Publications by authors named "A Reed Estes"

222 Publications

Age disparities in triple-negative breast cancer treatment and outcomes: An NCDB analysis.

Surgery 2022 Aug 1. Epub 2022 Aug 1.

Department of Surgery, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH; University Hospitals Research in Surgical Outcomes and Effectiveness (UH-RISES), Cleveland, OH. Electronic address:

Background: Race, access to care, and molecular features result in outcome disparities in triple-negative breast cancer (TNBC). We sought to determine the role of age in TNBC disparity by hypothesizing that younger patients receive more comprehensive treatment, resulting in survival differences.

Methods: The National Cancer Database was used to identify women with unilateral TNBC treated from 2005 through 2017. Patients were stratified by age (≤40, 41-70, >70); demographics, clinical characteristics, and treatment factors were compared. Logistic regression determined factors associated with treatment received. Survival outcomes were analyzed using a stratified log-rank test.

Results: Of the 168,715 patients, 16,287 (9.6%) were ≤40 years. Patients ≤40 were significantly more likely to present at higher clinical stage (P < .001) and receive neoadjuvant chemotherapy (NAC, P < .001). Bilateral mastectomy was the most common surgery for patients ≤40 (37%), whereas partial mastectomy was most often used in patients 41 to 70 years old (48%) and those >70 (49%) (P < .001). Patients ≤40 years were significantly more likely to undergo both NAC and mastectomy than those >40 (odds ratio 1.5, both P < .05) despite a greater in-breast tumor response in the youngest patients. Patients treated with mastectomy and axillary lymph node dissection had inferior survival outcomes compared to those treated with partial mastectomy and sentinel lymph node biopsy across all 3 age groups (P < .001).

Conclusion: The clinical characteristics of TNBC differ significantly at the extremes of age, likely driving treatment decisions. Although patients ≤40 present with a more advanced disease and appropriately receive NAC, they also undergo more extensive surgery that does not yield a survival benefit. Further research is needed to determine if age disparity is due to oncologic factors or patient and provider preferences.
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http://dx.doi.org/10.1016/j.surg.2022.05.026DOI Listing
August 2022

Infants later diagnosed with autism have lower canonical babbling ratios in the first year of life.

Mol Autism 2022 06 27;13(1):28. Epub 2022 Jun 27.

Center for Autism Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Background: Canonical babbling-producing syllables with a mature consonant, full vowel, and smooth transition-is an important developmental milestone that typically occurs in the first year of life. Some studies indicate delayed or reduced canonical babbling in infants at high familial likelihood for autism spectrum disorder (ASD) or who later receive an ASD diagnosis, but evidence is mixed. More refined characterization of babbling in the first year of life in infants with high likelihood for ASD is needed.

Methods: Vocalizations produced at 6 and 12 months by infants (n = 267) taking part in a longitudinal study were coded for canonical and non-canonical syllables. Infants were categorized as low familial likelihood (LL), high familial likelihood diagnosed with ASD at 24 months (HL-ASD) or not diagnosed (HL-Neg). Language delay was assessed based on 24-month expressive and receptive language scores. Canonical babble ratio (CBR) was calculated by dividing the number of canonical syllables by the number of total syllables. Generalized linear (mixed) models were used to assess the relationship between group membership and CBR, controlling for site, sex, and maternal education. Logistic regression was used to assess whether canonical babbling ratios at 6 and 12 months predict 24-month diagnostic outcome.

Results: No diagnostic group differences in CBR were detected at 6 months, but HL-ASD infants produced significantly lower CBR than both the HL-Neg and LL groups at 12 months. HL-Neg infants with language delay also showed reduced CBR at 12 months. Neither 6- nor 12-month CBR was significant predictors of 24-month diagnostic outcome (ASD versus no ASD) in logistic regression.

Limitations: Small numbers of vocalizations produced by infants at 6 months may limit the reliability of CBR estimates. It is not known if results generalize to infants who are not at high familial likelihood, or infants from more diverse racial and socioeconomic backgrounds.

Conclusions: Lower canonical babbling ratios are apparent by the end of the first year of life in ASD regardless of later language delay, but are also observed for infants with later language delay without ASD. Canonical babbling may lack specificity as an early marker when used on its own.
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http://dx.doi.org/10.1186/s13229-022-00503-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235227PMC
June 2022

Infant Visual Brain Development and Inherited Genetic Liability in Autism.

Am J Psychiatry 2022 Aug 26;179(8):573-585. Epub 2022 May 26.

Carolina Institute for Developmental Disabilities (Girault, Forsen, Shen, Hazlett, Piven), Department of Psychiatry (Girault, Shen, Kim, Hazlett, Styner, Piven), Department of Biostatistics (Donovan, Truong), and ; Department of Psychological and Brain Sciences (Hawks) and Department of Psychiatry (Talovic, Nishino, Davis, Botteron, Todorov, Pruett, Constantino), Washington University School of Medicine in St. Louis; Institute of Child Development (Elison) and Department of Psychology, School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, Tex. (Swanson); Department of Radiology, Washington University in St. Louis (Snyder, McKinstry); Department of Speech and Hearing Science, University of Washington, Seattle (Estes, St. John); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Tandon School of Engineering, New York University, New York (Gerig); Center for Autism Research, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum).

Objective: Autism spectrum disorder (ASD) is heritable, and younger siblings of ASD probands are at higher likelihood of developing ASD themselves. Prospective MRI studies of siblings report that atypical brain development precedes ASD diagnosis, although the link between brain maturation and genetic factors is unclear. Given that familial recurrence of ASD is predicted by higher levels of ASD traits in the proband, the authors investigated associations between proband ASD traits and brain development among younger siblings.

