CYP2C19*2、CYP2C19*3基因分型与急性缺血性脑卒中再发脑卒中的关系

目的探讨细胞色素P450药物代谢酶(CYP)2C19基因分型与氯吡格雷治疗的急性缺血性脑卒中患者再发脑卒中的关系。方法选取2018年5月—2018年12月常州市第一人民医院收治接受氯吡格雷治疗的159例急性缺血性脑卒中患者,检测患者入院后空腹外周血中CYP2C19*2,CYP2C19*3基因分型。对患者进行随访,随访截至2020年2月,观察再发脑卒中的情况,并分析CYP2C19*2,CYP2C19*3基因分型与再发脑卒中关系。结果随访时间14~22个月,平均随访时间为(18.2±1.5)个月,共7例患者失访,共20例(13.2%)患者复发缺血性脑卒中。再发脑卒中患者中CYP2C19*2 GG型及CYP2C19*3 GG型均低于无复发患者(P<0.05),CYP2C19*2 GA型,CYP2C19*2 AA型CYP2C19*3 GA型,CYP2C19*3AA型均高于无复发患者(P<0.05)。Kaplan-Meier法并Log-rank检验结果显示,CYP2C19*2 GG型无复发时间长于AA型,差异有统计学意义(Log-rank=6.759,P=0.034)。CYP2C19*3GG型无复发时间长于AA型,差异有统计学意义(Log-rank x2=8.660,P=0.013)。多因素Cox分析结果显示,糖尿病、氯吡格雷抵抗,CYP2C19*2及CYP2C19*3基因型是再发脑卒中影响因素(P<0.05)。结论在接受氯吡格雷治疗急性缺血性脑卒中患者中,CYP2C19*2及CYP2C19*3突变型再发脑卒中的风险明显增高。     

NUDT15 is a key genetic factor for prediction of hematotoxicity in pediatric patients who received a standard low dosage regimen of 6-mercaptopurine

6-Mercaptopurine (6-MP) is commonly used for treatment of acute lymphoblastic leukemia (ALL). The incidence of hematotoxicity caused by this drug is quite high in Asians even using a standard low dosage regimen. The present study was aimed to elucidate the impact of thiopurine S-methyltransferase (TPMT), a nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15), inosine triphosphatase (ITPA) and ATP Binding Cassette Subfamily C Member 4 (ABCC4) polymorphisms on hematotoxicity in pediatric patients who received a standard low starting dose of 6-MP. One hundred and sixty-nine pediatric patients were enrolled and their genotypes were determined. Patients who carried NUDT15¹3 and NUDT15¹2 genotypes were at a 10–15 fold higher risk of severe neutropenia than those of the wild-type during the early months of the maintenance phase. Risk of neutropenia was not significantly increased in patients with other NUDT15 variants as well as in patients with TPMT, ITPA or ABCC4 variants. These results suggest that NUDT15 polymorphisms particularly, NUDT15¹3 and NUDT15¹2, play major roles in 6-MP-induced severe hematotoxicity even when using a standard low dosage of 6-MP and genotyping of these variants is necessary in order to obtain precise tolerance doses and avoid severe hematotoxicity in pediatric patients.     

Lateral Lymph Nodes in Rectal Cancer: Do we all Think the Same? A Review of Multidisciplinary Obstacles and Treatment Recommendations

Lateral lymph nodes in low, locally advanced, rectal cancer have proven implications for local recurrence rates, which increase drastically in the presence of persistently enlarged lateral lymph nodes. These clinical implications warrant a thorough understanding of lateral nodal disease with awareness and knowledge from all three specialties involved – radiology, radiation oncology, and surgery – to ensure proper treatment. Relevant literature for each specialty, including all current guidelines and perspectives, were examined. Variations in definitions and treatment paradigms were evaluated. There is still no consensus for the standardized treatment of lateral nodal disease. Each discipline works according to their own available evidence, but relevant data are scarce. Current international guidelines and standard recommendations for the diagnostics and treatment of lateral lymph nodes are lacking. This results in differing perspectives and interpretations between the disciplines which can lead to challenging communication in an area where multidisciplinary collaboration is essential. This review addresses this by presenting the current evidence, perspectives and practices of each specialty and makes suggestions for each phase of the diagnostic and treatment process for patients with lateral nodal disease. By doing this, steps are taken toward achieving international consensus, and multidisciplinary collaboration.     

Donor lungs cold preservation at 10 °C offers a potential logistic advantage in lung transplantation

Donor lung preservation at 10 °C appears to be an innovative and promising method that may improve transplant logistics by extending the cold ischemia time with excellent outcomes. We report the case of two lung transplants from two different donors involving the use of two different preservation methods, highlighting the benefits of using 10 °C lung storage.