Characterization of the Glucocorticoid Receptor in Children Undergoing Cardiac Surgery*

Flores, Saúl; Cooper, David S.; Opoka, Amy; Iliopoulos, Ilias; Pluckebaum, Sarah; Alder, Matthew N.; Krallman, Kelli A.; Sahay, Rashmi; Lin, Fang; Wong, Hector R.

doi:10.1097/pcc.0000000000001572

Cited by 6 publications

(9 citation statements)

References 37 publications

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“…As we discuss in the study limitations of our manuscript, we have a small sample size that was analysed post hoc based off data from a previously described dataset. 4,5 However, we are pleased that our data agree with the recently published literature in the paediatric cardiac population and we hope that will strengthen the base of evidence on which a large multi-center study can be designed to overcome the shortcomings of our and other studies.…”

supporting

confidence: 83%

Reply to Letter: Predictive value of preoperative neutrophil–lymphocyte ratio predicts low cardiac output in children after cardiac surgery

2020

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supporting

confidence: 83%

Reply to Letter: Predictive value of preoperative neutrophil–lymphocyte ratio predicts low cardiac output in children after cardiac surgery

2020

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“…We performed a post hoc analysis of data collected as part of a prospective observational cohort of children evaluated previously for glucocorticoid receptor levels after heart surgery. 14 The initial cohort consisted of children (up to 17 years of age) admitted to the cardiac ICU of the Cincinnati Children's Hospital following congenital heart surgery with cardiopulmonary bypass during a 7-month period (1 July, 2015 to 31 January, 2016). Patients who did not require cardiopulmonary bypass were excluded.…”

Section: Methodsmentioning

confidence: 99%

Pre-operative neutrophil–lymphocyte ratio predicts low cardiac output in children after cardiac surgery

et al. 2020

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Neutrophil–lymphocyte ratio has been associated with clinical outcomes in several groups of cardiac patients, including patients with coronary artery disease, cardiac failure, and cardiac transplant recipients. We hypothesised that pre- and/or post-operative haematological cell counts are associated with clinical outcomes in children undergoing cardiac surgery for CHD. We performed a post hoc analysis of data collected as part of a prospective observational cohort study (n = 83, data available n = 47) of children evaluated for glucocorticoid receptor levels after cardiac surgery (July 2015–January 2016). The association of neutrophil–lymphocyte ratio with low cardiac output syndrome, time to inotrope free, and vasoactive-inotropic score was examined using proportional odds analysis, cox regression, and linear regression models, respectively. A majority (80%) of patients were infants (median/interquartile range 4.1/0.2–7.6 months) with conotruncal (36%) and left-sided obstructed lesions (28%). Two patients required mechanical circulatory support and three died. Higher pre-operative neutrophil–lymphocyte ratio was associated with higher cumulative odds of severe/moderate versus mild low cardiac output on post-operative day 1 (odds ratio 2.86; 95% confidence interval 1.18–6.93; p = 0.02). Pre-operative neutrophil–lymphocyte ratio was not significantly associated with time to inotrope free or vasoactive-inotrope score. Post-operative neutrophil–lymphocyte ratio was also not associated with outcomes. In children after congenital heart surgery, higher pre-operative neutrophil–lymphocyte ratio was associated with a higher chance of low cardiac output in the early post-operative period. Pre-operative neutrophil–lymphocyte ratio maybe a useful prognostic marker in children undergoing congenital heart surgery.

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“…TIF is equivalent to "inotropic support use" and "inotropic free days" recently used in a study of children undergoing congenital heart surgery. 4 The secondary outcome was low cardiac output scores (LCOS) classified into five categories as mild: single vasoactive agent or arterial lactate < 2; moderate: two vasoactive agents or arterial lactate between 2 and 5; severe: three or more vasoactive agents or arterial lactate > 5; mechanical support: requirement of extracorporeal membrane oxygenation or ventricular assist devices; and finally, death. This end point was chosen because elevated lactate levels and a greater number of vasoactive agents with higher dosage have been associated with worse clinical outcomes.…”

Section: End Points and Outcome Assessmentmentioning

confidence: 99%

“…9,10 GCR expression and cortisol levels from this cohort were previously characterized and published elsewhere. 4…”

Section: End Points and Outcome Assessmentmentioning

confidence: 99%

“…3 Corticosteroid activity depends on the glucocorticoid receptor (GCR) and, recently, increased GCR levels have been associated with worse clinical outcomes irrespective of cortisol levels in children undergoing congenital heart surgery. 4 Furthermore, recent research focused on identifying biomarkers such as single nucleotide polymorphisms (SNP) that may reliably predict responsiveness to medications to allow individualized treatment protocols. SNP are single-base pairs in genomic DNA that vary in at least 1% of the population and account for much of normal human genetic variation.…”

Section: Introductionmentioning

confidence: 99%

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Glucocorticoid Receptor Polymorphisms in Children Undergoing Congenital Heart Surgery with Cardiopulmonary Bypass

Flores

Iliopoulos

Loomba

et al. 2020

J Pediatr Intensive Care

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We conducted a candidate gene association study to test the hypothesis that different gene polymorphisms will be associated with corticosteroid responsiveness and study outcomes among children undergoing congenital heart surgery. This is a prospective observational cohort study at a large, tertiary pediatric cardiac center on children undergoing corrective or palliative congenital heart surgery. A total of 83 children were enrolled. DNA was isolated for three polymorphisms of interest namely N363 (rs56149945) and 9β (rs6198) associated with increased sensitivity to corticosteroids and BclI (rs41423247) associated with decreased sensitivity to corticosteroids. Duration of inotropic use, low cardiac output scores (LCOS), and vasoactive inotrope scores were examined in relation to these three polymorphisms. Using Kaplan–Meier analysis, heterozygous individuals showed longer transcriptional intermediary factor (TIF) compared with wild type for N363 polymorphism (p = 0.05). In multivariable Cox regression, heterozygous alleles for 9β polymorphism showed significantly shorter TIF compared with wild type (hazard ratio = 2.04 [1.08–3.87], p = 0.03). The relationship between lower LCOS scores and alleles groups was significant for 9β heterozygous polymorphism only (1.5 [1–2.2], p = 0.01) in comparison to wild type and homozygous. The presence of heterozygote alleles for the increased corticosteroid sensitivity is associated with longer TIF compared with wild type. Conversely, the presence of heterozygous alleles for the decreased sensitivity to corticosteroids is associated with shorter TIF compared with wild type.

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Characterization of the Glucocorticoid Receptor in Children Undergoing Cardiac Surgery*

Cited by 6 publications

References 37 publications

Reply to Letter: Predictive value of preoperative neutrophil–lymphocyte ratio predicts low cardiac output in children after cardiac surgery

Reply to Letter: Predictive value of preoperative neutrophil–lymphocyte ratio predicts low cardiac output in children after cardiac surgery

Pre-operative neutrophil–lymphocyte ratio predicts low cardiac output in children after cardiac surgery

Glucocorticoid Receptor Polymorphisms in Children Undergoing Congenital Heart Surgery with Cardiopulmonary Bypass

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