identified by BLASTn searches; in several cases, these had functions suggesting involvement in phytonutrient biosynthetic pathways. Analysis of a QTL on linkage group 3, which accounted for >30% of the variation in AO potential, revealed several candidate genes encoding multiple MYB transcription factors which regulate flavonoid biosynthesis and flavanone 3-hydroxylase, an enzyme involved in the biosynthesis of the flavonoids quercetin and kaempferol, which are known to have powerful AO activity. Follow-up quantitative RT-PCR of these candidates revealed that 5 out of 10 genes investigated were significantly differentially expressed between the wild and cultivated parents, providing further evidence of their potential involvement in determining the contrasting phenotypes. These results offer exciting opportunities to improve the nutritional content and health benefits of lettuce through marker-assisted breeding.

Thermal imaging has been used in the past for remote detection of regions of canopy showing symptoms of stress, including water deficit stress. Stress indices derived from thermal images have been used as an indicator of canopy water status, but these depend on the choice of reference surfaces and environmental conditions and can be confounded by variations in complex canopy structure. Therefore, in this work, instead of using stress indices, information from thermal and visible light imagery was combined along with machine learning techniques to identify regions of canopy showing a response to soil water deficit. Thermal and visible light images of a spinach canopy with different levels of soil moisture were captured. Statistical measurements from these images were extracted and used to classify between canopies growing in well-watered soil or under soil moisture deficit using Support Vector Machines (SVM) and Gaussian Processes Classifier (GPC) and a combination of both the classifiers. The classification results show a high correlation with soil moisture. We demonstrate that regions of a spinach crop responding to soil water deficit can be identified by using machine learning techniques with a high accuracy of 97%. This method could, in principle, be applied to any crop at a range of scales.

Watercress (Rorippa nasturtium-aquaticum), wild rocket (Diplotaxis tenuifolia), and spinach (Spinacia oleracea) are commercial crops reported to have high concentrations of antioxidants, possibly contributing to disease prevention following human consumption. Following analysis of supermarket-purchased salad leaves, we report the antioxidant content potential of these species using two comparable techniques assessing the consistency between the assays - by the ferric reducing antioxidant power (FRAP) assay and the oxygen radical absorbance capacity (ORAC) assay. The leaves were harvested from both conventionally and organically managed crops, to investigate whether organic agriculture results in improved crop quality. Watercress had the highest FRAP and ability to scavenge free radicals, followed by spinach and rocket. For watercress and rocket, there was no significant effect of organic agriculture on FRAP and ORAC, but for spinach, the antioxidant potential was reduced and this was significant at the 5% level of probability for FRAP but not ORAC, although the trend was clear in both tests. We conclude that there is variation in salad crop antioxidant potential and that FRAP and ORAC are useful techniques for measuring antioxidants in these salad crops with similar ranking for each salad crop studied.

It is proposed that post-harvest longevity and appearance of salad crops is closely linked to pre-harvest leaf morphology (cell and leaf size) and biophysical structure (leaf strength). Transgenic lettuce plants (Lactuca sativa cv. Valeria) were produced in which the production of the cell wall-modifying enzyme xyloglucan endotransglucosylase/hydrolase (XTH) was down-regulated by antisense inhibition. Independently transformed lines were shown to have multiple members of the LsXTH gene family down-regulated in mature leaves of 6-week-old plants and during the course of shelf life. Consequently, xyloglucan endotransglucosylase (XET) enzyme activity and action were down-regulated in the cell walls of these leaves and it was established that leaf area and fresh weight were decreased while leaf strength was increased in the transgenic lines. Membrane permeability was reduced towards the end of shelf life in the transgenic lines relative to the controls and bacteria were evident inside the leaves of control plants only. Most importantly, an extended shelf-life of transgenic lines was observed relative to the non-transgenic control plants. These data illustrate the potential for engineering cell wall traits for improving quality and longevity of salad crops using either genetic modification directly, or by using markers associated with XTH genes to inform a commercial breeding programme.

OBJECTIVES: To evaluate the impact the National Service Framework (NSF) for coronary heart disease has had on emergency treatment and outcomes in patients presenting with acute coronary syndromes. DESIGN: Retrospective cohort study. SETTING: Coronary care units of two district general hospitals. RESULTS: Data from 3371 patients were recorded, 1993 patients in the 27 months before the introduction of the NSF and 1378 patients in the 24 months afterwards. After the introduction of the NSF in-hospital mortality was significantly reduced (95 patients (4.8%) v 43 (3.2%), p = 0.02). This was associated with a reduction in the development of Q wave myocardial infarction (40.6% v 33.3%, p < 0.0001) and in the incidence of left ventricular failure (15.9% v 12.3%, p = 0.003). The proportion of patients receiving thrombolysis increased (69.4% v 84.7%, p < 0.0001) with a decrease in the time taken to receive it (proportion thrombolysed within 20 minutes 12.1% v 26.6%, p < 0.0001). The prescription of beta blockers (51.9% v 65.8%, p < 0.0001), angiotensin converting enzyme inhibitors (37% v 66.4%, p < 0.0001), and statins (55.2% v 72.7%, p < 0.0001) improved and the proportion of patients referred for invasive investigation increased (18.3% v 27.0%, p < 0.0001). Trend analysis showed that improvements in mortality and thrombolysis were directly associated with publication of the NSF, whereas the improvements seen in prescription of beta blockers and statins were the continuation of pre-existing trends. CONCLUSIONS: In the two years that followed publication of the NSF the initial treatment and outcome of patients presenting with acute coronary syndromes improved. Some of the improvements can be attributed to the NSF but others are continuations of pre-existing trends. [ABSTRACT FROM AUTHOR]

The first paper in this series itemised the research undertaken to discover the unexpressed needs of the village population. Community Participatory Appraisal methodology ensured that local people had the opportunity to express their opinions and health needs. Interviews were analysed and data offered to a focus group for ratification. This information was then used to create a questionnaire. The World Health Organization Quality of Life questionnaire (brief form) and Antonovsky's 'Orientation to Life' questionnaire were added to ensure as many aspects affecting the health of the population were covered. The questionnaire indicated the importance for planning purposes. The role of health visitors has recently returned to the broader remit outlined in 1977 by the Council for the Education of Health Visitors and framed in the four principles of health visiting. In the 1980s the medical model of health visiting prevailed and individual health promotion dominated. During the 1990s this expanded to encompass 'family public health' looking at the impact of a variety of attributes, for example; poverty, relationships, lifestyle and community. Now government is urging health visitors to work with populations; to determine health needs and collaborate with agencies to effect changes. Implementation of the research findings, detailed in this, the second paper, records the steps taken to accomplish 'micro' population public health and the success of this new way of working. Health visitors need to equip themselves with a variety of new ways of working, including community development, in order to maximise the health of their population. [ABSTRACT FROM AUTHOR]

Drug-coated balloon (DCB) catheters offer an alternative to drug-eluting stents (DES) by delivering anti-proliferative drugs directly to vessel walls, avoiding implantation of a permanent metallic structure. While DCBs have shown efficacy for in-stent restenosis, evidence for their application in de novo coronary disease and chronic total occlusion (CTO) PCI is growing. We present a case of a 49-year-old male with multivessel chronic total and subtotal occlusions who had complete percutaneous revascularisation using a DCB only strategy. Each lesion had unique characteristics involving its length and location, bifurcation anatomy, and vessel diameter for which this stent-free approach was favored. DCB use in CTO PCI may be promising in select cases and lesions, and further studies are warranted to ascertain long-term efficacy in this setting., (© 2024 Wiley Periodicals LLC.)

