Publications by authors named "Judith Ju Ming Wong"

25 Publications

  • Page 1 of 1

Large scale cytokine profiling uncovers elevated IL12-p70 and IL-17A in severe pediatric acute respiratory distress syndrome.

Sci Rep 2021 Jul 8;11(1):14158. Epub 2021 Jul 8.

KK Research Centre, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore, 229899, Singapore.

The specific cytokines that regulate pediatric acute respiratory distress syndrome (PARDS) pathophysiology remains unclear. Here, we evaluated the respiratory cytokine profile in PARDS to identify the molecular signatures associated with severe disease. A multiplex suspension immunoassay was used to profile 45 cytokines, chemokines and growth factors. Cytokine concentrations were compared between severe and non-severe PARDS, and correlated with oxygenation index (OI). Partial least squares regression modelling and regression coefficient plots were used to identify a composite of key mediators that differentially segregated severe from non-severe disease. The mean (standard deviation) age and OI of this cohort was 5.2 (4.9) years and 17.8 (11.3), respectively. Early PARDS patients with severe disease exhibited a cytokine signature that was up-regulated for IL-12p70, IL-17A, MCP-1, IL-4, IL-1β, IL-6, MIP-1β, SCF, EGF and HGF. In particular, pro-inflammatory cytokines (IL-6, MCP-1, IP-10, IL-17A, IL-12p70) positively correlated with OI early in the disease. Whereas late PARDS was characterized by a differential lung cytokine signature consisting of both up-regulated (IL-8, IL-12p70, VEGF-D, IL-4, GM-CSF) and down-regulated (IL-1β, EGF, Eotaxin, IL-1RA, and PDGF-BB) profiles segregating non-severe and severe groups. This cytokine signature was associated with increased transcription, T cell activation and proliferation as well as activation of mitogen-activated protein kinase pathway that underpin PARDS severity.
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http://dx.doi.org/10.1038/s41598-021-93705-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266860PMC
July 2021

Comparative Analysis of Pediatric COVID-19 Infection in Southeast Asia, South Asia, Japan, and China.

Am J Trop Med Hyg 2021 Jun 15. Epub 2021 Jun 15.

Duke-NUS Medical School, Singapore.

There is a scarcity of data regarding coronavirus disease 2019 (COVID-19) infection in children from southeast and south Asia. This study aims to identify risk factors for severe COVID-19 disease among children in the region. This is an observational study of children with COVID-19 infection in hospitals contributing data to the Pediatric Acute and Critical Care COVID-19 Registry of Asia. Laboratory-confirmed COVID-19 cases were included in this registry. The primary outcome was severity of COVID-19 infection as defined by the World Health Organization (WHO) (mild, moderate, severe, or critical). Epidemiology, clinical and laboratory features, and outcomes of children with COVID-19 are described. Univariate and multivariable logistic regression models were used to identify risk factors for severe/critical disease. A total of 260 COVID-19 cases from eight hospitals across seven countries (China, Japan, Singapore, Malaysia, Indonesia, India, and Pakistan) were included. The common clinical manifestations were similar across countries: fever (64%), cough (39%), and coryza (23%). Approximately 40% of children were asymptomatic, and overall mortality was 2.3%, with all deaths reported from India and Pakistan. Using the multivariable model, the infant age group, presence of comorbidities, and cough on presentation were associated with severe/critical COVID-19. This epidemiological study of pediatric COVID-19 infection demonstrated similar clinical presentations of COVID-19 in children across Asia. Risk factors for severe disease in children were age younger than 12 months, presence of comorbidities, and cough at presentation. Further studies are needed to determine whether differences in mortality are the result of genetic factors, cultural practices, or environmental exposures.
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http://dx.doi.org/10.4269/ajtmh.21-0299DOI Listing
June 2021

High burden of acquired morbidity in survivors of pediatric acute respiratory distress syndrome.

Pediatr Pulmonol 2021 Aug 8;56(8):2769-2775. Epub 2021 Jun 8.

Children's Intensive Care Unit, Department of Pediatric Subspecialties, KK Women's and Children's Hospital, Singapore, Singapore.

Introduction: With improving mortality rates in pediatric acute respiratory distress syndrome (PARDS), functional outcomes in survivors are increasingly important. We aim to describe the change in functional status score (FSS) from baseline to discharge and to identify risk factors associated with poor functional outcomes.

Methods: We examined clinical records of patients with PARDS admitted to our pediatric intensive care unit (PICU) from 2009 to 2016. Our primary outcome was acquired morbidity at PICU and hospital discharge (defined by an increase in FSS ≥3 points above baseline). We included severity of illness scores and severity of PARDS in our bivariate analysis for risk factors for acquired morbidity.

Results: There were 181 patients with PARDS, of which 90 (49.7%) survived. Median pediatric index of mortality 2 score was 4.05 (1.22, 8.70) and 21 (23.3%) survivors had severe PARDS. A total of 59 (65.6%) and 14 (15.6%) patients had acquired morbidity at PICU and hospital discharge, respectively. Median baseline FSS was 6.00 (6.00, 6.25), which increased to 11.00 (8.75, 12.00) at PICU discharge before decreasing to 7.50 (6.00, 9.25) at hospital discharge. All patients had significantly higher FSS at both PICU and hospital discharge median compared to baseline. Feeding and respiratory were the most affected domains. After adjusting for severity of illness, severity categories of PARDS were not a risk factor for acquired morbidity.

Conclusion: Acquired morbidity in respiratory and feeding domains was common in PARDS survivors. Specific attention should be given to these two domains of functional outcomes in these children.
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http://dx.doi.org/10.1002/ppul.25520DOI Listing
August 2021

Pediatric Severe Sepsis and Shock in Three Asian Countries: A Retrospective Study of Outcomes in Nine PICUs.

Pediatr Crit Care Med 2021 Mar 1. Epub 2021 Mar 1.

1 Division of Pediatric Critical Care, Department of Pediatrics, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. 2 Department of Pediatrics, KK Women's and Children's Hospital, Singapore. 3 Hat Yai Medical Center, Division of Pediatric Pulmonary & Critical care, Department of Pediatrics, Songkhla Province, Thailand. 4 Pediatric Critical Care Division, Department of Pediatrics, Ramathibodi Hospital, Bangkok, Thailand. 5 Division of Pulmonary and Critical Care Unit, Department of Pediatrics, Chiang Mai University, Chiang Mai, Thailand. 6 Pediatric Critical Care Division, Department of Pediatrics, National University, Singapore. 7 Pediatric Intensive Care Unit, Department of Pediatrics, Sarawak General Hospital, Sarawak, Malaysia. 8 Pediatric Intensive Care Unit, Department of Pediatrics, National University of Malaysia, Selangor, Malaysia. 9 Pediatric Critical Care Division, Department of Pediatrics, Siriraj Hospital, Bangkok, Thailand.

