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To investigate, in children, the correlation between the extent of lung contusion as detected on early radiologic examination (chest radiograph [CXR] and/or thoracic computed tomography [TCT]) and subsequent clinical outcome measures.Retrospective chart review study with blinded assessment of thoracic imaging.A university-affiliated, level 1 designated pediatric trauma center.None.Patients (1-18 yrs) who, between April 2000 and October 2005, were diagnosed with lung contusion were eligible for study entry. The medical records of those patients who underwent early (within the first 24 hrs of admission) thoracic imaging (CXR and/or TCT) were reviewed. A pulmonary contusion score (PCS) was assigned to each thoracic image according to the extent of contusion injury by two investigators blinded to each others score and the clinical details of the patient.Seventy-four patients were included in the study. Twenty patients had undergone CXR only, whereas 54 had undergone both CXR and TCT. The mean PCS on CXR was 3.9 +/- 3.6 compared with 6.5 +/- 3.49 on TCT (p.001). In eight patients (15%) who underwent TCT and CXR, the CXR failed to demonstrate a lung contusion. The PCS derived from CXR examination correlated positively with lower Pao2/Fio2 (r = -.36, p = .019), higher ventilation index (r = .35, p = .014), and longer length of ventilation (r = .28, p = .019). No such correlation was seen with TCT-derived PCS.The severity of lung contusion determined by CXR, but not TCT, correlates with impairment of oxygenation, CO2 exchange, and duration of ventilatory support.

CORM-released CO has been shown to be beneficial in resolution of acute inflammation. The acute phase of intestinal ischemia-reperfusion (I/R) injury is characterized by oxidative stress-related inflammation and leukocyte recruitment. In this study, we assessed the effects and potential mechanisms of CORM-2-released CO in modulation of inflammatory response in the small intestine following I/R-challenge. To this end mice (C57Bl/6) small intestine were challenged with ischemia by occluding superior mesenteric artery (SMA) for 45 min. CORM-2 (8 mg/kg; i.v.) was administered immediately before SMA occlusion. Sham operated mice were injected with vehicle (0.25% DMSO). Inflammatory response in the small intestine (jejunum) was assessed 4 h following reperfusion by measuring tissue levels of TNF-alpha protein (ELISA), adhesion molecules E-selectin and ICAM-1 (Western blot), NF-kappaB activation (EMSA), along with PMN tissue accumulation (MPO assay) and leukocyte rolling/adhesion in the microcirculation of jejunum (intravital microscopy). The obtained results indicate that tissue levels of TNF-alpha, E-selectin and ICAM-1 protein expression, activation of NF-kappaB, and subsequent accumulation of PMN were elevated in I/R-challenged jejunum. The above changes were significantly attenuated in CORM-2-treated mice. Taken together these findings indicate that CORM-2-released CO confers anti-inflammatory effects by interfering with NF-kappaB activation and subsequent up-regulation of vascular pro-adhesive phenotype in I/R-challenged small intestine.

To report the use of proximal splenic artery embolization for management of spontaneous splenic rupture.Case report and literature review.A tertiary pediatric critical care unit in a university teaching hospital.Proximal splenic artery embolization.An 8-yr-old boy presented with abdominal pain radiating to the left shoulder 9 days after completing induction chemotherapy for acute lymphoblastic leukemia. Imaging revealed a splenic rupture with parenchymal and subcapsular hematomas, with no evidence of active extravasations. The patient was admitted to the pediatric critical care unit for close hemodynamic monitoring and frequent measurements of hemoglobin. His lowest recorded hemoglobin and hematocrit were 63 g/L and 0.19 L/L, respectively. Posttransfusion of packed red blood cells, he was taken to interventional radiology for proximal splenic artery embolization under moderate sedation. Several coils were successfully placed in the proximal splenic arterial system resulting in a marked reduction of splenic blood flow without disruption of collaterals. The patient recovered well from proximal splenic artery embolization in the pediatric critical care unit and experienced short lasting abdominal pain and fever for 1 day. He was discharged home 4 days after the procedure and follow-up imaging showed resolving hematomas with preserved splenic blood flow.Proximal splenic artery embolization in children may be a safe therapeutic alternative to either conservative or surgical management in spontaneous splenic rupture. Preservation of splenic tissue with a reduced risk of repeated hemorrhage can be obtained with proximal splenic artery embolization.

Fusobacterium necrophorum infections are rare. We report a 15-year-old male who presented with tachycardia, nausea, vomiting, diarrhoea and ankle pain. He rapidly deteriorated requiring ventilation and vasopressors. Imaging of his thorax showed airspace consolidation, pulmonary cavitations and empyema. The ankle required drainage of purulent material. A thrombus in his internaljugular vein (Lemierre's syndrome) and an abscess in his obturator internus were subsequently found. Fusobacterium necrophorum was identified in blood culture on day nine. The patient recovered with antibiotics and surgical interventions for empyema and septic arthritis. Fusobacterium necrophorum should be a suspected pathogen in septic shock complicated by metastatic abscess formation.