X chromosome inactivation (XCI) generates clonal heterogeneity within XX individuals. Combined with sequence variation between human X chromosomes, XCI gives rise to intra-individual clonal diversity, whereby two sets of clones express mutually exclusive sequence variants present on one or the other X chromosome. Here we ask whether such clones merely co-exist or potentially interact with each other to modulate the contribution of X-linked diversity to organismal development. Focusing on X-linked coding variation in the human STAG2 gene, we show that Stag2 variant clones contribute to most tissues at the expected frequencies but fail to form lymphocytes in Stag2 WT Stag2 variant mouse models. Unexpectedly, the absence of Stag2 variant clones from the lymphoid compartment is due not solely to cell-intrinsic defects but requires continuous competition by Stag2 WT clones. These findings show that interactions between epigenetically diverse clones can operate in an XX individual to shape the contribution of X-linked genetic diversity in a cell-type-specific manner., (© 2024. The Author(s).)

Subclavian artery pseudoaneurysms are rare and associated with high morbidity and mortality. Alternative approaches to open surgical repair can include endovascular repair or ultrasound-guided thrombin injection. Here, we describe a safe and novel technique of closure of a subclavian artery pseudoaneurysm with Angio-Seal that was unresponsive to thrombin injection and in a difficult location for open repair., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024 The Author(s).)

Coho salmon ( Oncorhynchus kisutch ) are highly sensitive to 6PPD-Quinone (6PPD-Q). Details of the hydrological and biogeochemical processes controlling spatial and temporal dynamics of 6PPD-Q fate and transport from points of deposition to receiving waters (e.g., streams, estuaries) are poorly understood. To understand the fate and transport of 6PPD and mechanisms leading to salmon mortality Visualizing Ecosystem Land Management Assessments (VELMA), an ecohydrological model developed by US Environmental Protection Agency (EPA), was enhanced to better understand and inform stormwater management planning by municipal, state, and federal partners seeking to reduce stormwater contaminant loads in urban streams draining to the Puget Sound National Estuary. This work focuses on the 5.5 km2 Longfellow Creek upper watershed (Seattle, Washington, United States), which has long exhibited high rates of acute urban runoff mortality syndrome in coho salmon. We present VELMA model results to elucidate these processes for the Longfellow Creek watershed across multiple scales-from 5-m grid cells to the entire watershed. Our results highlight hydrological and biogeochemical controls on 6PPD-Q flow paths, and hotspots within the watershed and its stormwater infrastructure, that ultimately impact contaminant transport to Longfellow Creek and Puget Sound. Simulated daily average 6PPD-Q and available observed 6PPD-Q peak in-stream grab sample concentrations (ng/L) corresponds within plus or minus 10 ng/L. Most importantly, VELMA's high-resolution spatial and temporal analysis of 6PPD-Q hotspots provides a tool for prioritizing the locations, amounts, and types of green infrastructure that can most effectively reduce 6PPD-Q stream concentrations to levels protective of coho salmon and other aquatic species., Competing Interests: Conflict of interest Author KD was employed by Inoventures Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Purpose of Review: In-stent restenosis (ISR) is the most common cause of stent failure. Although the rate of ISR is significantly lower with contemporary drug-eluting stents (DES), it remains a challenging clinical entity to treat., Recent Findings: In this review, we focus on a practical approach to management of DES ISR with intravascular imaging at its core, as supported by several recently published articles. This facilitates assessment of the underlying mechanism(s) essential to the successful treatment of ISR allowing for a tailored selection of treatment modalities., Summary: The successful treatment of DES ISR requires identification of the causative mechanism(s). Individualized treatment may include high-pressure balloon angioplasty alone, cutting or scoring balloons, intravascular lithotripsy, atheroablative therapies and a selection of either repeat DES implantation or drug-coated balloon treatment., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Mussel foot protein 5 (fp5) found in the adhesive byssal plaque of Mediterranean mussel Mytilus galloprovincialis exhibits exceptional underwater adhesion to diverse surfaces to the extent that adhesion strength typically exceeds the cohesive strength of the plaque. While sequence effects such as presence of charged residues, metal ion coordination, and high catechol content have been identified to govern fp5's interaction with surfaces, molecular contributors to its cohesive strength remain to be fully understood. Addressing this issue is critical for designing mussel-inspired sequences for new adhesives and biomaterials enabled by synthetic biology. Here we carry out all-atom molecular dynamics simulations on hydrated model fp5 biopolymer melts to understand how sequence features such as tyrosine and charge content affect packing density and inter-residue and ionic interaction strengths and consequently influence the cohesive strength and toughness. Systematic serine (S) substitutions for lysine (K), arginine (R) and tyrosine (Y) residues reveal that Y to S substitution surprisingly results in improvement of cohesive strength due to densification of the material by removal of steric hindrances, whereas the removal of charge in K and R to S substitutions has a detrimental impact on strength and toughness as it reduces cohesive interactions facilitated by electrostatic interactions. Additionally, melts formed from split fp5 sequences with only C or N terminal halves show distinct mechanical responses that further illustrate the role of charge. Our findings provide new insights for designing materials that could potentially surpass the performance of existing biomolecular and bioinspired adhesives, specifically by tailoring sequences for balancing charge and excluded volume effects.