Objectives: Pediatric sepsis remains a major health problem and is a leading cause of death and long-term disability worldwide. This study aims to characterize epidemiologic, therapeutic, and outcome features of pediatric severe sepsis and septic shock in three Asian countries.

Design: A multicenter retrospective study with longitudinal clinical data over 1, 6, 24, 48, and 72 hours of PICU admission. The primary outcome was PICU mortality. Multivariable logistic regression analysis was used to identify factors at PICU admission that were associated with mortality SETTING:: Nine multidisciplinary PICUs in three Asian countries.

Patients: Children with severe sepsis or septic shock admitted to the PICU from January to December 2017.

Intervention: None.

Measurement And Main Results: A total of 271 children were included in this study. Median (interquartile range) age was 4.2 years (1.3-10.8 yr). Pneumonia (77/271 [28.4%]) was the most common source of infection. Majority of patients (243/271 [90%]) were resuscitated within the first hour, with fluid bolus (199/271 [73.4%]) or vasopressors (162/271 [59.8%]). Fluid resuscitation commonly took the form of normal saline (147/199 [74.2%]) (20 mL/kg [10-20 mL/kg] over 20 min [15-30 min]). The most common inotrope used was norepinephrine 81 of 162 (50.0%). Overall PICU mortality was 52 of 271 (19.2%). Improved hemodynamic variables (e.g., heart rate, blood pressure, and arterial lactate) were seen in survivors within 6 hours of admission as compared to nonsurvivors. In the multivariable model, admission severity score was associated with PICU mortality.

Conclusions: Mortality from pediatric severe sepsis and septic shock remains high in Asia. Consistent with current guidelines, most of the children admitted to these PICUs received fluid therapy and inotropic support as recommended.
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http://dx.doi.org/10.1097/PCC.0000000000002680DOI Listing
March 2021

Reassessing the Use of Proton Pump Inhibitors and Histamine-2 Antagonists in Critically Ill Children: A Systematic Review and Meta-Analysis.

J Pediatr 2021 01 9;228:164-176.e7. Epub 2020 Sep 9.

Duke-NUS Medical School, Singapore; Children's Intensive Care Unit, KK Women's and Children's Hospital, Singapore.

Objective: To determine the associations of stress ulcer prophylaxis with gastrointestinal (GI) bleeding, nosocomial pneumonia (NP), mortality, and length of stay in the pediatric intensive care unit (PICU).

Study Design: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies in the English language assessing the effects of proton pump inhibitors and histamine-2 receptor antagonists on patients in the PICU published before October 2018 from the PubMed, Embase, CINAHL, and Cochrane Central Register of Controlled Trials databases. A random-effects Mantel-Haenszel risk difference (MHRD) model was used to pool all the selected studies for meta-analysis. Primary outcomes were the incidences of GI bleeding and NP. Secondary outcomes included mortality and length of PICU stay.

Results: Seventeen studies (4 RCTs and 13 observational studies) with a total of 340 763 patients were included. The overall incidence of GI bleeding was 15.2%. There was no difference in the risk of GI bleeding based on stress ulcer prophylaxis status (MHRD, 5.0%; 95% CI, -1.0% to 11.0%; I = 62%). There was an increased risk of NP in patients who received stress ulcer prophylaxis compared with those who did not (MHRD, 5.3%; 95% CI, 3.5%-7.0%; I = 0%). An increased risk of mortality was seen in patients receiving stress ulcer prophylaxis (MHRD, 2.1%; 95% CI, 2.0%-2.2%; I = 0%), although this association was no longer found when 1 large study was removed in a sensitivity analysis. There was no statistically significant difference in length of PICU stay between the groups (standardized mean difference, 0.42 days; 95% CI, -0.16 to 1.01 days; I = 89.8%).

Conclusions: Stress ulcer prophylaxis does not show a clear benefit in reducing GI bleeding or length of PICU stay. Observational studies suggest an increased risk of NP and mortality with stress ulcer prophylaxis, which remains to be validated in clinical trials.
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http://dx.doi.org/10.1016/j.jpeds.2020.09.011DOI Listing
January 2021

The authors reply.

Pediatr Crit Care Med 2020 09;21(9):855-856

Children's Intensive Care Unit, KK Women's and Children's Hospital, Singapore.

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http://dx.doi.org/10.1097/PCC.0000000000002446DOI Listing
September 2020

Prediction of Acquired Morbidity Using Illness Severity Indices in Pediatric Intensive Care Patients.

Pediatr Crit Care Med 2020 11;21(11):e972-e980

Duke-NUS Medical School, Singapore.

Objectives: To assess the ability of two illness severity scores, Pediatric Logistic Organ Dysfunction Score 2 and Pediatric Index of Mortality 3, in predicting PICU-acquired morbidity.

Design: Retrospective chart review conducted from April 2015 to March 2016.

Setting: Single-center study in a multidisciplinary PICU in a tertiary pediatric hospital in Singapore.

Patients: The study included all index admissions of patients 0-18 years old to the PICU during the study period.

Interventions: None.

Measurements And Main Results: Three outcomes were assessed at hospital discharge: mortality, survival with new morbidity defined as an increase in the Functional Status Scale score of greater than or equal to 3 points from baseline, and survival without morbidity. Of 577 consecutive admissions, 95 were excluded: 82 readmissions, 10 patients greater than or equal to 18 years old, two patients with missing baseline data, and one transferred to another PICU. Of 482 patients, there were 37 hospital deaths (7.7%) and 39 (8.1%) with acquired new morbidity. Median admission Pediatric Logistic Organ Dysfunction Score 2 and Pediatric Index of Mortality 3 scores differed among the three outcome groups. In addition, differences were found in emergency admission and neurologic diagnosis rates, PICU mechanical ventilation usage rates, and PICU length of stay. The highest proportion of neurologic diagnoses was observed in the new morbidity group. The final model simultaneously predicted risks of mortality, survival with new morbidity and survival without morbidity using admission Pediatric Logistic Organ Dysfunction Score 2 score, admission type, neurologic diagnosis, and preexisting chronic disease. Pediatric Logistic Organ Dysfunction Score 2 was superior to Pediatric Index of Mortality 3 in predicting risks of mortality and new morbidity, as indicated by volume under surface values of 0.483 and 0.362, respectively.

