A Prospective Cohort Study of Fecal miR-223 and miR-451a as Noninvasive and Specific Biomarkers for Diagnosis of Necrotizing Enterocolitis in Preterm Infants.

OBJECTIVE: The objective of this study is to evaluate the usefulness of fecal microRNA (miR)-223 and miR-451a, as novel noninvasive biomarkers for early diagnosis of necrotizing enterocolitis (NEC) in preterm infants. METHODS: Among the top-listed target miRNAs in our previous differential microarray analysis, miR-223 and miR-451a were quantified in a pilot validation case-controlled study (NEC vs. non-NEC/nonsepsis infants; n = 6 in each group). A definitive prospective cohort study (n = 218) further assessed their clinical usefulness as noninvasive and specific diagnostic biomarkers. Fecal calprotectin was quantified in parallel for comparison. RESULTS: Of 43 proven NEC cases in the cohort study, 24 (55.8%) had fecal samples recovered within the first 3 days of clinical presentation. Fecal miRNA-223 (10.5 fold), miR-451a (4.5 fold), and calprotectin (2.1 fold) concentrations were significant higher in NEC compared with the non-NEC group (p < 0.009). Accepting a minimum sensitivity of 0.75, the positive predictive values (PPVs) ranged between 0.19 and 0.20. Combining fecal biomarkers and CRP (Day 1) could marginally increase the PPVs (0.31-0.34) but adversely lowered the sensitivity (0.54-0.63). CONCLUSIONS: Although fecal miRNA biomarkers and calprotectin concentrations were significantly higher in the NEC group, the considerable overlapping of concentrations between groups and low recovery of stool specimens within 72 h of clinical presentation rendered fecal noninvasive tests of limited clinical value in guiding diagnosis of NEC during the acute phase. A further study is underway to evaluate their roles in surveillance for predicting high-risk premature infants developing NEC.

Outcome of status asthmaticus at a pediatric intensive care unit in Hong Kong.

OBJECTIVES: To characterize the clinical course and outcome of children with status asthmaticus (SA) admitted to a pediatric intensive care unit (PICU) METHODS: All patients with SA who were admitted to a PICU from January 2003 to December 2018 were reviewed. Polymerase chain reaction (PCR) studies on nasopharyngeal aspirate for respiratory pathogens were performed from 2014 to 2018. RESULTS: Sixty-seven SA admissions constituted 2.4% of total PICU admissions (n = 2788). Fifteen (22.4%) children required noninvasive ventilation (NIV), while 7 children (10%) required invasive mechanical ventilation. Nonadherence to prior asthma therapy was common. PCR was positive for enterorvirus/rhinovirus in 84% (16 out of 19) and for any virus in 95% of nasopharyngeal aspirate (NPA) samples of patients between 2014 and 2018. Over the 16-year period, increased utilization of ipratropium bromide, magnesium sulfate and NIV was noted (P < .05). Patients who required invasive mechanical ventilation had significantly higher heart rate, lower pH and longer PICU length of stay (LOS) when compared to nonintubated children (P < .05). There was no mortality, gender difference, or seasonal characteristics in these SA admissions. Median LOS in PICU was 2 days (interquartile range 1-3 days). CONCLUSIONS: SA accounts for a small proportion of PICU admissions. LOS was short and prognosis generally good. Nonadherence to prior asthma therapy was common. The most common trigger is enterovirus/rhinovirus for children with severe asthma requiring PICU admission. A trend of increase in usage of ipratropium, magnesium sulfate and NIV was observed. Primary prevention and early treatment of exacerbation are the most important step in managing children with asthma. Regular follow-up to ensure compliance together with annual vaccination could possibly avoid PICU admissions.

Longitudinal Development of Segmental Trunk Control in Full Term and Preterm Infants- a Pilot Study: Part I.

Purpose: No previous study examined trunk control development in preterm infants. The present study examined the longitudinal development of segmental trunk control from 4 to 12 months of (corrected) age in preterm infants in comparison with full-term infants.Methods: Thirty-one preterm infants and 30 full-term infants were recruited. All infants were tested monthly using the Segmental Assessment of Trunk Control and the Alberta Infant Motor Scale at 4, 8 and 12 months of age.Results: Segmental trunk control development was significantly delayed in the preterm infants. Statistically significant positive correlations were found between trunk control status and gross motor skills.Conclusion: This was first study showing that segmental trunk control development was significantly different in preterm infants. Segmental trunk control and gross motor performance were coupled in young infants. A dual focus on training upright trunk control and specific motor skills may maximise therapy outcomes for infants with motor delay.