In the early stages of mitosis, cohesin is released from chromosome arms but not from centromeres. The protection of centromeric cohesin by SGO1 maintains the sister chromatid cohesion that resists the pulling forces of microtubules until all chromosomes are attached in a bipolar manner to the mitotic spindle. Here we present the X-ray crystal structure of a segment of human SGO1 bound to a conserved surface of the cohesin complex. SGO1 binds to a composite interface formed by the SA2 and SCC1 RAD21 subunits of cohesin. SGO1 shares this binding interface with CTCF, indicating that these distinct chromosomal regulators control cohesin through a universal principle. This interaction is essential for the localization of SGO1 to centromeres and protects centromeric cohesin against WAPL-mediated cohesin release. SGO1-cohesin binding is maintained until the formation of microtubule-kinetochore attachments and is required for faithful chromosome segregation and the maintenance of a stable karyotype., (© 2023. The Author(s).)

Unconjugated bilirubin (UCB) confers Th17-cells immunosuppressive features by activating aryl-hydrocarbon-receptor, a modulator of toxin and adaptive immune responses. In Crohn's disease, Th17-cells fail to acquire regulatory properties in response to UCB, remaining at an inflammatory/pathogenic state. Here we show that UCB modulates Th17-cell metabolism by limiting glycolysis and through downregulation of glycolysis-related genes, namely phosphoglycerate-kinase-1 (PGK1) and aldolase-A (ALDOA). Th17-cells of Crohn's disease patients display heightened PGK1 and ALDOA and defective response to UCB. Silencing of PGK1 or ALDOA restores Th17-cell response to UCB, as reflected by increase in immunoregulatory markers like FOXP3, IL-10 and CD39. In vivo, PGK1 and ALDOA silencing enhances UCB salutary effects in trinitro-benzene-sulfonic-acid-induced colitis in NOD/scid/gamma humanized mice where control over disease activity and enhanced immunoregulatory phenotypes are achieved. PGK1 and/or ALDOA blockade might have therapeutic effects in Crohn's disease by favoring acquisition of regulatory properties by Th17-cells along with control over their pathogenic potential., (© 2022. The Author(s).)

Background and Aims: The "gut homing" hypothesis suggests the pathogenesis of primary sclerosing cholangitis (PSC) is driven by aberrant hepatic expression of gut adhesion molecules and subsequent recruitment of gut-derived T cells to the liver. However, inconsistencies lie within this theory including an absence of investigations and comparisons with other chronic liver diseases (CLD). Here, we examine "the gut homing theory" in patients with PSC with associated inflammatory bowel disease (PSC-IBD) and across multiple inflammatory liver diseases., Approach and Results: Expression of MAdCAM-1, CCL25, and E-Cadherin were assessed histologically and using RT-PCR on explanted liver tissue from patients with CLD undergoing OLT and in normal liver. Liver mononuclear cells were isolated from explanted tissue samples and the expression of gut homing integrins and cytokines on hepatic infiltrating gut-derived T cells was assessed using flow cytometry. Hepatic expression of MAdCAM-1, CCL25 and E-Cadherin was up-regulated in all CLDs compared with normal liver. There were no differences between disease groups. Frequencies of α4β7, αEβ7, CCR9, and GPR15 expressing hepatic T cells was increased in PSC-IBD, but also in CLD controls, compared with normal liver. β7 expressing hepatic T cells displayed an increased inflammatory phenotype compared with β7 negative cells, although this inflammatory cytokine profile was present in both the inflamed and normal liver., Conclusions: These findings refute the widely accepted "gut homing" hypothesis as the primary driver of PSC and indicate that aberrant hepatic recruitment of gut-derived T cells is not unique to PSC, but is a panetiological feature of CLD., (© 2021 American Association for the Study of Liver Diseases.)

Background: Chronic total occlusions (CTO) are common and are associated with lower percutaneous coronary intervention (PCI) success rates, often due to failure of antegrade guidewire crossing. Local, intralesional delivery of collagenase (MZ-004) may facilitate guidewire crossing in CTO., Aims: To evaluate the effect of MZ-004 in facilitating antegrade wire crossing in CTO angioplasty., Methods: A total of 76 patients undergoing CTO PCI were enrolled at 13 international sites: 38 in the randomized training stage (collagenase [MZ-004] 900 or 1200 μg) and 38 in the placebo-controlled stage (MZ-004 900 or 1200 μg or placebo). Patients received the MZ-004 or identical volume saline (placebo group) in a double-blind design, injected via microcatheter directly into the proximal cap of the CTO. The following day patients underwent CTO PCI using antegrade wire techniques only., Results: Patients were generally similar except for a trend for higher Japanese chronic total occlusion (J-CTO) score in the MZ-004 group (MZ-004 J-CTO score 1.9 vs. 1.4, p = 0.07). There was a numerical increase in the rates of guidewire crossing in the MZ-004 groups compared to placebo (74% vs. 63%, p = 0.52). Guidewire crossing with a soft-tip guidewire (≤1.5 g tip load) was significantly higher in the MZ-004 groups (0% in placebo, 17% in 900 μg, and 29% in 1200 μg MZ-004 group, p = 0.03). Rates of the major adverse cardiovascular event were similar between groups., Conclusion: Local delivery of MZ-004 into coronary CTOs appears safe and may facilitate CTO crossing, particularly with softer tipped guidewires. These data support the development of a pivotal trial to further evaluate this agent., (© 2022 Wiley Periodicals LLC.)

Here we present an optimized protocol for transcriptome profiling of COVID-19 patient samples, including peripheral blood mononuclear cells (PBMCs) and formalin-fixed paraffin-embedded tissue samples obtained from the lung, liver, heart, kidney, and spleen, with the matched controls. We describe RNA extraction and subsequent transcriptome analysis using NanoString technology of the patient samples. The protocol provides information about sample preparation, RNA extraction, and NanoString profiling and analysis. It can be also applied to differentiated Th17 and Treg subsets or formalin-fixed colon tissue samples. For complete details on the use and execution of this protocol, please refer to Wang et al. (2021)., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

T cell exhaustion and dysfunction are hallmarks of severe COVID-19. To gain insights into the pathways underlying these alterations, we performed a comprehensive transcriptome analysis of peripheral-blood-mononuclear-cells (PBMCs), spleen, lung, kidney, liver, and heart obtained at autopsy from COVID-19 patients and matched controls, using the nCounter CAR-T-Characterization panel. We found substantial gene alterations in COVID-19-impacted organs, especially the lung where altered TCR repertoires are noted. Reduced TCR repertoires are also observed in PBMCs of severe COVID-19 patients. ENTPD1/CD39 , an ectoenzyme defining exhausted T-cells, is upregulated in the lung, liver, spleen, and PBMCs of severe COVID-19 patients where expression positively correlates with markers of vasculopathy. Heightened ENTPD1/CD39 is paralleled by elevations in STAT-3 and HIF-1α transcription factors; and by markedly reduced CD39 -antisense-RNA, a long-noncoding-RNA negatively regulating ENTPD1/CD39 at the post-transcriptional level. Limited TCR repertoire and aberrant regulation of ENTPD1/CD39 could have permissive roles in COVID-19 progression and indicate potential therapeutic targets to reverse disease., Competing Interests: C.D. and K.G. are employees and shareholders of NanoString Technologies, Inc. E.M.M. was an employee and shareholder of NanoString Technologies, Inc at the time of study., (© 2021 The Author(s).)

