Publications by authors named "Robert Riley"

198 Publications

Procedural effectiveness with a focused force scoring angioplasty catheter: Procedural and clinical outcomes from the Scoreflex NC trial.

Cardiovasc Revasc Med 2021 Mar 20. Epub 2021 Mar 20.

Beth Israel Deaconess Medical Center, Boston, MA, USA.

Background: The Scoreflex NC scoring angioplasty catheter is designed with a short rapid-exchange tip distal to a non-compliant, high-pressure balloon and an integral wire outside of the balloon, such that the guidewire and the integral wire act as scoring elements during balloon inflation. The external scoring elements enable a focal stress pattern facilitating expansion of resistant lesions at lower pressures using a focused force angioplasty effect.

Methods: Patients undergoing elective percutaneous coronary intervention (PCI) were enrolled in a prospective, single-arm study conducted at 12 centers in the United States. The primary endpoint was device procedural success, defined as the composite of successful device delivery to the target lesion with balloon inflation and deflation; absence of vessel perforation, flow-limiting dissection or reduction in TIMI flow from baseline; and achievement of final TIMI 3 flow.

Results: Among 200 patients (234 lesions), lesion complexities included: bifurcation disease (37.6%), moderate/severe calcification (36.6%), and total occlusions (5.0%). Successful delivery to the target lesion, inflation and removal of the balloon catheter was achieved in 95.5% of patients (191/200). Procedural success was achieved in 93.5% (187/200) of patients, and final TIMI 3 flow was observed in 99.0% of cases (198/200). No unanticipated device-related events occurred. In-hospital major adverse events were reported in 4.5% of patients (9/200), related to periprocedural myocardial infarction (8/200, 4.0%) and target lesion revascularization (1/200, 0.5%).

Conclusions: Among patients undergoing elective PCI and with varied lesion complexity, these results support the safety and effectiveness of a dilation strategy using the Scoreflex NC scoring catheter.
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http://dx.doi.org/10.1016/j.carrev.2021.03.013DOI Listing
March 2021

Gene family expansions and transcriptome signatures uncover fungal adaptations to wood decay.

Environ Microbiol 2021 Feb 4. Epub 2021 Feb 4.

INRAE, Aix Marseille Univ, UMR1163, Biodiversité et Biotechnologie Fongiques, Marseille, 13009, France.

Because they comprise some of the most efficient wood-decayers, Polyporales fungi impact carbon cycling in forest environment. Despite continuous discoveries on the enzymatic machinery involved in wood decomposition, the vision on their evolutionary adaptation to wood decay and genome diversity remains incomplete. We combined the genome sequence information from 50 Polyporales species, including 26 newly sequenced genomes and sought for genomic and functional adaptations to wood decay through the analysis of genome composition and transcriptome responses to different carbon sources. The genomes of Polyporales from different phylogenetic clades showed poor conservation in macrosynteny, indicative of genome rearrangements. We observed different gene family expansion/contraction histories for plant cell wall degrading enzymes in core polyporoids and phlebioids and captured expansions for genes involved in signalling and regulation in the lineages of white rotters. Furthermore, we identified conserved cupredoxins, thaumatin-like proteins and lytic polysaccharide monooxygenases with a yet uncharacterized appended module as new candidate players in wood decomposition. Given the current need for enzymatic toolkits dedicated to the transformation of renewable carbon sources, the observed genomic diversity among Polyporales strengthens the relevance of mining Polyporales biodiversity to understand the molecular mechanisms of wood decay.
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http://dx.doi.org/10.1111/1462-2920.15423DOI Listing
February 2021

Clinical and health status outcomes among patients treated with single as compared to multivessel angioplasty during chronic total occlusion percutaneous coronary interventions: a report from the OPEN CTO registry.

Coron Artery Dis 2021 Mar;32(2):112-118

St. Luke's Mid America Heart Institute, Kansas City, Kansas.

Background: Patients with coronary chronic total occlusions (CTO) often have multivessel coronary artery disease. We utilized the OPEN CTO study to evaluate patients who underwent single-vessel versus multivessel percutaneous coronary intervention (PCI) during CTO PCI.

Methods: Patients were considered to have undergone single-vessel CTO PCI if they underwent target-vessel only CTO PCI. Patients who underwent multivessel PCI during their index CTO PCI procedure were considered to have undergone multivessel PCI. The additional lesions treated in the multivessel group could be either a separate CTO lesion in a separate epicardial vessel or PCI attempt of any non-CTO stenosis during the same index procedure. Multivariate regression models were used to evaluate predictors of technical success, in-hospital major adverse cardiac and cerebrovascular events (MACCE), and health status measures.

