First name
Rui
Last name
Feng

Title

Impaired echocardiographic left ventricular global longitudinal strain after pediatric cardiac arrest children is associated with mortality.

Year of Publication

2023

Number of Pages

109936

Date Published

08/2023

ISSN Number

1873-1570

Abstract

BACKGROUND: Global longitudinal strain (GLS) is an echocardiographic method to identify left ventricular (LV) dysfunction after cardiac arrest that is less sensitive to loading conditions. We aimed to identify the frequency of impaired GLS following pediatric cardiac arrest, and its association with hospital mortality.

METHODS: This is a retrospective single-center cohort study of children <18 years of age treated in the pediatric intensive care unit (PICU) after in- or out-of-hospital cardiac arrest (IHCA and OHCA), with echocardiogram performed within 24 hours of initiation of post-arrest PICU care between 2013 and 2020. Patients with congenital heart disease, post-arrest extracorporeal support, or inability to measure GLS were excluded. Echocardiographic LV ejection fraction (EF) and shortening fraction (SF) were abstracted from the chart. GLS was measured post hoc; impaired strain was defined as LV GLS ≥ 2 SD worse than age-dependent normative values. Demographics and pre-arrest, arrest, and post-arrest characteristics were compared between subjects with normal versus impaired GLS. Correlation between GLS, SF and EF were calculated with Pearson comparison. Logistic regression tested the association of GLS with mortality. Area under the receiver operator curve (AUROC) was calculated for discriminative utility of GLS, EF, and SF with mortality.

RESULTS: GLS was measured in 124 subjects; impaired GLS was present in 46 (37.1%). Subjects with impaired GLS were older (median 7.9 vs. 1.9 years, p < 0.001), more likely to have ventricular tachycardia/fibrillation as initial rhythm (19.6% versus 3.8%, p = 0.017) and had higher peak troponin levels in the first 24 hours post-arrest (median 2.5 vs. 0.5, p = 0.002). There were no differences between arrest location or CPR duration by GLS groups. Subjects with impaired GLS compared to normal GLS had lower median EF (42.6% versus 62.3%) and median SF (23.3% versus 36.6%), all p < 0.001, with strong inverse correlation between GLS and EF (rho -0.76, p < 0.001) and SF (rho -0.71, p < 0.001). Patients with impaired GLS had higher rates of mortality (60% vs. 32%, p = 0.009). GLS was associated with mortality when controlling for age and initial rhythm [aOR 1.17 per 1% increase in GLS (95% CI 1.09-1.26), p < 0.001]. GLS, EF and SF had similar discrimination for mortality: GLS AUROC 0.69 (95% CI 0.60-0.79); EF AUROC 0.71 (95% CI 0.58-0.88); SF AUROC 0.71 (95% CI 0.61-0.82), p = 0.101.

CONCLUSIONS: Impaired LV function as measured by GLS after pediatric cardiac arrest is associated with hospital mortality. GLS is a novel complementary metric to traditional post-arrest echocardiography that correlates strongly with EF and SF and is associated with mortality. Future large prospective studies of post-cardiac arrest care should investigate the prognostic utilities of GLS, alongside SF and EF.

DOI

10.1016/j.resuscitation.2023.109936

Alternate Title

Resuscitation

PMID

37574003
Featured Publication
No

Title

Individualising care in severe bronchopulmonary dysplasia: a series of N-of-1 trials comparing transpyloric and gastric feeding.

