Publications by authors named "Michael Jacobs"

697 Publications

Nicotine promotes vascular calcification via intracellular Ca2+-mediated, Nox5-induced oxidative stress and extracellular vesicle release in vascular smooth muscle cells.

Cardiovasc Res 2021 Jul 17. Epub 2021 Jul 17.

Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.

Aims: Smokers are at increased risk of cardiovascular events. However, the exact mechanisms through which smoking influences cardiovascular disease resulting in accelerated atherosclerosis and vascular calcification are unknown. The aim of this study was to investigate effects of nicotine on initiation of vascular smooth muscle cell (VSMC) calcification and to elucidate underlying mechanisms.

Methods And Results: We assessed vascular calcification of 62 carotid lesions of both smoking and non-smoking patients using ex vivo micro-computed-tomography (µCT)-scanning. Calcification was present more often in carotid plaques of smokers (n = 22 of 30, 73.3%) compared to non-smokers (n = 11 of 32, 34.3%; p < 0.001), confirming higher atherosclerotic burden. The difference was particularly profound for microcalcifications, which was 17-fold higher in smokers compared to non-smokers. In vitro, nicotine induced human primary VSMC calcification, increased osteogenic gene expression (Runx2, Osx, BSP and OPN), and extracellular vesicle (EV) secretion. The pro-calcifying effects of nicotine were mediated by Ca2+-dependent Nox5. SiRNA knock-down of Nox5 inhibited nicotine-induced EV release and calcification. Moreover, pre-treatment of hVSMCs with vitamin K2 ameliorated nicotine-induced intracellular oxidative stress, EV secretion, and calcification. Using nicotinic acetylcholine receptor (nAChR) blockers α-bungarotoxin and hexamethonium bromide we found that the effects of nicotine on intracellular Ca2+ and oxidative stress were mediated by α7 and α3 nAChR. Finally, we showed that Nox5 expression was higher in carotid arteries of smokers and correlated with calcification levels in these vessels.

Conclusion: In this study we provide evidence that nicotine induces Nox5-mediated pro-calcific processes as novel mechanism of increased atherosclerotic calcification. We identified that activation of α7 and α3 nAChR by nicotine increases intracellular Ca2+ and initiates calcification of hVSMCs through increased Nox5 activity, leading to oxidative stress-mediated EV release. Identifying the role of Nox5-induced oxidative stress opens novel avenues for diagnosis and treatment of smoking-induced cardiovascular disease.
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http://dx.doi.org/10.1093/cvr/cvab244DOI Listing
July 2021

Surgical resection and graft replacement for primary inferior vena cava leiomyosarcoma: A multicenter experience.

J Vasc Surg Venous Lymphat Disord 2021 Jul 13. Epub 2021 Jul 13.

Department of Surgery, Division of Vascular Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL. Electronic address:

Objective: Primary leiomyosarcomas of the inferior vena cava (IVC) are best managed with surgical resection when technically feasible, however there is a lack of consensus regarding the best choice of conduit and reconstruction technique. The aim of this multicenter study was to perform a comprehensive assessment through the Vascular Low Frequency Disease Consortium (VLFDC) to determine the most effective method for caval reconstruction after resection of primary leiomyosarcoma of the IVC.

Methods: A multicenter, standardized database review of patients undergoing surgical resection and reconstruction of the IVC for primary leiomyosarcomas from 2007-2017 was performed. Demographics, periprocedural details, and post-operative outcomes were analyzed.

Results: A total of 92 patients (60 women and 32 men) were treated with a mean age of 60.1 years (range 30-88). Metastatic disease was present in 22%. Tumor location was distributed as: 53% (n=49) below the renal veins; 57% (n=52) between renal and hepatic veins; and 14% (n=13) above the hepatic veins. Conduits for reconstruction included: ringed polytetrafluoroethylene (PTFE) (n=80), non-ringed PTFE (n=1), Dacron (n=1), autogenous vein (n=1), bovine pericardium (n=4), cryopreserved tissue (n=5). Complete R0 resection was accomplished in 79% (n=73). In-hospital mortality was 2% with a median length of stay of 8 days. When comparing PTFE to non-PTFE reconstructions, primary patency of PTFE reconstructed IVCs was 97% and 92% at 1 year and 5 years respectively compared with 73% at 1 and 5 years amongst the non-PTFE reconstructed IVCs. Overall one, three, and five-year survival for the entire cohort were 94%, 86%, and 65%, respectively CONCLUSIONS: This multi-institutional study demonstrates that complete en bloc resection of IVC leiomyosarcomas with vascular surgical reconstruction in selected patients results in low perioperative mortality and is associated with excellent long-term patency. Ringed PTFE graft is the most commonly utilized conduit for caval reconstruction and yields excellent long-term primary patency.
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http://dx.doi.org/10.1016/j.jvsv.2021.06.021DOI Listing
July 2021

Multiparametric Magnetic Resonance Imaging to Characterize Cabotegravir Long-Acting Formulation Depot Kinetics in Healthy Adult Volunteers.

Br J Clin Pharmacol 2021 Jul 8. Epub 2021 Jul 8.

ViiV Healthcare, Research Triangle Park, NC, USA.

Aim: Cabotegravir long-acting (LA) intramuscular (IM) injection is being investigated for HIV preexposure prophylaxis due to its potent antiretroviral activity and infrequent dosing requirement. A subset of healthy adult volunteers participating in a phase I study assessing cabotegravir tissue pharmacokinetics underwent serial magnetic resonance imaging (MRI) to assess drug depot localization and kinetics following a single cabotegravir LA IM targeted injection.

Methods: Eight participants (four men, four women) were administered cabotegravir LA 600 mg under ultrasonographic-guided injection targeting the gluteal muscles. MRI was performed to determine injection-site location in gluteal muscle (IM), subcutaneous (SC) adipose tissue, and combined IM/SC compartments and to quantify drug depot characteristics, including volume and surface area, on Days 1 (≤2 hours postinjection), 3, and 8. Linear regression analysis examined correlations between MRI-derived parameters and plasma cabotegravir exposure metrics, including maximum observed concentration (C ) and partial area under the concentration-time curve (AUC) through Weeks 4 and 8.