Results: Eighty hundred twenty-one patients underwent single-vessel CTO PCI and 179 (17.9%) underwent multivessel PCI during their CTO PCI procedure. Baseline comorbidities, index CTO lesion complexity, and successful crossing strategies used were similar between the two groups. Total procedural time (142.6 versus 115.9 minutes, P < 0.01) and contrast administered (293.8 versus 255.0 ml, P < 0.01) were increased in the multivessel CTO PCI group. Single-vessel versus multivessel PCI during these cases did not affect the likelihood of achieving technical success [odds ratio (OR) 1.05, 95% confidence interval (CI) 0.63-1.75] nor the risk for MACCE (OR 1.23, 95% CI 0.72-2.11). Quality of life (QOL) metrics were similar between the two groups at baseline and 30-day follow-up.

Conclusion: There were no significant differences in technical success, in-hospital MACCE rates, or QOL metrics at 30-day follow-up for patients who underwent single-vessel versus multivessel PCI during CTO PCI.
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http://dx.doi.org/10.1097/MCA.0000000000000995DOI Listing
March 2021

Comparative genomics reveals dynamic genome evolution in host specialist ectomycorrhizal fungi.

New Phytol 2021 04 6;230(2):774-792. Epub 2021 Feb 6.

Department of Plant and Microbial Biology, University of Minnesota, St Paul, MN, 55108, USA.

While there has been significant progress characterizing the 'symbiotic toolkit' of ectomycorrhizal (ECM) fungi, how host specificity may be encoded into ECM fungal genomes remains poorly understood. We conducted a comparative genomic analysis of ECM fungal host specialists and generalists, focusing on the specialist genus Suillus. Global analyses of genome dynamics across 46 species were assessed, along with targeted analyses of three classes of molecules previously identified as important determinants of host specificity: small secreted proteins (SSPs), secondary metabolites (SMs) and G-protein coupled receptors (GPCRs). Relative to other ECM fungi, including other host specialists, Suillus had highly dynamic genomes including numerous rapidly evolving gene families and many domain expansions and contractions. Targeted analyses supported a role for SMs but not SSPs or GPCRs in Suillus host specificity. Phylogenomic-based ancestral state reconstruction identified Larix as the ancestral host of Suillus, with multiple independent switches between white and red pine hosts. These results suggest that like other defining characteristics of the ECM lifestyle, host specificity is a dynamic process at the genome level. In the case of Suillus, both SMs and pathways involved in the deactivation of reactive oxygen species appear to be strongly associated with enhanced host specificity.
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http://dx.doi.org/10.1111/nph.17160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969408PMC
April 2021

Rapid determination of the pharmacokinetics and metabolic fate of gefitinib in the mouse using a combination of UPLC/MS/MS, UPLC/QToF/MS, and ion mobility (IM)-enabled UPLC/QToF/MS.

Xenobiotica 2021 Apr 8;51(4):434-446. Epub 2021 Feb 8.

Computational and Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.

The metabolism and pharmacokinetics of gefitinib (Iressa, N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholino-propoxy)quinazolin-4-amine), a selective thymidylate kinase inhibitor for the epidermal growth factor receptor (EGFR), was studied after IV and PO administration to male C57BL6 mice at 10 and 50mg/kg respectively.The pharmacokinetics and metabolism of gefitinib were investigated using a range of rapid UHPLC-MS and UHPLC-IM-HRMS methods, using both reversed-phase (RP) and hydrophilic interaction liquid chromatography (HILIC), to rapidly determine the drugs pharmacokinetics and metabolic fate.Rapid oral absorption resulted in peak plasma concentrations at 1h of ca. 7µg/mL, that declined with a half-life of 3.8h (2.6h for the IV route), and providing an estimated oral bioavailability of 53%. Gefitinib itself was the major circulating drug-related compound in plasma extracts, with a total of 11 metabolites identified.The urinary profiles determined using both HILIC and RP-UPLC-IM-MS detected gefitinib and 10 metabolites or 15 metabolites respectively including the detection of a number of novel glucuronide conjugates.Despite rapid, sub 5min, LC profiling methods being employed metabolite coverage was shown to be high and compared well with that of previous studies.
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http://dx.doi.org/10.1080/00498254.2020.1859643DOI Listing
April 2021

Genomic Analysis Enlightens Agaricales Lifestyle Evolution and Increasing Peroxidase Diversity.

Mol Biol Evol 2021 Apr;38(4):1428-1446

Centro de Investigaciones Biológicas Margarita Salas (CIB), CSIC, Madrid, Spain.