Methods: In a sample of 384 proband-sibling pairs (89 pairs concordant for ASD), the authors examined associations between proband ASD traits and sibling brain development at 6, 12, and 24 months in key MRI phenotypes: total cerebral volume, cortical surface area, extra-axial cerebrospinal fluid, occipital cortical surface area, and splenium white matter microstructure. Results from primary analyses led the authors to implement a data-driven approach using functional connectivity MRI at 6 months.

Results: Greater levels of proband ASD traits were associated with larger total cerebral volume and surface area and larger surface area and reduced white matter integrity in components of the visual system in siblings who developed ASD. This aligned with weaker functional connectivity between several networks and the visual system among all siblings during infancy.

Conclusions: The findings provide evidence that specific early brain MRI phenotypes of ASD reflect quantitative variation in familial ASD traits. Multimodal anatomical and functional convergence on cortical regions, fiber pathways, and functional networks involved in visual processing suggest that inherited liability has a role in shaping the prodromal development of visual circuitry in ASD.
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http://dx.doi.org/10.1176/appi.ajp.21101002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356977PMC
August 2022

Examining the factor structure and discriminative utility of the Infant Behavior Questionnaire-Revised in infant siblings of autistic children.

Child Dev 2022 Apr 29. Epub 2022 Apr 29.

University of Minnesota, Minneapolis, Minnesota, USA.

Using the Infant Behavior Questionnaire-Revised in a longitudinal sample of infant siblings of autistic children (HR; n = 427, 171 female, 83.4% White) and a comparison group of low-risk controls (LR, n = 200, 86 female, 81.5% White), collected between 2007 and 2017, this study identified an invariant factor structure of temperament traits across groups at 6 and 12 months. Second, after partitioning the groups by familial risk and diagnostic outcome at 24 months, results reveal an endophenotypic pattern of Positive Emotionality at both 6 and 12 months, (HR-autism spectrum disorder [ASD] < HR-no-ASD < LR). Third, increased 'Duration of Orienting' at 12 months was associated with lower scores on the 24-month developmental outcomes in HR infants. These findings may augment efforts for early identification of ASD.
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http://dx.doi.org/10.1111/cdev.13781DOI Listing
April 2022

Subcortical Brain Development in Autism and Fragile X Syndrome: Evidence for Dynamic, Age- and Disorder-Specific Trajectories in Infancy.

Am J Psychiatry 2022 Aug 25;179(8):562-572. Epub 2022 Mar 25.

Carolina Institute for Developmental Disabilities and Department of Psychiatry (Shen, Girault, Kim, Smith, Graves, Weisenfeld, Gross, Styner, Hazlett, Piven) and UNC Neuroscience Center (Shen), University of North Carolina at Chapel Hill School of Medicine, Chapel Hill; Department of Educational Psychology (Wolff), Institute of Child Development (Elison), and Department of Pediatrics (Elison, Burrows), University of Minnesota, Minneapolis; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis (Flake, McKinstry, Botteron); Department of Radiology, University of Washington Medical Center, Seattle (Dager); Center for Autism Research, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia (Pandey, Schultz); Computer Science and Engineering, NYU Tandon School of Engineering, New York (Gerig); Montreal Neurological Institute, McGill University, Montreal (MacIntyre, Fonov, Collins, Evans); Department of Pediatrics, University of Alberta, Edmonton, Canada (Zwaigenbaum); Department of Speech and Hearing Science, University of Washington, Seattle (St. John, Estes); School of Behavioral and Brain Sciences, University of Texas at Dallas (Swanson).

Objective: Previous research has demonstrated that the amygdala is enlarged in children with autism spectrum disorder (ASD). However, the precise onset of this enlargement during infancy, how it relates to later diagnostic behaviors, whether the timing of enlargement in infancy is specific to the amygdala, and whether it is specific to ASD (or present in other neurodevelopmental disorders, such as fragile X syndrome) are all unknown.

Methods: Longitudinal MRIs were acquired at 6-24 months of age in 29 infants with fragile X syndrome, 58 infants at high likelihood for ASD who were later diagnosed with ASD, 212 high-likelihood infants not diagnosed with ASD, and 109 control infants (1,099 total scans).

Results: Infants who developed ASD had typically sized amygdala volumes at 6 months, but exhibited significantly faster amygdala growth between 6 and 24 months, such that by 12 months the ASD group had significantly larger amygdala volume (Cohen's d=0.56) compared with all other groups. Amygdala growth rate between 6 and 12 months was significantly associated with greater social deficits at 24 months when the infants were diagnosed with ASD. Infants with fragile X syndrome had a persistent and significantly enlarged caudate volume at all ages between 6 and 24 months (d=2.12), compared with all other groups, which was significantly associated with greater repetitive behaviors.

Conclusions: This is the first MRI study comparing fragile X syndrome and ASD in infancy, demonstrating strikingly different patterns of brain and behavior development. Fragile X syndrome-related changes were present from 6 months of age, whereas ASD-related changes unfolded over the first 2 years of life, starting with no detectable group differences at 6 months. Increased amygdala growth rate between 6 and 12 months occurs prior to social deficits and well before diagnosis. This gradual onset of brain and behavior changes in ASD, but not fragile X syndrome, suggests an age- and disorder-specific pattern of cascading brain changes preceding autism diagnosis.
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http://dx.doi.org/10.1176/appi.ajp.21090896DOI Listing
August 2022
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