Autoimmune hepatitis (AIH) is a chronic inflammatory disorder characterized by hypergammaglobulinemia, presence of serum autoantibodies and histological features of interface hepatitis. AIH therapeutic management still relies on the administration of corticosteroids, azathioprine and other immunosuppressants like calcineurin inhibitors and mycophenolate mofetil. Withdrawal of immunosuppression often results in disease relapse, and, in some cases, therapy is ineffective or associated with serious side effects. Understanding the mechanisms underlying AIH pathogenesis is therefore of paramount importance to develop more effective and well tolerated agents capable of restoring immunotolerance to liver autoantigens. Imbalance between effector and regulatory cells permits liver damage perpetuation and progression in AIH. Impaired expression and regulation of CD39, an ectoenzyme key to immunotolerance maintenance, have been reported in Tregs and effector Th17-cells derived from AIH patients. Interference with these altered immunoregulatory pathways may open new therapeutic avenues that, in addition to limiting aberrant inflammatory responses, would also reconstitute immune homeostasis. In this review, we highlight the most recent findings in AIH immunopathogenesis and discuss how these could inform and direct the development of novel therapeutic tools., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Vuerich, Wang, Kalbasi, Graham and Longhi.)

Purpose of Review: Coronary artery calcification (CAC) predisposes to suboptimal revascularization outcomes after percutaneous coronary intervention (PCI). Despite the availability of several plaque modification devices, their rates of use remain low despite the prevalence of CAC encountered in clinical practice. It is important to understand how each device can be utilized in clinical practice in order to improve outcomes after PCI., Recent Findings: This article summarizes the most recent clinical evidence for each plaque modification device. Although rotational atherectomy is the most frequently used device for plaque modification, the use of orbital atherectomy (OA) has been increasing. Balloon-based strategies including recent studies evaluating a novel intravascular lithotripsy balloon have shed light on the benefits of nonablative devices in modifying CAC during PCI., Summary: CAC poses significant technical challenges in achieving optimal stent results. Several intracoronary plaque modification devices are currently available and understanding the technical aspects, indications and contraindications to the use of each device is essential. Although rotational and OA are most commonly used, laser atherectomy and balloon-based devices may offer an advantage in certain lesion subsets., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction : Autoimmune hepatitis (AIH) is an immune mediated, inflammatory disease affecting the liver as a result of environmental triggers in susceptible individuals leading to loss of self-tolerance. The immunopathogenesis of AIH is not fully understood, which limits targeted therapeutic options. Areas covered : In this review, the authors provide an overview of current practice in the management of AIH, which include induction therapy with corticosteroids (± thiopurines), followed by maintenance therapy. Lack of early response to treatment may serve as a predictor of those at risk of requiring treatment escalation to second- and third-line agents such as mycophenolate mofetil (MMF), calcineurin inhibitors or biologics. Evidence for third-line agents from small retrospective studies or individual centers are reviewed. The nuances of AIH treatment in pregnancy, overlap syndromes, and drug induced liver injury (DILI) warrant further consideration. Expert opinion : Augmenting the balance of regulatory T cells (Treg) and effector T cells is an appealing therapeutic target with a multitude of agents in development. Many of the challenges in AIH research are due to its rarity and lack of randomized data. Management of AIH should strive towards individualized care through risk stratification and use of the best therapeutic modality for each patient.

Pregnancy presents the maternal immune system with a unique immunological challenge since it has to defend against pathogens while tolerating paternal allo-antigens expressed by fetal tissues. T helper (Th) cells play a central role in modulating immune responses and recent advances have defined distinct contributions of various Th cell subsets throughout each phase of human pregnancy, while dysregulation in Th responses show association with multiple obstetrical complications. In addition to localized decidual mechanisms, modulation of Th cell immunity during gestation is mediated largely by oscillations in sex hormone concentrations. Aberrant Th cell responses also underlie several autoimmune disorders while pregnancy-induced changes in the balance of Th cell immunity has been shown to exert favorable outcomes in the progression Th1 and Th17 driven autoimmune conditions only to be followed by post-partal exacerbations in disease., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Despite the abundance of coronary chronic total occlusions (CTO) percutaneous coronary intervention (PCI) studies, the literature is not easy to digest for both general PCI operators and CTO PCI specialists because of the many varied terms used for approaches and inconsistency in terminology. This inconsistency makes it challenging to understand the advantages and disadvantages of these different approaches and, most importantly, their downstream clinical outcomes. Accordingly, we conducted a systematic review of all published studies on CTO PCI to describe techniques and algorithms used in the last decade to provide an overview on the efficacy and safety of contemporary CTO PCI techniques., Methods: We performed a comprehensive search of the PubMed, EMBASE, and the Cochrane library databases for manuscripts about PCI of CTOs. We included studies published between the years 2005 and 2019. We categorized studies into those using a single approach (antegrade, retrograde) and those with a prespecified algorithm (ie, hybrid approach)., Results: Fifty-five observational studies including 28,907 patients who underwent CTO were included in this review. CTO PCI generally carries low risk of major procedural complications, with angiographic success rates being higher in studies that used an algorithmic vs single technical approach., Conclusions: This systematic review highlights the wide variation in definitions and practices in CTO PCI and calls for standardization in terminology and practice., Competing Interests: Dr Sanjog Kalra is a proctor, preceptor, speaker's bureau, advisory board member, and new product tester for Abiomed Inc, Boston Scientific, Philips Healthcare, Translumina Therapeutics, Cardiovascular Systems Inc, Abbott Vascular, and Asahi Intecc. The other authors have no conflicts of interest to declare., (© 2021 The Authors.)