Results: Cabotegravir LA depot locations varied by participant and were identified in the IM compartment (n=2), combined IM/SC compartments (n=4), SC compartment (n=1), and retroperitoneal cavity (n=1). Although several MRI parameter and exposure metric correlations were determined, total depot surface area on Day 1 strongly correlated with plasma cabotegravir concentration at Days 3 and 8, C , and partial AUC through Weeks 4 and 8.

Conclusion: MRI clearly delineated cabotegravir LA injection-site location and depot kinetics in healthy adults. Although injection-site variability was observed, drug depot surface area correlated with both plasma C and partial AUC independently of anatomical distribution.
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http://dx.doi.org/10.1111/bcp.14977DOI Listing
July 2021

: intriguing aerotolerant gut anaerobe with emerging antimicrobial resistance and pathogenic and probiotic roles in human health.

Gut Microbes 2021 Jan-Dec;13(1):1922241

Digestive Diseases Research Institute, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

is the type strain for the genus , a group of gram-negative anaerobic bacteria that commonly colonize the gastrointestinal tract of numerous species. First isolated in the 1930s from a clinical specimen as , the strain was re-classified to form the new genus in 2006. Currently, the genus consists of 15 species, 10 of which are listed as 'validly named' (, and ) and 5 'not validly named' (, and ) by the List of Prokaryotic names with Standing in Nomenclature. The genus has been associated with reports of both beneficial and pathogenic effects in human health. Herein, we review the literature on the history, ecology, diseases, antimicrobial resistance, and genetics of this bacterium, illustrating the effects of on human and animal health.
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http://dx.doi.org/10.1080/19490976.2021.1922241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253142PMC
July 2021

Xenogeneic materials for the surgical treatment of aortic infections.

J Thorac Dis 2021 May;13(5):3021-3032

European Vascular Center Aachen-Maastricht, Department of Vascular Surgery, RWTH University Hospital Aachen, Aachen, Germany.

Background: The surgical treatment of aortic infections (AIs) is challenging. In situ aortic reconstructions represent nowadays the favored therapy for fit patients and xenogeneic materials are used increasingly. The aim of this study was to present our experience with xenogeneic reconstructions for AI using self-made bovine pericardium tubes and/or the biosynthetic Omniflow II graft.

Methods: This retrospective single-center study included all patients undergoing xenogeneic aortic and aortoiliac reconstructions from December 2015 to June 2020. Patient comorbidities, symptoms, procedural characteristics, types of pathogens and postoperative outcomes were analyzed.

Results: Twenty-eight patients [23 male (82%), median age 68 (range, 28-84) years] were included. Ten patients (36%) had native AIs and 18 (64%) had graft infections, including 3 (11%) aortoesophageal and 2 (7%) aortoduodenal fistulas (ADF). Twenty-four patients (86%) were symptomatic, the most common symptoms being contained aortic rupture (n=8) and sepsis (n=4). The surgical procedures were infra- and juxtarenal aortic repairs (n=11, 39% and n=7, 25%), thoracoabdominal aortic repairs (type IV: n=1, 4%; type V: n=3, 11%), descending thoracic aortic repairs (n=4, 14%) and 2 reconstructions (7%) involving the ascending aorta/aortic arch. Most were urgent (n=10, 43%) or emergent operations (n=11, 35%). Identification of pathogen(s), mostly Gram-positive bacteria, was possible in 25 patients (89%). Twelve patients (43%) had polymicrobial infections and 6 (21%) infections with multi-resistant bacteria. In-hospital mortality was 32% (n=9) due to acute cardiac failure (1/9), endocarditis (1/9), bleeding (3/9) and sepsis (4/9). The most frequent complications were transient need for dialysis (n=12, 43%) and persisting sepsis (n=11, 39%). Two early occlusions of Omniflow II grafts were observed (7%). Median follow-up (FU), during which 2 patients died of non-aortic causes, was 14 months (95% CI: 9-19 months). Freedom from reoperation was 100%, there was no evidence for reinfection during FU.

Conclusions: Xenogeneic orthotopic reconstructions for AI can be performed at all aortic levels. Combining bovine pericardium and the Omniflow II graft can be useful for reconstructing the branched aortic segments and both materials show appropriate early to midterm outcomes. Nonetheless, AIs are serious conditions associated with relevant morbidity/mortality rates, even in a specialized center.
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http://dx.doi.org/10.21037/jtd-20-3481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182519PMC
May 2021

A kinetic description of how interfaces accelerate reactions in micro-compartments.

Chem Sci 2020 Jul 27;11(32):8533-8545. Epub 2020 Jul 27.

Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign Urbana Illinois 61801 USA.

A kinetic expression is derived to explain how interfaces alter bulk chemical equilibria and accelerate reactions in micro-compartments. This description, aided by the development of a stochastic model, quantitatively predicts previous experimental observations of accelerated imine synthesis in micron-sized emulsions. The expression accounts for how reactant concentration and compartment size together lead to accelerated reaction rates under micro-confinement. These rates do not depend solely on concentration, but rather the fraction of total molecules in the compartment that are at the interface. Although there are ∼10 to 10 solute molecules in a typical micro-compartment, a kind of "stochasticity" appears when compartment size and reagent concentration yield nearly equal numbers of bulk and interfacial molecules. Although this is distinct from the stochasticity produced by nano-confinement, these results show how interfaces can govern chemical transformations in larger atmospheric, geologic and biological compartments.
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http://dx.doi.org/10.1039/d0sc03189eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163377PMC
July 2020

A critical analysis of electrospray techniques for the determination of accelerated rates and mechanisms of chemical reactions in droplets.

Chem Sci 2020 Oct 26;11(48):13026-13043. Epub 2020 Oct 26.

