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
{"title":"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。","authors":"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","doi":"10.1097/PCC.0000000000003522","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Design: </strong>Ambidirectional multisite cohort study.</p><p><strong>Setting: </strong>Four tertiary children's hospitals.</p><p><strong>Patients: </strong>Children 0-18 years old in the PICU or CICU who underwent rWGS analysis, from May 2016 to June 2023.</p><p><strong>Interventions: </strong>None.</p><p><strong>Measurements and main results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":19760,"journal":{"name":"Pediatric Critical Care Medicine","volume":null,"pages":null},"PeriodicalIF":4.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300160/pdf/","citationCount":"0","resultStr":"{\"title\":\"Rapid Whole-Genome Sequencing and Clinical Management in the PICU: A Multicenter Cohort, 2016-2023.\",\"authors\":\"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\",\"doi\":\"10.1097/PCC.0000000000003522\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>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.</p><p><strong>Design: </strong>Ambidirectional multisite cohort study.</p><p><strong>Setting: </strong>Four tertiary children's hospitals.</p><p><strong>Patients: </strong>Children 0-18 years old in the PICU or CICU who underwent rWGS analysis, from May 2016 to June 2023.</p><p><strong>Interventions: </strong>None.</p><p><strong>Measurements and main results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":19760,\"journal\":{\"name\":\"Pediatric Critical Care Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300160/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pediatric Critical Care Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/PCC.0000000000003522\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/4/26 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CRITICAL CARE MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Critical Care Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/PCC.0000000000003522","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/4/26 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
Rapid Whole-Genome Sequencing and Clinical Management in the PICU: A Multicenter Cohort, 2016-2023.
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.
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.