Cerebral edema in diabetic ketoacidosis (DKA-CE) occurs primarily in children and can develop during DKA therapy. The treatment factors contributing to DKA-CE remain elusive. Our objectives were to characterize an age-appropriate DKA mouse model and to determine which DKA therapies contribute to DKA-CE. Juvenile mice were briefly fed a high-fat diet and injected with two pancreatic beta-cell toxins: streptozocin and alloxan. Severe insulin and leptin deficiencies associated with hyperosmolar ketoacidosis rapidly developed, indicating DKA. DKA mice were treated with re-hydration +/- insulin and brain water content (BWC) measured as an indicator of DKA-CE. As expected, glucose and beta-OH-butyrate corrected in DKA mice that received rehydration and insulin. BWC significantly increased above control levels only in DKA mice that received combined insulin and bicarbonate therapy, indicating the development of DKA-CE. Microscopically, DKA-CE brains had perineuronal and perivascular edema, with microvacuolation in the white matter tracts. These results indicate that insulin-deficient juvenile mice develop biochemical changes that are similar to those of DKA in children. Increased BWC was observed only in DKA mice that received combined insulin and bicarbonate therapy, suggesting that rapid systemic alkalinization in the presence of insulin may contribute to DKA-CE.

To report a rare case of secondary abdominal compartment syndrome during shock resuscitation in a pediatric trauma patient.Case report and literature review.A community hospital and a designated children's trauma hospital.A 17-yr-old trauma patient.Advanced trauma life support, trauma laparotomy, and superficial temporal artery ligation.A 17-yr-old trauma patient with ongoing blood loss from a lacerated superficial temporal artery received aggressive crystalloid resuscitation before arrival at a designated trauma hospital. His injury severity score was 16. The first hemoglobin drawn was 55 g/L with a hematocrit of 0.16 L/L. Within 3 hrs of the trauma, an abdominal computed tomography scan demonstrated a moderate amount of free peritoneal fluid, edematous bowel with marked enhancement, and a compressed inferior vena cava. Shortly after completion of imaging studies, the patient's abdomen became increasingly tense with poor perfusion to the lower extremities. Urgent laparotomy for abdominal compartment syndrome identified excessive ascites and extensive bowel edema with no blood or traumatic injuries. Abdominal decompression resulted in immediate improvement of hemodynamics and restored lower limb perfusion. Primary abdominal closure was obtained and the patient recovered fully with gentle diuresis.Secondary abdominal compartment syndrome developed in this pediatric trauma patient with hemorrhagic shock, possibly from aggressive crystalloid resuscitation. This trauma case highlights the importance of early hemorrhagic control with balanced crystalloid/transfusion therapy. Secondary abdominal compartment syndrome in pediatric trauma is rare and may reflect physiologic differences during development, less aggressive resuscitation practices, and/or underrecognition.

BACKGROUND: A triple-dose abusive head trauma (AHT) prevention program (Period of PURPLE Crying) was implemented. The third dose consisted of an education media campaign. The study objectives were to describe the qualitative and spatial methods developed to target AHT prevention and to evaluate this campaign. METHODS: A questionnaire on the level of importance of factors, rated on a 7-point Likert scale, was distributed to a panel of experts to determine the best advertising locations. Ranked factors were used to create weights for statistical modeling and mapping within a Geographic Information Systems to determine optimal ad locations. The media campaign was evaluated via a telephone survey of randomly selected households. RESULTS: The survey found locations of new families, high population density, and high percentage of lone parents to be the most important factors for selecting billboard sites. Spatial analysis revealed six areas that ranked highest in our factors. Five billboards, four media posters, and six transit shelters were selected for our advertisements. A population-based telephone survey revealed that 23% of respondents knew the campaign. Nearly half (42%) heard the radio public service announcements, and 9% saw billboards. CONCLUSION: Extending primary prevention efforts to the public helps to create a cultural change in the way inconsolable crying, the trigger for AHT, is viewed. With the use of ranked factors and Geographic Information Systems, geographic locations with high visibility and specific risk factors for AHTwere identified for targeting the campaign, facilitating the likelihood that our message was reaching the population in greatest need.

Solid tissues are critical for child-health research. Specimens are commonly obtained at the time of biopsy/surgery or postmortem. Research tissues can also be obtained at the time of organ retrieval for donation or from tissue that would otherwise have been discarded. Navigating the ethics of solid tissue collection from children is challenging, and optimal handling practices are imperative to maximize tissue quality. Fresh biopsy/surgical specimens can be affected by a variety of factors, including age, gender, BMI, relative humidity, freeze/thaw steps, and tissue fixation solutions. Postmortem tissues are also vulnerable to agonal factors, body storage temperature, and postmortem intervals. Nonoptimal tissue handling practices result in nucleotide degradation, decreased protein stability, artificial posttranslational protein modifications, and altered lipid concentrations. Tissue pH and tryptophan levels are 2 methods to judge the quality of solid tissue collected for research purposes; however, the RNA integrity number, together with analyses of housekeeping genes, is the new standard. A comprehensive clinical data set accompanying all tissue samples is imperative. In this review, we examined: the ethical standards relating to solid tissue procurement from children; potential sources of solid tissues; optimal practices for solid tissue processing, handling, and storage; and reliable markers of solid tissue quality.