Chemical Sciences Division, Lawrence Berkeley National Laboratory Berkeley 94720 CA USA

Electrospray and Electrosonic Spray Ionization Mass Spectrometry (ESI-MS and ESSI-MS) have been widely used to report evidence that many chemical reactions in micro- and nano-droplets are dramatically accelerated by factors of ∼10 to 10 relative to macroscale bulk solutions. Despite electrospray's relative simplicity to both generate and detect reaction products in charged droplets using mass spectrometry, substantial complexity exists in how the electrospray process itself impacts the interpretation of the mechanism of these observed accelerated rates. ESI and ESSI are both coupled multi-phase processes, in which analytes in small charged droplets are transferred and detected as gas-phase ions with a mass spectrometer. As such, quantitative examination is needed to evaluate the impact of multiple experimental factors on the magnitude and mechanisms of reaction acceleration. These include: (1) evaporative concentration of reactants as a function of droplet size and initial concentration, (2) competition from gas-phase chemistry and reactions on experimental surfaces, (3) differences in ionization efficiency and ion transmission and (4) droplet charge. We examine (1-4) using numerical models, new ESI/ESSI-MS experimental data, and prior literature to assess the limitations of these approaches and the experimental best practices required to robustly interpret acceleration factors in micro- and nano-droplets produced by ESI and ESSI.
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http://dx.doi.org/10.1039/d0sc04611fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163298PMC
October 2020

Never Change a Flowing System? The Effects of Retrograde Flow on Isolated Perfused Lungs and Vessels.

Cells 2021 May 15;10(5). Epub 2021 May 15.

Institute of Pharmacology and Toxicology, Medical Faculty, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany.

Retrograde perfusion may occur during disease, surgery or extracorporeal circulation. While it is clear that endothelial cells sense and respond to changes in blood flow, the consequences of retrograde perfusion are only poorly defined. Similar to shear stress or disturbed flow, retrograde perfusion might result in vasomotor responses, edema formation or inflammation in and around vessels. In this study we investigated in rats the effects of retrograde perfusion in isolated systemic vessels (IPV) and in pulmonary vessels of isolated perfused lungs (IPL). Anterograde and retrograde perfusion was performed for 480 min in IPV and for 180 min in the IPL. Perfusion pressure, cytokine levels in perfusate and bronchoalveolar lavage fluid (BALF), edema formation and mRNA expression were studied. In IPV, an increased perfusion pressure and initially also increased cytokine levels were observed during retrograde perfusion. In the IPL, increased edema formation occurred, while cytokine levels were not increased, though dilution of cytokines in BALF due to pulmonary edema cannot be excluded. In conclusion, effects of flow reversal were visible immediately after initiation of retrograde perfusion. Pulmonary edema formation was the only effect of the 3 h retrograde perfusion. Therefore, further research should focus on identification of possible long-term complications of flow reversal.
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http://dx.doi.org/10.3390/cells10051210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156646PMC
May 2021

Distal aortic perfusion-still of relevance for spinal cord protection during complex aortic surgery?

Eur J Cardiothorac Surg 2021 May 19. Epub 2021 May 19.

Department of Vascular Surgery, European Vascular Center Aachen-Maastricht, University Hospital RWTH Aachen, Aachen, Germany.

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http://dx.doi.org/10.1093/ejcts/ezab212DOI Listing
May 2021

The role of surgical and total endovascular techniques in the treatment of ruptured juxtarenal aortic aneurysms.

Vasa 2021 May 19:1-7. Epub 2021 May 19.

Department of Vascular Surgery and Research Vascular Centre, Asklepios Clinic Langen, University of Frankfurt, Langen, Germany.

Ruptured juxtarenal aortic aneurysms (RJAAA) represent a special challenge in clinical practice, but the evidence to guide therapeutic decision-making is scarce. The aim of this study was to present two different approaches, open surgical (OAR) and chimney endovascular repair (CHEVAR), for treating patients with RJAAA. This retrospective two-center study included all patients per center undergoing OAR or CHEVAR for RJAAA between February 2008 and January 2020. Juxtarenal aortic aneurysms were defined as having an infrarenal neck of 2-5 mm, measured after three-dimensional reconstruction of the computed tomography angiography scan. 12 OAR patients (10 male, median age 73 years [58-90 years]) and 6 CHEVAR patients (all male, median age 74 years [59-83 years]) were included. In the OAR group, the proximal aortic clamping was suprarenal in 7 and interrenal in 5 patients. Cold renal perfusion was used in 4 patients, in 2 with suprarenal aortic clamping and in 2 with interrenal aortic clamping. 3 CHEVAR patients received a single renal chimney, the other 3 received double renal chimneys. Technical success was 12/12 in the OAR group 5/6 in the CHEVAR group. In-hospital mortality and 30-day mortality were 3/12 after OAR and 0/6 after CHEVAR. 2 OAR patients required transient dialysis. Median in-hospital stay was 14 (10-63) and 8 (6-21) days and median follow-up (FU) was 20 (3-37) and 30 (7-101) months, respectively. No further deaths occurred during FU. One OAR patient and 4 CHEVAR patients required aortic reinterventions. RJAAAs are rare. Both OAR and CHEVAR can represent adequate treatments for RJAAAs. OAR is the traditional approach, but CHEVAR has - in a high-volume center - promising early results with nonetheless a need for continuous FU to prevent reinterventions. Defining the studied aortic pathology precisely is essential for future research in order to draw valid conclusions.
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http://dx.doi.org/10.1024/0301-1526/a000955DOI Listing
May 2021

Elevated sperm DNA fragmentation does not predict recurrent implantation failure.

Andrologia 2021 Aug 7;53(7):e14094. Epub 2021 May 7.

Department of Urology, University of Miami Miller School of Medicine, Miami, FL, USA.

