What is Endometriosis? Deep Phenotyping to Advance Diagnosis and Treatment

什么是子宫内膜异位症？

• 批准号: 10622684
• 负责人: Asgerally T. Fazleabas
• 金额: $ 4.87万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10622684
• 关键词: Adolescent; Adult; Affect; Age; Award; Blood; Characteristics; Classification; Clinical; Complement; Data; Diagnosis; Doctor of Philosophy; Endometrial; Female; Future; Gland; Health; Heterogeneity; Intervention; Medical Records; Mentors; Methods; Operative Surgical Procedures; Outcome; Pain; Pain Threshold; Pain-Free; Parents; Participant; Pathway interactions; Patient Selection; Patient Self-Report; Patients; Persistent pain; Phenotype; Postoperative Pain; Prevalence; Prognosis; Research; Research Support; Sampling; Selection for Treatments; Sensory; Staging System; Symptoms; Testing; Time; Tissue Sample; Universities; Urine; Uterine cavity; Woman; central pain; central sensitization; chronic pain; chronic pelvic pain; cohort; common symptom; disease classification; disease phenotype; doctoral student; endometriosis; experience; new therapeutic target; noninvasive diagnosis; novel; parent grant; patient subsets; phenomics; phenotypic data; precision medicine; professor; psychologic; reproductive

Endometriosis is a debilitating and often incurable condition characterized by the presence of endometrial- like glands and stroma thriving outside of the uterine cavity. The condition affects approximately 10–15% of all women of reproductive age. The most common symptom of endometriosis is pain, with endometriosis diagnosed in approximately 83% of all chronic pelvic pain (CPP) cases in the US. Current classification and staging systems for endometriosis have not found clinically useful associations with the level or chronicity of pain. Approximately 30% of women with endometriosis-associated pain (EAP) continue to experience persistent pain after surgery to treat the condition, possibly explained by central sensitization (CS). The parent grant, “What is Endometriosis? Deep Phenotyping to Advance Diagnosis and Treatment (WisE),” (PI: Missmer; R01 HD094842; Project dates 08/01/18 to 04/30/23) aims to identify unique classifications of patients with endometriosis that will inform non-invasive diagnostics, prognosis given current treatments, and novel treatment pathways. This Research Supplement to Promote Diversity in Health-Related Research application is requested to formally add Ms. Claire Lunde to the WisE team and support her research time during her final nine months as a doctoral student at the University of Oxford. The proposed mentoring team also includes Professor Vincent and Dr. Sieberg; both are Co-Is on the parent award and are Ms. Lunde’s current Ph.D. supervisors. As the parent R01 aims to discover informative subtypes of endometriosis and disease classifications, the candidate will supplement this research by analyzing existing sensory data (n=108) conducted on the same sample to further subdivide endometriosis participants by low and high CS. The most relevant aims of the parent award are Aims 3 and 4, which entail characterizing disease phenotypes by symptom presentation and heterogeneity of phenomics data for patients with endometriosis. The parent R01 uses harmonized medical records, participant data, blood, urine, and tissue samples for a diverse cohort of adolescents and adult females (n~2600). Integrating Quantitative Sensory Testing and phenomics data will further identify differences in functional pain characteristics between endometriosis participants and pain- free controls and provide a comprehensive set of objective patient phenotypes complementing the rich self- reported phenotype data. These results will elucidate the pain profiles in the clinical presentations (including pain thresholds and psychological variables) and if there is an association with outcomes after interventions (e.g., surgery). This will also allow for defining strategies for patient selection for future trials of novel therapeutics targeting these mechanisms. This critical research will expand upon our current collaborative research by enhancing our understanding of the impact of centralized pain on patients with endometriosis through establishing characteristics of patient subgroups using a mixed-method approach.