Background: The BIOFLOW-III Canada registry aimed to evaluate the safety and efficacy of Orsiro sirolimus-eluting stents (SES) with biodegradable polymer, in an all-comers patient population., Methods: We conducted a prospective, non-randomized, multi-center, observational all-comers registry of patients undergoing percutaneous coronary intervention (PCI) with Orsiro SES at two high-volume Canadian centers. The primary endpoint was one-year target lesion failure (TLF) defined as a composite of cardiac death, target-vessel myocardial infarction (MI), coronary artery bypass grafting and clinically driven target lesion revascularization. Four subgroups were pre-defined: i) diabetic patients; ii) small vessels (≤2.75 mm); iii) chronic total occlusions (CTO) and iv) acute MI., Results: From May 2014 to July 2016, 250 patients (mean age 66.2 ± 10.8 years, 75.6% males, 30% diabetes) underwent PCI with Orsiro SES for 385 coronary lesions. The mean stent diameter was 2.98 ± 0.50 mm and the mean stent length was 22 ± 8 mm. Clinical device and procedural success rates were with 99.5% and 97.6%, respectively. The overall one-year TLF rate was 2.8% [95% confidence interval (CI) 1.4-5.8%], whereas TLF rates were 4.1% [95%CI 1.3-12.2%], 3.2% [95%CI 1.2-8.4%], 8.3% [95%CI 2.2-29.4%], and 2.6% [95%CI 0.7-9.9%] in patients with diabetes, small vessels, CTO, and acute MI, respectively. One case of possible stent thrombosis (ST) was reported (0.4% [95%CI 0.1-2.8%]), while no cases of definite/probable ST was observed at one year., Conclusion: Our data provide further evidence of the safety and clinical performance of Orsiro SES in an unselected, real-world, complex patient population., Condensed Abstract: The BIOFLOW-III Canada registry is a prospective, non-randomized, multi-center, observational all-comers registry designed to evaluate the safety and performance of the Orsiro SES in non-selected, real-world patients. A total of 250 patients (mean age 66.2 ± 10.8 years, 75.6% males, 30% diabetes) who underwent PCI with Orsiro SES, were enrolled at two high-volume Canadian centers. The overall rate of TLF at one year was 2.8% [95%CI 1.4-5.8%], whereas TLF rates were 4.1%, 3.2%, 8.3%, and 2.6% in patients with diabetes, small vessels ≤2.75 mm, CTO, and acute MI, respectively. No case of definite/probable ST was observed., Competing Interests: Declaration of competing interest Dr. Mansour: research grant from Astra-Zeneca, Abbott Vascular; speaker and adviser honoraria from Astra-Zeneca, Pfizer, Bayer, Soundbite, Abbott Vascular and Boston Scientific. Dr. Graham: speaker and adviser honoraria from Astra Zeneca, Teleflex and Abbott Vascular. Other Authors: none to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We evaluated temporal changes in early diastolic strain rates by cardiovascular magnetic resonance (CMR) as an early detector of trastuzumab-induced ventricular dysfunction. We conducted a prospective, multi-centre, longitudinal observational study of 41 trastuzumab-treated breast cancer women who underwent serial CMR (baseline, 6, 12, and 18 months). Two blinded readers independently measured left ventricular ejection fraction (LVEF), peak systolic strain parameters (global longitudinal strain [GLS] and global circumferential strain [GCS]), and early diastolic strain rate parameters (global longitudinal diastolic strain rate [GLSR-E], global circumferential diastolic strain rate [GCSR-E], and global radial diastolic strain rate [GRSR-E]), by feature tracking (FT-CMR) using CMR42. There was a significant decline in peak systolic strain GLS and GCS at 6 months (p = 0.024 and p < 0.001, respectively) and 12 months (p = 0.002 and p < 0.001, respectively), followed by recovery at 18 months, which paralleled decline in LVEF at 6 months (p = 0.034) and 12 months (p = 0.012). Conversely, early diastolic strain rates GLSR-E and GCSR-E did not significantly change over 18 months (p > 0.10), while GRSR-E was marginally significant at 12 months (p = 0.021). There was no significant correlation between changes at 6 months in LVEF and GLSR-E or GRSR-E (p > 0.10), and a marginally significant weak correlation between LVEF and GCSR-E (p = 0.046). Among trastuzumab-treated patients without overt cardiotoxicity, there was no consistent temporal change in FT-CMR-derived diastolic strain rate parameters up to 18 months, in contrast to decline in systolic strain and LVEF. Systolic strains by FT-CMR are likely more useful than diastolic strain rates for monitoring subclinical trastuzumab-related myocardial dysfunction.ClinicalTrials.gov identifier NCT01022086.

Landscape solar energy is a significant environmental driver, yet it remains complicated to model well. Several solar radiation models simplify the complexity of light by estimating it at discrete point locations or by averaging values over larger areas. These modeling approaches may be useful in certain cases, but they are unable to provide spatially distributed and temporally dynamic representations of solar energy across entire landscapes. We created a landscape-scale ground-level shade and solar energy model called Penumbra to address this deficiency. Penumbra simulates spatially distributed ground-level shade and incident solar energy at user-defined timescales by modeling local and distant topographic shading and vegetative shading. Spatially resolved inputs of a digital elevation model, a normalized digital surface model, and landscape object transmittance are used to estimate spatial variations in solar energy at user-defined temporal timesteps. The research goals for Penumbra included: 1) simulations of spatiotemporal variations of shade and solar energy caused by both objects and topographic features, 2) minimal user burden and parameterization, 3) flexible user defined temporal parameters, and 4) flexible external model coupling. We test Penumbra's predictive skill by comparing the model's predictions with monitored open and forested sites, and achieve calibrated mean errors ranging from -17.3 to 148.1 μmoles/m2/s. Penumbra is a dynamic model that can produce spatial and temporal representations of shade percentage and ground-level solar energy. Outputs from Penumbra can be used with other ecological models to better understand the health and resilience of aquatic, near stream terrestrial, and upland ecosystems., Competing Interests: The authors have declared that no competing interests exist.

