Response to Yates and Halliday regarding CMV DNAemia and time-to-mortality in a Randomized Trial of PET vs AP in CMV D+R-Liver Transplant Recipients.
Response to Yates and Halliday regarding CMV DNAemia and time-to-mortality in a Randomized Trial of PET vs AP in CMV D+R-Liver Transplant Recipients.
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在 CMV D R 肝移植受者中进行 PET 与 AP 随机试验中，Yates 和 Halliday 关于 CMV DNA 血症和死亡时间的反应。
DOI：
10.1093/cid/ciae005
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Limaye,AjitP
中科院分区：
文献类型：
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作者：
Kumar,Lakshin;Dasgupta,Sayan;Murray-Krezan,Cristina;Singh,Nina;Rakita,RobertM;Fisher,CynthiaE;Limaye,AjitP
难以解释的生存率估计值，不能推广到接受干预的人群。本研究的主要原理是评估长期随访期间关注的协变量（晚期DNA血症）与死亡风险的相关性。仅在移植后6个月和12个月对研究参与者进行了巨细胞病毒（CMV）DNA血症的系统评估。因此，在12个月时间点对存活的亚组进行里程碑分析是探索性事后分析的适当方法，认识到不包括全随机化人群所带来的局限性。该事后分析并不旨在通过时间推断来预测移植初始时尚未接受指定干预的患者的结局，而是检查完成指定预防策略（即“符合方案”分析）并测量了相关协变量（6个月和12个月时的DNA血症）的患者的结局。我们明确表示，这是一项探索性事后分析，研究结果应被视为产生假设，而不是确定因果关系。另一个问题是，DNA血症-死亡率相关性的潜在混杂因素，如移植时的年龄和免疫抑制程度，未作为协变量纳入，因为在一般人群中，血液中的CMV病毒载量（VL）随年龄增长而增加。在之前对CAPSIL研究参与者中CMV DNA血症风险因素的分析中，我们的研究小组没有发现与年龄或较高免疫抑制措施（抗胸腺细胞球蛋白[ATG]使用）的相关性，部分缓解了对这些潜在混杂因素的担忧[3]。在存活至12个月的患者亚组中，年龄（Pearson's R2= 0.06）或ATG使用（P=. 33)最大CMV VL增加。此外，在包含最大值的考克斯比例风险模型中，
estimates of survival that are hard to interpret and cannot be generalized to the population to whom the intervention is to be offered. The primary rationale for the current study was to assess the association of the covariate of interest (late DNAemia) with mortality risk during long-term follow-up. Systematic assessment of cytomegalovirus (CMV) DNAemia was conducted in study participants only at 6 and 12 months after transplantation. Thus, a landmark analysis at the 12-month time point restricted to the subset who survived was an appropriate approach for an exploratory post hoc analysis, recognizing the limitations introduced by not including the full randomized population. This post hoc analysis was not intended to extrapolate back in time to predict outcomes in those at the initial time of transplantation who had not yet undergone the assigned intervention, but rather to examine outcomes in those who completed the assigned preventive strategy (ie, a “per-protocol” analysis) and had the covariate of interest measured (DNAemia at 6 and 12 months). We explicitly stated that this was an exploratory post hoc analysis and that the findings should be considered hypothesis generating rather than definitively causal. Another concern was that potential confounders of the DNAemia-mortality association, such as age at transplantation and degree of immunosuppression, were not included as covariates, since in the general population, the CMV viral load (VL) in blood increases with advancing age. In a previous analysis of risk factors for CMV DNAemia in CAPSIL study participants, our group did not find an association with age or measures of higher immunosuppression (antithymocyte globulin [ATG] use), partially mitigating concerns about these as potential confounders [3]. In the subset of patients who survived to 12 months, there was no significant association between age (Pearson’s R2= 0.06) or ATG use (P=. 33) with increased maximum CMV VL. Furthermore, in a Cox proportional hazards model including maximum