As actors of global carbon cycle, Agaricomycetes (Basidiomycota) have developed complex enzymatic machineries that allow them to decompose all plant polymers, including lignin. Among them, saprotrophic Agaricales are characterized by an unparalleled diversity of habitats and lifestyles. Comparative analysis of 52 Agaricomycetes genomes (14 of them sequenced de novo) reveals that Agaricales possess a large diversity of hydrolytic and oxidative enzymes for lignocellulose decay. Based on the gene families with the predicted highest evolutionary rates-namely cellulose-binding CBM1, glycoside hydrolase GH43, lytic polysaccharide monooxygenase AA9, class-II peroxidases, glucose-methanol-choline oxidase/dehydrogenases, laccases, and unspecific peroxygenases-we reconstructed the lifestyles of the ancestors that led to the extant lignocellulose-decomposing Agaricomycetes. The changes in the enzymatic toolkit of ancestral Agaricales are correlated with the evolution of their ability to grow not only on wood but also on leaf litter and decayed wood, with grass-litter decomposers as the most recent eco-physiological group. In this context, the above families were analyzed in detail in connection with lifestyle diversity. Peroxidases appear as a central component of the enzymatic toolkit of saprotrophic Agaricomycetes, consistent with their essential role in lignin degradation and high evolutionary rates. This includes not only expansions/losses in peroxidase genes common to other basidiomycetes but also the widespread presence in Agaricales (and Russulales) of new peroxidases types not found in wood-rotting Polyporales, and other Agaricomycetes orders. Therefore, we analyzed the peroxidase evolution in Agaricomycetes by ancestral-sequence reconstruction revealing several major evolutionary pathways and mapped the appearance of the different enzyme types in a time-calibrated species tree.
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http://dx.doi.org/10.1093/molbev/msaa301DOI Listing
April 2021

Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Artery Disease.

J Am Coll Cardiol 2020 12 15;76(22):2635-2646. Epub 2020 Oct 15.

The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: https://twitter.com/GreggWStone.

Background: Coronary calcification hinders stent delivery and expansion and is associated with adverse outcomes. Intravascular lithotripsy (IVL) delivers acoustic pressure waves to modify calcium, enhancing vessel compliance and optimizing stent deployment.

Objectives: The purpose of this study was to assess the safety and effectiveness of IVL in severely calcified de novo coronary lesions.

Methods: Disrupt CAD III (NCT03595176) was a prospective, single-arm multicenter study designed for regulatory approval of coronary IVL. The primary safety endpoint was freedom from major adverse cardiovascular events (cardiac death, myocardial infarction, or target vessel revascularization) at 30 days. The primary effectiveness endpoint was procedural success. Both endpoints were compared with a pre-specified performance goal (PG). The mechanism of calcium modification was assessed in an optical coherence tomography (OCT) substudy.

Results: Patients (n = 431) were enrolled at 47 sites in 4 countries. The primary safety endpoint of the 30-day freedom from major adverse cardiovascular events was 92.2%; the lower bound of the 95% confidence interval was 89.9%, which exceeded the PG of 84.4% (p < 0.0001). The primary effectiveness endpoint of procedural success was 92.4%; the lower bound of the 95% confidence interval was 90.2%, which exceeded the PG of 83.4% (p < 0.0001). Mean calcified segment length was 47.9 ± 18.8 mm, calcium angle was 292.5 ± 76.5°, and calcium thickness was 0.96 ± 0.25 mm at the site of maximum calcification. OCT demonstrated multiplane and longitudinal calcium fractures after IVL in 67.4% of lesions. Minimum stent area was 6.5 ± 2.1 mm and was similar regardless of demonstrable fractures on OCT.

Conclusions: Coronary IVL safely and effectively facilitated stent implantation in severely calcified lesions.
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http://dx.doi.org/10.1016/j.jacc.2020.09.603DOI Listing
December 2020

Large-scale genome sequencing of mycorrhizal fungi provides insights into the early evolution of symbiotic traits.

Nat Commun 2020 10 12;11(1):5125. Epub 2020 Oct 12.

Université de Lorraine, Institut national de recherche pour l'agriculture, l'alimentation et l' environnement, UMR Interactions Arbres/Microorganismes, Centre INRAE Grand Est-Nancy, 54280, Champenoux, France.

