ABSTRACT
INTRODUCTION: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a prevailing option for the management of severe early graft dysfunction. This systematic review and individual patient data (IPD) meta-analysis aims to evaluate (1) mortality, (2) rates of major complications, (3) prognostic factors, and (4) the effect of different VA-ECMO strategies on outcomes in adult heart transplant (HT) recipients supported with VA-ECMO. METHODS AND RESULTS: We conducted a systematic search and included studies of adults (≥18 years) who received VA-ECMO during their index hospitalization after HT and reported on mortality at any timepoint. We pooled data using random effects models. To identify prognostic factors, we analysed IPD using mixed effects logistic regression. We assessed the certainty in the evidence using the GRADE framework. We included 49 observational studies of 1477 patients who received VA-ECMO after HT, of which 15 studies provided IPD for 448 patients. There were no differences in mortality estimates between IPD and non-IPD studies. The short-term (30-day/in-hospital) mortality estimate was 33% (moderate certainty, 95% confidence interval [CI] 28%-39%) and 1-year mortality estimate 50% (moderate certainty, 95% CI 43%-57%). Recipient age (odds ratio 1.02, 95% CI 1.01-1.04) and prior sternotomy (OR 1.57, 95% CI 0.99-2.49) are associated with increased short-term mortality. There is low certainty evidence that early intraoperative cannulation and peripheral cannulation reduce the risk of short-term death. CONCLUSIONS: One-third of patients who receive VA-ECMO for early graft dysfunction do not survive 30 days or to hospital discharge, and one-half do not survive to 1 year after HT. Improving outcomes will require ongoing research focused on optimizing VA-ECMO strategies and care in the first year after HT.
Subject(s)
Extracorporeal Membrane Oxygenation , Heart Failure , Heart Transplantation , Adult , Humans , Extracorporeal Membrane Oxygenation/methods , Heart Transplantation/adverse effects , Hospital Mortality , Patient Discharge , Retrospective StudiesABSTRACT
Methicillin-resistant Staphylococcus aureus (MRSA) causes severe infections with only few effective antibiotic therapies currently available. To approach this challenge, chemical entities with a novel and resistance-free mode of action are desperately needed. Here, we introduce a new hydroxyamide compound that effectively reduces the expression of devastating toxins in various S. aureus and MRSA strains. The molecular mechanism was investigated by transcriptome analysis as well as by affinity-based protein profiling. Down-regulation of several pathogenesis associated genes suggested the inhibition of a central virulence-related pathway. Mass spectrometry-based chemical proteomics revealed putative molecular targets. Systemic treatment with the hydroxyamide showed significant reduction of abscess sizes in a MRSA mouse skin infection model. The absence of resistance development in vitro further underlines the finding that targeting virulence could lead to prolonged therapeutic options in comparison to antibiotics that directly address bacterial survival.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/chemistry , Hydroxamic Acids/chemistry , Hydroxamic Acids/pharmacology , Methicillin-Resistant Staphylococcus aureus/chemistry , Methicillin-Resistant Staphylococcus aureus/drug effects , Staphylococcal Infections/microbiology , Staphylococcus aureus/drug effects , Animals , Bacterial Proteins/metabolism , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Mice , Microbial Sensitivity Tests , Staphylococcus aureus/pathogenicityABSTRACT
Pseudocoarctation of the aorta is an abnormality of the descending portion of the aortic arch at the level of the isthmus without a real pressure gradient. We report a case of a stenotic pseudocoarctation causing severe refractory hypertension.
Subject(s)
Antihypertensive Agents/therapeutic use , Aortic Coarctation/complications , Hypertension/etiology , Aortic Coarctation/diagnostic imaging , Aortic Coarctation/surgery , Aortography , Humans , Hypertension/diagnostic imaging , Hypertension/drug therapy , Hypertension/surgery , Imaging, Three-Dimensional , Male , Middle Aged , Radiographic Image Interpretation, Computer-Assisted , Severity of Illness Index , Tomography, Spiral Computed , Treatment Failure , Treatment Outcome , Vascular Surgical ProceduresABSTRACT
The direct magnesiation of highly functionalized aromatics bearing an ester, a nitrile, or a ketone can be readily performed by using an OBoc as a directing group and TMPMgCl.LiCl as a base. It allows, for example, the preparation of a meta-magnesiated benzophenone in >95%. After quenching, highly functionalized and substituted benzenes are obtained. [reaction: see text].
Subject(s)
Benzene/chemical synthesis , Lithium Chloride/chemistry , Magnesium/chemistry , Acylation , Benzophenones/chemical synthesis , Carbamates/chemical synthesis , Catalysis , Copper/chemistry , Indicators and Reagents , Ketones/chemistryABSTRACT
In the last few years, we have demonstrated that the halogen/magnesium-exchange reaction is a unique method for preparing a variety of new functionalized aryl, alkenyl, heteroaryl magnesium compounds which has considerably extended the range of functionalized Grignard reagents available for synthetic purposes. A variety of functional groups such as an ester, nitrile, iodide, imine and even sensitive groups like nitro, hydroxyl and boronic ester can be tolerated in these organomagnesium compounds. We wish to describe the application of this halogen/magnesium-exchange reaction for the preparation of a broad range of five- and six-membered functionalized heteroaryl magnesium compounds and their reactions with various electrophiles providing a new entry to a range of polyfunctional heterocycles such as thiophene, furan, pyrrole, imidazole, thiazole, antipyrine, pyridine, quinoline and uracil derivatives.