Conclusions: Risk of mortality, survival with new morbidity, and survival without morbidity can be predicted simultaneously using admission Pediatric Logistic Organ Dysfunction Score 2, admission type, admission diagnosis, and preexisting chronic disease. Future independent studies will be required to validate the proposed model before clinical implementation.
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http://dx.doi.org/10.1097/PCC.0000000000002417DOI Listing
November 2020

Lung-Protective Mechanical Ventilation Strategies in Pediatric Acute Respiratory Distress Syndrome.

Pediatr Crit Care Med 2020 08;21(8):720-728

Children's Intensive Care Unit, Department of Pediatric Subspecialties, KK Women's and Children's Hospital, Singapore.

Objectives: Reduced morbidity and mortality associated with lung-protective mechanical ventilation is not proven in pediatric acute respiratory distress syndrome. This study aims to determine if a lung-protective mechanical ventilation protocol in pediatric acute respiratory distress syndrome is associated with improved clinical outcomes.

Design: This pilot study over April 2016 to September 2019 adopts a before-and-after comparison design of a lung-protective mechanical ventilation protocol. All admissions to the PICU were screened daily for fulfillment of the Pediatric Acute Lung Injury Consensus Conference criteria and included.

Setting: Multidisciplinary PICU.

Patients: Patients with pediatric acute respiratory distress syndrome.

Interventions: Lung-protective mechanical ventilation protocol with elements on peak pressures, tidal volumes, end-expiratory pressure to FIO2 combinations, permissive hypercapnia, and permissive hypoxemia.

Measurements And Main Results: Ventilator and blood gas data were collected for the first 7 days of pediatric acute respiratory distress syndrome and compared between the protocol (n = 63) and nonprotocol groups (n = 69). After implementation of the protocol, median tidal volume (6.4 mL/kg [5.4-7.8 mL/kg] vs 6.0 mL/kg [4.8-7.3 mL/kg]; p = 0.005), PaO2 (78.1 mm Hg [67.0-94.6 mm Hg] vs 74.5 mm Hg [59.2-91.1 mm Hg]; p = 0.001), and oxygen saturation (97% [95-99%] vs 96% [94-98%]; p = 0.007) were lower, and end-expiratory pressure (8 cm H2O [7-9 cm H2O] vs 8 cm H2O [8-10 cm H2O]; p = 0.002] and PaCO2 (44.9 mm Hg [38.8-53.1 mm Hg] vs 46.4 mm Hg [39.4-56.7 mm Hg]; p = 0.033) were higher, in keeping with lung protective measures. There was no difference in mortality (10/63 [15.9%] vs 18/69 [26.1%]; p = 0.152), ventilator-free days (16.0 [2.0-23.0] vs 19.0 [0.0-23.0]; p = 0.697), and PICU-free days (13.0 [0.0-21.0] vs 16.0 [0.0-22.0]; p = 0.233) between the protocol and nonprotocol groups. After adjusting for severity of illness, organ dysfunction and oxygenation index, the lung-protective mechanical ventilation protocol was associated with decreased mortality (adjusted hazard ratio, 0.37; 95% CI, 0.16-0.88).

Conclusions: In pediatric acute respiratory distress syndrome, a lung-protective mechanical ventilation protocol improved adherence to lung-protective mechanical ventilation strategies and potentially mortality.
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http://dx.doi.org/10.1097/PCC.0000000000002324DOI Listing
August 2020

Critical illness epidemiology and mortality risk in pediatric oncology.

Pediatr Blood Cancer 2020 06 18;67(6):e28242. Epub 2020 Mar 18.

Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Objective: Pediatric oncology patients admitted to the pediatric intensive care unit (PICU) are at high risk of mortality. This study aims to describe the epidemiology of and the risk factors for mortality in these patients.

Study Design: This is a retrospective cohort study including all consecutive PICU oncology admissions from 2011 to 2017. Demographic and clinical risk factors between survivors and nonsurvivors were compared. Both univariate and multivariate Cox proportional hazard regression models were used to quantify the association between 60-day mortality and admission categories, accounting for other covariates (Pediatric Risk Of Mortality [PRISM] III score and previous bacteremia).

Main Outcome Measures: The primary outcome was 60-day mortality.

Results: The median (interquartile range) age and PRISM III scores of pediatric oncology patients admitted to the PICU were 7 (3, 12) years and 3 (0, 5), respectively. The most common underlying oncological diagnoses were brain tumors (73/200 [36.5%]) and acute lymphoblastic leukemia (36/200 [18.0%]). Emergency admissions accounted for approximately half of all admissions (108/200 [54.0%]), including cardiovascular (24/108 [22.2%]), neurology (24/108 [22.2%]), respiratory (22/108 [20.4%]), and "other" indications (38/108 [35.2%]). The overall 60-day mortality was 35 of 200 (17.5%). Independent risk factors for mortality were emergency respiratory and neurology categories of admission (adjusted hazard ratio[aHR]: 5.62, 95% confidence interval [95% CI]: 1.57, 20.19; P = .008 and aHR: 6.96, 95% CI: 2.04, 23.75; P = .002, respectively) and previous bacteremia (aHR: 3.37, 95% CI: 1.57, 7.20; P = .002).

Conclusion: Emergency respiratory and neurology admissions and previous bacteremia were independent risk factors for 60-day mortality for pediatric oncological patients admitted to the PICU.
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http://dx.doi.org/10.1002/pbc.28242DOI Listing
June 2020

Characteristics and trajectory of patients with pediatric acute respiratory distress syndrome.

Pediatr Pulmonol 2020 04 3;55(4):1000-1006. Epub 2020 Feb 3.

Children's Intensive Care Unit, KK Women's and Children's Hospital, Singapore.

Objective: This study delineates the disease trajectory of patients with pediatric acute respiratory distress syndrome (PARDS) defined by the Pediatric Acute Lung Injury Consensus Conference (PALICC) definition, and evaluates the impact of comorbidities on outcomes.

Methods: This prospective study over November 2017-October 2019 was conducted in a single-center multidisciplinary pediatric intensive care unit (PICU) and included patients <21years of age with PARDS. Clinical history of those requiring mechanical ventilation for <3 days was interrogated and cases in which the diagnosis of PARDS were unlikely, identified. The impact of chronic comorbidities on clinical outcomes, in particular, pulmonary disease and immunosuppression, were analyzed.

