Background and purpose Trimethylamine‐N‐oxide (TMAO) is a biomarker of the gut microbiome and correlates with the risk of cardiovascular diseases. However, conflicting data exist on the specific role of TMAO in ischaemic stroke patients. We aimed to analyze the time course of TMAO levels in stroke patients compared with controls. Methods In this prospective, case‐control study, patients suffering from ischaemic stroke (onset <24 h) and control patients with less than two cardiovascular risk factors were enrolled. Plasma TMAO levels were analyzed on admission, after 48 h and after 3 months. The primary endpoint was the difference in TMAO levels on admission between stroke patients and controls. Results A total of 196 patients with ischaemic stroke and 100 controls were included between February 2018 and April 2019. Plasma TMAO levels on admission were significantly higher in stroke patients than in controls [median value 4.09 (2.87–6.49) vs. 3.16 (2.08–5.16) µmol/L, P = 0.001]. There was a significant decrease in TMAO levels in stroke patients after 48 h [median at 48 h, 3.49 (2.30–5.39) µmol/L, P = 0.027]. TMAO levels increased again 3 months after stroke [median 4.23 (2.92–8.13) µmol/L, P = 0.047]. In controls, TMAO levels did not change between admission and after 48 h [median at 48 h, 3.14 (1.63–4.61) µmol/L, P = 0.11]. An inverse correlation between TMAO values and kidney function was found (Spearman rho −0.334, P < 0.001). Conclusions Our study emphasizes the importance of the time course of TMAO levels after ischaemic stroke. Future studies should define the time point of TMAO analysis, preferably in the acute phase (<24 h).

Background and aims Inborn errors of purine and pyrimidine metabolism are a diverse group of disorders with possible serious or life-threatening symptoms. They may be associated with neurological symptoms, renal stone disease or immunodeficiency. However, the clinical presentation can be nonspecific and mild so that a number of cases may be missed. Previously published assays lacked detection of certain diagnostically important biomarkers, including SAICAr, AICAr, beta-ureidoisobutyric acid, 2,8-dihydroxyadenine and orotidine, necessitating the use of separate assays for their detection. Moreover, the limited sensitivity for some analytes in earlier assays may have hampered the reliable detection of mild cases. Therefore, we aimed to develop a liquid chromatography–tandem mass spectrometry (LC-MS/MS) assay that allows the simultaneous and sensitive detection of an extended range of purine and pyrimidine biomarkers in urine. Methods The assay was developed and validated using LC-MS/MS and clinically tested by analyzing ERNDIM Diagnostic Proficiency Testing (DPT) samples and further specimens from patients with various purine and pyrimidine disorders. Results Reliable determination of 27 analytes including SAICAr, AICAr, beta-ureidoisobutyric acid, 2,8-dihydroxyadenine and orotidine was achieved in urine following a simple sample preparation. The method clearly distinguished pathological and normal samples and differentiated between purine and pyrimidine defects in all clinical specimens. Conclusions A LC-MS/MS assay allowing the simultaneous, sensitive and reliable diagnosis of an extended range of purine and pyrimidine disorders has been developed. The validated method has successfully been tested using ERNDIM Diagnostic Proficiency Testing (DPT) samples and further clinical specimens from patients with various purine and pyrimidine disorders. Sample preparation is simple and assay duration is short, facilitating an easier inclusion of the assay into the diagnostic procedures.

The human gut microbiome and its metabolite Trimethylamine N-oxide (TMAO) are sensitive to the human diet and are involved in the complex pathomechanisms that underpin diabetes, obesity, and cardiovascular diseases. A potential involvement of increased TMAO in atrial fibrillation (AF) manifestation and progression is not clear. We measured TMAO in peripheral blood of 45 AF patients and 20 non-AF individuals (matched for age, sex, BMI, prevalence of hypertension and diabetes). TMAO levels in AF (median [IQR] 3.5 µM [2.51–4.53]) were comparable with those in non-AF individuals (3.62 µM [2.49–5.46]) (p = 0.629). There was no association between TMAO and AF progression phenotypes (p = 0.588). In 35 AF patients, TMAO was additionally measured 12–18 months after AF catheter ablation. TMAO levels at baseline and follow-up were correlated (r = 0.481, p = 0.003), and TMAO was increased independent from the success (restoration of sinus rhythm) of the ablation procedure. The data of this pilot study indicate that TMAO is not generally higher in AF and is not associated with AF progression phenotypes. The observed TMAO increase 12–18 months after AF catheter ablation needs further investigation in a larger cohort.