Longitudinal Development of Segmental Trunk Control in Full Term and Preterm Infants- a Pilot Study: Part II.

Purpose: To explore the relationship between segmental trunk control and specific gross motor skills at 4, 8 and 12 months of (corrected) age in young infants.Methods: Thirty-one preterm infants and 30 full-term infants were recruited by convenience. All infants were tested using the Segmental Assessment of Trunk Control and the Alberta Infant Motor Scale at 4, 8 and 12 months of age.Results: The gross motor function in supine at 4 months and in the standing position at 12 months was significantly delayed in the preterm infants. Positive correlations were found between segmental trunk control levels and specific motor skills in prone, supine, sitting and standing positions at 8 and 12 months of age.Conclusion: This report was the first to demonstrate the association between segmental trunk control and specific gross motor skills in young infants. This new information provides clinicians with greater understanding about infant development.

Relationship between segmental trunk control and gross motor development in typically developing infants aged from 4 to 12 months: a pilot study.

BACKGROUND: Trunk control is generally considered to be related to gross motor development. However, this assumption has not been validated with clinical data. This pilot study was the first of its kind to examine the longitudinal development of segmental trunk control and gross motor development from 4 to 12 months of age in typically developing full-term infants. METHODS: A convenience cohort of 20 healthy full-term infants (mean gestation = 39.0 weeks, SD 1.2; mean birthweight = 2975.0 g, SD 297.0; males = 10) was recruited. All study infants were tested and scored monthly by independent assessors using the Segmental Assessment of Trunk Control and the Alberta Infant Motor Scale from 4 to 12 months of age. RESULTS: A developmental trend of segmental trunk control was found in the infants. Static vertical upright trunk control developed prior to active and reactive control. Statistically significant correlations were found between trunk control status and gross motor development mainly in prone and sitting positions from 8 months of age onwards (all p < 0.004, Spearman's r ranged from 0.644 to 0.798). CONCLUSIONS: This pilot study provides preliminary clinical evidence to support the inter-dependency between vertical upright trunk control and gross motor development in young infants, particularly as upright functional skills are gained. This suggests that a dual focus on training upright trunk control alongside gross motor skills could be of benefit in the treatment of infants with movement disorders.

Mortality And Morbidity of Severe Traumatic Brain Injuries; A Pediatric Intensive Care Unit Experience Over 15 Years.

OBJECTIVE: To determine the mortality, morbidity, types of intracranial hemorrhages, and factors associated with length of stay (LOS) associated with accidental traumatic brain injury (TBI) at a pediatric intensive care unit (PICU) of a regional trauma center in an Asian city. METHODS: This study is a retrospective review of types of head injury, mortality and morbidity demographics of patients admitted to a PICU with TBI. All patients with accidental TBI were included, namely road traffic injury (RTI) and fall, and their demographics compared. Non-accidental injuries (NAI) were excluded. RESULTS: 95 children (78% males) were admitted to a PICU with RTI or falls from 2002 to 2017. They accounted for 3.7% of PICU admissions. Comparing with falls, victims of RTI were older (p<0.001) and more likely to suffer from skull fracture (p=0.017). There were 4 deaths with falls (6.8%) but none with RTI. Subarachnoid hemorrhages, extradural hemorrhages, the use of mechanical ventilation, inotropes and neurological supports were associated with longer LOS in PICU in these injuries (p<0.001). CONCLUSION: A longer PICU LOS is associated with extradural and subarachnoid hemorrhages, usage of inotropes, mechanical ventilation and neurological supports in falls and RTI. Three-quarters of victims are males. Preventive health education should be especially directed to boys to reduce severe TBI in this Asian city.

Magnetic Foreign Body Ingestion in Children: The Attractive Hazards.

Foreign body ingestions are frequent in the childhood population. Most foreign bodies are passed spontaneously through the gastrointestinal tract. However, on occasion, they can also be a rare cause of morbidity and even mortality, such as in the case of multiple magnetic foreign body ingestion, which can cause injury via magnetic attraction through bowel walls. We present two cases of multiple magnetic foreign body ingestion, which to our knowledge are the first ones reported in Hong Kong. One patient presented with shock and intestinal necrosis requiring extensive intestinal resection, whereas the other patient had no gastrointestinal injury but surgical removal was deemed necessary.