Mycorrhizal fungi are mutualists that play crucial roles in nutrient acquisition in terrestrial ecosystems. Mycorrhizal symbioses arose repeatedly across multiple lineages of Mucoromycotina, Ascomycota, and Basidiomycota. Considerable variation exists in the capacity of mycorrhizal fungi to acquire carbon from soil organic matter. Here, we present a combined analysis of 135 fungal genomes from 73 saprotrophic, endophytic and pathogenic species, and 62 mycorrhizal species, including 29 new mycorrhizal genomes. This study samples ecologically dominant fungal guilds for which there were previously no symbiotic genomes available, including ectomycorrhizal Russulales, Thelephorales and Cantharellales. Our analyses show that transitions from saprotrophy to symbiosis involve (1) widespread losses of degrading enzymes acting on lignin and cellulose, (2) co-option of genes present in saprotrophic ancestors to fulfill new symbiotic functions, (3) diversification of novel, lineage-specific symbiosis-induced genes, (4) proliferation of transposable elements and (5) divergent genetic innovations underlying the convergent origins of the ectomycorrhizal guild.
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http://dx.doi.org/10.1038/s41467-020-18795-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550596PMC
October 2020

Outcomes of retrograde chronic total occlusion percutaneous coronary intervention: A report from the OPEN-CTO registry.

Catheter Cardiovasc Interv 2020 Sep 2. Epub 2020 Sep 2.

Center for Interventional Vascular Therapy, Columbia University Irving Medical Center, New York, New York.

Objectives: We sought to assess in-hospital and long-term outcomes of retrograde compared with antegrade-only percutaneous coronary intervention for chronic total occlusion (CTO PCI).

Background: Procedural and clinical outcomes following retrograde compared with antegrade-only CTO PCI remain unknown.

Methods: Using the core-lab adjudicated OPEN-CTO registry, we compared the outcomes of retrograde to antegrade-only CTO PCI. Primary endpoints included were in-hospital major adverse cardiac and cerebrovascular events (MACCE) (all-cause death, stroke, myocardial infarction [MI], emergency cardiac surgery, or clinically significant perforation) and MACCE at 1-year (all-cause death, MI, stroke, target lesion revascularization, or target vessel reocclusion).

Results: Among 885 single CTO procedures from the OPEN-CTO registry, 454 were retrograde and 431 were antegrade-only. Lesion complexity was higher (J-CTO score: 2.7 vs. 1.9; p < .001) and technical success lower (82.4 vs. 94.2%; p < .001) in retrograde compared with antegrade-only procedures. All-cause death was higher in the retrograde group in-hospital (2 vs. 0%; p = .003), but not at 1-year (4.9 vs. 3.3%; p = .29). Compared with antegrade-only procedures, in-hospital MACCE rates (composite of all-cause death, stroke, MI, emergency cardiac surgery, and clinically significant perforation) were higher in the retrograde group (10.8 vs. 3.3%; p < .001) and at 1-year (19.5 vs. 13.9%; p = .03). In sensitivity analyses landmarked at discharge, there was no difference in MACCE rates at 1 year following retrograde versus antegrade-only CTO PCI. Improvements in Seattle Angina Questionnaire Quality of Life scores at 1-year were similar between the retrograde and antegrade-only groups (29.9 vs 30.4; p = .58).

Conclusions: In the OPEN-CTO registry, retrograde CTO procedures were associated with higher rates of in-hospital MACCE compared with antegrade-only; however, post-discharge outcomes, including quality of life improvements, were similar between technical modalities.
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http://dx.doi.org/10.1002/ccd.29230DOI Listing
September 2020

"Back to the Future" for STEMI?: The COVID-19 Experience.

JACC Case Rep 2020 Aug 19;2(10):1651-1653. Epub 2020 Aug 19.

Carl and Edyth Lindner Center for Research and Education, Christ Hospital Health Network, Cincinnati, Ohio.

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http://dx.doi.org/10.1016/j.jaccas.2020.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438036PMC
August 2020

Maxillomandibular Advancement and Upper Airway Stimulation: Extrapharyngeal Surgery for Obstructive Sleep Apnea.

Clin Exp Otorhinolaryngol 2020 Aug 21;13(3):225-233. Epub 2020 Jul 21.

Division of Sleep Surgery, Department of Otolaryngology-Head and Neck Surgery, Stanford Hospital and Clinics, Stanford, CA, USA.

