背景与目的:弥漫性大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)分子遗传学特征和患者治疗前^(18)F-FDG PET/CT检查评估的SUV_(max)值均与患者预后密切相关,但两者的关系及其与R-CHOP治疗方案治疗反应的相关性尚不清楚。本研究...背景与目的:弥漫性大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)分子遗传学特征和患者治疗前^(18)F-FDG PET/CT检查评估的SUV_(max)值均与患者预后密切相关,但两者的关系及其与R-CHOP治疗方案治疗反应的相关性尚不清楚。本研究旨在分析DLBCL分子遗传学特征与治疗前经^(18)F-FDG PET/CT检测的SUV_(max)值的关系及其与临床病理学特征、R-CHOP治疗反应的相关性。方法:回顾性收集复旦大学附属肿瘤医院2022-2023年同时经淋巴瘤481基因DNA panel二代测序(next-generation sequencing,NGS)和治疗前经PET/CT检查的DLBCL患者225例,本研究通过复旦大学附属肿瘤医院医学伦理委员会的审查(伦理批号:050432-4-2307E)并获得患者知情同意;除基因突变特征外,同时收集荧光原位杂交法检测的BCL2、BCL6和MYC基因易位情况;另收集该组病例的临床病理学参数以及经R-CHOP治疗后的PET/CT检查结果。结果:总计191例DLBCL患者纳入最终分析,重要基因MYD88突变、TP53突变、CDKN2A/2B拷贝数异常、CD79B突变发生率分别为24.6%、27.2%、32.5%和16.8%。治疗前SUV_(max)值范围是5.10~63.10(24.44±10.70,中位22.80)。MYD88L265P突变型DLBCL的治疗前SUV_(max)值显著高于MYD88野生型DLBCL(P=0.039),SUV_(max)值与DLBCL其他基因变异类型包括TP53突变、CDKN2A/B拷贝数减少、CD79B突变、KMT2D突变、TNFAIP3突变、B2M突变、EZH2突变、BTG1/2突变、CREBBP突变、MYC、BCL2、BCL6基因重排之间无显著的相关性。治疗前高SUV_(max)值与高血清乳酸脱氢酶(lactate dehydrogenase,LDH)水平(P=0.012)及非生发中心(non-germinal center B-cell-like,non-GCB)亚型显著相关(P=0.040),但与R-CHOP治疗反应无显著的相关性(P=0.714)。DLBCL中TP53基因突变与R-CHOP治疗反应差显著相关(P=0.001),是R-CHOP治疗后非完全代谢缓解的独立预测因子。联合TP53基因突变、Ann Arbor分期、国际预后指数(International Prognostic Index,IPI)及血清LDH水平能够更好地预测患者对R-CHOP治疗的反应。结论:在DLBCL中,MYD88L265P突变型患者具有较高的治疗前SUV_(max)值。DLBCL治疗前SUV_(max)值与R-CHOP治疗反应无关,而TP53基因突变与R-CHOP治疗反应差显著相关,并且是独立预测因子。TP53基因突变联合临床病理学参数可更好地预测R-CHOP治疗反应。关于各基因变异特征及SUV_(max)值与患者预后的关系尚需作进一步随访研究。展开更多
The present study aims to establish a reproducible large animal experimental unit using a minipig model to monitor cardiac function changes.A 90-min closed-chest bal-loon occlusion of the left anterior descending bran...The present study aims to establish a reproducible large animal experimental unit using a minipig model to monitor cardiac function changes.A 90-min closed-chest bal-loon occlusion of the left anterior descending branch of the coronary artery was used to induce myocardial infarction in Pannon minipigs.To monitor the cardiac function,measurements were made by cardiac magnetic resonance imaging(cMRI),invasive pressure monitoring,and a Pulse index Continuous Cardiac Output(PiCCO)hemo-dynamic system at 0,72,and 720 h during the follow-up period.End-diastolic and end-systolic volumes(EDV,ESV),left ventricular ejection fraction(LVEF)obtained by cMRI evaluation,global ejection fraction and aortic dP/dt_(max)obtained by the invasive method,were recorded and compared.The 72-and 720-h EDV data showed a signifi-cant increase(p=0.012,<0.001)compared to baseline,and the Day 30 data showed a significant increase compared to Day 3(p=0.022).The ESV 72 h after the infarction showed a significant increase(p=0.001)compared to baseline,which did not change significantly by Day 30(p=0.781)compared to Day 3.EDV and ESV were signifi-cantly negatively correlated with aortic dp_(max),and ESV was significantly correlated with LVEF.For LVEF and dP_(max),a significant(p<0.001 and p=0.002)worsening was demonstrated at Day 3 compared to baseline,which was no longer statistically de-tectable for LVEF at Day 30(p=0.141),while the difference for dP_(max)was maintained(p=0.002).The complementary use of PiCCO hemodynamic measurements in large animal models makes the previously used methodologies more robust and reliable.展开更多