Plasma miR-1290 Is a Novel and Specific Biomarker for Early Diagnosis of Necrotizing Enterocolitis-Biomarker Discovery with Prospective Cohort Evaluation.

OBJECTIVE: To discover specific circulating microRNA (miRNA) biomarkers for the early differentiation of necrotizing enterocolitis (NEC) from neonatal sepsis and inflammatory conditions. STUDY DESIGN: The study comprised 3 distinct phases: differential microarray analysis to compare plasma miRNA expression profiles of NEC vs sepsis and non-NEC/nonsepsis cases, a case-control study to quantify dysregulated miRNAs as potential specific biomarkers of NEC, and a prospective cohort study to assess the diagnostic usefulness of the best miRNA biomarker(s). RESULTS: A distinct miRNA expression profile was observed in the NEC compared with the sepsis and non-NEC/nonsepsis groups. miR-1290, miR-1246, and miR-375 were discovered to be specific biomarkers of NEC in the case-control study. In the cohort study (n = 301), plasma miR-1290 (day 0; >220 copies/µL) provided the greatest diagnostic usefulness for identifying both mild medical and severe surgical NEC cases. Of 20 infants with miR-1290 >650 copies/µL, 15 were diagnosed with NEC. Incorporating C-reactive protein (day 1; >15.8 mg/L) for cases with intermediate levels (220-650 copies/µL) in a 2-stage algorithm further optimized the diagnostic profile with a sensitivity of 0.83, a specificity of 0.96, a positive predictive value of 0.75, and a negative predictive value of 0.98. Importantly, 7 of 36 infants with NEC (19.4%) could be diagnosed 7.8-32.2 hours earlier (median, 13.3 hours) using miR-1290. CONCLUSIONS: Plasma miR-1290 is a novel and specific biomarker that can effectively differentiate NEC cases from neonatal sepsis. miR-1290 facilitates neonatologists to confidently and timely reach a decision for early transfer of sick infants with NEC from community-based hospitals to tertiary surgical centers.

Segmental Assessment of Trunk Control in infants from 4 to 9 months of age- a psychometric study.

BACKGROUND: Efficient trunk control is crucial in infant motor development when infants first learn how to move against gravity. Traditional assessments of trunk control commonly treat the trunk as one unit but the Segmental Assessment of Trunk Control (SATCo) assesses trunk control segment by segment. Good reliability and validity of the SATCo have been proved in children with neuro-disability but not yet validated in young infants. The present study was to examine if the SATCo was reliable, valid and responsive for infants aged 4 to 9 months. METHODS: Infants born at full-term and at less than 30 weeks of gestation were recruited and assessed using the SATCo monthly from 4 to 9 months of age (corrected for prematurity). Intra-class correlation coefficients (ICC) were used to examine intra- and inter-rater reliability between 2 raters. The ability of the SATCo to demonstrate differences between the full-term and preterm infants was examined using the Mann Whitney U test. The responsiveness of the SATCo on the full-term infants was tested using the Friedman test. RESULTS: Twenty full-term (mean gestation = 38.7 weeks; birthweight = 3019.9 g) and 20 preterm infants (mean gestation = 27.2 weeks; birthweight = 989.6 g) were recruited. The intra and inter-rater reliability of the SATCo levels on full-term infants was good (all ICC > 0.75), except inter-rater reliability at 6 months. The preterm infants scored significantly lower in reactive trunk control at 8 months (Mann Whitney U = 102.0, p = 0.016) but this was the only difference noted. A significant developmental trend was shown in the static, active and reactive trunk control of the full-term infants (Chi-square = 81.4, 75.6 and 79.5 respectively, all p < 0.001. CONCLUSIONS: The SATCo was reliable and responsive in assessing trunk control in young infants aged from 4 to 9 months. Care should be exercised when testing infants aged 5 to 6 months, who are more likely to use subtle hand support, and for those who have already achieved independent sitting. The SATCo could differentiate the reactive trunk control between the full-term and preterm infants at 8 months but not earlier. Psychometric properties of the SATCo in infants with motor disorders requires further investigation.

Occurrence of Potential Adverse Drug Events from Prescribing Errors in a Pediatric Intensive and High Dependency Unit in Hong Kong: An Observational Study.