In this study, we sought to determine whether sperm DNA fragmentation (DFI%) and high DNA stainability (HDS%) evaluated by sperm chromatin structure assay (SCSA) predict recurrent implantation failure (RIF) or pregnancy rate. A retrospective study was performed of consecutive cycles of ICSI treatment from 2009 to 2018. A total of 386 couples that underwent 1,216 frozen embryo transfer (FET) cycles were analysed. Mean female and male age was 34 ± 3.6 years and 37.3 ± 6.6 years, respectively, and a median total motile sperm count (TMSC) was 43.5 [9.9-105.5] million. Overall median DFI% and HDS% was 12 [7.1-18.9] and 9.6 [6.5-14.4] respectively. On multivariable analysis, DFI% and HDS% were not associated with RIF (DFI%: OR = 1.01, 95% CI: 0.98-1.04, p = .414; HDS%: OR = 0.97, 95% CI: 0.94-1.01, p = .107) or IVF success, defined as clinical pregnancy (DFI%: OR = 1.00, 95% CI: 0.99-1.01, p = .641; HDS%: OR = 1.01, 95% CI: 0.99-1.02, p = .565). We found that neither DFI% or HDS%, as assessed by SCSA, were predictive of RIF or pregnancy rate. This finding suggests that sperm DNA fragmentation does not predict RIF or pregnancy rate.
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http://dx.doi.org/10.1111/and.14094DOI Listing
August 2021

A phase Ib/IIa, open-label, multiple ascending-dose trial of domagrozumab in fukutin-related protein limb-girdle muscular dystrophy.

Muscle Nerve 2021 Aug 24;64(2):172-179. Epub 2021 May 24.

Center for Genetic Muscle Disorders, Kennedy Krieger Institute, Baltimore, Maryland, USA.

Introduction/aims: In this study we report the results of a phase Ib/IIa, open-label, multiple ascending-dose trial of domagrozumab, a myostatin inhibitor, in patients with fukutin-related protein (FKRP)-associated limb-girdle muscular dystrophy.

Methods: Nineteen patients were enrolled and assigned to one of three dosing arms (5, 20, or 40 mg/kg every 4 weeks). After 32 weeks of treatment, participants receiving the lowest dose were switched to the highest dose (40 mg/kg) for an additional 32 weeks. An extension study was also conducted. The primary endpoints were safety and tolerability. Secondary endpoints included muscle strength, timed function testing, pulmonary function, lean body mass, pharmacokinetics, and pharmacodynamics. As an exploratory outcome, muscle fat fractions were derived from whole-body magnetic resonance images.

Results: Serum concentrations of domagrozumab increased in a dose-dependent manner and modest levels of myostatin inhibition were observed in both serum and muscle tissue. The most frequently occurring adverse events were injuries secondary to falls. There were no significant between-group differences in the strength, functional, or imaging outcomes studied.

Discussion: We conclude that, although domagrozumab was safe in patients in limb-girdle muscular dystrophy type 2I/R9, there was no clear evidence supporting its efficacy in improving muscle strength or function.
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http://dx.doi.org/10.1002/mus.27259DOI Listing
August 2021

A γ-lactam siderophore antibiotic effective against multidrug-resistant Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter spp.

Eur J Med Chem 2021 Aug 8;220:113436. Epub 2021 Apr 8.

Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, 44106, USA; Department of Biochemistry, Case Western Reserve University, Cleveland, OH, 44106, USA; Department of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA; Geriatric Research, Education and Clinical Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, 44106, USA; Departments of Pharmacology, Molecular Biology & Microbiology, And Proteomics & Bioinformatics, Case Western Reserve University, Cleveland, OH, 44106, USA; CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Cleveland, OH, 44106, USA. Electronic address:

Serious infections caused by multidrug-resistant (MDR) organisms (Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii) present a critical need for innovative drug development. Herein, we describe the preclinical evaluation of YU253911, 2, a novel γ-lactam siderophore antibiotic with potent antimicrobial activity against MDR Gram-negative pathogens. Penicillin-binding protein (PBP) 3 was shown to be a target of 2 using a binding assay with purified P. aeruginosa PBP3. The specific binding interactions with P. aeruginosa were further characterized with a high-resolution (2.0 Å) X-ray structure of the compound's acylation product in P. aeruginosa PBP3. Compound 2 was shown to have a concentration >1 μg/ml at the 6 h time point when administered intravenously or subcutaneously in mice. Employing a meropenem resistant strain of P. aeruginosa, 2 was shown to have dose-dependent efficacy at 50 and 100 mg/kg q6h dosing in a mouse thigh infection model. Lastly, we showed that a novel γ-lactam and β-lactamase inhibitor (BLI) combination can effectively lower minimum inhibitory concentrations (MICs) against carbapenem resistant Acinetobacter spp. that demonstrated decreased susceptibility to 2 alone.
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http://dx.doi.org/10.1016/j.ejmech.2021.113436DOI Listing
August 2021

Recent advances in rapid antimicrobial susceptibility testing systems.

Expert Rev Mol Diagn 2021 Jun 20;21(6):563-578. Epub 2021 May 20.

Section Head of Microbiology, Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.

Introduction: Until recently antimicrobial susceptibility testing (AST) methods based on the demonstration of phenotypic susceptibility in 16-24 h remained largely unchanged.

Areas Covered: Advances in rapid phenotypic and molecular-based AST systems.

Expert Opinion: AST has changed over the past decade, with many rapid phenotypic and molecular methods developed to demonstrate phenotypic or genotypic resistance, or biochemical markers of resistance such as β-lactamases associated with carbapenem resistance. Most methods still require isolation of bacteria from specimens before both legacy and newer methods can be used. Bacterial identification by MALDI-TOF mass spectroscopy is now widely used and is often key to the interpretation of rapid AST results. Several PCR arrays are available to detect the most frequent pathogens associated with bloodstream infections and their major antimicrobial resistance genes. Many advances in whole-genome sequencing of bacteria and fungi isolated by culture as well as directly from clinical specimens have been made but are not yet widely available. High cost and limited throughput are the major obstacles to uptake of rapid methods, but targeted use, continued development and decreasing costs are expected to result in more extensive use of these increasingly useful methods.
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http://dx.doi.org/10.1080/14737159.2021.1924679DOI Listing
June 2021

Indigenous Community Perspectives of Food Security, Sustainable Food Systems and Strategies to Enhance Access to Local and Traditional Healthy Food for Partnering Williams Treaties First Nations (Ontario, Canada).

