The safety of tranexamic acid administration in total knee arthroplasty: a population-based study from Taiwan.

Tranexamic acid is an effective treatment to reduce blood loss. We performed a retrospective observational study to evaluate safety in unilateral total knee arthroplasty. We utilised Taiwan's national health insurance database to identify relevant patients and to retrieve information on peri-operative blood transfusions and tranexamic acid administration within 60 days of follow-up. We examined changes in the rate of transfusions and adverse events with respect to tranexamic acid administration using logistic regression. We observed a total of 226,719 knee arthroplasty cases during 2010-2019. Transfusion and tranexamic acid administration rates were 38.9% (88,258) and 42.9% (97,237), respectively. Tranexamic acid was associated with a 50% decrease in blood transfusions (RR: 0.50, 95%CI: 0.48-0.51). After propensity-score matching, tranexamic acid was not associated with pulmonary embolism; deep vein thromboembolism; artery vein thromboembolism; acute myocardial infarction; ischaemic stroke; or in-hospital mortality, but was significantly associated with acute kidney injury. Patients with existing chronic kidney disease suffered a high absolute risk of kidney injury irrespective of tranexamic acid administration (832 per 10,000, 95%CI 797-869). Tranexamic acid was also associated with surgical site infection. There was strong interaction between blood transfusion; tranexamic aid administration; and development of surgical site infection. In conclusion, tranexamic acid use was associated with decreased blood transfusion and was not associated with thromboembolic events. However, careful consideration is required before use in patients with pre-existing renal disease. Further, our observed interaction between patients given tranexamic acid who subsequently require transfusion requires careful consideration with respect to enhanced prophylaxis against surgical site infection.

Genetic polymorphisms of N-acetyltransferase 1 and 2 and risk of cigarette smoking-related bladder cancer.

Aromatic amines from cigarette smoking or occupational exposure, recognized risk factors for bladder cancer, are metabolized by N-acetyltransferases (NAT). This study examined the association of (NAT) 1 and 2 genotypes with the risk of smoking-related bladder cancer. A total of 74 pathologically confirmed bladder cancer patients and 184 controls were serially recruited from the National Taiwan University Hospital. History of cigarette smoking and other risk factors for bladder cancer was obtained through standardized questionnaire interview. Peripheral blood lymphocytes were collected from each subject and genotyped for NAT1 and NAT2 by DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism methods. Allele frequency distributions of NAT1 and NAT2 were similar between cases and controls. There was a significant dose-response relationship between the risk of bladder cancer and the quantity and duration of cigarette smoking. The biological gradients were significant among subjects carrying NAT1*10 allele or NAT2 slow acetylators, but not among NAT2 rapid acetylators without NAT1*10 allele. The results are consistent with the hypothesis that NAT1 and NAT2 might modulate the susceptibility to bladder cancer associated with cigarette smoking.

Arsenic methylation capacity, body retention, and null genotypes of glutathione S-transferase M1 and T1 among current arsenic-exposed residents in Taiwan.

In order to elucidate the relationships among arsenic methylation capacity, body retention, and genetic polymorphisms of glutathione S-transferase (GST) M1 and T1, a total of 115 study subjects were recruited from Lanyang Basin located on the northeast coast of Taiwan. Specimens of drinking water, blood, urine, hair and toenail were collected from each study subject. Urinary inorganic and methylated arsenic were speciated by high performance liquid chromatography combined with hydride-generation atomic absorption spectrometry. Arsenic concentration in hair and toenail were quantitated by atomic absorption spectrophotometry. The polymerase chain reaction was used to determine genetic polymorphisms of GST M1 and T1. Arsenic concentrations in urine, hair, and toenail of study subjects were positively correlated with arsenic levels in their drinking water. Percentages of various arsenic species in urine (mean +/- standard error (SE) were 11.8 +/- 1.0, 26.9 +/- 1.2 and 61.3 +/- 1.4, respectively, for inorganic arsenic, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Men and women had similar arsenic methylation capability. No associations were observed between arsenic methylation capability and arsenic content in either drinking water or urine. Ratios of arsenic contents in hair and toenail to urinary arsenic content (mean +/- standard error) were 6.2 +/- 0.7 and 16.5 +/- 1.7, respectively. Genetic polymorphisms of GST M1 and T1 were significantly associated with arsenic methylation. Subjects having the null genotype of GST M1 had an increased percentage of inorganic arsenic in urine, while those with null genotype of GST T1 had an elevated percentage of DMA in urine. Arsenic contents in hair and toenail were significantly correlated with the increase in arsenic concentrations of drinking water and urine, while no significant associations were observed between arsenic contents in hair and toenail and polymorphisms of GST M1 and T1. The relationship between arsenic methylation capability and body retention was modified by genetic polymorphisms of GST M1 and T1. Arsenic contents in hair and toenail were negatively associated with MMA percentage and positively associated with DMA percentage among subjects having null genotypes of GST M1 and T1, but not among those with non-null genotypes.