Results: Eighty-five of 1272 PICU admissions (6.7%) met the criteria for PARDS and were included. Median age and oxygenation indexes were 2.8 (0.6, 8.3) years and 10.6 (7.6, 15.4), respectively. Overall mortality was 12 out of 85 (14.1%). Despite fulfilling criteria in 6/85 (7.1%), hypoxemia contributed by bronchospasm, mucus plugging, fluid overload, and atelectasis was quickly reversible and PARDS was unlikely in these patients. Comorbidities (57/85 [67.1%]) were not associated with worsened outcomes. However, pre-existing pulmonary disease and immunosuppression were associated with severe PARDS (12/20 [60.0%] vs 19/65 [29.2%]; P = .017), extracorporeal membrane oxygenation use (5/20 [25.0%] vs 3/65 [4.6%]; P = .016) and reduced ventilator free days (VFD) (15 [0, 19] vs 21 [6, 23]; P = .039), compared with those without them.

Conclusion: A small percentage of children fulfilling the PALICC definition had quickly reversible hypoxemia with likely alternate pathophysiology to PARDS. Patients with pulmonary comorbidities and immunosuppression had a more severe course of PARDS compared with others.
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http://dx.doi.org/10.1002/ppul.24674DOI Listing
April 2020

The impact of high frequency oscillatory ventilation on mortality in paediatric acute respiratory distress syndrome.

Crit Care 2020 01 31;24(1):31. Epub 2020 Jan 31.

Children's Intensive Care Unit, Department of Pediatric Subspecialties, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore, 229899, Singapore.

Background: High-frequency oscillatory ventilation (HFOV) use was associated with greater mortality in adult acute respiratory distress syndrome (ARDS). Nevertheless, HFOV is still frequently used as rescue therapy in paediatric acute respiratory distress syndrome (PARDS). In view of the limited evidence for HFOV in PARDS and evidence demonstrating harm in adult patients with ARDS, we hypothesized that HFOV use compared to other modes of mechanical ventilation is associated with increased mortality in PARDS.

Methods: Patients with PARDS from 10 paediatric intensive care units across Asia from 2009 to 2015 were identified. Data on epidemiology and clinical outcomes were collected. Patients on HFOV were compared to patients on other modes of ventilation. The primary outcome was 28-day mortality and secondary outcomes were 28-day ventilator- (VFD) and intensive care unit- (IFD) free days. Genetic matching (GM) method was used to analyse the association between HFOV treatment with the primary outcome. Additionally, we performed a sensitivity analysis, including propensity score (PS) matching, inverse probability of treatment weighting (IPTW) and marginal structural modelling (MSM) to estimate the treatment effect.

Results: A total of 328 patients were included. In the first 7 days of PARDS, 122/328 (37.2%) patients were supported with HFOV. There were significant differences in baseline oxygenation index (OI) between the HFOV and non-HFOV groups (18.8 [12.0, 30.2] vs. 7.7 [5.1, 13.1] respectively; p < 0.001). A total of 118 pairs were matched in the GM method which found a significant association between HFOV with 28-day mortality in PARDS [odds ratio 2.3, 95% confidence interval (CI) 1.3, 4.4, p value 0.01]. VFD was indifferent between the HFOV and non-HFOV group [mean difference - 1.3 (95%CI - 3.4, 0.9); p = 0.29] but IFD was significantly lower in the HFOV group [- 2.5 (95%CI - 4.9, - 0.5); p = 0.03]. From the sensitivity analysis, PS matching, IPTW and MSM all showed consistent direction of HFOV treatment effect in PARDS.

Conclusion: The use of HFOV was associated with increased 28-day mortality in PARDS. This study suggests caution but does not eliminate equivocality and a randomized controlled trial is justified to examine the true association.
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http://dx.doi.org/10.1186/s13054-020-2741-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995130PMC
January 2020

Insights into the immuno-pathogenesis of acute respiratory distress syndrome.

Ann Transl Med 2019 Oct;7(19):504

Translational Immunology Institute, Singhealth/Duke-NUS Academic Medical Centre, Singapore.

Acute respiratory distress syndrome (ARDS) is a clinical syndrome associated with oxygenation failure resulting from a direct pulmonary or indirect systemic insult. It is a complex etiological phenomenon involving an array of immune cells acting in a delicate balance between pathogen clearance and immunopathology. There is emerging evidence of the involvement of different immune cell types in ARDS pathogenesis. This includes polarization of alveolar macrophages (AMs), neutrophil netosis, the pro-inflammatory response of T helper 17 subsets, and the anti-inflammatory and regenerative role of T regulatory cell subsets. Knowledge of these pathogenic mechanisms has led to translational opportunities, for example, research in the use of methylprednisolone, DNAse, aspirin, keratinocyte growth factor and in the development of stem cell therapy for ARDS. Discovering subgroups of patients with ARDS afflicted with homogenous pathologic mechanisms can provide prognostic and/or predictive insight that will enable precision medicine. Lastly, new high dimensional immunomic technologies are promising tools in evaluating the host immune response in ARDS and will be discussed in this review.
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http://dx.doi.org/10.21037/atm.2019.09.28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828790PMC
October 2019

The Impact of Pre-operative Nutritional Status on Outcomes Following Congenital Heart Surgery.

Front Pediatr 2019 23;7:429. Epub 2019 Oct 23.

Children's Intensive Care Unit, Department of Pediatric Subspecialties, KK Women's and Children's Hospital, Singapore, Singapore.