Int J Environ Res Public Health 2021 04 21;18(9). Epub 2021 Apr 21.

School of Public Health and Health Systems, Faculty of Health, University of Waterloo, Waterloo, ON N2L 3G1, Canada.

In partnership with communities of the Williams Treaties First Nations in southern Ontario (Canada), we describe an approach to work with communities, and highlight perspectives of food security and sustainability, including priorities and opportunities to revitalize local food systems as a pathway to food security and food sovereignty. The objectives of our project were: (1) to build a shared understanding of food security and sustainability; and (2) to document community priorities, challenges and opportunities to enhance local food access. Utilizing an Indigenous methodology, the conversational method, within the framework of community-based participatory research, formative work undertaken helped to conceptualize food security and sustainability from a community perspective and solidify interests within the four participating communities to inform community-led action planning. Knowledge generated from our project will inform development of initiatives, programs or projects that promote sustainable food systems. The community-based actions identified support a path towards holistic wellbeing and, ultimately, Indigenous peoples' right to food security and food sovereignty.
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http://dx.doi.org/10.3390/ijerph18094404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122547PMC
April 2021

Detection of mcr-1 gene in a clinical Escherichia coli strain in North Carolina: first report.

J Glob Antimicrob Resist 2021 06 28;25:154-156. Epub 2021 Mar 28.

Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jgar.2021.03.014DOI Listing
June 2021

A living WHO guideline on drugs to prevent covid-19.

BMJ 2021 03 1;372:n526. Epub 2021 Mar 1.

Sheikh Shakhbout Medical City, Abu Dhabi, UAE.

Clinical Question: What is the role of drugs in preventing covid-19? WHY DOES THIS MATTER?: There is widespread interest in whether drug interventions can be used for the prevention of covid-19, but there is uncertainty about which drugs, if any, are effective. The first version of this living guideline focuses on the evidence for hydroxychloroquine. Subsequent updates will cover other drugs being investigated for their role in the prevention of covid-19.

Recommendation: The guideline development panel made a strong recommendation against the use of hydroxychloroquine for individuals who do not have covid-19 (high certainty).

How This Guideline Was Created: This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development panel of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Understanding The New Recommendation: The linked systematic review and network meta-analysis (6 trials and 6059 participants) found that hydroxychloroquine had a small or no effect on mortality and admission to hospital (high certainty evidence). There was a small or no effect on laboratory confirmed SARS-CoV-2 infection (moderate certainty evidence) but probably increased adverse events leading to discontinuation (moderate certainty evidence). The panel judged that almost all people would not consider this drug worthwhile. In addition, the panel decided that contextual factors such as resources, feasibility, acceptability, and equity for countries and healthcare systems were unlikely to alter the recommendation. The panel considers that this drug is no longer a research priority and that resources should rather be oriented to evaluate other more promising drugs to prevent covid-19.

Updates: This is a living guideline. New recommendations will be published in this article and signposted by update notices to this guideline.

Readers Note: This is the first version of the living guideline for drugs to prevent covid-19. It complements the WHO living guideline on drugs to treat covid-19. When citing this article, please consider adding the update number and date of access for clarity.
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http://dx.doi.org/10.1136/bmj.n526DOI Listing
March 2021

Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance.

Eur Heart J 2021 05;42(19):1866-1878

Royal Free London NHS Foundation Trust, Pond Street, London NW3 2QG, UK.

Background: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients.

Methods And Results: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms).

Conclusions: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.
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http://dx.doi.org/10.1093/eurheartj/ehab075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928984PMC
May 2021

Analysis of an Ebola virus disease survivor whose host and viral markers were predictive of death indicates the effectiveness of medical countermeasures and supportive care.

Genome Med 2021 Jan 11;13(1). Epub 2021 Jan 11.

Health Protection Research Unit in Emerging and Zoonotic Infections, National Institute for Health Research, Liverpool, UK.

Background: Ebola virus disease (EVD) is an often-fatal infection where the effectiveness of medical countermeasures is uncertain. During the West African outbreak (2013-2016), several patients were treated with different types of anti-viral therapies including monoclonal antibody-based cocktails that had the potential to neutralise Ebola virus (EBOV). However, at the time, the efficacy of these therapies was uncertain. Given the scale of the outbreak, several clinical phenotypes came to the forefront including the ability of the same virus to cause recrudescence in the same patient-perhaps through persisting in immune privileged sites. Several key questions remained including establishing if monoclonal antibody therapy was effective in humans with severe EVD, whether virus escape mutants were selected during treatment, and what is the potential mechanism(s) of persistence. This was made possible through longitudinal samples taken from a UK patient with EVD.

Methods: Several different sample types, plasma and cerebrospinal fluid, were collected and sequenced using Illumina-based RNAseq. Sequence reads were mapped both to EBOV and the human genome and differential gene expression analysis used to identify changes in the abundance of gene transcripts as infection progressed. Digital Cell Quantitation analysis was used to predict the immune phenotype in samples derived from blood.

Results: The findings were compared to equivalent data from West African patients. The study found that both virus and host markers were predictive of a fatal outcome. This suggested that the extensive supportive care, and most likely the application of the medical countermeasure ZMab (a monoclonal antibody cocktail), contributed to survival of the UK patient. The switch from progression to a 'fatal' outcome to a 'survival' outcome could be seen in both the viral and host markers. The UK patient also suffered a recrudescence infection 10 months after the initial infection. Analysis of the sequencing data indicated that the virus entered a period of reduced or minimal replication, rather than other potential mechanisms of persistence-such as defective interfering genomes.