BACKGROUND: Critically ill pediatric patients are considered at high risk for medication errors. Although much research focuses on the actual errors, equally important are medication errors that, although intercepted, carried the potential for an adverse drug event. The aim of this study was to determine the occurrence of prescribing errors and potential adverse drug events (pADEs) in a local pediatric intensive and critical care unit (PICU) in Hong Kong. Our secondary objective was to determine the type of error, nature of medication involved and the time of error occurrence. METHODS: We conducted a prospective observational chart review among patients in a pediatric intensive and high dependency unit between January 16, 2015 and April 20, 2015. Medical charts for each patient were reviewed for the occurrence of a prescribing error or pADE. Each pADE was assessed for the type of error, the classification of agent involved, clinical severity of the error, and the time the error occurred. RESULTS: Forty-one patients with a mean age of 3.2 years were included in our study. Of these patients, 19 (46.3%) experienced at least one pADE. We identified 131 pADEs, 129 of which were prescribing errors conferring a rate of 6.8 errors per affected patient or 3.1 errors per patient admitted to the PICU. The most common error found in the study was incorrect dose calculation (48.1%), with intravenous fluids (41.7%), cardiovascular agents (15.0%), and anti-infectives (12.5%) the most common agents involved with an error. The majority of the pADEs in our study were either clinically serious (33.1%) or significant (44.9%) in nature. Nearly one in every four errors required monitoring and/or intervention to prevent harm, and almost all (96.9%) of the prescribing errors were intercepted before reaching the patient. CONCLUSION: This study highlights incorrect dose calculation as the most common prescribing error in a pediatric critical care setting. Intravenous fluids, cardiovascular agents, and anti-infectives were the classes of medication most commonly involved with a pADE. Due to the high-risk nature of medications used and the critical condition of these patients, more than three-quarters of pADEs were considered to be clinically serious or significant in causing patient harm.

Attitudes of Parents and Health Care Workers to Major Surgery for High-Risk Preterm Infants.

OBJECTIVES: To assess preferences of health care workers (HCWs) and parents of term and preterm infants to adverse health outcomes, and how perceived surgical mortality influences decision-making. STUDY DESIGN: A total of 536 participants (157 HCWs, 201 parents of term infants, and 178 parents of preterm infants) were recruited to take part in a structured interview. Preferences related to treatment of a critically ill preterm infant with necrotizing enterocolitis were measured by health state rank permutation analysis and pivotal risk analysis. Between-group and subgroup comparisons were performed. RESULTS: HCWs rank adverse health states less favorably than parents of preterm infants, consistently ranking 2 of the most adverse health states worse than death. Pivotal risk values of HCWs for all health states were consistently the lowest of the 3 groups. High operative mortality was associated uniformly with reduction in pivotal risks for all groups both in favorable and adverse health states. Subgroup analyses revealed significant discrepancies in preferences between fathers and mothers as well as doctors and nurses. Regular religious practice was significantly associated with increased pivotal risks in parental subgroups. CONCLUSIONS: As discrepancies in health state preferences existed between subgroups (ie, doctors vs nurses, mothers vs fathers) and perceived operative mortality consistently biased parental and HCW health state preferences, we recommend that HCWs should first identify differences regarding patient management before interviewing the parents together. HCWs should be aware of inadvertently biasing parents when discussing the risks and outcomes of surgery in conjunction with the overall long-term prognosis of the underlying condition.

Dysregulated expression of arginine metabolic enzymes in human intestinal tissues of necrotizing enterocolitis and response of CaCO2 cells to bacterial components.

