Rapid Whole-Genome Sequencing and Clinical Management in the PICU: A Multicenter Cohort, 2016-2023.

IF 4 2区 医学 Q1 CRITICAL CARE MEDICINE
Pediatric Critical Care Medicine Pub Date : 2024-08-01 Epub Date: 2024-04-26 DOI:10.1097/PCC.0000000000003522
Katherine M Rodriguez, Jordan Vaught, Lisa Salz, Jennifer Foley, Zaineb Boulil, Heather M Van Dongen-Trimmer, Drewann Whalen, Okonkwo Oluchukwu, Kuang Chuen Liu, Jennifer Burton, Prachi Syngal, Ofelia Vargas-Shiraishi, Stephen F Kingsmore, Erica Sanford Kobayashi, Nicole G Coufal
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引用次数: 0

Abstract

Objectives: Analysis of the clinical utility of rapid whole-genome sequencing (rWGS) outside of the neonatal period is lacking. We describe the use of rWGS in PICU and cardiovascular ICU (CICU) patients across four institutions.

Design: Ambidirectional multisite cohort study.

Setting: Four tertiary children's hospitals.

Patients: Children 0-18 years old in the PICU or CICU who underwent rWGS analysis, from May 2016 to June 2023.

Interventions: None.

Measurements and main results: A total of 133 patients underwent clinical, phenotype-driven rWGS analysis, 36 prospectively. A molecular diagnosis was identified in 79 patients (59%). Median (interquartile range [IQR]) age was 6 months (IQR 1.2 mo-4.6 yr). Median time for return of preliminary results was 3 days (IQR 2-4). In 79 patients with a molecular diagnosis, there was a change in ICU management in 19 patients (24%); and some change in clinical management in 63 patients (80%). Nondiagnosis changed management in 5 of 54 patients (9%). The clinical specialty ordering rWGS did not affect diagnostic rate. Factors associated with greater odds ratio (OR [95% CI]; OR [95% CI]) of diagnosis included dysmorphic features (OR 10.9 [95% CI, 1.8-105]) and congenital heart disease (OR 4.2 [95% CI, 1.3-16.8]). Variables associated with greater odds of changes in management included obtaining a genetic diagnosis (OR 16.6 [95% CI, 5.5-62]) and a shorter time to genetic result (OR 0.8 [95% CI, 0.76-0.9]). Surveys of pediatric intensivists indicated that rWGS-enhanced clinical prognostication ( p < 0.0001) and contributed to a decision to consult palliative care ( p < 0.02).

Conclusions: In this 2016-2023 multiple-PICU/CICU cohort, we have shown that timely genetic diagnosis is feasible across institutions. Application of rWGS had a 59% (95% CI, 51-67%) rate of diagnostic yield and was associated with changes in critical care management and long-term patient management.

快速全基因组测序与重症监护病房的临床管理:多中心队列,2016-2023 年。
目的:目前还缺乏对新生儿期以外的快速全基因组测序(rWGS)临床实用性的分析。我们介绍了四家医疗机构在重症监护病房(PICU)和心血管重症监护病房(CICU)患者中使用 rWGS 的情况:环境:四家三级儿童医院:四所三级儿童医院:2016年5月至2023年6月期间在PICU或CICU接受rWGS分析的0-18岁儿童:无干预措施:共有 133 名患者接受了临床、表型驱动的 rWGS 分析,其中 36 名为前瞻性分析。79名患者(59%)确定了分子诊断。中位(四分位数间距 [IQR])年龄为 6 个月(IQR 1.2 个月-4.6 年)。返回初步结果的中位时间为 3 天(IQR 2-4)。在 79 名获得分子诊断的患者中,19 名患者(24%)的重症监护室管理发生了变化;63 名患者(80%)的临床管理发生了一些变化。54 例患者中有 5 例(9%)因未确诊而改变了治疗方案。下达 rWGS 命令的临床专科并不影响诊断率。与诊断几率(OR [95% CI];OR [95% CI])较大相关的因素包括畸形特征(OR 10.9 [95% CI, 1.8-105])和先天性心脏病(OR 4.2 [95% CI, 1.3-16.8])。与改变管理相关的变量包括获得基因诊断(OR 16.6 [95% CI, 5.5-62])和更短的基因结果时间(OR 0.8 [95% CI, 0.76-0.9])。对儿科重症监护医师的调查显示,rWGS可增强临床预后(p < 0.0001),并有助于做出姑息治疗的决定(p < 0.02):在这组 2016-2023 年多重症监护病房/重症监护病房队列中,我们发现及时的基因诊断在不同机构间是可行的。应用 rWGS 的诊断率为 59%(95% CI,51-67%),并与重症监护管理和长期患者管理的变化相关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Pediatric Critical Care Medicine
Pediatric Critical Care Medicine 医学-危重病医学
CiteScore
7.40
自引率
14.60%
发文量
991
审稿时长
3-8 weeks
期刊介绍: Pediatric Critical Care Medicine is written for the entire critical care team: pediatricians, neonatologists, respiratory therapists, nurses, and others who deal with pediatric patients who are critically ill or injured. International in scope, with editorial board members and contributors from around the world, the Journal includes a full range of scientific content, including clinical articles, scientific investigations, solicited reviews, and abstracts from pediatric critical care meetings. Additionally, the Journal includes abstracts of selected articles published in Chinese, French, Italian, Japanese, Portuguese, and Spanish translations - making news of advances in the field available to pediatric and neonatal intensive care practitioners worldwide.
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