Malnutrition is common in children with congenital heart disease and may contribute to adverse outcomes. This study evaluates the impact of pre-operative nutritional status on outcomes after congenital heart surgery. We conducted a retrospective cohort study enrolling children under 10 years old who underwent congenital heart surgery at a tertiary children's hospital from 2012 to 2016. Patients who had patent ductus arteriosus ligation only, genetic syndromes, or global developmental delay were excluded. Outcome measures included 30-day mortality, intensive care unit (ICU) length of stay (LOS), hospital LOS, duration of mechanical ventilation, and number of inotropes used post-operatively. We performed univariate/multivariable logistic regression analysis, adjusting for age, cyanotic cardiac lesion, co-morbidity, and Risk Adjustment for Congenital Heart Surgery (RACHS-1) score. Three hundred two children of median age 16.2 [interquartile range (IQR) 3.1, 51.4)] months were included. The most common cardiac lesions were ventricular septal defect (27.8%), atrial septal defect (17.9%), and Tetralogy of Fallot (16.6%). Median weight-for-age z-score (WAZ) was -1.46 (IQR -2.29, -0.61), height-for-age z-score (HAZ) was -0.94 (IQR -2.10, -0.10), and body mass index (BMI)-for-age z-score (BAZ) was -1.11 (IQR -2.19, -0.30). In multivariable analysis, there was an increased risk of 30-day mortality for WAZ ≤-2 vs. WAZ >-2 [adjusted odds ratio (aOR): 4.01, 95% CI: 1.22, 13.13; = 0.022]. For HAZ ≤-2 vs. HAZ > -2, there was increased risk of hospital LOS ≥ 7 days (aOR: 2.08, 95% CI: 1.12, 3.89; = 0.021), mechanical ventilation ≥48 h (aOR: 2.63, 95% CI: 1.32, 5.24; = 0.006) and of requiring ≥3 inotropes post-operatively (aOR: 3.00, 95% CI: 1.37, 6.59; = 0.006). In children undergoing congenital heart surgery, WAZ ≤ -2 is associated with higher 30-day mortality, while HAZ ≤ -2 is associated with longer durations of hospital LOS and mechanical ventilation, and increased risk of use of 3 or more inotropes post-operatively. Future studies are necessary to develop safe and efficacious peri-operative nutritional interventions, particularly in patients with WAZ and HAZ ≤ -2.
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http://dx.doi.org/10.3389/fped.2019.00429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820300PMC
October 2019

Global Case-Fatality Rates in Pediatric Severe Sepsis and Septic Shock: A Systematic Review and Meta-analysis.

JAMA Pediatr 2019 04;173(4):352-362

Duke-NUS Medical School, Singapore.

Importance: The global patterns and distribution of case-fatality rates (CFRs) in pediatric severe sepsis and septic shock remain poorly described.

Objective: We performed a systematic review and meta-analysis of studies of children with severe sepsis and septic shock to elucidate the patterns of CFRs in developing and developed countries over time. We also described factors associated with CFRs.

Data Sources: We searched PubMed, Web of Science, Excerpta Medica database, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Cochrane Central systematically for randomized clinical trials and prospective observational studies from earliest publication until January 2017, using the keywords "pediatric," "sepsis," "septic shock," and "mortality."

Study Selection: Studies involving children with severe sepsis and septic shock that reported CFRs were included. Retrospective studies and studies including only neonates were excluded.

Data Extraction And Synthesis: We conducted our systematic review and meta-analysis in close accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled case-fatality estimates were obtained using random-effects meta-analysis. The associations of study period, study design, sepsis severity, age, and continents in which studies occurred were assessed with meta-regression.

Main Outcomes And Measures: Meta-analyses to provide pooled estimates of CFR of pediatric severe sepsis and septic shock over time.

Results: Ninety-four studies that included 7561 patients were included. Pooled CFRs were higher in developing countries (31.7% [95% CI, 27.3%-36.4%]) than in developed countries (19.3% [95% CI, 16.4%-22.7%]; P < .001). Meta-analysis of CFRs also showed significant heterogeneity across studies. Continents that include mainly developing countries reported higher CFRs (adjusted odds ratios: Africa, 7.89 [95% CI, 6.02-10.32]; P < .001; Asia, 3.81 [95% CI, 3.60-4.03]; P < .001; South America, 2.91 [95% CI, 2.71-3.12]; P < .001) than North America. Septic shock was associated with higher CFRs than severe sepsis (adjusted odds ratios, 1.47 [95% CI, 1.41-1.54]). Younger age was also a risk factor (adjusted odds ratio, 0.95 [95% CI, 0.94-0.96] per year of increase in age). Earlier study eras were associated with higher CFRs (adjusted odds ratios for 1991-2000, 1.24 [95% CI, 1.13-1.37]; P < .001) compared with 2011 to 2016. Time-trend analysis showed higher CFRs over time in developing countries than developed countries.

Conclusions And Relevance: Despite the declining trend of pediatric severe sepsis and septic shock CFRs, the disparity between developing and developed countries persists. Further characterizations of vulnerable populations and collaborations between developed and developing countries are warranted to reduce the burden of pediatric sepsis globally.
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http://dx.doi.org/10.1001/jamapediatrics.2018.4839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450287PMC
April 2019

Differences Between Pulmonary and Extrapulmonary Pediatric Acute Respiratory Distress Syndrome: A Multicenter Analysis.

Pediatr Crit Care Med 2018 10;19(10):e504-e513

Children's Intensive Care Unit, Department of Pediatric Subspecialties, KK Women's and Children's Hospital, Singapore.

Objectives: Extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome are poorly described in the literature. We aimed to describe and compare the epidemiology, risk factors for mortality, and outcomes in extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome.

Design: This is a secondary analysis of a multicenter, retrospective, cohort study. Data on epidemiology, ventilation, therapies, and outcomes were collected and analyzed. Patients were classified into two mutually exclusive groups (extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome) based on etiologies. Primary outcome was PICU mortality. Cox proportional hazard regression was used to identify risk factors for mortality.

Setting: Ten multidisciplinary PICUs in Asia.

Patients: Mechanically ventilated children meeting the Pediatric Acute Lung Injury Consensus Conference criteria for pediatric acute respiratory distress syndrome between 2009 and 2015.

Interventions: None.

Measurements And Main Results: Forty-one of 307 patients (13.4%) and 266 of 307 patients (86.6%) were classified into extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome groups, respectively. The most common causes for extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome were sepsis (82.9%) and pneumonia (91.7%), respectively. Children with extrapulmonary pediatric acute respiratory distress syndrome were older, had higher admission severity scores, and had a greater proportion of organ dysfunction compared with pulmonary pediatric acute respiratory distress syndrome group. Patients in the extrapulmonary pediatric acute respiratory distress syndrome group had higher mortality (48.8% vs 24.8%; p = 0.002) and reduced ventilator-free days (median 2.0 d [interquartile range 0.0-18.0 d] vs 19.0 d [0.5-24.0 d]; p = 0.001) compared with the pulmonary pediatric acute respiratory distress syndrome group. After adjusting for site, severity of illness, comorbidities, multiple organ dysfunction, and severity of acute respiratory distress syndrome, extrapulmonary pediatric acute respiratory distress syndrome etiology was not associated with mortality (adjusted hazard ratio, 1.56 [95% CI, 0.90-2.71]).