子宫内膜异位症是一种使人衰弱且通常无法治愈的疾病，其特征在于存在子宫内膜- 比如子宫腔外的腺体和间质这种情况影响大约10-15%的 所有育龄妇女。子宫内膜异位症最常见的症状是疼痛， 在美国，大约83%的慢性盆腔疼痛（CPP）病例被诊断为盆腔炎。目前的分类和 子宫内膜异位症的分期系统尚未发现临床有用的关联， 痛苦大约30%的女性乳腺癌相关性疼痛（EAP）继续经历 手术治疗后持续疼痛，可能由中枢致敏（CS）解释。母 什么是子宫内膜异位症？深入表型分析以推进诊断和治疗（WisE），”（PI： Missmer; R 01 HD 094842;项目日期：2018年8月1日至2023年4月30日）旨在确定 子宫内膜异位症患者，将告知非侵入性诊断，目前治疗的预后， 新的治疗途径。本研究补充促进健康相关研究的多样性 申请正式添加克莱尔伦德女士到WisE团队，并支持她的研究时间 在她作为牛津大学博士生的最后九个月里。拟议的指导小组 还包括文森特教授和西伯格博士;两人都是共同的是对家长奖，是女士伦德的 现任博士监事由于母体R 01旨在发现子宫内膜异位症的信息亚型， 疾病分类，候选人将通过分析现有的感官数据来补充这项研究 （n=108）对同一样本进行进一步细分子宫内膜异位症参与者低和高CS。 最相关的目标是目标3和目标4，这需要描述疾病表型 子宫内膜异位症患者的症状表现和表型组学数据的异质性。母 R 01使用统一的医疗记录、受试者数据、血液、尿液和组织样本进行多样化队列研究 青少年和成年女性（n~2600）。整合定量感官测试和表型组学数据 将进一步确定子宫内膜异位症参与者和疼痛之间功能性疼痛特征的差异- 免费对照，并提供一套全面的客观患者表型，补充丰富的自我， 报告的表型数据。这些结果将阐明临床表现中的疼痛特征（包括 疼痛阈值和心理变量）以及是否与干预后的结果相关 (e.g.,外科手术）。这也将允许为将来的新药物试验定义患者选择策略。 针对这些机制的治疗。这项重要的研究将扩大我们目前的合作 通过加强我们对集中性疼痛对子宫内膜异位症患者影响的理解， 通过使用混合方法建立患者亚组的特征。

项目成果

Differences in characteristics and use of complementary and alternative methods for coping with endometriosis-associated acyclic pelvic pain across adolescence and adulthood.

• DOI: 10.3389/frph.2023.1306380
• 发表时间: 2023
• 期刊: FRONTIERS IN REPRODUCTIVE HEALTH
• 作者: Mongiovi, Jennifer M.;Wallace, Britani;Goodwin, Mckenzie;Vitonis, Allison F.;Karevicius, Sarah;Shafrir, Amy L.;Sasamoto, Naoko;Divasta, Amy D.;Sieberg, Christine B.;Terry, Kathryn L.;Missmer, Stacey A.
• 通讯作者: Missmer, Stacey A.

Chronic pelvic pain: importance of compatible clinical trial outcomes.

慢性盆腔疼痛：相容的临床试验结果的重要性。

• DOI: 10.1111/1471-0528.16492
• 发表时间: 2021
• 期刊: BJOG : an international journal of obstetrics and gynaecology
• 作者: Shafrir,AL

Epidemiology of Adenomyosis.

• DOI: 10.1055/s-0040-1718920
• 发表时间: 2020-05
• 期刊: Seminars in reproductive medicine
• 影响因子: 2.7
• 作者: Upson K;Missmer SA
• 通讯作者: Missmer SA

Circulating proteomic profiles associated with endometriosis in adolescents and young adults.

• DOI: 10.1093/humrep/deac146
• 发表时间: 2022-06
• 期刊: Human reproduction
• 影响因子: 6.1
• 作者: Naoko Sasamoto;L. Ngo;A. Vitonis;S. Dillon;S. Missmer;T. Libermann;K. Terry