Year of Publication

2019

Date Published

2019 Nov 04

ISSN Number

1468-2052

Abstract

<p><strong>OBJECTIVE: </strong>Compare rates of hypoxaemia during transpyloric and gastric feedings in very preterm infants with severe bronchopulmonary dysplasia.</p>

<p><strong>DESIGN: </strong>N-of-1 multiple crossover trials with individual patient and pooled data analyses.</p>

<p><strong>SETTING: </strong>Level IV intensive care nursery.</p>

<p><strong>PATIENTS: </strong>Infants receiving positive airway pressure between 36 and 55 weeks postmenstrual age were enrolled between December 2014-July 2016.</p>

<p><strong>INTERVENTION: </strong>N-of-1 trial consisting of two blocks, each with a 4-day gastric and 4-day transpyloric feeding period assigned in random order.</p>

<p><strong>MAIN OUTCOME MEASURES: </strong>The primary outcome was the frequency of daily intermittent hypoxaemic events (SpO ≤80% lasting 10-180 s). Secondary outcomes included the daily proportion of time with an SpO ≤80% and mean daily fraction of inspired oxygen.</p>

<p><strong>RESULTS: </strong>Of 15 infants, 13 completed the trial and 2 stopped early for transient worsening in respiratory status during gastric feedings. In the intention-to-treat analyses, transpyloric feedings resulted in increased rates of intermittent hypoxaemia in five infants, greater time per day in hypoxaemia in three infants and more supplemental oxygen use in three infants. One infant received more supplemental oxygen during gastric feedings. The remaining study outcomes were similar between the feeding routes in all other infants. Pooling all data, transpyloric feedings resulted in a higher frequency of intermittent hypoxaemic events (median 7.5/day (IQR 1-23.5) vs 3/day (1-11); adjusted incidence rate ratio 1.8, 95% CI 1.3 to 2.5) and a greater proportion of daily hypoxaemia time (median 0.8% (IQR 0.1-2.3) vs 0.4% (0.07-1.8); adjusted mean difference 1.6, 95% CI 1.1 to 2.5).</p>

<p><strong>CONCLUSIONS: </strong>Transpyloric compared with gastric feedings modestly increased rates of hypoxaemia among study participants.</p>

<p><strong>TRIAL REGISTRATION NUMBER: </strong>NCT02142621.</p>

DOI

10.1136/archdischild-2019-317148

Alternate Title

Arch. Dis. Child. Fetal Neonatal Ed.

PMID

31685527

Title

Evaluation of the reliability and validity of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) in pediatric cutaneous lupus among pediatric dermatologists and rheumatologists.

Year of Publication

2018

Date Published

2018 Jul 23

ISSN Number

1365-2133

Abstract

<p><strong>BACKGROUND: </strong>The CLASI is a reliable outcome measure for cutaneous lupus erythematosus (CLE) in adults used in clinical trials. However, it has not been validated in children, limiting clinical trials for pediatric CLE.</p>

<p><strong>OBJECTIVE: </strong>This study aims to validate the CLASI in pediatrics.</p>

<p><strong>METHODS: </strong>Eleven pediatric patients with CLE, six dermatologists and six rheumatologists, participated. Physicians were trained to use the CLASI and Physician Global Assessment (PGA). Physicians individually rated all patients using both tools. Each physician reassessed two randomly selected patients. Within each physician group, Intraclass Correlation Coefficient (ICC) was calculated to assess the reliability of each measure.</p>

<p><strong>RESULTS: </strong>CLASI activity scores demonstrated excellent inter- and intra-rater reliability (ICC&gt;0.90), while the PGA activity scores had good inter-rater reliability (ICC 0.73-0.77) among both specialties. PGA activity scores showed excellent intra-rater reliability (ICC=0.89) and good intra-rater reliability (ICC=0.76) for dermatologists and rheumatologists, respectively.</p>

<p><strong>LIMITATIONS: </strong>Limitations of this study included the small sample size of patients and potential recall bias during the physician re-rating session.</p>

<p><strong>CONCLUSION: </strong>CLASI activity measurement showed excellent inter- and intra-rater reliability in pediatric CLE and superiority to findings with the PGA. These results demonstrate that the CLASI is a reliable and valid outcome instrument for pediatric CLE. This article is protected by copyright. All rights reserved.</p>

DOI

10.1111/bjd.17012

Alternate Title

Br. J. Dermatol.