Conclusions: The data showed that comprehensive supportive care and the application of medical countermeasures are worth pursuing despite an initial unfavourable prognosis.
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http://dx.doi.org/10.1186/s13073-020-00811-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798020PMC
January 2021

Case report: Keeping a cool head - A delayed open repair of a ruptured TAAA.

Int J Surg Case Rep 2021 Jan 25;78:326-330. Epub 2020 Dec 25.

Department of Vascular Surgery, University Hospital RWTH Aachen, 52074, Aachen, Germany.

Introduction: The limited resources available for complex surgical procedures during the nightshift can influence the postoperative outcome and are associated with increased complication rates and 30-day mortality. On the other hand, cases of the nightshift are often urgent and demand prompt reaction.

Presentation Of Case: Hereby we report a patient with a ruptured thoracoabdominal aortic aneurysm, who was admitted during nightshift and was operated 12 h later to gain optimal conditions for such a complex surgical treatment and bypass the nightshift-effect.

Discussion: A review of the literature shows a significant short-term mortality increase on elective procedures performed during the weekend or during the nightshift, however it remains undecisive on the impact of the weekend-effect on emergent procedures.

Conclusion: The fortunate recovering of the patient during his hospital stay as well as in the following months emphasizes the importance of critical risk assessment during emergency management, which may justify a delayed surgical treatment.
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http://dx.doi.org/10.1016/j.ijscr.2020.12.070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787939PMC
January 2021

Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19).

Rev Cardiovasc Med 2020 12;21(4):517-530

Emergency Medicine, Phoenix, 85016, AZ, USA.

The SARS-CoV-2 virus spreading across the world has led to surges of COVID-19 illness, hospitalizations, and death. The complex and multifaceted pathophysiology of life-threatening COVID-19 illness including viral mediated organ damage, cytokine storm, and thrombosis warrants early interventions to address all components of the devastating illness. In countries where therapeutic nihilism is prevalent, patients endure escalating symptoms and without early treatment can succumb to delayed in-hospital care and death. Prompt early initiation of sequenced multidrug therapy (SMDT) is a widely and currently available solution to stem the tide of hospitalizations and death. A multipronged therapeutic approach includes 1) adjuvant nutraceuticals, 2) combination intracellular anti-infective therapy, 3) inhaled/oral corticosteroids, 4) antiplatelet agents/anticoagulants, 5) supportive care including supplemental oxygen, monitoring, and telemedicine. Randomized trials of individual, novel oral therapies have not delivered tools for physicians to combat the pandemic in practice. No single therapeutic option thus far has been entirely effective and therefore a combination is required at this time. An urgent immediate pivot from single drug to SMDT regimens should be employed as a critical strategy to deal with the large numbers of acute COVID-19 patients with the aim of reducing the intensity and duration of symptoms and avoiding hospitalization and death.
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http://dx.doi.org/10.31083/j.rcm.2020.04.264DOI Listing
December 2020

A Deep Learning System for Synthetic Knee Magnetic Resonance Imaging: Is Artificial Intelligence-Based Fat-Suppressed Imaging Feasible?

Invest Radiol 2021 06;56(6):357-368

From the The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins Medical Institutions.

Materials And Methods: This single-center study was approved by the institutional review board. Artificial intelligence-based FS MRI scans were created from non-FS images using a deep learning system with a modified convolutional neural network-based U-Net that used a training set of 25,920 images and validation set of 16,416 images. Three musculoskeletal radiologists reviewed 88 knee MR studies in 2 sessions, the original (proton density [PD] + FSPD) and the synthetic (PD + AFSMRI). Readers recorded AFSMRI quality (diagnostic/nondiagnostic) and the presence or absence of meniscal, ligament, and tendon tears; cartilage defects; and bone marrow abnormalities. Contrast-to-noise rate measurements were made among subcutaneous fat, fluid, bone marrow, cartilage, and muscle. The original MRI sequences were used as the reference standard to determine the diagnostic performance of AFSMRI (combined with the original PD sequence). This is a fully balanced study design, where all readers read all images the same number of times, which allowed the determination of the interchangeability of the original and synthetic protocols. Descriptive statistics, intermethod agreement, interobserver concordance, and interchangeability tests were applied. A P value less than 0.01 was considered statistically significant for the likelihood ratio testing, and P value less than 0.05 for all other statistical analyses.

Results: Artificial intelligence-based FS MRI quality was rated as diagnostic (98.9% [87/88] to 100% [88/88], all readers). Diagnostic performance (sensitivity/specificity) of the synthetic protocol was high, for tears of the menisci (91% [71/78], 86% [84/98]), cruciate ligaments (92% [12/13], 98% [160/163]), collateral ligaments (80% [16/20], 100% [156/156]), and tendons (90% [9/10], 100% [166/166]). For cartilage defects and bone marrow abnormalities, the synthetic protocol offered an overall sensitivity/specificity of 77% (170/221)/93% (287/307) and 76% (95/125)/90% (443/491), respectively. Intermethod agreement ranged from moderate to substantial for almost all evaluated structures (menisci, cruciate ligaments, collateral ligaments, and bone marrow abnormalities). No significant difference was observed between methods for all structural abnormalities by all readers (P > 0.05), except for cartilage assessment. Interobserver agreement ranged from moderate to substantial for almost all evaluated structures. Original and synthetic protocols were interchangeable for the diagnosis of all evaluated structures. There was no significant difference for the common exact match proportions for all combinations (P > 0.01). The conspicuity of all tissues assessed through contrast-to-noise rate was higher on AFSMRI than on original FSPD images (P < 0.05).

Conclusions: Artificial intelligence-based FS MRI (3D AFSMRI) is feasible and offers a method for fast imaging, with similar detection rates for structural abnormalities of the knee, compared with original 3D MR sequences.
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http://dx.doi.org/10.1097/RLI.0000000000000751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087629PMC
June 2021

Sperm DNA fragmentation index and high DNA stainability do not influence pregnancy success after intracytoplasmic sperm injection.

F S Rep 2020 Dec 15;1(3):233-238. Epub 2020 Aug 15.