There are many ways to categorize surgery for obstructive sleep apnea (OSA), one of which is to distinguish between intrapharyngeal and extrapharyngeal procedures. While the general otolaryngologist treating OSA is familiar with intrapharyngeal procedures, such as uvulopalatopharyngoplasty and tongue base reduction, extrapharyngeal sleep operations such as maxillomandibular advancement (MMA) and upper airway stimulation (UAS) have evolved rapidly in the recent decade and deserve a dedicated review. MMA and UAS have both shown predictable high success rates with low morbidity. Each approach has unique strengths and limitations, and for the most complex of OSA patients, the two in combination complement each other. Extrapharyngeal airway operations are critical for achieving favorable outcomes for sleep surgeons.
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http://dx.doi.org/10.21053/ceo.2020.00360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435433PMC
August 2020

Surgical Algorithm for Obstructive Sleep Apnea: An Update.

Clin Exp Otorhinolaryngol 2020 Aug 1;13(3):215-224. Epub 2020 Jul 1.

Division of Sleep Surgery, Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford Hospital and Clinics, Stanford, CA, USA.

Sleep surgery is part of a continuum of care for obstructive sleep apnea (OSA) that involves medical, pharmacologic, and behavioral therapy. Upper airway surgery for OSA can significantly improve stability by way of modulating the critical negative closing pressure. This is the same mechanism of action as positive airway pressure or oral appliance therapy. The updated surgical algorithm in this review adds precision in three areas: patient selection, identification of previously unaddressed anatomic phenotypes with associated treatment modality, and improved techniques of previously established procedures. While the original Riley and Powell phase 1 and 2 approach to sleep surgery has focused on individual surgical success rate, this algorithm strives for an overall treatment success with multi-modal and patient-centric treatments.
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http://dx.doi.org/10.21053/ceo.2020.01053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435437PMC
August 2020

Terabase-scale metagenome coassembly with MetaHipMer.

Sci Rep 2020 07 1;10(1):10689. Epub 2020 Jul 1.

Computational Research Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.

Metagenome sequence datasets can contain terabytes of reads, too many to be coassembled together on a single shared-memory computer; consequently, they have only been assembled sample by sample (multiassembly) and combining the results is challenging. We can now perform coassembly of the largest datasets using MetaHipMer, a metagenome assembler designed to run on supercomputers and large clusters of compute nodes. We have reported on the implementation of MetaHipMer previously; in this paper we focus on analyzing the impact of very large coassembly. In particular, we show that coassembly recovers a larger genome fraction than multiassembly and enables the discovery of more complete genomes, with lower error rates, whereas multiassembly recovers more dominant strain variation. Being able to coassemble a large dataset does not preclude one from multiassembly; rather, having a fast, scalable metagenome assembler enables a user to more easily perform coassembly and multiassembly, and assemble both abundant, high strain variation genomes, and low-abundance, rare genomes. We present several assemblies of terabyte datasets that could never be coassembled before, demonstrating MetaHipMer's scaling power. MetaHipMer is available for public use under an open source license and all datasets used in the paper are available for public download.
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http://dx.doi.org/10.1038/s41598-020-67416-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329831PMC
July 2020

Conserved white-rot enzymatic mechanism for wood decay in the Basidiomycota genus Pycnoporus.

DNA Res 2020 Apr;27(2)

INRAE, UMR1163, Biodiversity and Biotechnology of Fungi, Aix Marseille University, 13009 Marseille, France.

White-rot (WR) fungi are pivotal decomposers of dead organic matter in forest ecosystems and typically use a large array of hydrolytic and oxidative enzymes to deconstruct lignocellulose. However, the extent of lignin and cellulose degradation may vary between species and wood type. Here, we combined comparative genomics, transcriptomics and secretome proteomics to identify conserved enzymatic signatures at the onset of wood-decaying activity within the Basidiomycota genus Pycnoporus. We observed a strong conservation in the genome structures and the repertoires of protein-coding genes across the four Pycnoporus species described to date, despite the species having distinct geographic distributions. We further analysed the early response of P. cinnabarinus, P. coccineus and P. sanguineus to diverse (ligno)-cellulosic substrates. We identified a conserved set of enzymes mobilized by the three species for breaking down cellulose, hemicellulose and pectin. The co-occurrence in the exo-proteomes of H2O2-producing enzymes with H2O2-consuming enzymes was a common feature of the three species, although each enzymatic partner displayed independent transcriptional regulation. Finally, cellobiose dehydrogenase-coding genes were systematically co-regulated with at least one AA9 lytic polysaccharide monooxygenase gene, indicative of enzymatic synergy in vivo. This study highlights a conserved core white-rot fungal enzymatic mechanism behind the wood-decaying process.
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http://dx.doi.org/10.1093/dnares/dsaa011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406137PMC
April 2020

Management of Percutaneous Coronary Intervention Complications: Algorithms From the 2018 and 2019 Seattle Percutaneous Coronary Intervention Complications Conference.