Objective: Current guidelines provide left ventricular ejection fraction (LVEF) criterion for use of implantable cardioverter defibrillators (ICD) but do not specify which modality to use for measurement. We compared LVEF measurements by radionuclide ventriculography (RNV) vs cardiac MRI (CMR) in ICD candidates to assess impact on clinical decision making., Methods: This single-centre study included 124 consecutive patients referred for assessment of ICD implantation who underwent RNV and CMR within 30 days for LVEF measurement. RNV and CMR were interpreted independently by experienced readers., Results: Among 124 patients (age 64 ± 11 years, 77% male), median interval between CMR and RNV was 1 day; mean LVEF was 32 ± 12% by CMR and 33 ± 11% by RNV (p = 0.60). LVEF by CMR and RNV showed good correlation, but Bland-Altman analysis showed relatively wide limits of agreement (-12.1 to 11.4). CMR LVEF reclassified 26 (21%) patients compared to RNV LVEF (kappa = 0.58). LVEF by both modalities showed good interobserver reproducibility (ICC 0.96 and 0.94, respectively) (limits of agreement -7.27 to 5.75 and -8.63 to 6.34, respectively)., Conclusion: Although LVEF measurements by CMR and RNV show moderate agreement, there is frequent reclassification of patients for ICD placement based on LVEF between these modalities. Future studies should determine if a particular imaging modality for LVEF measurement may enhance ICD decision making and treatment benefit., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Modeling the spatial and temporal dynamics of soil temperature is deterministically complex due to the wide variability of several influential environmental variables, including soil column composition, soil moisture, air temperature, and solar energy. Landscape incident solar radiation is a significant environmental driver that affects both air temperature and ground-level soil energy loading; therefore, inclusion of solar energy is important for generating accurate representations of soil temperature. We used the U.S. Environmental Protection Agency's Oregon Crest-to-Coast (O'CCMoN) Environmental Monitoring Transect dataset to develop and test the inclusion of ground-level solar energy driver data within an existing soil temperature model currently utilized within an ecohydrology model called Visualizing Ecosystem Land Management Assessments (VELMA). The O'CCMoN site data elucidate how localized ground-level solar energy between open and forested landscapes greatly influence the resulting soil temperature. We demonstrate how the inclusion of local ground-level solar energy significantly improves the ability to deterministically model soil temperature at two depths. These results suggest that landscape and watershed-scale models should incorporate spatially distributed solar energy to improve spatial and temporal simulations of soil temperature., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest. Findings and conclusions in this article are those of the authors and do not necessarily reflect or represent the views or policies of the U.S. Environmental Protection Agency. Any mention of trade names, products, or services does not imply an endorsement by the U.S. Government or the U.S. Environmental Protection Agency. The EPA does not endorse any commercial products, services, or enterprises.

Coronary chronic total occlusions (CTOs) are found in approximately 20% of angiograms. We sought to assess the variation in the management of patients with CTOs and to compare the clinical outcomes of CTO lesions with those of non-CTO lesions. We conducted a population-based cohort study and included all patients with stable angina who underwent cardiac catheterization from October 1, 2012, to June 30, 2013, in Ontario, Canada. The primary outcome was a composite of mortality and hospitalization for myocardial infarction. A total of 7,864 patients were included, of whom 2,279 (29%) had a CTO. There were substantial differences in revascularization rates for patients with CTOs across hospitals in Ontario (44.9% to 94.1%). Revascularization was associated with improved outcomes in the overall cohort. Although the advantage of coronary artery bypass grafting over medical therapy was consistent in both patients with CTOs and patients without CTOs, the benefit of percutaneous coronary intervention (PCI) was limited to patients without CTOs (hazard ratio 0.56, 95% confidence interval 0.40- to 0.78), with no difference in patients with CTOs. The CTO lesion, however, was revascularized in few of the PCI cases (41.1%), with PCI limited to the non-CTO lesion in most patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to develop a hybrid approach-specific model to predict chronic total coronary artery occlusion (CTO) percutaneous coronary intervention success, useful for experienced but not ultra-high-volume operators., Background: CTO percutaneous coronary intervention success rates vary widely and have improved with the "hybrid approach," but current predictive models for success have major limitations., Methods: Data were obtained from consecutively attempted patients from 7 clinical sites (9 operators, mean annual CTO volume 61 ± 17 cases). Angiographic analysis of 21 lesion variables was performed centrally. Statistical modeling was performed on a randomly designated training group and tested in a separate validation cohort. The primary outcome of interest was technical success., Results: A total of 436 patients (456 lesions) met entry criteria. Twenty-five percent of lesions had prior failed percutaneous coronary interventions at the site. The right coronary artery was the most common location (56.4%), and mean occlusion length was 24 ± 20 mm. The initial approach was most often antegrade wire escalation (70%), followed by retrograde (22%). Success was achieved in 79.4%. Failure was most closely correlated with presence of an ambiguous proximal cap, and in the presence of an ambiguous proximal cap, specifically defined collateral score (combination of Werner and tortuosity scores) and retrograde tortuosity. Without an ambiguous proximal cap, poor distal target, occlusion length >10 mm, ostial location, and 1 operator variable contributed. Prior failure, and Werner and tortuosity scores alone, were only weakly correlated with outcomes. The basic 7-item model predicted success, with C statistics of 0.753 in the training cohort and 0.738 in the validation cohort, the later superior (p < 0.05) to that of the J-CTO (Multicenter CTO Registry of Japan) (0.55) and PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) (0.61) scores., Conclusions: Success can be reasonably well predicted, but that prediction requires modification and combination of angiographic variables. Differences in operator skill sets may make it challenging to create a powerful, generalizable, predictive tool., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: We sought to assess the relationships between left ventricular (LV) remodelling and the mechanical and uremic stressors in hemodialysis patients., Methods: In this prospective 2-centre cohort study, 67 prevalent hemodialysis patients were followed for 1 year. Data on routine bloodwork and predialysis blood pressure (BP) measurements were collected over a 12-week period. LV end-diastolic volume (LVEDV) and LV mass (LVM) were measured using cardiac magnetic resonance imaging and indexed. High-sensitivity troponin-I (hsTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), fibroblast growth factor 23 (FGF-23), and high-sensitivity C-reactive protein (hsCRP) were also measured. All study procedures were performed at baseline and at 1 year. We examined the relationships between LV remodelling and (1) NT-proBNP and hsTnI (LV stretch and injury); (2) ultrafiltration volume (UFV) and interdialytic weight gain (IDWT; volume overload); (3) predialysis BP measurements (pressure overload); and (4) biomarkers of inflammation (hsCRP) and fibrosis (FGF-23)., Results: LVEDV was significantly associated with UFV and with IDWT, at baseline as well as at 1 year. NT-proBNP was significantly and negatively correlated with UFV and IDWT, respectively, at 1 year. There were significant correlations between systolic BP and LVM index, at baseline and at 1 year as well as longitudinally. Systolic BP was the only parameter longitudinally correlated with LVM/LVEDV. hsTnI was not associated with urea, parathyroid hormone, calcium, phosphorus, FGF-23, hsCRP, or hemoglobin., Conclusions: We did not observe significant relationships between myocardial injury and markers of fibrosis, inflammation, and LV remodelling. Elevated predialysis systolic BP, which might represent a common mediator of pressure and volume overload, appears to be a dominant stimulus for LV remodelling., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Background: The objective of this study was to assess the efficacy of sealing intermediate nonobstructive coronary saphenous vein graft (SVG) lesions with drug-eluting stents (DES; paclitaxel- or everolimus-eluting stents) for reducing major adverse cardiac events (MACE)., Methods and Results: This was a randomized controlled multicenter clinical trial that enrolled patients with a previous coronary artery bypass graft who had developed at least 1 intermediate nonobstructive SVG lesion (30%-60% diameter stenosis by visual estimation). Patients were randomized (1:1) to DES implantation (SVG-DES) or medical treatment (SVG-MT) of the target SVG lesion. The primary efficacy outcome was the first occurrence of MACE defined as the composite of cardiac death, myocardial infarction, or coronary revascularization related to the target SVG during the duration of follow-up (minimum of 2 years). Secondary efficacy outcomes included MACE related to the target SVG lesion and overall MACE. A total of 125 patients (mean age 70±9 years, 87% men) were included, with a mean time from coronary artery bypass graft of 12±5 years. Sixty and 65 patients were allocated to the SVG-DES and SVG-MT groups, respectively. There were no events related to the target SVG at 30 days. After a median follow-up of 3.4 (interquartile range: 2.8-3.9) years, the MACE rate related to the target SVG was not significantly different in the 2 groups (SVG-DES: 15.0%, SVG-MT: 20.0%; hazard ratio, 0.65; 95% confidence interval, 0.23-1.53; P=0.33). There were no significant differences between groups in MACE related to the target SVG lesion (SVG-DES: 10.0%, SVG-MT: 16.9%; hazard ratio, 0.53; 95% confidence interval, 0.20-1.43; P=0.21) or global MACE (SVG-DES: 36.7%, SVG-MT: 44.6%; hazard ratio, 0.73; 95% confidence interval, 0.42-1.27; P=0.26)., Conclusions: Sealing intermediate nonobstructive SVG lesions with DES was safe but was not associated with a significant reduction of cardiac events at 3-year follow-up., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01223443., (© 2016 American Heart Association, Inc.)