The small intestine is the exclusive site of arginine synthesis in neonates. Low levels of circulating arginine have been associated with the occurrence of necrotizing enterocolitis (NEC) but the mechanism of arginine dysregulation has not been fully elucidated. We aimed to investigate (i) expressional changes of arginine synthesizing and catabolic enzymes in human intestinal tissues of NEC, spontaneous intestinal perforation (SIP) and noninflammatory surgical conditions (Surg-CTL) and to investigate the (ii) mechanisms of arginine dysregulation and enterocyte proliferation upon stimulation by bacterial components, arginine depletion, ARG1 overexpression and nitric oxide (NO) supplementation. Our results showed that expressions of arginine synthesizing enzymes ALDH18A1, ASL, ASS1, CPS1, GLS, OAT and PRODH were significantly decreased in NEC compared with Surg-CTL or SIP tissues. Catabolic enzyme ARG1 was increased (>100-fold) in NEC tissues and histologically demonstrated to be expressed by infiltrating neutrophils. No change in arginine metabolic enzymes was observed between SIP and Surg-CTL tissues. In CaCO2 cells, arginine metabolic enzymes were differentially dysregulated by lipopolysaccharide or lipoteichoic acid. Depletion of arginine reduced cell proliferation and this phenomenon could be partially rescued by NO. Overexpression of ARG1 also reduced enterocyte proliferation. We provided the first expressional profile of arginine metabolic enzymes at the tissue level of NEC. Our findings suggested that arginine homeostasis was severely disturbed and could be triggered by inflammatory responses of enterocytes and infiltrating neutrophils as well as bacterial components. Such reactions could reduce arginine and NO, resulting in mucosal damage. The benefit of arginine supplementation for NEC prophylaxis merits further clinical evaluation.

Radiologic, Neurologic and Cardiopulmonary Aspects of Submersion Injury.

Many indices and scores are used in critical care medicine to aid management and predict risk of mortality. We report 2 cases of submersion injury and discuss the usefulness and application of common respiratory and critical care indices. The respiratory indices help better understand the pulmonary pathophysiology and characterize the severity of lung injury and ventilation/perfusion mismatch. Severe lung injury resolved after ventilation support with appropriate positive end-expiratory pressure in both cases. The 6-year-old girl survived the near-fatal submersion injury intact despite grossly abnormal initial Glasgow Coma Scale (GCS) and high Pediatric Index of Mortality 2 scores, whereas the 5-year-old boy with grossly abnormal GCS and Pediatric Index of Mortality 2 scores died despite resolution of lung injury. These cases illustrate that resuscitation should be promptly instituted at the scene to ensure optimal outcome because initial pulmonology and neurology indices may not reliably predict mortality or intact survival. The GCS score was not initially designed for prognostication. Nevertheless, 2 serial GCS scores of 3, one performed at emergency department and one at the pediatric intensive care unit, were associated with nonsurvival in our second patient.

Comparative MiRNA Expressional Profiles and Molecular Networks in Human Small Bowel Tissues of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation.

BACKGROUND: Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are acute intestinal conditions which could result in mortality and severe morbidity in preterm infants. Our objective was to identify dysregulated micro-RNAs (miRNAs) in small bowel tissues of NEC and SIP, and their possible roles in disease pathophysiology. METHODS: We performed differential miRNA arrays on tissues of NEC (n = 4), SIP (n = 4) and surgical-control (Surg-CTL; n = 4), and validated target miRNAs by qPCR (n = 10 each group). The association of target miRNAs with 52 dysregulated mRNAs was investigated by bioinformatics on functional and base-pair sequence algorithms, and correlation in same tissue samples. RESULTS: We presented the first miRNA profiles of NEC, SIP and Surg-CTL intestinal tissues in preterm infants. Of 28 validated miRNAs, 21 were significantly different between NEC or SIP and Surg-CTL. Limited overlapping in the aberrant expression of miRNAs between NEC and SIP indicated their distinct molecular mechanisms. A proposed network of dysregulated miRNA/mRNA pairs in NEC suggested interaction at bacterial receptor TLR4 (miR-31, miR-451, miR-203, miR-4793-3p), mediated via key transcription factors NFKB2 (miR-203), AP-1/FOSL1 (miR-194-3p), FOXA1 (miR-21-3p, miR-431 and miR-1290) and HIF1A (miR-31), and extended downstream to pathways of angiogenesis, arginine metabolism, cell adhesion and chemotaxis, extracellular matrix remodeling, hypoxia/oxidative stress, inflammation and muscle contraction. In contrast, upregulation of miR-451 and miR-223 in SIP suggested modulation of G-protein-mediated muscle contraction. CONCLUSIONS: The robust response of miRNA dysregulation in NEC and SIP, and concerted involvement of specific miRNAs in the molecular networks indicated their crucial roles in mucosa integrity and disease pathophysiology.

A baby with symmetrical hand injuries and rhabdomyolysis following nonfatal electrocution by an unusual mechanism.

