Publications by authors named "Brian K Jordan"

10 Publications

  • Page 1 of 1

Single-Examination Risk Prediction of Severe Retinopathy of Prematurity.

Pediatrics 2021 Nov 23. Epub 2021 Nov 23.

Departments of Ophthalmology.

Background And Objectives: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. Screening and treatment reduces this risk, but requires multiple examinations of infants, most of whom will not develop severe disease. Previous work has suggested that artificial intelligence may be able to detect incident severe disease (treatment-requiring retinopathy of prematurity [TR-ROP]) before clinical diagnosis. We aimed to build a risk model that combined artificial intelligence with clinical demographics to reduce the number of examinations without missing cases of TR-ROP.

Methods: Infants undergoing routine ROP screening examinations (1579 total eyes, 190 with TR-ROP) were recruited from 8 North American study centers. A vascular severity score (VSS) was derived from retinal fundus images obtained at 32 to 33 weeks' postmenstrual age. Seven ElasticNet logistic regression models were trained on all combinations of birth weight, gestational age, and VSS. The area under the precision-recall curve was used to identify the highest-performing model.

Results: The gestational age + VSS model had the highest performance (mean ± SD area under the precision-recall curve: 0.35 ± 0.11). On 2 different test data sets (n = 444 and n = 132), sensitivity was 100% (positive predictive value: 28.1% and 22.6%) and specificity was 48.9% and 80.8% (negative predictive value: 100.0%).

Conclusions: Using a single examination, this model identified all infants who developed TR-ROP, on average, >1 month before diagnosis with moderate to high specificity. This approach could lead to earlier identification of incident severe ROP, reducing late diagnosis and treatment while simultaneously reducing the number of ROP examinations and unnecessary physiologic stress for low-risk infants.
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http://dx.doi.org/10.1542/peds.2021-051772DOI Listing
November 2021

Trajectories of Lung Function in Infants and Children: Setting a Course for Lifelong Lung Health.

Pediatrics 2020 10 16;146(4). Epub 2020 Sep 16.

Doernbecher Children's Hospital, Oregon Health & Science University, Portland, Oregon.

For healthy individuals, it is increasingly accepted that lung function follows along an individual percentile established early in life and that the level of maximal function reached as a young adult can affect the subsequent development of lung disease that occurs with the normal aging process. This emphasizes the need to maximize early lung function. The trajectories of lung function are at least partially established by perinatal factors, including prematurity and in utero exposures (tobacco exposure, nutrition, inflammation, etc), although they can also be affected by a variety of additional factors and exposures throughout the life span. Whether lung function trajectories can be impacted or reset if established under suboptimal conditions is an unanswered question, offering new avenues for research. In this review, we will summarize important articles outlining lung function trajectories and linking pediatric lung function tests to adult lung function tests decades later. We will focus on perinatal factors and outline progress and opportunities for further investigation into the potential ability to reset trajectories to impact long-term lung health.
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http://dx.doi.org/10.1542/peds.2020-0417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546086PMC
October 2020

The window of improved neonatal respiratory compliance after rescue antenatal steroids.

J Perinatol 2018 07 24;38(7):828-833. Epub 2018 May 24.

Division of Neonatology, Department of Pediatrics, Oregon Health and Science University, Portland, OR, USA.

Objective: To evaluate whether premature infants delivered ≤7 days after rescue antenatal steroid treatment (ideal treatment) have increased passive respiratory compliance compared to those delivered >7 days after treatment (remote treatment).

Methods: Secondary analysis of a randomized trial of rescue antenatal steroids on respiratory compliance. Infants in the treatment group were stratified by the interval between rescue antenatal steroids and delivery. We then compared the respiratory compliance in the ideal vs. remote groups.

Results: Forty-four women (56 infants) received rescue antenatal steroids. Forty-nine infants had evaluable respiratory compliance measurements, with 27 (GA 30.1 weeks, BW 1362 g) "ideally" treated, and 22 (GA 33.8 weeks, BW 2248 g) "remotely" treated. Respiratory compliance was significantly higher for the ideal compared to the remote group (1.32 vs. 1.06 mL/cm HO/kg; p = 0.037).

Conclusion: Infants treated with rescue antenatal steroids have a significantly higher respiratory compliance if delivery occurs within 7 days after treatment.
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http://dx.doi.org/10.1038/s41372-018-0124-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070394PMC
July 2018

Pulmonary Function at Hospital Discharge in Preterm Infants Randomized to a Single Rescue Course of Antenatal Steroids.

J Pediatr 2017 02 7;181:62-66.e1. Epub 2016 Nov 7.

Department of Pediatrics, Division of Neonatology, Oregon Health & Science University, Portland, OR.

Objective: To compare the pulmonary function, measured at birth and at hospital discharge, of infants whose mothers had been randomized to a single rescue course of antenatal steroids versus those whose mothers had been randomized to placebo.