Department of Urology, University of Miami, Miller School of Medicine, Miami, FL, USA.

Objective: To evaluate the ability of sperm DNA fragmentation index (DFI%) and high DNA stainability (HDS%) to influence the chance of achieving pregnancy in couples undergoing intracytoplasmic sperm injection (ICSI) cycles.

Design: A retrospective study evaluating couples that underwent an ICSI cycle between 2009 - 2018.

Setting: High-volume reproductive center.

Patients: Consecutive couples who underwent an ICSI cycle and had a semen analysis with subsequent DFI% and HDS% testing, evaluated by Sperm Chromatin Structure Assay (SCSA).

Interventions: Measurement of DFI% and HDS% prior to ICSI cycle.

Main Outcome Measures: To determine whether DFI% or HDS% of sperm was predictive of the number of ICSI cycles until the first clinical intrauterine pregnancy.

Results: A total of 550 couples who underwent 1050 ICSI cycles were analyzed. Of those, a total of 330 couples achieved pregnancy. As expected, in couples that achieved pregnancy, females were younger (33.7 ± 3.6 years vs 35.3 ± 3.4 years; p < 0.001) and underwent fewer cycles (2 [1-2] vs 2 [1-3]; p =0.001). Importantly, the DFI% and HDS% were similar between couples who achieved pregnancy (DFI% = 12.9 [8-20]; HDS% = 9.3 [6.1-14.6]) and couples who did not (DFI% =12.2 [7.1-20.2]; HDS% = 9.1 [6.7-14]). A multivariable-adjusted analysis evaluating female age at the first cycle was negatively associated with pregnancy (OR = 0.827, 95% CI: 0.778 - 0.879; p < 0.001).

Conclusions: Neither DFI nor HDS at baseline influence the chances of a couple to achieve pregnancy after ICSI. Increased female age and couples who underwent more ICSI cycles were associated with lower chances of achieving pregnancy.
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http://dx.doi.org/10.1016/j.xfre.2020.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748016PMC
December 2020

The Groin: A Vascular Surgeon's Achilles Heel.

Eur J Vasc Endovasc Surg 2021 04 10;61(4):647. Epub 2020 Dec 10.

European Vascular Centre Aachen-Maastricht, Department of Vascular Surgery, University Hospital RWTH Aachen, Germany.

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http://dx.doi.org/10.1016/j.ejvs.2020.11.022DOI Listing
April 2021

The Mechanisms of Benefit of High-Flow Nasal Therapy in Stable COPD.

J Clin Med 2020 Nov 26;9(12). Epub 2020 Nov 26.

Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.

High-flow nasal therapy (HFNT) is a unique system that delivers humidified, heated oxygen-enriched air via nasal cannula at high flow rates. It is a promising therapy for chronic obstructive pulmonary disease (COPD) patients. Several studies have examined the physiologic effects of this therapy in the patient population and have revealed that it improves mucociliary clearance, reduces nasopharyngeal dead space, and subsequently increases CO washout. It also improves alveolar recruitment and gas exchange. These mechanisms may explain the promising results observed in recently published studies that examined the role of HFNT in stable COPD patients.
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http://dx.doi.org/10.3390/jcm9123832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760186PMC
November 2020

In-hospital mortality and organ failure after open and endovascular thoraco-abdominal aortic surgery can be predicted by increased levels of circulating dipeptidyl peptidase 3.

Eur J Cardiothorac Surg 2021 04;59(4):750-757

Department of Intensive Care and Intermediate Care, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.

Objectives: Endovascular and open thoraco-abdominal aortic aneurysm (TAAA) repair is associated with specific complications. Circulating dipeptidyl peptidase 3 (cDPP3) is a novel biomarker that shows a strong association with organ failure which has not been assessed in surgical settings. Therefore, the objective of this study was to assess the prognostic capabilities of cDPP3 for predicting patient survival and organ failure following open and endovascular TAAA repair.

Methods: Thirty-three patients undergoing TAAA repair were assessed in this prospective observational single-centre study. cDPP3 levels were serially measured perioperatively until 72 h after admission to the intensive care unit (ICU). In-hospital mortality and any organ failure were the clinical end points.

Results: Postoperative organ failure was detected in 17 patients (51.5%), and 6 patients died after surgery (18.2%). At 12 h after admission to the ICU, cDPP3 levels were significantly increased in patients who died or developed organ failure (P < 0.001). cDPP3 levels after surgery demonstrated a remarkable predictive accuracy for in-hospital mortality [12 h area under the receiver operating characteristic curve (AUC): 0.907 (P < 0.001), 24 h AUC: 0.815 (P = 0.016), 48 h AUC: 0.914 (P = 0.003)] and the development of organ failure [12 h AUC: 0.882 (P < 0.001), 24 h AUC: 0.850 (P < 0.001), 48 h AUC: 0.846 (P < 0.001)]. Additionally, a significant correlation between cDPP3, the sequential organ failure assessment score and procalcitonin, C-reactive protein and interleukin-6 levels (P < 0.001, P < 0.001, P = 0.011, P = 0.007, respectively) based on all available measurements and time points was observed.

Conclusions: The present findings highlight the role of cDPP3 as an early, highly specific postoperative biomarker for prediction of in-hospital mortality and organ failure after TAAA repair.
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http://dx.doi.org/10.1093/ejcts/ezaa413DOI Listing
April 2021

Co-Morbidity Patterns Identified Using Latent Class Analysis of Medications Predict All-Cause Mortality Independent of Other Known Risk Factors: The COPDGene Study.

Clin Epidemiol 2020 27;12:1171-1181. Epub 2020 Oct 27.

Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Purpose: Medication patterns include all medications in an individual's clinical profile. We aimed to identify chronic co-morbidity treatment patterns through medication use among COPDGene participants and determine whether these patterns were associated with mortality, acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and quality of life.