Childhood electrical injuries are rare in the city of Hong Kong. We report the case of a 21-month boy with severe electrical injuries of both hands and explored underlying mechanism for the incident. Meticulous orthopedic repair and reconstruction ensures satisfactory cosmetic and functional outcomes. Our case concurs with the literature that young children may be predisposed to this mode of incident with their curious exploring hands. Despite regulations on electrical home safety standards, extension power boards can still pose a dangerous risk for severe morbidity in the household with young children. Prevention strategies often involve commonsense approach in home safety measures such as (1) use proper fuses in electrical boxes, (2) do not overload outlets, (3) use insulated and grounded electrical cords, (4) keep electrical cords away from a child's reach, and (5) cover electrical outlets so children will not stick items in the outlet.

Expression profile of cord blood neutrophils and dysregulation of HSPA1A and OLR1 upon challenge by bacterial peptidoglycan.

In newborn infants, the innate cellular system plays a crucial role in the first line of defense against pathogens. Neutrophils are the most abundant leukocytes, and their response to the commonly encountered nosocomial bacterial (Gram positive) infection in newborns remains largely unclear. In this study, a genome-wide expression array analysis was performed on CB neutrophils after challenge by PGN in vitro and compared with neutrophils in CTL cultures without PGN. We investigated responses of neutrophils to PGN and LPS, with respect to cytokine synthesis, chemotaxis, ROS production, cell death, and pathways of HSP response. Our results provide the first comprehensive expressional profile of neonatal neutrophils stimulated by PGN. mRNA levels of 16 up-regulated genes and 6 down-regulated genes were validated by qPCR. Their regulatory networks were identified downstream of TLR-2 and NOD-2, which work in concert toward signals of death, cytoprotection, inflammation, and stress responses. Members of the HSP family were significantly up-regulated in PGN-stimulated neutrophils, compared with those in LPS-stimulated cells. We confirmed protein co-precipitation of HSPA1A and OLR1 in stimulated neutrophils, and their transcription, induced by NF-κB but not by MAPK signals. We found increased CD11b, chemotaxis, TNF-α, and IL-8 in neutrophils stimulated by PGN or LPS. PGN, but not LPS, increased ROS production. We conclude that neonatal neutrophils are capable of vigorous molecular and functional responses to PGN and suggest that HSP plays a critical role in the host defense mechanism, possibly involving proinflammatory OLR1 and CD11b-facilitated chemotaxis.

Genome-wide expression profiles of necrotizing enterocolitis versus spontaneous intestinal perforation in human intestinal tissues: dysregulation of functional pathways.

OBJECTIVE: To provide a comprehensive database of gene regulation and compare differentially regulated molecular networks in human tissues of necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP). BACKGROUND: Both NEC and SIP are devastating surgical emergencies associated with high morbidity and mortality in preterm infants. Their pathophysiology and molecular mechanisms remain unclear. METHODS: Differential whole genome microarray analysis was performed on intestinal tissues collected from NEC (n = 15) and SIP (n = 12) infants and compared with tissues collected from surgical-control patients with noninflammatory intestinal conditions (n = 14). Validation of 52 target gene expressions was performed by quantitative polymerase chain reaction. Regulatory networks of significantly affected genes were constructed according to functional pathways. RESULTS: Extensive and significant changes of gene expression were observed in NEC tissues, which comprised multiple pathways of angiogenesis, arginine metabolism, cell adhesion and chemotaxis, extracellular matrix remodeling, hypoxia and oxidative stress, inflammation, and muscle contraction. These dysregulated genes could be networked downstream of key receptors, TLR2, TLR4, and TREM1, and mediated via NF-κB, AP-1, and HIF1A transcription factor pathways, indicating predominant microbial and inflammatory involvement. In contrast, SIP tissues exhibited much milder and less diversified expressional changes, with target genes significantly associated with G-protein-mediated muscle contraction and extracellular matrix remodeling. CONCLUSIONS: The molecular evidence suggests that NEC and SIP are likely 2 different diseases caused by distinct etiology and pathophysiology. This first comprehensive database on differential gene expression profiles of human NEC and SIP tissues could lead to development of disease-specific diagnostic and prognostic biomarkers and new therapeutic strategies for improving outcomes.

Prolonged non-survival in PICU: does a do-not-attempt-resuscitation order matter.

