No abstract

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ObjectiveTrimethylamine-N-oxide (TMAO) is a metabolite derived from the microbial processing of dietary phosphatidylcholine and carnitine and the subsequent hepatic oxidation. Due to its prothrombotic and inflammatory mechanisms, we aimed to assess its role in the prediction of adverse events in a susceptible population, namely patients with atrial fibrillation.MethodsBaseline TMAO plasma levels were measured by liquid chromatography-tandem mass spectrometry in 2379 subjects from the ongoing Swiss Atrial Fibrillation cohort. 1722 underwent brain MRI at baseline. Participants were prospectively followed for 4 years (Q1–Q3: 3.0–5.0) and stratified into baseline TMAO tertiles. Cox proportional hazards and linear and logistic mixed effect models were employed adjusting for risk factors.ResultsSubjects in the highest TMAO tertile were older (75.4±8.1 vs 70.6±8.5 years, p<0.01), had poorer renal function (median glomerular filtration rate: 49.0 mL/min/1.73 m2(35.6–62.5) vs 67.3 mL/min/1.73 m2(57.8–78.9), p<0.01), were more likely to have diabetes (26.9% vs 9.1%, p<0.01) and had a higher prevalence of heart failure (37.9% vs 15.8%, p<0.01) compared with patients in the lowest tertile. Oral anticoagulants were taken by 89.1%, 94.0% and 88.2% of participants, respectively (from high to low tertiles). Cox models, adjusting for baseline covariates, showed increased total mortality (HR 1.65, 95% CI 1.17 to 2.32, p<0.01) as well as cardiovascular mortality (HR 1.86, 95% CI 1.21 to 2.88, p<0.01) in the highest compared with the lowest tertile. When present, subjects in the highest tertile had more voluminous, large, non-cortical and cortical infarcts on MRI (log-transformed volumes; exponentiated estimate 1.89, 95% CI 1.11 to 3.21, p=0.02) and a higher chance of small non-cortical infarcts (OR 1.61, 95% CI 1.16 to 2.22, p<0.01).ConclusionsHigh levels of TMAO are associated with increased risk of cardiovascular mortality and cerebral infarction in patients with atrial fibrillation.Trial registration numberNCT02105844.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has become an essential life-saving tool. Being resource-intensive, judicious use and optimising the outcomes of this precious resource is important. This retrospective, explanatory, observational study aimed to quantify associations between factors and outcome after pulmonary ECMO in children.METHODS: This study included 39 consecutive ECMO runs in 38 children performed for pulmonary indications at our hospital from 2008 to 2018. Indications included acute respiratory distress syndrome, infection, drowning, meconium aspiration and pulmonary hypertension, among others. Depending on the need for haemodynamic support, 21 patients (53.8%) received veno-venous ECMO, while 18 (46.2%) received veno-arterial ECMO. We sought to compare the 11 non-survivors with the 27 survivors with respect to time-independent and time-dependent variables. Logistic regression models and Cox proportional hazards models were used. Threshold analysis was done using the "minimum p-value approach". RESULTS: 27/39 (69%) ECMO runs could be weaned; 27/38 (71%) patients were discharged. 20/27 (74%) survivors had unremarkable neurological status, six (22%) had mild findings (convulsions, muscular hypotony, neuropathy) and one (4%) had a hemi-syndrome at discharge. Univariate analyses showed a hazard ratio (HR) of 0.48 for log(pH) (95% confidence interval [CI] 0.22 to 1.02, p = 0.055) and an HR of 4.48 for log(lactate) (95% CI 1.92 to 10.48, p = 0.0005). Multivariate models showed an HR of 0.99 for log(pH) (95% CI 0.43 to 2.26, p = 0.98) and an HR of 4.44 for log(lactate) (95% CI 1.65 to 11.95, p = 0.003). Threshold analysis showed lactate >4.1 to be associated with mortality, with an HR of 32.7 (95% CI 4.8 to 221.7, p = 0.0002). This threshold should, however, be interpret-ed very cautiously. Evidence of an association between serum lactate at 24 hours and mortality was found (difference between survivors and non-survivors: −2.78, 95% CI −5.36 to −0.20, p = 0.037). CONCLUSIONS:The results of ECMO for pulmonary indications are very good. Serum lactate may be an early prognostic indicator.

No abstract