PMID

30033560

Title

Variation in Antibiotic Use for Children Hospitalized With Inflammatory Bowel Disease Exacerbation: A Multicenter Validation Study.

Year of Publication

2012

Number of Pages

306-13

Date Published

2012 Dec

ISSN Number

2048-7193

Abstract

<p><strong>BACKGROUND: </strong>Antibiotics are often given for inflammatory bowel disease (IBD) exacerbations, but their use among pediatric inpatients has not been assessed. We aimed to validate administrative data for identifying hospitalizations for IBD exacerbation and to characterize antibiotic use for IBD exacerbations across children's hospitals.</p>

<p><strong>METHODS: </strong>To validate administrative data for identifying IBD exacerbation, we reviewed charts of 409 patients with IBD at 3 US tertiary care children's hospitals. Using the case definition with optimal test characteristics, we identified 3450 children with 5063 hospitalizations for IBD exacerbation at 36 children's hospitals between January 1, 2007 and December 31, 2009, excluding those with diagnosis codes for specific bacterial infections. We estimated predicted and expected hospital-specific antibiotic utilization rates using mixed-effects logistic regression, adjusting for patient- and hospital-level factors.</p>

<p><strong>RESULTS: </strong>Administrative codes for receipt of intravenous steroids or endoscopy provided 79% positive predictive value and 71% sensitivity for identifying hospitalizations for IBD exacerbation. Antibiotics were administered for ≥2 of the first 3 hospital days during 40.7% of IBD exacerbations in US children's hospitals; however, the proportion of patients receiving antibiotics varied significantly across hospitals from 27% to 71% (P&nbsp;&lt;&nbsp;.001), despite adjustment for several patient- and hospital-level variables. Among those given antibiotics, the 3 most common regimens were metronidazole alone (26.9%), metronidazole with ciprofloxacin (10.3%), and ampicillin with gentamicin and metronidazole (7.0%).</p>

<p><strong>CONCLUSIONS: </strong>Significant variability exists in antibiotic use for children hospitalized with IBD exacerbation, which is unexplained by disease severity or hospital volume. Further study should determine the optimal antibiotic therapy for this condition.</p>

DOI

10.1093/jpids/pis053

Alternate Title

J Pediatric Infect Dis Soc

PMID

23687581

Title

Antibiotic exposure and IBD development among children: a population-based cohort study.

Year of Publication

2012

Number of Pages

e794-803

Date Published

2012 Oct

ISSN Number

1098-4275

Abstract

<p><strong>OBJECTIVE: </strong>To determine whether childhood antianaerobic antibiotic exposure is associated with the development of inflammatory bowel disease (IBD).</p>

<p><strong>METHODS: </strong>This retrospective cohort study employed data from 464 UK ambulatory practices participating in The Health Improvement Network. All children with ≥ 2 years of follow-up from 1994 to 2009 were followed between practice enrollment and IBD development, practice deregistration, 19 years of age, or death; those with previous IBD were excluded. All antibiotic prescriptions were captured. Antianaerobic antibiotic agents were defined as penicillin, amoxicillin, ampicillin, penicillin/β-lactamase inhibitor combinations, tetracyclines, clindamycin, metronidazole, cefoxitin, carbapenems, and oral vancomycin.</p>

<p><strong>RESULTS: </strong>A total of 1072426 subjects contributed 6.6 million person-years of follow-up; 748 developed IBD. IBD incidence rates among antianaerobic antibiotic unexposed and exposed subjects were 0.83 and 1.52/10000 person-years, respectively, for an 84% relative risk increase. Exposure throughout childhood was associated with developing IBD, but this relationship decreased with increasing age at exposure. Exposure before 1 year of age had an adjusted hazard ratio of 5.51 (95% confidence interval [CI]: 1.66-18.28) but decreased to 2.62 (95% CI: 1.61-4.25) and 1.57 (95% CI: 1.35-1.84) by 5 and 15 years, respectively. Each antibiotic course increased the IBD hazard by 6% (4%-8%). A dose-response effect existed, with receipt of &gt;2 antibiotic courses more highly associated with IBD development than receipt of 1 to 2 courses, with adjusted hazard ratios of 4.77 (95% CI: 2.13-10.68) versus 3.33 (95% CI: 1.69-6.58).</p>

