Evidence map›Paper›PMID 33119063›Full record

ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2021

Liquid Biopsy for Invasive Mold Infections in Hematopoietic Cell Transplant Recipients With Pneumonia Through Next-Generation Sequencing of Microbial Cell-Free DNA in Plasma.

Joshua A Hill, Sudeb C Dalai, David K Hong, Asim A Ahmed, Carine Ho, Desiree Hollemon, Lily Blair, Joyce Maalouf, Jacob Keane-Candib, Terry Stevens-Ayers and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.

  1. Pooled it
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  11. Plasma Microbial Cell-free DNA Metagenomic Sequencing for Diagnosis of Invasive Fungal Diseases Among High-risk Outpatient and Inpatient Immunocompromised Hosts.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025
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  19. Mucormycosis.Infectious disease clinics of North America · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Joshua A HillFred Hutchinson Cancer Research Center, Seattle, Washington, USA.ORCID 0000-0002-7665-7100
Sudeb C DalaiKarius, Inc, Redwood City, California, USA.
David K HongKarius, Inc, Redwood City, California, USA.
Asim A AhmedKarius, Inc, Redwood City, California, USA.
Carine HoKarius, Inc, Redwood City, California, USA.
Desiree HollemonKarius, Inc, Redwood City, California, USA.
Lily BlairKarius, Inc, Redwood City, California, USA.
Joyce MaaloufFred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Jacob Keane-CandibFred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Terry Stevens-AyersFred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Michael BoeckhFred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Timothy A BlauwkampKarius, Inc, Redwood City, California, USA.
Cynthia E FisherFred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Fred Hutch Cancer Center · USUniversity of Washington · USStanford University · US

Funding

VIRUS-MEDIATED MYELOSUPPRESSIONP01CA018029 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Geoffrey Roger HILL · 1985 to 2026
$128.4M
Project 3: Stem Cell Allografts for Lymphoid MalignanciesP01CA078902 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI SANDMAIER, BRENDA MARIE · 1999 to 2025
$46.1M
Project 3: Gene Therapy for Correction of Blood DisordersP01HL122173 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI KIEM, HANS-PETER · 2015 to 2019
$12.9M
Respiratory Viral Determinants of Chronic Lung Allograft DysfunctionK23HL143050 · NHLBI · UNIVERSITY OF WASHINGTON · PI FISHER, CYNTHIA E · 2018 to 2022
$986k
Human Herpesvirus 6 in Lower Respiratory Tract Disease and Chromosomal Integration after Hematopoietic Cell TransplantationK23AI119133 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI HILL, JOSHUA AIDEN · 2015 to 2019
$922k
Impact of Comorbidities on Outcomes of Allogeneic TransplantationR00HL088021 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI SORROR, MOHAMED · 2011 to 2013
$735k
Impact of Comorbidities on Outcomes of Allogeneic TransplantationK99HL088021 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI SORROR, MOHAMED · 2007 to 2008
$178k
Karius, IncNCI NIH HHS P01 CA018029NCI NIH HHS P01 CA078902NHLBI NIH HHS K23 HL143050NHLBI NIH HHS K99 HL088021NHLBI NIH HHS P01 HL122173NHLBI NIH HHS R00 HL088021NIAID NIH HHS K23 AI119133
6 · The paper itself

Abstract

backgroundNoninvasive diagnostic options are limited for invasive mold infections (IMIs). We evaluated the performance of a plasma microbial cell-free DNA sequencing (mcfDNA-Seq) test for diagnosing pulmonary IMI after hematopoietic cell transplant (HCT).

methodsWe retrospectively assessed the diagnostic performance of plasma mcfDNA-Seq next-generation sequencing in 114 HCT recipients with pneumonia after HCT who had stored plasma obtained within 14 days of diagnosis of proven/probable Aspergillus IMI (n = 51), proven/probable non-Aspergillus IMI (n = 24), possible IMI (n = 20), and non-IMI controls (n = 19). Sequences were aligned to a database including >400 fungi. Organisms above a fixed significance threshold were reported.

resultsAmong 75 patients with proven/probable pulmonary IMI, mcfDNA-Seq detected ≥1 pathogenic mold in 38 patients (sensitivity, 51% [95% confidence interval {CI}, 39%-62%]). When restricted to samples obtained within 3 days of diagnosis, sensitivity increased to 61%. McfDNA-Seq had higher sensitivity for proven/probable non-Aspergillus IMI (sensitivity, 79% [95% CI, 56%-93%]) compared with Aspergillus IMI (sensitivity, 31% [95% CI, 19%-46%]). McfDNA-Seq also identified non-Aspergillus molds in an additional 7 patients in the Aspergillus subgroup and Aspergillus in 1 patient with possible IMI. Among 19 non-IMI pneumonia controls, mcfDNA-Seq was negative in all samples, suggesting a high specificity (95% CI, 82%-100%) and up to 100% positive predictive value (PPV) with estimated negative predictive values (NPVs) of 81%-99%. The mcfDNA-Seq assay was complementary to serum galactomannan index testing; in combination, they were positive in 84% of individuals with proven/probable pulmonary IMI.

conclusionsNoninvasive mcfDNA-Seq had moderate sensitivity and high specificity, NPV, and PPV for pulmonary IMI after HCT, particularly for non-Aspergillus species.

Indexed as

Cell-Free Nucleic AcidsHematopoietic Stem Cell TransplantationPneumoniaFungiHigh-Throughput Nucleotide SequencingHumansLiquid BiopsyRetrospective StudiesTransplant RecipientsCell-Free Nucleic AcidsAspergilluscell-free DNAHCTmoldnext-generation sequencingpneumoniatransplant

Identifiers

PMID33119063
PMCPMC8664431
OpenAlexW3097629286

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.