Effect of genetic factors on the interindividual variability of warfarin dosage requirements in Japanese patients after adjusting for renal function.

Renal function significantly influences the appropriate warfarin dosage. However, studies investigating the impact of genetic factors on warfarin dosage, considering renal function, are limited. This study aimed to assess the role of genetic polymorphisms in VKORC1, CYP2C9, CYP2C19, CYP4F2, GGCX, and APOE in warfarin dosage adjustment considering renal function. A total of 108 outpatients receiving warfarin treatment with controlled prothrombin time-targeted international normalized ratio (1.5-3.0) were included. Patient data, warfarin dosage, and laboratory results were collected from electronic medical records. Each SNP [VKORC1 rs9923231, CYP2C9 rs1057910, CYP4F2 rs2108622, CYP2C19* 2 (rs4244285) and* 3 (rs4986893), GGCX rs699664 and rs12714145, and APOE rs7421] was analyzed. Multiple regression analysis revealed estimated glomerular filtration rate as the most significant factor influencing warfarin dose (p <0.001) (ß = -0.445). VKORC1 rs9923231 AA, CYP4F2 rs2108622 CT/TT, GGCX rs12714145 CT/TT, and CYP2C9 rs1057910 AC carriers were associated with warfarin dose (p <0.001, 0.015, 0.020, 0.038 and ß = -0.317, 0.191, -0.188, -0.162, respectively); however, other genes showed no significant association. In conclusion, after adjusting for renal function, genetic factors of VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs12714145, and CYP2C9 rs1057910 were found to contribute to warfarin dosage, having impact in that order. In contrast, the contribution of other genes to warfarin dosage was absent or negligible.

Comparison of the Antiemetic Effect of Aprepitant/granisetron and Palonosetron Combined with Dexamethasone in Gynecological Cancer Patients Treated with Paclitaxel and Carboplatin Combination Regimen.

A triple antiemetic therapy combining aprepitant (APR) with conventional double antiemetic therapy, including 5-hydroxytryptamine 3 receptor antagonist (5-HT3-RA) and dexamethasone (DEX), is recommended for preventing chemotherapy-induced nausea and vomiting induced by a carboplatin (CBDCA) regimen. However, consensus on the additive effects of APR for gynecological patients on a combined regimen of paclitaxel and CBDCA (TC regimen) has yet to be reached. This retrospective study investigated the antiemetic effects of palonosetron and DEX (PD therapy) and granisetron and DEX with APR (GDA therapy) in patients with gynecologic cancer and who underwent their first TC regimen cycle between April 2017 and March 2020 at the Gunma University Hospital Outpatient Chemotherapy Center. The results showed that the complete response rate of the 92 patients who underwent PD therapy (PD group) and the 46 patients who underwent GDA therapy (GDA group) were both 80.4% (p = 1.000), and the complete control rates of the PD and GDA groups were 78.3% and 80.4%, respectively (p = 0.828), resulting in no significant difference. Furthermore, we observed no significant difference between the PD and GDA groups in the incidence of grade ≥2 nausea, vomiting, and anorexia (nausea: 7.6% vs. 0%, p = 0.095; vomiting: 4.3% vs. 0%, p = 0.301; and anorexia: 9.8% vs. 2.2%, p = 0.164). Concerning adverse events, compared to the PD group, the GDA group showed significantly higher incidence of grade ≥2 malaise (7.6% vs. 19.6%, p = 0.039). Given the lack of difference in the antiemetic effects of PD and GDA therapies, antiemetic therapy should be selected carefully for individual patients by accounting for the incidence of adverse reactions and interactions with APR.

Negative predictors of clinical response to triptans in patients with migraine.

Moderate to severe migraine attacks are treated with triptans. However, about 25% of migraineurs fail to respond to triptans. We investigated the involvement of gene polymorphisms, personality traits and characteristics of headache, and made a scoring system for prediction of clinical response to triptans in patients with migraine. Gene polymorphisms including serotonin (5-HT)(1B) receptor G861C and dopamine receptor 2 (DRD2) C939T, personality traits and characteristics of headache were investigated in 46 consistent responders and 14 inconsistent responders to triptans. The multivariate stepwise logistic regression analysis revealed that age, periorbital/deep orbital pain and C/C genotype carrier at DRD2 C939T were significant factors that contributed independently to the negative response to triptans in patients with migraine. Their odds ratios were 6.329 (40-69 vs. 20-39 years, 95% CI 1.441-27.778), 6.772 (no vs. yes, periorbital/deep orbital pain, 95% CI 1.159-39.580) and 14.085 (non-C/C vs. C/C genotype at DRD2 C939T, 95% CI 1.253-166.667), respectively. The predictive index (PI) of clinical response to triptans in patients with migraine was calculated using these three factors. The score in inconsistent responders (1.6 ± 0.6) was significantly higher than that in consistent responders (0.8 ± 0.7, P < 0.001). Sensibility of low-score (RI = 0) group was 100%, and specificity of high-score (PI ≥ 2) group was 87%. The proposed scoring system should in the future be the object of larger studies to confirm its validity.

[Vacuum-assisted wound closure in the management of deep sternal wound infection].

We herein present a case who underwent vacuum-assisted wound closure (VAC) therapy for post-sternotomy mediastinitis. A 71-year-old female with chronic renal failure on dialysis underwent a graft replacement of the ascending aortic aorta for the treatment of an acute aortic dissection. After she was discharged from the hospital, a purulent discharge was noted to occur from the median sternal wound. The wound was therefore reopened and all sternal wires were removed. Thereafter, polyurethane foam which was shaped to fit the defect was placed within the cavity. The area was covered with adhesive drape and suction drainage was carried out at -100 mmHg. The polyurethane foam was replaced every few days. The wound was finally closed using a muscle flap at 49 days after surgery. VAC therapy is therefore considered to be a useful treatment modality for deep sternal wound infections.