Conclusions: Patients with extrapulmonary pediatric acute respiratory distress syndrome were sicker and had poorer clinical outcomes. However, after adjusting for confounders, it was not an independent risk factor for mortality.
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http://dx.doi.org/10.1097/PCC.0000000000001667DOI Listing
October 2018

Changes in Near-Infrared Spectroscopy After Congenital Cyanotic Heart Surgery.

Front Pediatr 2018 13;6:97. Epub 2018 Apr 13.

Children's Intensive Care Unit, Department of Paediatric Subspecialties, KK Women's and Children's Hospital, Singapore, Singapore.

Background: Since oxygen saturation from pulse oximetry (SpO) and partial pressure of arterial oxygen (PaO) are observed to improve immediately after surgical correction of cyanotic congenital heart disease (CHD), we postulate that cerebral (CrO) and somatic (SrO) oximetry also improves immediately post-correction. We aim to prospectively examine CrO and SrO, before, during, and after surgical correction as well as on hospital discharge in children with cyanotic CHD to determine if and when these variables increase.

Methods: This is a prospective observational trial. Eligibility criteria included children below 18 years of age with cyanotic CHD who required any cardiac surgical procedure. CrO and SrO measurements were summarized at six time-points for comparison: (1) pre-cardiopulmonary bypass (CPB); (2) during CPB; (3) post-CPB; (4) Day 1 in the pediatric intensive care unit (PICU); (5) Day 2 PICU; and (6) discharge. Categorical and continuous variables are presented as counts (percentages) and median (interquartile range), respectively.

Results: Twenty-one patients were analyzed. 15 (71.4%) and 6 (28.6%) patients underwent corrective and palliative surgeries, respectively. In the corrective surgery group, SpO increased immediately post-CPB compared to pre-CPB [99 (98, 100) vs. 86% (79, 90);  < 0.001] and remained in the normal range through to hospital discharge. Post-CPB CrO did not change from pre-CPB [72.8 (58.8, 79.0) vs. 72.1% (63.0, 78.3);  = 0.761] and even decreased on hospital discharge [60.5 (53.6, 62.9) vs. 72.1% (63.0, 78.3);  = 0.005]. Post-CPB SrO increased compared to pre-CPB [87.3 (77.2, 89.5) vs. 72.7% (65.6, 77.3);  = 0.001] but progressively decreased during PICU stay to a value lower than baseline at hospital discharge [66.9 (57.3, 76.9) vs. 72.7% (65.6, 77.3);  = 0.048].

Conclusion: CrO and SrO did not increase after corrective surgery of cyanotic CHD even up to hospital discharge. Future larger studies are required to validate these findings. (This study is registered with ClinicalTrials.gov ID: NCT02417259.).
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http://dx.doi.org/10.3389/fped.2018.00097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908891PMC
April 2018

Characteristics and Outcomes of Long-Stay Patients in the Pediatric Intensive Care Unit.

J Pediatr Intensive Care 2018 Mar 20;7(1):1-6. Epub 2017 Mar 20.

Children's Intensive Care Unit, Department of Pediatric Subspecialties, KK Women's and Children's Hospital, Singapore.

Long-stay patients in the PICU have a higher risk of mortality as compared with non-long-stay patients. We aim to describe mortality and characteristics of long-stay patients and to determine the risk factors for mortality in these children. Total 241 (4.8%) long-stay admissions were identified. Mortality of long-stayers was 48/241 (20%). Higher severity-of-illness score at admission, need for organ support therapies, number of nosocomial infections, and bloodstream nosocomial infection were associated with a higher mortality in long-stay patients in the PICU. Based on multivariate analysis, oncologic diagnosis as a preexisting comorbidity is a strong independent predictor of mortality for long-stay patients.
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http://dx.doi.org/10.1055/s-0037-1601337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260322PMC
March 2018

Establishing the entity of neonatal acute respiratory distress syndrome.

J Thorac Dis 2017 Nov;9(11):4244-4247

Children's Intensive Care Unit, KK Women's and Children's Hospital, Singapore.

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http://dx.doi.org/10.21037/jtd.2017.10.64DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721011PMC
November 2017

Risk Stratification in Pediatric Acute Respiratory Distress Syndrome: A Multicenter Observational Study.

Crit Care Med 2017 Nov;45(11):1820-1828

1Children's Intensive Care Unit, Department of Pediatric Subspecialities, KK Women's and Children's Hospital, Singapore. 2Duke-NUS Medical School, Singapore. 3Pediatric Intensive Care Unit, National Children's Hospital, Hanoi, Vietnam. 4Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. 5Pediatric Intensive Care Unit, Department of Pediatrics, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, Singapore. 6Department of Pediatrics, Sarawak General Hospital, Kuching, Malaysia. 7Pediatric Intensive Care Unit, Beijing Children's Hospital, Capital Medical University, Beijing, China. 8Division of Pediatric Critical Care, Department of Pediatrics, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. 9Pediatric Department, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 10Department of Pediatrics, University Malaya Medical Centre, University of Malaya, Kuala Lumpur, Malaysia. 11Children's Hospital of Chongqing Medical University, Chongqing, China. 12Center for Quantitative Medicine, Duke-NUS Medical School, Singapore.

Objectives: The Pediatric Acute Lung Injury Consensus Conference developed a pediatric specific definition for acute respiratory distress syndrome (PARDS). In this definition, severity of lung disease is stratified into mild, moderate, and severe groups. We aim to describe the epidemiology of patients with PARDS across Asia and evaluate whether the Pediatric Acute Lung Injury Consensus Conference risk stratification accurately predicts outcome in PARDS.

Design: A multicenter, retrospective, descriptive cohort study.

Setting: Ten multidisciplinary PICUs in Asia.

Patients: All mechanically ventilated children meeting the Pediatric Acute Lung Injury Consensus Conference criteria for PARDS between 2009 and 2015.

Interventions: None.

Measurements And Main Results: Data on epidemiology, ventilation, adjunct therapies, and clinical outcomes were collected. Patients were followed for 100 days post diagnosis of PARDS. A total of 373 patients were included. There were 89 (23.9%), 149 (39.9%), and 135 (36.2%) patients with mild, moderate, and severe PARDS, respectively. The most common risk factor for PARDS was pneumonia/lower respiratory tract infection (309 [82.8%]). Higher category of severity of PARDS was associated with lower ventilator-free days (22 [17-25], 16 [0-23], 6 [0-19]; p < 0.001 for mild, moderate, and severe, respectively) and PICU free days (19 [11-24], 15 [0-22], 5 [0-20]; p < 0.001 for mild, moderate, and severe, respectively). Overall PICU mortality for PARDS was 113 of 373 (30.3%), and 100-day mortality was 126 of 317 (39.7%). After adjusting for site, presence of comorbidities and severity of illness in the multivariate Cox proportional hazard regression model, patients with moderate (hazard ratio, 1.88 [95% CI, 1.03-3.45]; p = 0.039) and severe PARDS (hazard ratio, 3.18 [95% CI, 1.68, 6.02]; p < 0.001) had higher risk of mortality compared with those with mild PARDS.

