Moderate dosage of tranexamic acid during cardiac surgery with cardiopulmonary bypass and convulsive seizures: incidence and clinical outcome.

BACKGROUND: Convulsive seizures (CS) occur in ∼1% of the patients after cardiac surgery with cardiopulmonary bypass. Recent investigations indicate an up to seven-fold increase in CS in cardiac surgical patients receiving high doses (≥60 mg kg(-1) body weight) of tranexamic acid (TA). METHODS: In a retrospective data analysis of 4883 cardiac surgical patients, we investigated the incidence of CS in patients receiving a moderate dose of TA (24 mg kg(-1) body weight) compared with a reference group not receiving TA as a primary endpoint. Secondary endpoints were intensive care unit stay and in-hospital mortality. We performed propensity score (PS)-adjusted logistic regression analysis to test the association between TA use/non-use and clinical outcomes. RESULTS: Compared with the reference group, the PS-adjusted odds ratio (OR) for CS in the TA group was 1.703 [95% confidence interval (CI): 1.01-2.87; P=0.045; incidence 2.5% vs 1.2%]. Log-ICU-stay was significantly longer (P=0.004) and PS-adjusted relative in-hospital mortality risk was significantly higher for the TA group compared with the reference group (OR=1.89; 95% CI: 1.21-2.96; P=0.005). Both the TA-associated CS incidence and the in-hospital mortality risk were only significant in patients undergoing open-heart surgery (OR=2.034, 95% CI: 1.07-3.87; P=0.034 and OR=2.20, 95% CI: 1.32-3.69; P=0.003, respectively) but not in patients undergoing coronary artery bypass grafting (OR=1.21, 95% CI: 0.49-3.03; P=0.678 and OR=1.13, 95% CI: 0.42-3.02; P=0.809, respectively). CONCLUSIONS: In open-heart surgery, even moderate TA doses are associated with a doubled rate of CS and in-hospital mortality. Prospective trials are needed to further evaluate the safety profile of TA in cardiac surgery.

ACT-5 is an essential Caenorhabditis elegans actin required for intestinal microvilli formation.

Investigation of Caenorhabditis elegans act-5 gene function revealed that intestinal microvillus formation requires a specific actin isoform. ACT-5 is the most diverged of the five C. elegans actins, sharing only 93% identity with the other four. Green fluorescent protein reporter and immunofluorescence analysis indicated that act-5 gene expression is limited to microvillus-containing cells within the intestine and excretory systems and that ACT-5 is apically localized within intestinal cells. Animals heterozygous for a dominant act-5 mutation looked clear and thin and grew slowly. Animals homozygous for either the dominant act-5 mutation, or a recessive loss of function mutant, exhibited normal morphology and intestinal cell polarity, but died during the first larval stage. Ultrastructural analysis revealed a complete loss of intestinal microvilli in homozygous act-5 mutants. Forced expression of ACT-1 under the control of the act-5 promoter did not rescue the lethality of the act-5 mutant. Together with immuno-electron microscopy experiments that indicated ACT-5 is enriched within microvilli themselves, these results suggest a microvillus-specific function for act-5, and further, they raise the possibility that specific actins may be specialized for building microvilli and related structures.