Circ Cardiovasc Interv 2020 06 12;13(6):e008962. Epub 2020 Jun 12.

University of Washington, Seattle, WA (J.A.D., R.S.H., K.E.K., J.M.M., W.L.).

Complications of percutaneous coronary intervention (PCI) may have significant impact on patient survival and healthcare costs. PCI procedural complexity and patient risk are increasing, and operators must be prepared to recognize and treat complications, such as perforations, dissections, hemodynamic collapse, no-reflow, and entrapped equipment. Unfortunately, few resources exist to train operators in PCI complication management. Uncertainty regarding complication management could contribute to the undertreatment of patients with high-complexity coronary disease. We, therefore, coordinated the Learning From Complications: How to Be a Better Interventionalist courses to disseminate the collective experience of high-volume PCI operators with extensive experience in chronic total occlusion and high-risk PCI. From these conferences in 2018 and 2019, we developed algorithms that emphasize early recognition, effective treatment, and team-based care of PCI complications. We think that an algorithmic approach will result in a logical and systematic response to life-threatening complications. This construct may be useful for operators who plan to perform complex PCI procedures.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.008962DOI Listing
June 2020

The evolution of strategies to minimise the risk of human drug-induced liver injury (DILI) in drug discovery and development.

Arch Toxicol 2020 08 6;94(8):2559-2585. Epub 2020 May 6.

Cyprotex Discovery Ltd., No.24 Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK.

Early identification of toxicity associated with new chemical entities (NCEs) is critical in preventing late-stage drug development attrition. Liver injury remains a leading cause of drug failures in clinical trials and post-approval withdrawals reflecting the poor translation between traditional preclinical animal models and human clinical outcomes. For this reason, preclinical strategies have evolved over recent years to incorporate more sophisticated human in vitro cell-based models with multi-parametric endpoints. This review aims to highlight the evolution of the strategies adopted to improve human hepatotoxicity prediction in drug discovery and compares/contrasts these with recent activities in our lab. The key role of human exposure and hepatic drug uptake transporters (e.g. OATPs, OAT2) is also elaborated.
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http://dx.doi.org/10.1007/s00204-020-02763-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395068PMC
August 2020

Multivessel Versus Culprit-Vessel Percutaneous Coronary Intervention in Cardiogenic Shock.

JACC Cardiovasc Interv 2020 05 29;13(10):1171-1178. Epub 2020 Apr 29.

Department of Cardiology, Henry Ford Hospital, Detroit, Michigan.

Objectives: This study sought to compare outcomes of patients enrolled in the NCSI (National Cardiogenic Shock Initiative) trial who were treated using a revascularization strategy of percutaneous coronary intervention (PCI) of multivessel PCI (MV-PCI) versus culprit-vessel PCI (CV-PCI).

Background: In patients with multivessel disease who present with acute myocardial infarction and cardiogenic shock (AMICS), intervening on the nonculprit vessel is controversial. There are conflicting published reports and lack of evidence, particularly in patients treated with early mechanical circulatory support (MCS).

Methods: From July 2016 to December 2019, patients who presented with AMICS to 57 participating hospitals were included in this analysis. All patients were treated using a standard shock protocol emphasizing early MCS, revascularization, and invasive hemodynamic monitoring. Patients with multivessel coronary artery disease (MVCAD) were analyzed according to whether CV-PCI or MV-PCI was undertaken during the index procedure.

Results: Of 198 patients with MVCAD, 126 underwent MV-PCI (64%) and 72 underwent CV-PCI (36%). Demographics between the cohorts were similar with respect to age, sex, history of diabetes, prior PCI or coronary artery bypass grafting, and prior history of myocardial infarction. Patients who underwent MV-PCI had a trend toward more severe impairment of cardiac output and worse lactate clearance on presentation, and cardiac performance was significantly worse at 12 h. However, 24 h from PCI, the hemometabolic derangements were similar. Survival and rates of acute kidney injury were not significantly different between groups (69.8% MV-PCI vs. 65.3% CV-PCI; p = 0.51; and 29.9% vs. 34.2%; p = 0.64, respectively).

Conclusions: In patients with MVCAD presenting with AMICS treated with early MCS, revascularization of nonculprit lesions was associated with similar hospital survival and acute kidney injury when compared with culprit-only PCI. Selective nonculprit PCI can be safety performed in AMICS in patients supported with mechanical circulatory support.
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http://dx.doi.org/10.1016/j.jcin.2020.03.012DOI Listing
May 2020

Heavy Metals Make a Chain: A Catenated Bismuth Compound.