BACKGROUND: Etiologies of pediatric intensive care unit (PICU) mortality are diverse. This study aimed to investigate the pattern of PICU mortality in a regional trauma center, and explore factors associated with prolonged non-survival. METHODS: Demographic data of all PICU deaths in a regional trauma center were analyzed. Factors associated with prolonged nonsurvival (length of stay) were investigated with univariate log rank and multivariate Cox-Regression forward stepwise tests. RESULTS: There were 88 deaths (males 61%; infants 23%) over 10 years (median PICU stay = 3.5 days, interquartile range: 1 and 11 days). The mean annual mortality rate of PICU admissions was 5.8%. Septicemia with gram positive, gram negative and fungal pathogens were present in 13 (16%), 13 (16%) and 4 (5%) of these patients, respectively. Viruses were isolated in 25 patients (28%). Ninety percent of these 88 patients were ventilated, 75% required inotropes, 92% received broad spectrum antibiotic coverage, 32% received systemic corticosteroids, 56% required blood transfusion and 39% received anticonvulsants. Thirty nine patients (44%) had a DNAR (Do-Not-Attempt-Resuscitation) order with their deaths at the PICU. Comparing with non-trauma category, trauma patients had higher mortality score, no premorbid disease, suffered asystole preceding PICU admission and subsequent brain death. Oncologic conditions were the most prevalent diagnosis in the non-trauma category. There was no gunshot or asthma death in this series. Prolonged non-survival was significantly associated with DNAR, fungal infections, and mechanical ventilation but negatively associated with bacteremia. CONCLUSIONS: Death in the PICU is a heterogeneous event that involves infants and children. Resuscitation was not attempted at the time of their deaths in nearly half of the patients in honor of parents' wishes. Parents often make DNAR decision when medical futility becomes evident. They could be reassured that DNAR did not mean "abandoning" care. Instead, DNAR patients had prolonged PICU stay and received the same level of PICU supports as patients who did not respond to cardiopulmonary resuscitation.

Complications of bezoar in children: what is new?

A bezoar is a mass found trapped in the gastrointestinal system. The condition may be associated with pica, especially in developmentally retarded children. Clinical manifestations are usually nonspecific. Endoscopic diagnosis and removal of the foreign materials is often indicated. Occasionally, severe complications may occur. We report two cases to illustrate the clinical features and complications in these children. In the first case, a reliable history was not obtained in the developmentally delayed girl which precluded prompt diagnosis, but the grossly dilated stomach on plain abdominal radiograph gave clues to an underlying insidious mechanical obstruction of upper gastrointestinal tract. In the second case of a normal child, the unrelenting symptoms and weight loss prompt further investigations which revealed the diagnosis. Literature on pediatric bezoar is reviewed. Oesophagoduodenoscopy is the investigation of choice for diagnostic confirmation, but surgical facilities must be available to deal with acute complications.

Neutrophil CD64 for daily surveillance of systemic infection and necrotizing enterocolitis in preterm infants.

BACKGROUND: Early detection and treatment of infected preterm infants could decrease morbidity and mortality. Neutrophil CD64 has been shown to be an excellent early diagnostic biomarker of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC). We aimed to study whether using CD64 as a daily surveillance biomarker could predict LOS/NEC before clinical manifestation. METHODS: We collected 0.1 mL whole blood from very low birth weight (VLBW) infants from day 7 postnatal age until routine daily blood tests were no longer required. Four categories of responses were defined: proven sepsis, clinical sepsis, nonsepsis/non-NEC, and asymptomatic CD64 activation. RESULTS: A total of 146 infants were consecutively recruited and 155 episodes of sepsis evaluation were performed. The biomarker screening utility, sensitivity, specificity, positive predictive value, and negative predictive value for surveillance of LOS/NEC using a cutoff of 5655 antibody-PE (phycoerythrin) molecules bound/cell were 89%, 98%, 41%, and 99.8%, respectively. LOS/NEC was detected a mean of 1.5 days before clinical presentation. However, 63 episodes of CD64 activation occurred in asymptomatic infants who would not otherwise have required sepsis evaluations. CONCLUSIONS: As a surveillance biomarker, neutrophil CD64 detected LOS/NEC 1.5 days before clinical presentation, but at the expense of performing 41% additional sepsis evaluations. This was mainly attributed to an unexpected group of asymptomatic infants with CD64 activation, who recovered spontaneously and did not require antimicrobial treatment. The latter group has not been previously recognized in VLBW infants and could represent subclinical infection secondary to transient bacterial translocation or mild viral infection.