Study Design: This study involved follow-up at hospital discharge of subjects of a randomized, double-blinded trial. In the original trial, pregnant women at ≥14 days after their initial course of antenatal steroids and <34 weeks' gestation were randomized to rescue antenatal steroids (44 mothers, 56 infants) or placebo (41 mothers, 57 infants). Passive respiratory compliance (Crs), passive respiratory resistance, and functional residual capacity were measured in all infants at birth and again at discharge to evaluate changes in pulmonary mechanics over time. Statistical analyses were based on intention to treat.

Results: We previously reported that compared with infants in the placebo group, infants in the rescue antenatal steroids group had a higher mean Crs value measured within 72 hours of birth (1.21 vs 1.01 mL/cm HO/kg; P < .05). Here we show that the Crs benefit in the antenatal steroids group was sustained until discharge. Infants in the placebo group demonstrated improvement in Crs such that by discharge, there was no difference in mean Crs between the rescue antenatal steroids and placebo groups (1.18 vs 1.22 mL/cm HO/kg).

Conclusions: Rescue antenatal steroids significantly increased Crs measured within 72 hours of birth, and this increase was sustained until hospital discharge. Preterm infants in the placebo group demonstrated a decreased initial Crs compared with the rescue antenatal steroids group, but achieved a comparable Crs by the time of discharge.

Trial Registration: ClinicalTrials.gov: NCT00669383.
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http://dx.doi.org/10.1016/j.jpeds.2016.10.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5274607PMC
February 2017

Relationship between acute kidney injury and brain MRI findings in asphyxiated newborns after therapeutic hypothermia.

Pediatr Res 2014 Mar 2;75(3):431-5. Epub 2013 Dec 2.

Department of Pediatrics & Communicable Diseases, Division of Nephrology, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, Michigan.

Background: We hypothesized that acute kidney injury (AKI) in asphyxiated neonates treated with therapeutic hypothermia would be associated with hypoxic-ischemic lesions on brain magnetic resonance imaging (MRI).

Methods: Medical records of 88 cooled neonates who had had brain MRI were reviewed. All neonates had serum creatinine assessed before the start of cooling; at 24, 48, and 72 h through cooling; and then on day 5 or 7 of life. A neonatal modification of the Kidney Disease: Improving Global Outcomes guidelines was used to classify AKI. MRI images were evaluated by a neuroradiologist masked to outcomes. Outcome of interest was abnormal brain MRI at 7-10 d of life.

Results: AKI was found in 34 (39%) of 88 neonates, with 15, 7, and 12 fulfilling criteria for stages 1, 2, and 3, respectively. Brain MRI abnormalities related to hypoxia-ischemia were present in 50 (59%) newborns. Abnormal MRI was more frequent in infants from the AKI group (AKI: 25 of 34, 73% vs. no AKI: 25 of 54, 46%; P = 0.012; odds ratio (OR) = 3.2; 95% confidence interval (CI) = 1.3-8.2). Multivariate analysis identified AKI (OR = 2.9; 95% CI = 1.1-7.6) to be independently associated with the primary outcome.

Conclusion: AKI is independently associated with the presence of hypoxic-ischemic lesions on postcooling brain MRI.
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http://dx.doi.org/10.1038/pr.2013.230DOI Listing
March 2014

Lucinactant for the prevention of respiratory distress syndrome in premature infants.

Expert Rev Clin Pharmacol 2013 Mar;6(2):115-21

Department of Pediatrics & Communicable Diseases, Division of Neonatal-Perinatal Medicine, CS Mott Children's Hospital, University of Michigan Health System, Ann Arbor, MI 48109, USA.

Respiratory distress syndrome (RDS) is the leading cause of neonatal morbidity and mortality in premature infants. It is caused by surfactant deficiency and lung immaturity. Lucinactant is a synthetic surfactant containing sinapultide, a bioengineered peptide mimic of surfactant-associated protein B. A meta-analysis of clinical trials demonstrates that lucinactant is as effective as animal-derived surfactants in preventing RDS in premature neonates, and in vitro studies suggest it is more resistant to oxidative and protein-induced inactivation. Its synthetic origin confers lower infection and inflammation risks as well other potential benefits, which may make lucinactant an advantageous alternative to its animal-derived counterparts, which are presently the standard treatment for RDS.
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http://dx.doi.org/10.1586/ecp.12.80DOI Listing
March 2013

Acute kidney injury in asphyxiated newborns treated with therapeutic hypothermia.

J Pediatr 2013 Apr 10;162(4):725-729.e1. Epub 2012 Nov 10.

Division of Nephrology, Department of Pediatrics and Communicable Diseases, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, MI 48109-5297, USA.

Objective: To test the hypothesis that acute kidney injury (AKI) would be independently associated with increased morbidity and mortality.

Study Design: A total of 96 consecutively cooled infants were reviewed retrospectively. Modified Acute Kidney Injury Network criteria were used to classify AKI based on absolute rise in serum creatinine (SCr) level from a previous trough (stage I, rise in SCr of 0.3 mg/dL or SCr 150-<200%; stage II, rise in SCr of 200-<300%; stage III, rise in SCr of ≥300%, SCr 2.5 mg/dL, or dialysis). Outcomes were mortality, duration of neonatal intensive care unit (NICU) stay, and duration of mechanical ventilation.