Chemistry 2020 Jun 25;26(34):7711-7719. Epub 2020 May 25.

Department of Chemistry, Saint Mary's University, Halifax, Nova Scotia, B3H 3C3, Canada.

Catenation is common for the light main-group elements whereas it is rare for the heavy elements. Herein, we report the first example of a neutral molecule containing a Bi chain. It is prepared in a one-step reaction between bismuth trichloride and bis(diisopropylphosphino)amine in methanol suspension. The same reaction carried out in dichloromethane gives quite different products. All products have been characterized spectroscopically and using single-crystal X-ray analysis.
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http://dx.doi.org/10.1002/chem.202001295DOI Listing
June 2020

Genome sequencing of Rigidoporus microporus provides insights on genes important for wood decay, latex tolerance and interspecific fungal interactions.

Sci Rep 2020 03 23;10(1):5250. Epub 2020 Mar 23.

Faculty of Agriculture and Forestry, Department of Forest Sciences, University of Helsinki, P.O. Box 27, FIN-00014, Helsinki, Finland.

Fungal plant pathogens remain a serious threat to the sustainable agriculture and forestry, despite the extensive efforts undertaken to control their spread. White root rot disease is threatening rubber tree (Hevea brasiliensis) plantations throughout South and Southeast Asia and Western Africa, causing tree mortality and severe yield losses. Here, we report the complete genome sequence of the basidiomycete fungus Rigidoporus microporus, a causative agent of the disease. Our phylogenetic analysis confirmed the position of R. microporus among the members of Hymenochaetales, an understudied group of basidiomycetes. Our analysis further identified pathogen's genes with a predicted role in the decay of plant cell wall polymers, in the utilization of latex components and in interspecific interactions between the pathogen and other fungi. We also detected putative horizontal gene transfer events in the genome of R. microporus. The reported first genome sequence of a tropical rubber tree pathogen R. microporus should contribute to the better understanding of how the fungus is able to facilitate wood decay and nutrient cycling as well as tolerate latex and utilize resinous extractives.
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http://dx.doi.org/10.1038/s41598-020-62150-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089950PMC
March 2020

Reply to: Letter to the Editor.

Authors:
Robert F Riley

Catheter Cardiovasc Interv 2020 Nov 5;96(5):E562. Epub 2020 Mar 5.

Department of Cardiology, The Christ Hospital Heart & Vascular Center and the Lindner Center for Research and Education, Cincinnati, Ohio, USA.

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http://dx.doi.org/10.1002/ccd.28831DOI Listing
November 2020

Complex, Higher-Risk, and Indicated PCI (CHIP) Fellowship: Putting Training Into Practice.

Authors:
Robert F Riley

J Am Coll Cardiol 2020 03;75(8):980-984

Christ Hospital and Lindner Center for Research and Education, Cincinnati, Ohio. Electronic address:

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http://dx.doi.org/10.1016/j.jacc.2020.01.025DOI Listing
March 2020

A comparative genomics study of 23 Aspergillus species from section Flavi.

Nat Commun 2020 02 27;11(1):1106. Epub 2020 Feb 27.

Department of Biotechnology and Bioengineering, Technical University of Denmark, Søltoft Plads 223, 2800, Kongens Lyngby, Denmark.

Section Flavi encompasses both harmful and beneficial Aspergillus species, such as Aspergillus oryzae, used in food fermentation and enzyme production, and Aspergillus flavus, food spoiler and mycotoxin producer. Here, we sequence 19 genomes spanning section Flavi and compare 31 fungal genomes including 23 Flavi species. We reassess their phylogenetic relationships and show that the closest relative of A. oryzae is not A. flavus, but A. minisclerotigenes or A. aflatoxiformans and identify high genome diversity, especially in sub-telomeric regions. We predict abundant CAZymes (598 per species) and prolific secondary metabolite gene clusters (73 per species) in section Flavi. However, the observed phenotypes (growth characteristics, polysaccharide degradation) do not necessarily correlate with inferences made from the predicted CAZyme content. Our work, including genomic analyses, phenotypic assays, and identification of secondary metabolites, highlights the genetic and metabolic diversity within section Flavi.
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http://dx.doi.org/10.1038/s41467-019-14051-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046712PMC
February 2020

Point-of-Care Troponin Testing during Ambulance Transport to Detect Acute Myocardial Infarction.

Prehosp Emerg Care 2020 Nov-Dec;24(6):751-759. Epub 2020 Mar 3.