Background: To investigate the relationship between arterial access site choice (radial versus femoral) and clinical outcomes among STEMI patients undergoing routine PCI after fibrinolysis., Methods: Patient-level data from trials of STEMI patients evaluating routine PCI after fibrinolysis were included. The primary endpoint was 30-day major bleeding; secondary endpoints included 30-day death and re-infarction., Results: 1891 patients underwent PCI (trans-radial n=338, trans-femoral n=1553). Trans-radial PCI patients were less likely to be >75years (2% vs. 8%, p=0.0001), heavier (median weight 82 [72-90] vs. 80 [70-90] kg, p=0.0013) and more likely in Killip class I at presentation (87% vs. 82%, p=0.03). At 30days, trans-radial PCI was associated with a similar unadjusted risk for major bleeding (3.7% vs. 1.2%, Odds Ratio [OR] 0.43 [95% CI 0.13-1.48], p=0.18), mortality (3.4% vs. 1.2%, OR 0.34 [0.09-1.28], p=0.11) and re-infarction (3.9% vs. 4.7%, OR 1.25 [0.60-2.58], p=0.56). In multivariable analysis, radial access was associated with similar estimates for bleeding and death/reinfarction risk., Conclusions: In STEMI patients treated with fibrinolysis and undergoing an early routine invasive strategy, radial compared to femoral PCI is chosen in younger, less ill patients and is independently associated with similar risk of bleeding, re-infarction, and mortality., Summary: This study evaluated the relationship between arterial access choice (radial versus femoral) and in-hospital and 30-day outcomes in patients undergoing routine PCI after fibrinolysis for STEMI. We included patient-level data from trials evaluating a strategy of routine PCI after fibrinolysis for STEMI. Of 1891 patients undergoing PCI, trans-radial access (n=338) was chosen in younger, lower risk patients. At 30days, trans-radial access was associated with a similar unadjusted and adjusted risk of major bleeding, re-infarction and mortality., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: In regional systems of ST-segment elevation myocardial infarction (STEMI) care, patients presenting to hospitals without percutaneous coronary intervention (PCI) are transferred to PCI-capable hospitals for primary PCI. Repatriation, a practice whereby such patients are transferred back to non-PCI referral hospitals after reperfusion is prevalent in many jurisdictions, yet little is known of this practice and its safety., Methods: We studied 979 consecutive STEMI patients transported from the emergency department and catchment area of two non-PCI hospitals in Ontario, Canada to a regional PCI-hospital for primary PCI between January 2008 and June 2014. Logistic regression modeling was performed to determine factors associated with delayed repatriation beyond 24 hours and to evaluate the association between repatriation and index-admission mortality., Results: Eight hundred and fifteen (83.2%) patients were repatriated with 524 (65.2%) patients repatriated within 24 hours. Factors independently associated with delayed repatriation included systolic blood pressure (OR 1.03 per 5 mmHg decrease, 95% CI 1.01-1.06, P= .04), requirement for mechanical ventilation (OR 24.9, 95% CI 5.4-115.3, P< .0001), ventricular arrhythmia (OR 3.0, 95% CI 1.3-6.6, P= .01), infarct-related artery (P= .03), final TIMI flow grade (P= .01) and access-site complications (OR 2.36, 95% CI 1.04-5.4, P= .04). After repatriation, 9 (1.3%) patients returned to the PCI-hospital for urgent care, and 16 (2.0%) died during index-admission. After adjustment, repatriation was not associated with increase in index-admission mortality (adjusted OR 0.46, 95% CI 0.16-1.32, P= .15)., Conclusions: In a regional STEMI care system in Ontario, Canada, patients are routinely repatriated to non-PCI hospitals after primary PCI. This practice was associated with very low and acceptable rate of return to the PCI-hospital during index-admission without an adverse impact on short-term outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The aim of this study was to assess the efficacy and safety of an early invasive strategy post-fibrinolysis in relation to time from symptom onset to fibrinolysis in patients with ST-elevation myocardial infarction (STEMI). The Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized 1,059 patients receiving fibrinolysis for STEMI to an early invasive strategy versus standard therapy. The primary end point was the composite of death, reinfarction, recurrent ischemia, new or worsening heart failure, or cardiogenic shock at 30 days. In this post hoc subgroup analysis, we examined the effect of an early invasive strategy on efficacy and safety outcomes after stratification by time from symptom onset to fibrinolysis (<2 or ≥2 hours). Of 1,059 patients in TRANSFER-AMI, 557 (53%) received fibrinolysis <2 hours and 502 (47%) ≥2 hours after symptom onset. Compared to patients who received fibrinolysis within 2 hours of symptoms, patients who received fibrinolysis ≥2 hours after symptom onset had higher Global Registry of Acute Coronary Events risk scores (median 127 vs 122, p = 0.004). The effect of an early invasive strategy did not differ between symptom-to-fibrinolysis time strata for the primary efficacy end point (p-heterogeneity = 0.67), 30-day mortality, the composite of death or reinfarction at 30 days, 6 months, or 1 year, or bleeding (all p-heterogeneity >0.40). In conclusion, the efficacy and safety of an early invasive strategy in patients undergoing fibrinolysis for STEMI do not vary in relation to time (<2 or ≥2 hours) from symptom onset to fibrinolysis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We present a case that elegantly illustrates the utility of two novel noninvasive imaging techniques, computed tomography (CT) coronary angiography and cardiac MRI, in the diagnosis and management of a 27-year-old man with exertion-induced cardiac arrest caused by an anomalous right coronary artery. CT coronary angiography with 3D reformatting delineated the interarterial course of an anomalous right coronary artery compressed between the aorta and pulmonary artery, whereas cardiac MRI showed a small myocardial infarction in the right coronary artery territory not detected on echocardiography. This case highlights the value of novel multimodality imaging techniques in the risk stratification and management of patients with resuscitated cardiac arrest.

