Publications by authors named "G D Baird"

485 Publications

Quantification of Human Epidermal Growth Factor Receptor 2 by Immunopeptide Enrichment and Targeted Mass Spectrometry in Formalin-Fixed Paraffin-Embedded and Frozen Breast Cancer Tissues.

Clin Chem 2021 Jun 17. Epub 2021 Jun 17.

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Background: Conventional HER2-targeting therapies improve outcomes for patients with HER2-positive breast cancer (BC), defined as tumors showing HER2 protein overexpression by immunohistochemistry and/or ERBB2 gene amplification determined by in situ hybridization (ISH). Emerging HER2-targeting compounds show benefit in some patients with neither HER2 protein overexpression nor ERBB2 gene amplification, creating a need for new assays to select HER2-low tumors for treatment with these compounds. We evaluated the analytical performance of a targeted mass spectrometry-based assay for quantifying HER2 protein in formalin-fixed paraffin-embedded (FFPE) and frozen BC biopsies.

Methods: We used immunoaffinity-enrichment coupled to multiple reaction monitoring-mass spectrometry (immuno-MRM-MS) to quantify HER2 protein (as peptide GLQSLPTHDPSPLQR) in 96 frozen and 119 FFPE BC biopsies. We characterized linearity, lower limit of quantification (LLOQ), and intra- and inter-day variation of the assay in frozen and FFPE tissue matrices. We determined concordance between HER2 immuno-MRM-MS and predicate immunohistochemistry and ISH assays and examined the benefit of multiplexing the assay to include proteins expressed in tumor subcompartments (e.g., stroma, adipose, lymphocytes, epithelium) to account for tissue heterogeneity.

Results: HER2 immuno-MRM-MS assay linearity was ≥103, assay coefficient of variation was 7.8% (FFPE) and 5.9% (frozen) for spiked-in analyte, and 7.7% (FFPE) and 7.9% (frozen) for endogenous measurements. Immuno-MRM-MS-based HER2 measurements strongly correlated with predicate assay HER2 determinations, and concordance was improved by normalizing to glyceraldehyde-3-phosphate dehydrogenase. HER2 was quantified above the LLOQ in all tumors.

Conclusions: Immuno-MRM-MS can be used to quantify HER2 in FFPE and frozen BC biopsies, even at low HER2 expression levels.
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http://dx.doi.org/10.1093/clinchem/hvab047DOI Listing
June 2021

Experimental design of the Effects of Dehydroepiandrosterone in Pulmonary Hypertension (EDIPHY) trial.

Pulm Circ 2021 Apr-Jun;11(2):2045894021989554. Epub 2021 May 21.

Department of Medicine, Alpert Medical School of Brown University, Providence, RI, USA.

Pulmonary arterial hypertension (PAH) remains life-limiting despite numerous approved vasodilator therapies. Right ventricular (RV) function determines outcome in PAH but no treatments directly target RV adaptation. PAH is more common in women, yet women have better RV function and survival as compared to men with PAH. Lower levels of the adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate ester are associated with more severe pulmonary vascular disease, worse RV function, and mortality independent of other sex hormones in men and women with PAH. DHEA has direct effects on nitric oxide (NO) and endothelin-1 (ET-1) synthesis and signaling, direct antihypertrophic effects on cardiomyocytes, and mitigates oxidative stress. Effects of Dehydroepiandrosterone in Pulmonary Hypertension (EDIPHY) is an on-going randomized double-blind placebo-controlled crossover trial of DHEA in men ( = 13) and pre- and post-menopausal women ( = 13) with Group 1 PAH funded by the National Heart, Lung and Blood Institute. We will determine whether orally administered DHEA 50 mg daily for 18 weeks affects RV longitudinal strain measured by cardiac magnetic resonance imaging, markers of RV remodeling and oxidative stress, NO and ET-1 signaling, sex hormone levels, other PAH intermediate end points, side effects, and safety. The crossover design will elucidate sex-based phenotypes in PAH and whether active treatment with DHEA impacts NO and ET-1 biosynthesis. EDIPHY is the first clinical trial of an endogenous sex hormone in PAH. Herein we present the study's rationale and experimental design.
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http://dx.doi.org/10.1177/2045894021989554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142004PMC
May 2021

The association of adverse life events and parental mental health with emotional and behavioral outcomes in young adults with autism spectrum disorder.

Autism Res 2021 Jun 2. Epub 2021 Jun 2.

Department of Child and Adolescent Psychiatry, King's College London, Institute of Psychiatry, Psychology & Neuroscience, and South London and Maudsley Foundation Trust, London, UK.