Conclusions: Mortality from PARDS is high in Asia. The Pediatric Acute Lung Injury Consensus Conference definition of PARDS is a useful tool for risk stratification.
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November 2017

Mortality in Pediatric Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

J Intensive Care Med 2019 Jul 1;34(7):563-571. Epub 2017 May 1.

2 Duke-NUS Medical School, Singapore, Singapore.

Objective: Sparse and conflicting evidence exists regarding mortality risk from pediatric acute respiratory distress syndrome (ARDS). We aimed to determine the pooled mortality in pediatric ARDS and to describe its trend over time.

Data Sources And Study Selection: MEDLINE, EMBASE, and Web of Science were searched from 1960 to August 2015. Keywords or medical subject headings (MESH) terms used included "respiratory distress syndrome, adult," "acute lung injury," "acute respiratory insufficiency," "acute hypoxemic respiratory failure," "pediatrics," and "child." Study inclusion criteria were (1) pediatric patients aged 0 days to 18 years, (2) sufficient baseline data described in the pediatric ARDS group, and (3) mortality data. Randomized controlled trials (RCTs) and prospective observational studies were eligible.

Data Extraction And Synthesis: Data on study characteristics, patient demographics, measures of oxygenation, and mortality were extracted using a standard data extraction form. Independent authors conducted the search, applied the selection criteria, and extracted the data. Methodological quality of studies was assessed. Meta-analysis using a random-effects model was performed to obtain pooled estimates of mortality. Meta-regression was performed to analyze variables contributing to change in mortality over time. Eight RCTs and 21 observational studies (n = 2274 patients) were included. Pooled mortality rate was 24% (95% confidence interval [CI]: 19-31). There was a decrease in mortality rates over 3 epochs (≤2000, 2001-2009, and ≥2010: 40% [95% CI: 24-59], 35% [95% CI: 21-51], and 18% [95% CI: 12-26], respectively, P < .001). Observational studies reported a higher mortality rate than RCTs (27% [95% CI: 24-29] versus 16% [95% CI: 12-20], P < .001). Earlier year of publication was an independent factor associated with mortality.

Conclusion: Overall mortality rate in pediatric ARDS is approximately 24%. Studies conducted and published later were associated with better survival.
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http://dx.doi.org/10.1177/0885066617705109DOI Listing
July 2019

Risk factors for mortality in children with pneumonia admitted to the pediatric intensive care unit.

Pediatr Pulmonol 2017 08 3;52(8):1076-1084. Epub 2017 Apr 3.

Duke-NUS Medical School Singapore, Singapore.

Aims: To describe the epidemiology of children with severe pneumonia and identify risk factors for poor outcomes.

Methods: We conducted a retrospective study of children admitted to pediatric intensive care unit (PICU) from 2010 to 2014 with a diagnosis of pneumonia. Clinical microbiological, ventilation and other pertinent PICU data were collected. Primary outcome was PICU mortality. Univariate and multivariate logistic regression model were used to identify risk factors for mortality.

Results: Severe pneumonia consisted of 237/3539 (6.7%) of PICU admissions. Of these, 162/237 (68.4%) required mechanical ventilation. 32/237 (13.5%) patients died. The majority of patients had no organisms identified 82/237 (34.6%). A sole bacterial or viral pathogen was identified in 48/237 (20.1%) and 41/237 (17.9%) patients, respectively. Patients with viral pneumonias were more likely to develop acute respiratory distress syndrome compared to other etiologies (7/41[17.1%] vs 8/196 [4.0%]; P = 0.006). Bacterial pneumonias were associated with lung abscess (4/48 [8.3%] vs 2/189 [1.5%]; P = 0.016) and necrotizing pneumonia (18/48 [37.5%] vs 15/189 [7.9%]; P < 0.001) compared to other etiologies. Co-detections (>1 respiratory pathogens isolated) occurred in 62/237 (26.2%) patients and were associated a higher rate of mechanical ventilation, and decreased ventilator and PICU free days. After adjusting for severity of illness, risk factors for mortality were: hospital acquired pneumonia (HAP) (aOR: 2.92 [95%CI 1.15, 7.40]; P = 0.024) and bacteremia (aOR: 5.03 [95%CI 1.77, 14.35]; P = 0.003).

Conclusions: Severe pediatric pneumonia accounts for a significant number of PICU admissions and is associated with significant mortality risk. The presence of co-morbidities, HAP and bacteremia were early prognostic variables independently associated with poor clinical outcomes.
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http://dx.doi.org/10.1002/ppul.23702DOI Listing
August 2017

Nutrition Delivery Affects Outcomes in Pediatric Acute Respiratory Distress Syndrome.

JPEN J Parenter Enteral Nutr 2017 08 9;41(6):1007-1013. Epub 2016 Mar 9.

4 Children's Intensive Care Unit, Department of Pediatric Subspecialities, KK Women's and Children's Hospital, Singapore.

Background: Malnutrition is prevalent in critically ill children. We aim to describe nutrition received by children with acute respiratory distress syndrome (ARDS) and to determine whether provision of adequate nutrition is associated with improved clinical outcomes.

Materials And Methods: We studied characteristics and outcomes of 2 groups of patients: (1) those who received adequate calories (defined as ≥80% of predicted resting energy expenditure) and (2) those who received adequate protein (defined as ≥1.5g/kg/d of protein). Outcomes of interest were mortality, ventilator-free days (VFDs), intensive care unit (ICU)-free days, multiorgan dysfunction, and need for extracorporeal membrane oxygenation. Categorical variables were analyzed using the Fisher exact test, and continuous variables were analyzed using the Mann-Whitney U test. Univariate and multivariate logistic regression models were used to identify associated risk factors related to these outcomes of interest.

Results: In total, 107 patients with ARDS were identified. There was a reduction in ICU mortality in patients who received adequate calories (34.6% vs 60.5%, P = .025) and adequate protein (14.3% vs 60.2%, P = .002) compared with those that did not. Patients with adequate protein intake also had more VFDs (median [interquartile range], 12 [3.0-19.0] vs 0 [0.0-14.8] days; P = .005). After adjusting for severity of illness, adequate protein remained significantly associated with decreased mortality (adjusted odds ratio [95% confidence interval], 0.09 [0.01-0.94]; P = .044).

