Screening costs associated with donor selection for fecal microbiota transplantation for treatment of PD-1 refractory melanoma patients.
Screening costs associated with donor selection for fecal microbiota transplantation for treatment of PD-1 refractory melanoma patients.
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DOI：
10.1097/cmr.0000000000000871
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发表时间：
2023-04-01
影响因子：
2.2
通讯作者：
Davar, Diwakar
中科院分区：
文献类型：
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作者：
Fortman, Dylan;Avellan, Maria G. Pazan;Hurd, Drew;Schwartz, Marc;Dubner, Howard;Hewitt, Corey;Berton, Samantha;Ernst, Scarlett;Rose, Amy;Wang, Hong;Zarour, Hassane;Davar, Diwakar
肠道微生物组作为对靶向PD-1和CTLA-4受体的免疫检查点抑制剂（ICI）的反应的肿瘤外在调节剂。对于难治性黑色素瘤患者，可以通过反应者来源的粪便微生物群移植（FMT）来逆转对抗PD-1 ICI的原发性耐药性。事实证明，为FMT建立粪便库的努力是困难的。因此，我们的目的是建立一种新的供体筛选程序，以产生用于PD-1难治性黑色素瘤的应答者来源的FMT。候选PD-1应答者供体和PD-1难治性受体通过匹兹堡大学医学中心医院的临床接触招募。合格的供体和受体接受了医生评估和血清，粪便和鼻咽部的传播因子筛查，其中包括SARS-CoV-2修饰。计算供、受者筛查费用。最初，对29名捐献者进行了筛选，排除后确定了14名合格捐献者;在这14名捐献者中，有8名用于临床试验。筛选的总效率为48%。巨细胞病毒、EB病毒、HSV-2、HHV-6、HTLV-1、HTLV-2和梅毒的血清阳性率与美国健康献血者的已发表统计数据相似。供体粪便研究表明，E。溶组织原虫和诺如病毒感染率分别为3.7%和7.1%。很难一名捐献者仅在粪便中检测出SARS-CoV-2阳性。寻找一名合资格捐献者的成本为2260. 24美元（新冠肺炎前）和2，460. 24美元（新冠肺炎后）。观察到的筛选效率表明，一个资源充足的筛选程序可以产生足够的反应者来源的供体材料用于临床试验目的。取消对低流行率微生物的检测可能会提高成本效益。
The gut microbiome acts as a tumor-extrinsic regulator of responses to immune-checkpoint inhibitors (ICIs) targeting PD-1 and CTLA-4 receptors. Primary resistance to anti-PD-1 ICI can be reversed via responder-derived fecal microbiota transplant (FMT) in patients with refractory melanoma. Efforts to create stool banks for FMT have proved difficult. Therefore, we aimed to establish a novel donor-screening program to generate responder-derived FMT for use in PD-1 refractory melanoma. Candidate PD-1 responder donors and PD-1 refractory recipients were recruited via clinic-based encounters at the University of Pittsburgh Medical Center hospitals. Eligible donors and recipients underwent physician assessment and screening of serum, stool and nasopharynx for transmissible agents, which included SARS-CoV-2 modification. The cost of donor and recipient screening was calculated. Initially, 29 donors were screened with 14 eligible donors identified after exclusion; of the 14 donors, eight were utilized in clinical trials. The overall efficiency of screening was 48%. Seroprevalence rates for cytomegalovirus, Epstein-Barr virus, HSV-2, HHV-6, HTLV-1, HTLV-2, and syphilis were similar to published statistics from healthy blood donors in the USA. Donor stool studies indicated a 3.6% incidence of E. histolytica and norovirus, 3.7% incidence of giardia and 7.1% incidence of C. difficile. A single donor tested positive for SARS-CoV-2 in stool only. The cost for finding a single eligible donor was $2260.24 (pre-COVID) and $2,460.24 (post-COVID). The observed screening efficiency suggests that a well-resourced screening program can generate sufficient responder-derived donor material for clinical trial purposes. Eliminating testing for low-prevalence organisms may improve cost-effectiveness.
在国家强化监测后，成人重症监护病房患者中耐甲氧西林的葡萄球菌金黄色葡萄球菌的区域流行病学。
DOI：
10.1093/cid/cix1056
发表时间：
2018-05-02
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Lin MY;Hayden MK;Lyles RD;Lolans K;Fogg LF;Kallen AJ;Weber SG;Weinstein RA;Trick WE;Prevention Epicenters Program, Centers for Disease Control and Prevention
通讯作者：
Prevention Epicenters Program, Centers for Disease Control and Prevention