15 research outputs found
IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) criteria : guidelines of the EU-CARDIOPROTECTION COST Action
Get PDFFull list of the EU-CARDIOPROTECTION COST Action CA16225 Working group members is provided at the end of the article in Acknowledgements section. Funding Information: This article is based on the work from COST Action EU-CARDIOPROTECTION CA16225 supported by COST (European Cooperation in Science and Technology). DJH is supported by the Duke-National University Singapore Medical School, Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist-Senior Investigator scheme (NMRC/CSA-SI/0011/2017) and Collaborative Centre Grant scheme (NMRC/CGAug16C006). SL is supported by grants from the South African Department of Science and Technology and the South African National Research Foundation. SMD is supported by grants from the British Heart Foundation (PG/19/51/34493 and PG/16/85/32471). GH is supported by the German Research Foundation (SFB 1116 B8). MRM is supported by the Spanish Institute of Health Carlos III (FIS PI19/01196 and CIBER-CV). RS is supported by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [Project number 268555672—SFB 1213, Project B05]. PF is supported by the National Research, Development and Innovation Office of Hungary (Research Excellence Program—TKP, National Heart Program NVKP 16-1-2016-0017) and by the Higher Education Institutional Excellence Program of the Ministry of Human Capacities in Hungary, within the framework of the Therapeutic Development thematic program of the Semmelweis University. Funding Information: The IMPACT criteria were presented for approval to the Management Committee of the EU-CARDIOPROTECTION COST Action CA16225: Pavle Adamovski, Ioanna Andreadou, Saime Batirel, Monika Bartekov?, Luc Bertrand, Christophe Beauloye, David Biedermann, Vilmante Borutaite, Hans Erik Botker, Stefan Chlopicki, Maija Dambrova, Sean Davidson, Yvan Devaux, Fabio Di Lisa, Dragan Djuric, David Erlinge, Ines Falcao-Pires, P?ter Ferdinandy, Eleftheria Galatou, Alfonso Garcia-Sosa, Henrique Girao, Zoltan Giricz, Mariann Gyongyosi, Derek J Hausenloy, Donagh Healy, Gerd Heusch, Vladimir Jakovljevic, Jelena Jovanic, George Kararigas, Risto Kerkal, Frantisek Kolar, Brenda Kwak, Przemys?aw Leszek, Edgars Liepinsh , Jacob Lonborg, Sarah Longnus, Jasna Marinovic, Danina Mirela Muntean, Lana Nezic, Michel Ovize, Pasquale Pagliaro, Clarissa Pedrosa Da Costa Gomes, John Pernow, Andreas Persidis, S?ren Erik Pischke, Bruno Podesser, Ines Poto?njak, Fabrice Prunier, Tanya Ravingerova, Marisol Ruiz-Meana, Alina Serban, Katrine Slagsvold, Rainer Schulz, Niels van Royen, Belma Turan, Marko Vendelin, Stewart Walsh, Nace Zidar, Coert Zuurbier, Derek Yellon. Publisher Copyright: © 2021, The Author(s).Acute myocardial infarction (AMI) and the heart failure (HF) which may follow are among the leading causes of death and disability worldwide. As such, new therapeutic interventions are still needed to protect the heart against acute ischemia/reperfusion injury to reduce myocardial infarct size and prevent the onset of HF in patients presenting with AMI. However, the clinical translation of cardioprotective interventions that have proven to be beneficial in preclinical animal studies, has been challenging. One likely major reason for this failure to translate cardioprotection into patient benefit is the lack of rigorous and systematic in vivo preclinical assessment of the efficacy of promising cardioprotective interventions prior to their clinical evaluation. To address this, we propose an in vivo set of step-by-step criteria for IMproving Preclinical Assessment of Cardioprotective Therapies (‘IMPACT’), for investigators to consider adopting before embarking on clinical studies, the aim of which is to improve the likelihood of translating novel cardioprotective interventions into the clinical setting for patient benefit.publishersversionPeer reviewe
Quantification of myocardial creatine and triglyceride content in the human heart: precision and accuracy of in vivo proton magnetic resonance spectroscopy