People with autism spectrum disorder (ASD) are at increased risk of developing co-occurring mental health difficulties across the lifespan. Exposure to adverse life events and parental mental health difficulties are known risk factors for developing a range of mental health difficulties. This study investigates the association of adverse life events, parental stress and mental health with emotional and behavioral problems in young adults with ASD. One hundred and fifteen young adults with ASD derived from a population-based longitudinal study were assessed at three time-points (12-, 16-, and 23-year) on questionnaire measures of emotional and behavioral problems. Parent-reported exposure to adverse life events and parental stress/mental health were measured at age 23. We used structural equation modeling to investigate the stability of emotional and behavioral problems over time, and the association between adverse life events and parental stress and mental health and emotional and behavioral outcomes at 23-year. Our results indicate that exposure to adverse life events was significantly associated with increased emotional and behavioral problems in young adults with ASD, while controlling for symptoms in childhood and adolescence. Higher reported parental stress and mental health difficulties were associated with a higher frequency of behavioral, but not emotional problems, and did not mediate the impact of adverse life events. These results suggest that child and adolescent emotional and behavioral problems, exposure to life events and parent stress and mental health are independently associated, to differing degrees, with emotional or behavioral outcomes in early adulthood. LAY SUMMARY: People with autism experience high rates of mental health difficulties throughout childhood and into adult life. Adverse life events and parental stress and mental health may contribute to poor mental health in adulthood. We used data at three time points (12-, 16-, and 23-year) to understand how these factors relate to symptoms at 23-year. We found that emotional and behavioral problems in childhood, adverse life events and parent mental health were all associated with increased emotional and behavioral problems in adulthood.
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http://dx.doi.org/10.1002/aur.2548DOI Listing
June 2021

Calculating estimated glomerular filtration rate without the race correction factor: Observations at a large academic medical system.

Clin Chim Acta 2021 May 28;520:16-22. Epub 2021 May 28.

Department of Laboratory Medicine and Pathology; Kidney Research Institute; Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine; University of Washington, School of Medicine, United States. Electronic address:

Background And Aims: Creatinine-based MDRD and CKD-EPI equations include a race correction factor, which results in higher eGFR in Black patients. We evaluated the impact on our patient population upon adoption of the CKD-EPI equation and the removal of the race correction factor from the equation.

Materials And Methods: Retrospective analysis of blood creatinine results and respective eGFR values calculated by the MDRD or CKD-EPI equation without the race correction factor (CKD-EPI) in a large academic medical system over a 20.5-month period.

Results: In our population, when changing from MDRD to CKD-EPI, we observed that 3.5% of all patients were reclassified to categorically have worse kidney function. However, we also observed fewer patients overall with eGFR below 60 mL/min/1.73 m. Around 60 and 20 mL/min/1.73 m, 2.96% and 0.16% of all patients > 65 years of age were reclassified, as were 4.29% and 0.03% of all Black patients, respectively. When calculated with CKD-EPI, median eGFR was not meaningfully different between Black and non-Black patients (p = 0.02).

Conclusions: Changing from MDRD to CKD-EPI could lead to a lower referral rate to nephrology. The distributions of creatinine and eGFR calculated with CKD-EPI were not meaningfully different in Black and non-Black patients.
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http://dx.doi.org/10.1016/j.cca.2021.05.022DOI Listing
May 2021

PET/computed tomography in inpatients: part 1, international survey.

Nucl Med Commun 2021 May 17. Epub 2021 May 17.

Department of Diagnostic Imaging, The Warren Alpert Medical School of Brown University Lifespan Biostatistics Core, Providence, Rhode Island Department of Radiology, Boston Children's Hospital Harvard Medical School Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Purpose: The purposes of this study are to (1) identify patterns of inpatient PET/computed tomography (CT) use in and outside of the USA and (2) characterize inpatient PET/CT use by location and indication.

Materials And Methods: The study was deemed exempt by the Institutional Review Board. A survey link through REDCap was emailed to the Society of Nuclear Medicine and Molecular Imaging (SNMMI) members and PET Centers of Excellence members and posted on the SNMMI website. Data were collected from May 2018 to August 2018. Analyses were conducted using SAS Software 9.4 with the NPAR1WAY procedure. Differences were evaluated using the Kruskal-Wallis test with statistical significance defined as P ≤ 0.05.

Results: A total of 124 people responded to the survey, 71.8% (89/124) in the USA, and 26.6% (33/124) outside the USA [1.6% (2/124) no response]. 81.5% (101/124) read inpatient PET/CTs. Median percent of inpatient PET/CTs was 8.0% (range 0-100). Use of inpatient PET/CT was different (P < 0.0001) in the USA (5%, range 0-80%) versus outside USA (17.7%, range 0-100%). Use of inpatient PET/CT was different by institution type: median percent of inpatient PET/CTs in community teaching hospitals was 4.5% (range 0-50) versus 1.1% (range 0-20) in community nonteaching, 10% (range 0-80) in academic medical centers, and 20.0% (range 6.3-40) in government-affiliated institutions (P = 0.0001).

Conclusions: Most US and non-US respondents read inpatients PET/CTs. Non-US respondents read a higher percentage of inpatient PET/CTs than US respondents. Respondents in government-affiliated institutions read the highest percent of inpatient PET/CTs and community nonteaching institutions the least. Results of this survey may help physicians evaluate whether their practice of providing inpatient PET/CT fits with current practice patterns.
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http://dx.doi.org/10.1097/MNM.0000000000001418DOI Listing
May 2021