<p><strong>CONCLUSIONS: </strong>Childhood antianaerobic antibiotic exposure is associated with IBD development.</p>

DOI

10.1542/peds.2011-3886

Alternate Title

Pediatrics

PMID

23008454

Title

IL1RN coding variant is associated with lower risk of acute respiratory distress syndrome and increased plasma IL-1 receptor antagonist.

Year of Publication

2013

Number of Pages

950-9

Date Published

2013 May 1

ISSN Number

1535-4970

Abstract

<p><strong>RATIONALE: </strong>Acute respiratory distress syndrome (ARDS) behaves as a complex genetic trait, yet knowledge of genetic susceptibility factors remains incomplete.</p>

<p><strong>OBJECTIVES: </strong>To identify genetic risk variants for ARDS using large scale genotyping.</p>

<p><strong>METHODS: </strong>A multistage genetic association study was conducted of three critically ill populations phenotyped for ARDS. Stage I, a trauma cohort study (n = 224), was genotyped with a 50K gene-centric single-nucleotide polymorphism (SNP) array. We tested SNPs associated with ARDS at P &lt; 5 × 10(-4) for replication in stage II, a trauma case-control population (n = 778). SNPs replicating their association in stage II (P &lt; 0.005) were tested in a stage III nested case-control population of mixed subjects in the intensive care unit (n = 2,063). Logistic regression was used to adjust for potential clinical confounders. We performed ELISA to test for an association between ARDS-associated genotype and plasma protein levels.</p>

<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>A total of 12 SNPs met the stage I threshold for an association with ARDS. rs315952 in the IL1RN gene encoding IL-1 receptor antagonist (IL1RA) replicated its association with reduced ARDS risk in stages II (P &lt; 0.004) and III (P &lt; 0.02), and was robust to clinical adjustment (combined odds ratio = 0.81; P = 4.2 × 10(-5)). Plasma IL1RA level was associated with rs315952C in a subset of critically ill subjects. The effect of rs315952 was independent from the tandem repeat variant in IL1RN.</p>

<p><strong>CONCLUSIONS: </strong>The IL1RN SNP rs315952C is associated with decreased risk of ARDS in three populations with heterogeneous ARDS risk factors, and with increased plasma IL1RA response. IL1RA may attenuate ARDS risk.</p>

DOI

10.1164/rccm.201208-1501OC

Alternate Title

Am. J. Respir. Crit. Care Med.

PMID

23449693

Title

Gastric Acid Suppressant Prophylaxis in Pediatric Intensive Care: Current Practice as Reflected in a Large Administrative Database.

Year of Publication

2015

Number of Pages

605-12

Date Published

2015 Sep

ISSN Number

1529-7535

Abstract

<p><strong>OBJECTIVES: </strong>Stress-related gastrointestinal bleeding may occur in PICU patients. Raising gastric pH with acid suppressant medications is the accepted treatment. We describe the use of histamine 2 receptor blockers and proton pump inhibitors and associated factors among a national sample of PICU patients.</p>

<p><strong>DESIGN: </strong>Retrospective cohort analysis using Pediatric Health Information System clinically detailed administrative database.</p>

<p><strong>SETTING: </strong>Forty-two children's hospitals throughout the United States.</p>

<p><strong>PATIENTS: </strong>All hospitalizations for all patients 20 years old or younger, admitted directly to a PICU, from January 1, 2007, through December 31, 2011.</p>

