BackgroundHigh-dose erythromycin used as antibiotic prolongs QTc interval. Low-dose erythromycin is frequently used as a prokinetic agent, especially in patients in the intensive care unit (ICU). It is unknown whether low-dose erythromycin affects cardiac repolarisation and puts patients at risk for torsades de pointes.MethodsIn this prospective study, we included ICU patients treated with erythromycin as prokinetic in a dose of 200 mg twice a day. An ECG was performed before, 15 min and 24 hours after the start of erythromycin. Cardiac repolarisation was assessed by rate-corrected analysis of the QT interval (QTc) on the ECG by two independent investigators. Starting or stopping other possibly QTc prolonging drugs during the study period was an exclusion criterion. Wilcoxon signed-rank test and Friedman's test were used for statistical analysis to assess prolongation of QTc. Primary outcome was defined by the prolongation of QTc after 15 min and 24 hours.Results51 patients were eligible for this study. In these patients, QTc increased significantly from 430 ms at baseline to 439 ms (p=0.03) after 15 min and 444 ms (p=0.01) after 24 hours. After 15 min and 24 hours, the upper limit of 95% CI for prolongation of QTc was well above 10 ms. No QTc-related arrhythmias were seen.ConclusionsDuring treatment with erythromycin in a dose of 200 mg twice a day. QTc prolonged mildly but significantly. Sequential ECG registration should be performed when low-dose erythromycin is prescribed, especially in the presence of other risk factor for QTc prolongation.

DNMT3A Overgrowth Syndrome (DOS, also known as Tatton-Brown Rahman Syndrome/TBRS) is one of several overgrowth syndromes with complex phenotypes caused by constitutional mutations in genes encoding epigenetic regulators. The clinical features of DOS are variable but include overgrowth (tall stature and/or obesity) and intellectual disability. DNMT3A is essential for de novo DNA methylation and plays an important role in hematopoiesis. Somatic mutations in DNMT3A are among the most common initiating mutations in normal karyotype acute myeloid leukemia (AML) patients and in elderly people with clonal hematopoiesis. The natural history of DOS has not been fully explored since the first description of this rare condition in 2014. Because of the association of somatic DNMT3A mutations and leukemia development, we assessed information from the ~200 known DOS patients world-wide and were able to document eight with hematologic malignancies. Based on this prevalence, we suggest DOS is a cancer predisposition syndrome, especially for hematologic malignancies. Using recommendations from an expert panel, we suggest DOS patients should be prospectively monitored for hematologic malignancies, which may allow for early intervention and permit its natural history to be better defined.

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