Conclusion: Our study demonstrated that adequate nutrition delivery in children with ARDS was associated with improved clinical outcomes. Protein delivery may have potentially more impact than overall caloric delivery.
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http://dx.doi.org/10.1177/0148607116637937DOI Listing
August 2017

Epidemiology of pediatric acute respiratory distress syndrome in singapore: risk factors and predictive respiratory indices for mortality.

Front Pediatr 2014 25;2:78. Epub 2014 Jul 25.

Children's Intensive Care Unit, Department of Pediatric Subspecialties, KK Women's and Children's Hospital , Singapore , Singapore ; Duke-NUS Graduate School of Medicine , Singapore , Singapore.

Aim: Acute respiratory distress syndrome (ARDS) represents the most severe form of acute lung injury. The aim of our study is to describe the epidemiology of pediatric ARDS in Singapore and compare the outcomes of ARDS using the following respiratory indices: PaO2/FiO2 ratio (P/F ratio), SpO2/FiO2 ratio (S/F ratio), oxygenation index (OI), and oxygen saturation index (OSI).

Methods: We examined medical records of patients admitted to the Children's Intensive Care Unit in KK Women's and Children's Hospital from 2009 to 2012. Those who fulfilled criteria for the American-European Consensus Conference definition for ARDS were identified. Demographic, clinical, and radiographic information were extracted and analyzed.

Results: We identified 70 patients with ARDS. Median age (interquartile range) was 6.2 (1.4, 10.4) years. The most common risk factor was pneumonia [50 (71%)]. Overall mortality was 44 (63%) patients. Thirty-two (56%) patients had an underlying chronic comorbidity; 18 (46%) were hematology-oncology conditions. Fifty-six (80%) patients had multiorgan dysfunction. Adjunct therapies used in our patients included inhaled nitric oxide [5 (7%)], prone position [22 (31%)], steroids [26 (37%)], and neuromuscular blockade [26 (37%)]. A high OI and low PF ratio after 24 h of diagnosis of ARDS were associated with mortality. From day 3 onward, all four respiratory indices appropriately differentiated survivors from non-survivors. Severity based on the S/F ratio and OSI demonstrated association with decreased ventilator free days and ICU free days.

Conclusion: Risk factors for mortality included having an underlying comorbidity, multiorgan dysfunction, a low PF ratio, and high OI at 24 h of ARDS. Abnormal SpO2-based measurements were reliable markers of poor outcomes in pediatric ARDS.
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http://dx.doi.org/10.3389/fped.2014.00078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110624PMC
August 2014

Nutrition biomarkers and clinical outcomes in critically ill children: A critical appraisal of the literature.

Clin Nutr 2014 Apr 2;33(2):191-7. Epub 2014 Jan 2.

Children's Intensive Care Unit, Department of Pediatric Subspecialties, KK Women's and Children's Hospital, Singapore; Office of Clinical Sciences, Duke-NUS Graduate School of Medicine, Singapore.

Background & Aims: Malnutrition can significantly affect clinical outcomes in critically ill children. In view of the limitations of anthropometry, nutrition-related serum biomarkers have been used to assess the degree of malnutrition in the pediatric intensive care unit. The aim of this review is to critically appraise the use of nutrition-related serum biomarkers in predicting clinical outcomes in critically ill children.

Methods: We searched major databases (MEDLINE, EMBASE, CINAHL, Cochrane Library) using MeSH terms and key words related to "biomarkers", "nutrition" and "critically ill children". All studies that explored the relationship between any nutrition-related serum biomarker and clinical outcomes in critically ill children (1 day-18 years) were included. The clinical outcomes of interest were duration of intensive care unit or hospital stay, duration of mechanical ventilation and mortality.

Results: We found one randomized controlled trial and 15 observational studies involving 2068 children. In these 16 studies, 16 different nutritional biomarkers and two nutrition indices were examined. Albumin (n = 7), magnesium (n = 4), transferrin, prealbumin and calcium (n = 3 respectively) were the most commonly studied biomarkers. Seven biomarkers (25-hydroxyvitamin D, albumin, calcium, magnesium, total protein, transferrin, triglycerides) and two indices (modified nutritional index and Onodera's prognostic nutritional index) had positive associations with clinical outcomes. However, no biomarkers or nutrition indices consistently predicted clinical outcomes.

Conclusions: Current medical literature does not provide convincing data to demonstrate any association between nutrition-related serum biomarkers and clinical outcomes in critically ill children. Further research is required to identify novel and clinically robust nutrition-related biomarkers.
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http://dx.doi.org/10.1016/j.clnu.2013.12.010DOI Listing
April 2014

Protocol-driven enteral nutrition in critically ill children: a systematic review.

JPEN J Parenter Enteral Nutr 2014 Jan 26;38(1):29-39. Epub 2013 Sep 26.

Department of Pediatric Medicine, KK Women's and Children's Hospital, Singapore.

Enteral nutrition (EN) protocols are thought to improve clinical outcomes in the pediatric intensive care unit (PICU); however, critical evaluation of their efficacy is limited. We conducted a systematic review with the aim of assessing the effect of EN protocols on important clinical outcomes in these children. We searched MEDLINE, Cochrane Database for Reviews, Embase, and CINAHL using predetermined keywords and MESH terms. We included randomized controlled trials (RCTs) and observational studies that involved EN protocols in children admitted to the PICU for >24 hours. We included studies that reported at least 1 of our outcomes of interest. Studies that exclusively studied premature neonates or adults were excluded. Primary outcomes were PICU or hospital mortality, PICU or hospital length of stay (LOS), duration of mechanical ventilation, gastrointestinal (GI) complications, and infective complications. Secondary outcomes were time to initiate feeds and time to achieve goal feeds. In total, we included 9 studies (total 1564 children) in our systematic review (1 RCT, 4 before-and-after studies, 1 single-arm cohort study, 1 prospective descriptive study, and 2 audits). There is low-level evidence that the use of EN protocols is associated with a reduction in GI and infective complications and improved timeliness of feed initiation and achievement of goal feeds. Current medical literature does not have compelling data on the effects of an EN protocol on clinical outcomes among critically ill children. Future clinical trials should look into using standardized interventions and outcome measures to strengthen the existing evidence.
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http://dx.doi.org/10.1177/0148607113502811DOI Listing
January 2014
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