Use of point-of-care (POC) troponin (cTn) testing in the Emergency Department (ED) is well established. However, data examining POC cTn measurement in the prehospital setting, during ambulance transport, are limited. The objective of this study was to prospectively test the performance of POC cTn measurement by paramedics to detect myocardial infarction (MI) among patients transported to the ED for acute chest pain. A prospective cohort study of adults with non-traumatic chest pain was conducted in three Emergency Medical Services agencies (December 2016 to January 2018). Patients with ST-elevation MI on ECG were excluded. During ambulance transport paramedics initiated intravenous access, collected blood, and used a POC device (i-STAT; Abbott Laboratories) to measure cTn. Following ED arrival, participants received standard evaluations including clinical blood draws for cTn measurement in the hospital central lab (AccuTnI +3 assay; Beckman Coulter, or cTnI-Ultra assay; Siemens). Blood collected during ambulance transport was also analyzed for cTn in the central lab. Index visit MI was adjudicated by 3 experts using central lab cTn measures from the patient's clinical blood draws. Test characteristics (sensitivity, specificity, and predictive values) for detection of MI were calculated for POC and central lab cTn measurement of prehospital blood and compared with McNemar's test. During the study period prehospital POC cTn results were obtained on 421 patients, of which 5.0% (21/421) had results >99th percentile upper reference limit. MI was adjudicated in 16.2% (68/421) during the index visit. The specificity and positive predictive value of the POC cTn measurement were 99.2% (95% CI 97.5-99.8%) and 85.7% (95% CI 63.7-97.0%) for MI. However, the sensitivity and NPV of prehospital POC cTn were 26.5% (95% CI 16.5-38.6%) and 87.5% (95% CI 83.9-90.6%). Compared to POC cTn, the central lab cTn measurement of prehospital blood resulted in a higher sensitivity of 67.9% (95% CI 53.7-80.1%,  < 0.0001), but lower specificity of 92.4% (95% CI 88.4-95.4%,  = 0.0001). Prehospital POC i-STAT cTn measurement in patients transported with acute chest pain was highly specific for MI but had low sensitivity. This suggests that prehospital i-STAT POC cTn could be useful to rule-in MI, but should not be used to exclude MI.
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http://dx.doi.org/10.1080/10903127.2020.1721740DOI Listing
March 2020

A CHIP fellow's transition into practice: Building a complex coronary therapeutics program.

Catheter Cardiovasc Interv 2020 Nov 25;96(5):1058-1064. Epub 2019 Nov 25.

Division of Cardiology, University of Washington, Seattle, Washington.

Background: Both the prevalence and complexity of coronary artery disease are on the rise in the United States, leading to a resurgence in novel techniques and equipment utilized to treat complex coronary disease. However, declining percutaneous coronary intervention (PCI) volumes and lack of formal post-graduate education opportunities have created a gap in treatment delivery for this patient population. Several complex, high-risk, and indicated PCI (CHIP) fellowships have been developed in an attempt to bridge this disparity. We present data from the first year of practice from a former CHIP fellow during development of a formal complex coronary therapeutics program.

Methods: Data was prospectively collected for PCIs performed during the first 12 months of practice for the lead author and compared to procedures performed in the 12 months prior to the study period.

Results: Out of 371 PCIs performed during the study period, 53.4% (198/371) were considered complex, including 126 chronic total occlusion (CTO) procedures. Compared to the previous 12 months, there was a significant increase in the number and complexity (median J-CTO score 2.1 vs. 1.3, p .04) of CTOs performed during the study period. CTO procedural characteristics and complication rates were similar to those previously published in large U.S. registries, with technical success in 93.4% (118/126) and procedural success in 85.7% (108/126).

Conclusion: Following dedicated CHIP fellowship training and establishment of a formal CHIP program, procedural success and complication rates were achieved similar to those published in prior studies evaluating CTO PCI at high volume centers.
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http://dx.doi.org/10.1002/ccd.28599DOI Listing
November 2020

Myocardial Perfusion After Coronary Chronic Total Occlusion Percutaneous Coronary Intervention: Does It Matter to Myocytes How You Cross the Lesion?

Circ Cardiovasc Interv 2019 11 1;12(11):e008568. Epub 2019 Nov 1.

Smith Center for Outcomes Research in Cardiology (R.W.Y.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.119.008568DOI Listing
November 2019

CTO PCI: When at first you don't succeed….

Catheter Cardiovasc Interv 2019 10;94(4):525-526

The Christ Hospital and Lindner Center for Research and Education, Cincinnati, Ohio.

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http://dx.doi.org/10.1002/ccd.28518DOI Listing
October 2019