Get PDFBackground Proton magnetic resonance spectroscopy (H-1-MRS) of the human heart is deemed to be a quantitative method to investigate myocardial metabolite content, but thorough validations of in vivo measurements against invasive techniques are lacking.Purpose To determine measurement precision and accuracy for quantifications of myocardial total creatine and triglyceride content with localized H-1-MRS.Study type Test-retest repeatability and measurement validation study.Subjects Sixteen volunteers and 22 patients scheduled for open-heart aortic valve replacement or septal myectomy.Field Strength/Sequence Prospectively ECG-triggered respiratory-gated free-breathing single-voxel point-resolved spectroscopy (PRESS) sequence at 3 T.Assessment Myocardial total creatine and triglyceride content were quantified relative to the total water content by fitting the H-1-MR spectra. Precision was assessed with measurement repeatability. Accuracy was assessed by validating in vivo H-1-MRS measurements against biochemical assays in myocardial tissue from the same subjects.Statistical Tests Intrasession and intersession repeatability was assessed using Bland-Altman analyses. Agreement between H-1-MRS measurements and biochemical assay was tested with regression analyses.Results The intersession repeatability coefficient for myocardial total creatine content was 41.8% with a mean value of 0.083% +/- 0.020% of the total water signal, and 36.7% for myocardial triglyceride content with a mean value of 0.35% +/- 0.13% of the total water signal. Ex vivo myocardial total creatine concentrations in tissue samples correlated with the in vivo myocardial total creatine content measured with H-1-MRS: n = 22, r = 0.44; P < 0.05. Likewise, ex vivo myocardial triglyceride concentrations correlated with the in vivo myocardial triglyceride content: n = 20, r = 0.50; P < 0.05.Data Conclusion We validated the use of localized H-1-MRS of the human heart at 3 T for quantitative assessments of in vivo myocardial tissue metabolite content by estimating the measurement precision and accuracy.Level of Evidence 2Technical Efficacy Stage 2Cardiovascular Aspects of Radiolog
Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial
Get PDFBackground:
Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19.
Methods:
This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.
Findings:
Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79).
Interpretation:
In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes.
Funding:
UK Research and Innovation (Medical Research Council) and National Institute of Health Research
Cerebral venous thrombosis: Epidemiology, clinical course, and outcome
Get PDFThe first part of this thesis focuses on the epidemiology of CVT. Chapter 2 describes a cross-sectional study that investigates the incidence of CVT among hospitalized adult patients located in two provinces in The Netherlands. Chapter 3 is a systematic review of the literature regarding the shift in sex ratio over time among patients with CVT. Chapter 4 describes a case-control study in which we investigated the association between obesity and CVT. In chapter 5, we report the results of a systematic analysis of the literature on the decline in mortality over time in CVT. In the second part of this thesis, we highlight the clinical course and outcome of CVT. Chapter 6 describes a retrospective study that reports the clinical course of adults with CVT during treatment for acute lymphoblastic leukemia. The relevance of early symptoms and treatments are explored. Chapter 7 describes a cohort study that aimed to assess the association between hyperglycemia and clinical outcome in CVT. Chapter 8 is a post hoc-analysis of the International Study on Cerebral Venous and dural sinus Thrombosis (ISCVT) study, in which we examined CVT associated with an infection of the head or neck. Chapter 9 describes the frequency, pathophysiology and clinical manifestations of hydrocephalus in patients with CVT, and discusses how hydrocephalus may contribute to poor clinical outcome in these patients. Chapter 10 describes a prospective cohort study on the efficacy of decompressive hemicraniectomy for severe cases of CVT with impending herniation. Finally, chapter 11 summarizes the results and conclusions presented in this thesis and addresses future directions for research on CVT
Admission Hyperglycemia and Clinical Outcome in Cerebral Venous Thrombosis
No full textParoxysmal Cerebral Disorder
Association Between Anemia and Cerebral Venous Thrombosis Case-Control Study
No full textClinical epidemiolog