Results: AKI occurred in 36 of 96 infants (38%). Overall mortality was 7% and was higher for those with AKI, with the difference approaching statistical significance (14% vs 3% in those without AKI; P = .099). Patients with AKI stayed longer in the NICU (mean, 15.4 ± 9.3 days vs 11 ± 5.9 days; P = .014) and required prolonged mechanical ventilation (mean, 9.7 ± 5.9 days vs 4.8 ± 3.7 days; P < .001). On multivariate analysis, AKI remained predictive of prolonged duration of mechanical ventilation and prolonged NICU stay.

Conclusion: We used the Acute Kidney Injury Network definition for AKI in asphyxiated newborns undergoing therapeutic hypothermia to demonstrate that the incidence of AKI remains high, but lower than rates published before the advent of therapeutic hypothermia. We highlight the importance of recognizing AKI in asphyxiated newborns undergoing therapeutic hypothermia, along with the potential benefits of early recognition.
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http://dx.doi.org/10.1016/j.jpeds.2012.10.002DOI Listing
April 2013

Wnt4 overexpression disrupts normal testicular vasculature and inhibits testosterone synthesis by repressing steroidogenic factor 1/beta-catenin synergy.

Proc Natl Acad Sci U S A 2003 Sep 29;100(19):10866-71. Epub 2003 Aug 29.

Department of Human Genetics, University of California School of Medicine, Los Angeles, CA 90095-7088, USA.

Genetic studies in mice suggest that Wnt4 signaling antagonizes expression of male hormones and effectively blocks male development in the female embryo. We recently identified an XY intersex patient carrying a chromosomal duplication of the WNT4 locus and proposed that this patient's feminization arises from an increased dosage of WNT4. To test this hypothesis, a transgenic mouse was generated with a large genomic P1 containing the human WNT4. Although a complete male to female intersex phenotype was not observed in WNT4 transgenic male mice, a dramatic reduction in steroidogenic acute regulatory protein was detected consistent with the marked reduction in serum and testicular androgen levels. Furthermore, a mild reduction of germ cells and a disorganized vascular system were observed in testes of WNT4 transgenic males. Consistent with these in vivo data, Wnt4 repressed steroidogenesis in adrenocortical and Leydig cell lines, as evidenced by reduced progesterone secretion and 3beta-hydroxysteroid dehydrogenase activity. In vitro studies showed that Wnt4 antagonizes the functional synergy observed between the major effector of the Wnt signaling pathway, beta-catenin and steroidogenic factor 1, and chromatin immunoprecipitation showed that Wnt4 attenuates recruitment of beta-catenin to the steroidogenic acute regulatory protein promoter. Our findings suggest a model in which Wnt4 acts as an anti-male factor by disrupting recruitment of beta-catenin at or near steroidogenic factor 1 binding sites present in multiple steroidogenic genes.
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http://dx.doi.org/10.1073/pnas.1834480100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC196894PMC
September 2003

Sry and the genetics of sex determination.

Adv Exp Med Biol 2002 ;511:1-13; discussion 13-4

Department of Human Genetics, UCLA School of Medicine, Los Angeles, California, USA.

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http://dx.doi.org/10.1007/978-1-4615-0621-8_1DOI Listing
August 2003

Familial mutation in the testis-determining gene SRY shared by an XY female and her normal father.

J Clin Endocrinol Metab 2002 Jul;87(7):3428-32

Department of Human Genetics, University of California at Los Angeles, 6954 Charles E. Young Drive South, Gonda Center, Los Angeles, CA 90095-7088, USA.

In humans, mutations in the testis-determining gene SRY result in XY sex reversal with pure gonadal dysgenesis (PGD). However, only about 10-15% of the cases of PGD can be explained by mutations within the SRY open reading frame, suggesting the existence of other sex-determining genes. Although SRY is known to bind and bend DNA, its target and mode of action remain elusive. Here, we describe a novel mutation in SRY at codon 127, resulting in a tyrosine (Y) to phenylalanine (F) substitution in the protein. This sequence variant was found not only in the XY female patient but also in her father, who is a phenotypically normal male. However, this Y127F variant was not found in the SRY sequences of 93 other randomly chosen males. This substitution affects a highly conserved tyrosine residue in the HMG box of SRY, in which two de novo mutations have been described previously in XY females with PGD. Furthermore, electromobility shift studies demonstrate that SRY protein harboring the Y127F variant is incapable of binding consensus SRY binding sites in vitro. Taken together, these data suggest that the Y127F variant is a novel mutation with functional consequences and not simply a polymorphism. The allelic variant of SRY transmitted in this family and shared by both a phenotypic female (proband) and a phenotypic male (proband's father) emphasizes the importance of modifier genes in the sex determination pathway.
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http://dx.doi.org/10.1210/jcem.87.7.8646DOI Listing
July 2002
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