<p><strong>INTERVENTIONS: </strong>None.</p>

<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>The exposure of interest was treatment with a histamine 2 receptor blocker, proton pump inhibitor, or both on the first day of PICU admission. Demographics, principal and additional diagnoses, and procedure codes were assessed. For each hospitalization, principal diagnosis, coagulation disorder, head trauma, spinal trauma, severe burns, sepsis, gastrointestinal hemorrhage, mechanical ventilation, blood product transfusion, and 10 complex chronic conditions were identified. The frequency of principal diagnoses was determined to identify the most prevalent PICU diseases. Acid suppressant use was categorized as high or low. Three hundred and thirty-six thousand ten inpatient hospitalizations were sampled. Histamine 2 receptor blocker or proton pump inhibitor was used in 60.0%, with histamine 2 receptor blocker alone in 70.4%, proton pump inhibitor alone in 17.8%, and both agents in 11.8%. Use increased over the sample years 2007 through 2011. Gastrointestinal bleeding occurred in 1.32% of hospitalizations with transfusion needed in 0.1%. Among most prevalent diagnoses, histamine 2 receptor blocker and proton pump inhibitor use ranged from 33% to 87%. Sepsis, coagulopathy, and mechanical ventilation identified higher use. Use of histamine 2 receptor blocker or proton pump inhibitor among hospitals varied considerably ranging from 28% to 87%.</p>

<p><strong>CONCLUSIONS: </strong>Histamine 2 receptor blocker and proton pump inhibitor are prescribed in most PICU patients, but significant variation exists across health conditions and hospitals. Institutional preferences likely influence variation. Gastrointestinal hemorrhage is infrequent in the current era. Study data limitations prevent examination of associations between medication use and patient outcomes.</p>

DOI

10.1097/PCC.0000000000000427

Alternate Title

Pediatr Crit Care Med

PMID

25901549

Title

Oxidant stress regulatory genetic variation in recipients and donors contributes to risk of primary graft dysfunction after lung transplantation.

Year of Publication

2015

Number of Pages

596-602

Date Published

02/2015

ISSN Number

1097-685X

Abstract

<p><strong>OBJECTIVE: </strong>Oxidant stress pathway activation during ischemia reperfusion injury may contribute to the development of primary graft dysfunction (PGD) after lung transplantation. We hypothesized that oxidant stress gene variation in recipients and donors is associated with PGD.</p>

<p><strong>METHODS: </strong>Donors and recipients from the Lung Transplant Outcomes Group (LTOG) cohort were genotyped using the Illumina IBC chip filtered for oxidant stress pathway genes. Single nucleotide polymorphisms (SNPs) grouped into SNP sets based on haplotype blocks within 49 oxidant stress genes selected from gene ontology pathways and literature review were tested for PGD association using a sequencing kernel association test. Analyses were adjusted for clinical confounding variables and population stratification.</p>

<p><strong>RESULTS: </strong>Three hundred ninety-two donors and 1038 recipients met genetic quality control standards. Thirty percent of patients developed grade 3 PGD within 72 hours. Donor NADPH oxidase 3 (NOX3) was associated with PGD (P = .01) with 5 individual significant loci (P values between .006 and .03). In recipients, variation in glutathione peroxidase (GPX1) and NRF-2 (NFE2L2) was significantly associated with PGD (P = .01 for both). The GPX1 association included 3 individual loci (P values between .006 and .049) and the NFE2L2 association included 2 loci (P = .03 and .05). Significant epistatic effects influencing PGD susceptibility were evident between 3 different donor blocks of NOX3 and recipient NFE2L2 (P = .026, P = .017, and P = .031).</p>

<p><strong>CONCLUSIONS: </strong>Our study has prioritized GPX1, NOX3, and NFE2L2 genes for future research in PGD pathogenesis, and highlights a donor-recipient interaction of NOX3 and NFE2L2 that increases the risk of PGD.</p>

DOI

10.1016/j.jtcvs.2014.09.077

Alternate Title

J. Thorac. Cardiovasc. Surg.

PMID

25439478

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