Phenotyping Men With Lower Urinary Tract Symptoms: Results From the Symptoms of Lower Urinary Tract Dysfunction Research Network.

IF 1.8 3区 医学 Q3 UROLOGY & NEPHROLOGY
Margaret E Helmuth, Abigail R Smith, Alexander P Glaser, Claire C Yang, Anne P Cameron, H Henry Lai, James W Griffith, J Eric Jelovsek, J Quentin Clemens, Brian T Helfand, Robert M Merion, Victor P Andreev
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引用次数: 0

Abstract

Aims: Men with lower urinary tract symptoms (LUTS) represent a heterogeneous group, and treatment decisions are often based on severity of symptoms and physical examination findings. Identification of clinically meaningful subtypes could allow for more personalized care. This study advances phenotyping efforts from the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) by adding data domains to previous phenotyping using urologic symptoms alone.

Methods: Two-hundred-seventeen LUTS, demographics, medical history, and physical examination datapoints from the LURN Observational Cohort study were assessed among 519 men with at least one bothersome LUTS, using weighted Tanimoto indices, semi-supervised learning, and resampling-based consensus clustering to identify distinct clusters of participants. Differentially abundant serum proteins of 220 men were compared across identified clusters.

Results: Five refined male clusters (RM1-RM5) were identified. Two clusters reported mild LUTS (RM1: n = 66; RM2: n = 84). RM1 was older than RM2 (70.3 vs. 56.1 years), had more comorbidities (functional comorbidity index 2.4 vs. 1.5) and erectile dysfunction. Two benign prostatic hyperplasia-like symptom clusters were identified (RM3: n = 64; RM4: n = 188). RM3 has the largest postvoid residual volume (275 mL); RM4 reported more urinary frequency, urgency, urinary incontinence, pain, and psychosocial symptoms. RM5 (n = 119) was characterized by urgency urinary incontinence, frequency, and significant comorbidities and psychosocial symptoms. Fifteen (RM2) to 87 (RM1) differentially abundant proteins were identified within each cluster. Minimal overlap was observed between affected proteins and pathways across clusters.

Conclusions: Protein signatures across newly discovered subgroups suggest identified subtypes are biochemically distinct. Findings should be validated, but may represent populations with separate pathophysiology and therapeutic needs.

Clinical trial registration: The LURN ClinicalTrials.gov Identifier is NCT02485808.

对有下尿路症状的男性进行表型分析:下尿路功能障碍症状研究网络的结果。
目的:患有下尿路症状(LUTS)的男性是一个异质性群体,治疗决定往往基于症状的严重程度和体格检查结果。确定具有临床意义的亚型可使治疗更加个性化。本研究在以往仅使用泌尿系统症状进行表型的基础上增加了数据域,从而推进了下尿路功能障碍症状研究网络(LURN)的表型工作:方法: 使用加权Tanimoto指数、半监督学习和基于重采样的共识聚类,对519名至少有一次下尿路症状的男性进行了评估。比较了220名男性血清蛋白在不同聚类中的不同含量:结果:确定了五个细化的男性聚类(RM1-RM5)。其中两个群组报告了轻度LUTS(RM1:n = 66;RM2:n = 84)。RM1的年龄比RM2大(70.3岁对56.1岁),有更多的合并症(功能性合并症指数2.4对1.5)和勃起功能障碍。确定了两个良性前列腺增生症样症状群(RM3:n = 64;RM4:n = 188)。RM3 的排尿后残余尿量最大(275 毫升);RM4 报告的尿频、尿急、尿失禁、尿痛和心理社会症状较多。RM5(n = 119)的特点是尿急尿失禁、尿频、严重的合并症和社会心理症状。在每个群组中发现了 15 个(RM2)至 87 个(RM1)不同含量的蛋白质。在不同群组中,受影响的蛋白质和通路之间的重叠极少:结论:新发现亚群的蛋白质特征表明,已确定的亚型在生物化学上是不同的。结论:新发现亚群的蛋白质特征表明,已确定的亚型具有不同的生化特征。研究结果有待验证,但可能代表了具有不同病理生理学和治疗需求的人群:LURN ClinicalTrials.gov 标识符为 NCT02485808。
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来源期刊
Neurourology and Urodynamics
Neurourology and Urodynamics 医学-泌尿学与肾脏学
CiteScore
4.30
自引率
10.00%
发文量
231
审稿时长
4-8 weeks
期刊介绍: Neurourology and Urodynamics welcomes original scientific contributions from all parts of the world on topics related to urinary tract function, urinary and fecal continence and pelvic floor function.
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