Materials And Methods: Participants analyzed here completed Phase 1 (P1) and/or Phase 2 (P2) of COPDGene. Latent class analysis (LCA) was used to identify medication patterns and assign individuals into unobserved LCA classes. Mortality, AECOPD, and the St. George's Respiratory Questionnaire (SGRQ) health status were compared in different LCA classes through survival analysis, logistic regression, and Kruskal-Wallis test, respectively.

Results: LCA identified 8 medication patterns from 32 classes of chronic comorbid medications. A total of 8110 out of 10,127 participants with complete covariate information were included. Survival analysis adjusted for covariates showed, compared to a low medication use class, mortality was highest in participants with hypertension+diabetes+statin+antiplatelet medication group. Participants in hypertension+SSRI+statin medication group had the highest odds of AECOPD and the highest SGRQ score at both P1 and P2.

Conclusion: Medication pattern can serve as a good indicator of an individual's comorbidities profile and improves models predicting clinical outcomes.
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http://dx.doi.org/10.2147/CLEP.S279075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602898PMC
October 2020

Rationale and Strategies for Development of an Optimal Bundle of Management for Cardiac Arrest.

Crit Care Explor 2020 Oct 15;2(10):e0214. Epub 2020 Oct 15.

University of Texas Southwestern Medical Center, Dallas, TX.

Objectives: To construct a highly detailed yet practical, attainable roadmap for enhancing the likelihood of neurologically intact survival following sudden cardiac arrest.

Design Setting And Patients: Population-based outcomes following out-of-hospital cardiac arrest were collated for 10 U.S. counties in Alaska, California, Florida, Ohio, Minnesota, Utah, and Washington. The 10 identified emergency medical services systems were those that had recently reported significant improvements in neurologically intact survival after introducing a more comprehensive approach involving citizens, hospitals, and evolving strategies for incorporating technology-based, highly choreographed care and training. Detailed inventories of in-common elements were collated from the ten 9-1-1 agencies and assimilated. For reference, combined averaged outcomes for out-of-hospital cardiac arrest occurring January 1, 2017, to February 28, 2018, were compared with concurrent U.S. outcomes reported by the well-established Cardiac Arrest Registry to Enhance Survival.

Interventions: Most commonly, interventions and components from the ten 9-1-1 systems consistently included extensive public cardiopulmonary resuscitation training, 9-1-1 system-connected smart phone applications, expedited dispatcher procedures, cardiopulmonary resuscitation quality monitoring, mechanical cardiopulmonary resuscitation, devices for enhancing negative intrathoracic pressure regulation, extracorporeal membrane oxygenation protocols, body temperature management procedures, rapid cardiac angiography, and intensive involvement of medical directors, operational and quality assurance officers, and training staff.

Measurements And Main Results: Compared with Cardiac Arrest Registry to Enhance Survival ( = 78,704), the cohorts from the 10 emergency medical services agencies examined ( = 2,911) demonstrated significantly increased likelihoods of return of spontaneous circulation (mean 37.4% vs 31.5%; < 0.001) and neurologically favorable hospital discharge, particularly after witnessed collapses involving bystander cardiopulmonary resuscitation and shockable cardiac rhythms (mean 10.7% vs 8.4%; < 0.001; and 41.6% vs 29.2%; < 0.001, respectively).

Conclusions: The likelihood of neurologically favorable survival following out-of-hospital cardiac arrest can improve substantially in communities that conscientiously and meticulously introduce a well-sequenced, highly choreographed, system-wide portfolio of both traditional and nonconventional approaches to training, technologies, and physiologic management. The commonalities found in the analyzed systems create a compelling case that other communities can also improve out-of-hospital cardiac arrest outcomes significantly by conscientiously exploring and adopting similar bundles of system organization and care.
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http://dx.doi.org/10.1097/CCE.0000000000000214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566870PMC
October 2020

The Role of Ribonuclease 1 and Ribonuclease Inhibitor 1 in Acute Kidney Injury after Open and Endovascular Thoracoabdominal Aortic Aneurysm Repair.

J Clin Med 2020 Oct 14;9(10). Epub 2020 Oct 14.

Department of Intensive Care and Intermediate Care, University Hospital RWTH Aachen, 52062 Aachen, Germany.

Acute kidney injury (AKI) is one of the most common post-operative complications and is closely associated with increased mortality after open and endovascular thoracoabdominal aortic aneurysm (TAAA) repair. Ribonuclease (RNase) 1 belongs to the group of antimicrobial peptides elevated in septic patients and indicates the prediction of two or more organ failures. The role of RNase 1 and its antagonist RNase inhibitor 1 (RNH1) after TAAA repair is unknown. In this study, we analyzed RNase 1 and RNH1 serum levels in patients undergoing open ( = 14) or endovascular ( = 19) TAAA repair to determine their association with post-operative AKI and in-hospital mortality. Increased RNH1 serum levels after open TAAA repair as compared with endovascular TAAA repair immediately after surgery and 12, 48, and 72 h after surgery (all < 0.05) were observed. Additionally, elevated RNase 1 and RNH1 serum levels 12, 24, and 48 h after surgery were shown to be significantly associated with AKI (all < 0.05). RNH1 serum levels before and RNase 1 serum levels 12 h after TAAA repair were significantly correlated with in-hospital mortality (both < 0.05). On the basis of these findings, RNase 1 and RNH1 may be therapeutically relevant and may represent biomarkers for post-operative AKI and in-hospital mortality.
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http://dx.doi.org/10.3390/jcm9103292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602227PMC
October 2020

Mortality in Octogenarians With Chronic Limb Threatening Ischaemia After Revascularisation or Conservative Therapy Alone.

Eur J Vasc Endovasc Surg 2021 02 13;61(2):350-351. Epub 2020 Oct 13.

Department of Vascular Surgery, Maastricht University Medical Centre, the Netherlands; European Vascular Centre Aachen-Maastricht, Aachen, Germany; Maastricht, the Netherlands. Electronic address:

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http://dx.doi.org/10.1016/j.ejvs.2020.09.018DOI Listing
February 2021
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