文摘背景与目的:弥漫性大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)分子遗传学特征和患者治疗前^(18)F-FDG PET/CT检查评估的SUV_(max)值均与患者预后密切相关,但两者的关系及其与R-CHOP治疗方案治疗反应的相关性尚不清楚。本研究旨在分析DLBCL分子遗传学特征与治疗前经^(18)F-FDG PET/CT检测的SUV_(max)值的关系及其与临床病理学特征、R-CHOP治疗反应的相关性。方法:回顾性收集复旦大学附属肿瘤医院2022-2023年同时经淋巴瘤481基因DNA panel二代测序(next-generation sequencing,NGS)和治疗前经PET/CT检查的DLBCL患者225例,本研究通过复旦大学附属肿瘤医院医学伦理委员会的审查(伦理批号:050432-4-2307E)并获得患者知情同意;除基因突变特征外,同时收集荧光原位杂交法检测的BCL2、BCL6和MYC基因易位情况;另收集该组病例的临床病理学参数以及经R-CHOP治疗后的PET/CT检查结果。结果:总计191例DLBCL患者纳入最终分析,重要基因MYD88突变、TP53突变、CDKN2A/2B拷贝数异常、CD79B突变发生率分别为24.6%、27.2%、32.5%和16.8%。治疗前SUV_(max)值范围是5.10~63.10(24.44±10.70,中位22.80)。MYD88L265P突变型DLBCL的治疗前SUV_(max)值显著高于MYD88野生型DLBCL(P=0.039),SUV_(max)值与DLBCL其他基因变异类型包括TP53突变、CDKN2A/B拷贝数减少、CD79B突变、KMT2D突变、TNFAIP3突变、B2M突变、EZH2突变、BTG1/2突变、CREBBP突变、MYC、BCL2、BCL6基因重排之间无显著的相关性。治疗前高SUV_(max)值与高血清乳酸脱氢酶(lactate dehydrogenase,LDH)水平(P=0.012)及非生发中心(non-germinal center B-cell-like,non-GCB)亚型显著相关(P=0.040),但与R-CHOP治疗反应无显著的相关性(P=0.714)。DLBCL中TP53基因突变与R-CHOP治疗反应差显著相关(P=0.001),是R-CHOP治疗后非完全代谢缓解的独立预测因子。联合TP53基因突变、Ann Arbor分期、国际预后指数(International Prognostic Index,IPI)及血清LDH水平能够更好地预测患者对R-CHOP治疗的反应。结论:在DLBCL中,MYD88L265P突变型患者具有较高的治疗前SUV_(max)值。DLBCL治疗前SUV_(max)值与R-CHOP治疗反应无关,而TP53基因突变与R-CHOP治疗反应差显著相关,并且是独立预测因子。TP53基因突变联合临床病理学参数可更好地预测R-CHOP治疗反应。关于各基因变异特征及SUV_(max)值与患者预后的关系尚需作进一步随访研究。
文摘The present study aims to establish a reproducible large animal experimental unit using a minipig model to monitor cardiac function changes.A 90-min closed-chest bal-loon occlusion of the left anterior descending branch of the coronary artery was used to induce myocardial infarction in Pannon minipigs.To monitor the cardiac function,measurements were made by cardiac magnetic resonance imaging(cMRI),invasive pressure monitoring,and a Pulse index Continuous Cardiac Output(PiCCO)hemo-dynamic system at 0,72,and 720 h during the follow-up period.End-diastolic and end-systolic volumes(EDV,ESV),left ventricular ejection fraction(LVEF)obtained by cMRI evaluation,global ejection fraction and aortic dP/dt_(max)obtained by the invasive method,were recorded and compared.The 72-and 720-h EDV data showed a signifi-cant increase(p=0.012,<0.001)compared to baseline,and the Day 30 data showed a significant increase compared to Day 3(p=0.022).The ESV 72 h after the infarction showed a significant increase(p=0.001)compared to baseline,which did not change significantly by Day 30(p=0.781)compared to Day 3.EDV and ESV were signifi-cantly negatively correlated with aortic dp_(max),and ESV was significantly correlated with LVEF.For LVEF and dP_(max),a significant(p<0.001 and p=0.002)worsening was demonstrated at Day 3 compared to baseline,which was no longer statistically de-tectable for LVEF at Day 30(p=0.141),while the difference for dP_(max)was maintained(p=0.002).The complementary use of PiCCO hemodynamic measurements in large animal models makes the previously used methodologies more robust and reliable.