Objectives: This study investigated the relationship between time to invasive assessment and outcomes among ST-segment elevation myocardial infarction patients randomized to early angiography after fibrinolysis., Background: The optimal timing of coronary angiography after fibrinolysis and the association with clinical outcomes is uncertain., Methods: Patient-level data from 6 randomized trials, with a median time to angiography <12 h after fibrinolysis, were pooled. The primary endpoint was 30-day death or reinfarction. The key secondary endpoint was in-hospital major bleeding. The relationship between fibrinolysis to angiography time and symptom onset to angiography time with outcomes was studied using 2- and 4-h intervals, respectively, and in multivariable models., Results: Among 1,238 patients, the median fibrinolysis to angiography time was 165 min, and the median symptom onset to angiography time was 5.33 h. The primary and key secondary endpoints occurred in 5.7% and 4.7%, respectively. These main endpoints did not vary significantly with increasing fibrinolysis to angiography time. Early angiography (<2 h) after fibrinolysis was not associated with increased bleeding. Recurrent ischemia increased with increasing fibrinolysis to angiography time (3.7% to 7.9%, p for trend = 0.02). Thirty-day and 1-year death/reinfarction and 30-day recurrent ischemia increased significantly with increasing symptom onset to angiography time. Neither fibrinolysis to angiography time nor symptom onset to angiography time was an independent predictor of the primary endpoint. Only symptom onset to angiography time was an independent predictor of 1-year death/reinfarction (hazard ratio: 1.07, 95% confidence interval: 1.02 to 1.12, p = 0.01)., Conclusions: Very early angiography (<2 h) after fibrinolysis was not associated with an increased risk of 30-day death/reinfarction or in-hospital major bleeding, and angiography within 4 h after fibrinolysis was associated with reduced 30-day recurrent ischemia. A shorter symptom onset to angiography time (<4 h) was associated with reduced 30-day and 1-year death/reinfarction and 30-day recurrent ischemia. In the current environment of regional networks of 24/7 primary percutaneous coronary intervention (PCI) centers, the clinical implication of these findings is that patients initially treated with fibrinolysis should also be promptly transferred to the nearest PCI center for immediate angiography and PCI. (Early Percutaneous Coronary Intervention [PCI] After Fibrinolysis Versus Standard Therapy in ST Segment Elevation Myocardial Infarction [STEMI] Patients; NCT01014182)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the potentially improved detection and quantification of cardiac involvement using novel late-gadolinium-enhancement (LGE) cardiac magnetic resonance imaging (MRI) and quantitative T2 measurement to achieve better myocardial tissue characterization in systemic sarcoidosis., Materials and Methods: Twenty-eight patients with systemic sarcoidosis underwent a cardiac magnetic resonance imaging (CMR) study on a 1.5T system. Precontrast CMR included left ventricular (LV) and right ventricular (RV) function and quantitative T2 measurement. Postcontrast LGE-MRI included inversion-recovery fast-gradient-echo (IR-FGRE) and multicontrast late-enhancement imaging (MCLE)., Results: LV functional parameters were normal in all patients (LVEF=61.2±8.5%) including with cardiac involvement (LVEF=59.4±12.1%) and without (LVEF=61.7±7.5%) while the average RV function was comparatively decreased (RVEF=48.0±6.6%, P<0.0001). 21.4% of patients had cardiac involvement showing patchy or multiple focal hyperenhancement patterns in LV free wall, papillary muscles (PM), or interventricular septum. In two cases with PM involvement, the PM abnormal LGE foci were only observed on MCLE. For precontrast T2 measurements, a significantly decreased T2 measurement was observed in regions demonstrating LGE, compared to the LGE-negative group (focal LGE-positive regions vs. negative: 40.0±2.4 msec vs. 53.0±2.6 msec, P<0.0001)., Conclusion: LGE-MRI can identify cardiac involvement in systemic sarcoidosis. MCLE might be more sensitive at detecting subtle myocardial lesion. The decreased T2 observed in cardiac sarcoid may reflect its inactive phase, thus might provide a noninvasive method for monitoring disease activity or therapy., (Copyright © 2013 Wiley Periodicals, Inc.)

Aim: Cell therapy has been shown to be effective in improving LV function postmyocardial infarction (MI). We hypothesized that eNOS-transfected bone marrow cells (BMCs) are safe in a swine model of myocardial infarction (MI). We also hypothesized that endothelial nitric oxide synthase (eNOS) transfection would enhance cell function, as assessed by myocardial functional recovery post-MI., Methods: Fifteen female Yorkshire pigs underwent bone marrow aspiration and creation of MI. Bone marrow cells were cultured for 7 days, and each pig received either autologous BMCs transiently transfected with eNOS plasmid (eNOS-BMC, n = 5), nontransfected BMCs (nt-BMC, n = 4), or phosphate-buffered saline (PBS) control (n = 6). Cardiac MRI was performed at baseline (1 week post-MI) and 6 weeks post-MI., Results: There was no difference in safety outcomes between groups. Absolute left ventricular ejection fraction (LVEF) at 6 weeks showed a trend toward improvement in both cell therapy groups compared with baseline but worsened in the PBS control group. The absolute improvement in LVEF was significantly greater in both cell therapy groups compared with PBS control. Infarct mass was significantly lower in the eNOS-BMC group between baseline and 6 weeks, but the absolute change in infarct mass was not different between groups. Finally, there was a trend toward reduced LV mass in the eNOS-BMC group., Conclusions: Bone marrow cell delivery, with and without eNOS overexpression, is safe and leads to improvement in LVEF when administered in the coronary circulation 7 days following acute MI in swine. Transfection of healthy BMCs with eNOS resulted in some improvement in left ventricular remodeling. Further study is warranted in a preclinical model that approximates the impact of cardiovascular risk factors on BMC function., (© 2013 John Wiley & Sons Ltd.)