Early mobilization of critically ill patients is beneficial, suggesting that it should be incorporated into daily clinical practice. Early passive, active, and combined progressive mobilizations can be safely initiated in intensive care units (ICUs). Adult patients receiving early mobilization have fewer ventilator-dependent days, shorter ICU and hospital stays, and better functional outcomes. Pediatric ICU data are limited, but recent studies also suggest that early mobilization is achievable without increasing patient risk. In this review, we provide a current and comprehensive appraisal of ICU mobilization techniques in both adult and pediatric critically ill patients. Contraindications and perceived barriers to early mobilization, including cost and health care provider views, are identified. Methods of overcoming barriers to early mobilization and enhancing sustainability of mobilization programs are discussed. Optimization of patient outcomes will require further studies on mobilization timing and intensity, particularly within specific ICU populations.

Basal skull fractures (BSFs) are caused by blunt force trauma, occurring in the temporal, occipital, sphenoid, and/or ethmoid bones. In pediatric severe traumatic brain injury (sTBI), there is a paucity of data on BSFs. Our goal was to investigate the BSF prevalence, anatomy, and association with short-term outcomes in pediatric sTBI.We retrospectively reviewed all severely injured (Injury Severity Score ≥12) pediatric patients (aged18 years) admitted to our hospital after experiencing an sTBI (Glasgow Coma Scale score ≤8 and head Abbreviated Injury Scale score ≥4). Neuroimaging for all sTBI patients was reviewed for skull fractures. Data were analyzed with both univariate and multivariate techniques.Of the 180 patients with sTBI, 47 had BSFs for a prevalence of 26% (69 BSFs in total; 16 sTBI patients had ≥2 BSFs). The squamous temporal bone was fractured most frequently (n=30/47 sTBI patients with BSFs). Patients with BSFs were heavier and had more facial injuries than those without (p0.05) but were similar in all other admission demographics, injury profiles, and clinical characteristics. Cerebrospinal fluid leak was found in 32% (n = 15 of 47) of BSF patients (otorrhea, n = 12; rhinorrhea, n = 1; otorrhea/rhinorrhea, n = 2; p0.001). Mortality, acute central diabetes insipidus, and fewer ventilator-free days were associated with BSFs (p0.005), whereas in sTBI survivors, BSFs were associated with longer lengths of stay (p0.05). Multiple logistic regression showed that BSFs were positively associated with the presence of subarachnoid hemorrhage (odds ratio [OR], 4.00; p = 0.001), contusion (OR, 2.48; p = 0.029), herniation (OR, 3.40; p = 0.037), and cerebral edema (OR, 2.30; p = 0.047) but negatively associated with diffuse axonal injury (OR, 0.20; p = 0.003). BSFs and mortality were strongly associated (OR, 6.87; p = 0.019).BSFs occurred in 26% of pediatric sTBI patients. The temporal bone was fractured in two thirds of sTBI patients with BSFs, and one third was associated with cerebrospinal fluid leaks. BSFs represent a significant linear blunt force and are independent predictors of mortality.Prognostic and epidemiologic study, level III.

Background. Chronic or persistent pain and disability following noncatastrophic “musculoskeletal” (MSK) trauma is a pervasive public health problem. Recent intervention trials have provided little evidence of benefit from several specific treatments for preventing chronic problems. Such findings may appear to argue against formal targeted intervention for MSK traumas. However, these negative findings may reflect a lack of understanding of the causal mechanisms underlying the transition from acute to chronic pain, rendering informed and objective treatment decisions difficult. The Canadian Institutes of Health Research (CIHR) Institute of Musculoskeletal Health and Arthritis (IMHA) has recently identified better understanding of causal mechanisms as one of three priority foci of their most recent strategic plan.Objectives. A 2-day invitation-only active participation workshop was held in March 2015 that included 30 academics, clinicians, and consumers with the purpose of identifying consensus research priorities in the field of trauma-related MSK pain and disability, prediction, and prevention.Methods. Conversations were recorded, explored thematically, and member-checked for accuracy.Results. From the discussions, 13 themes were generated that ranged from a focus on identifying causal mechanisms and models to challenges with funding and patient engagement.Discussion. Novel priorities included the inclusion of consumer groups in research from the early conceptualization and design stages and interdisciplinary longitudinal studies that include evaluation of integrated phenotypes and mechanisms.

A common complication of type 1 diabetes mellitus is diabetic ketoacidosis (DKA), a state of severe insulin deficiency. A potentially harmful consequence of DKA therapy in children is cerebral edema (DKA-CE); however, the mechanisms of therapy-induced DKA-CE are unknown. Our aims were to identify the DKA treatment factors and membrane mechanisms that might contribute specifically to brain cell swelling. To this end, DKA was induced in juvenile mice with the administration of the pancreatic toxins streptozocin and alloxan. Brain slices were prepared and exposed to DKA-like conditions in vitro. Cell volume changes were imaged in response to simulated DKA therapy. Our experiments showed that cell swelling was elicited with isolated DKA treatment components, including alkalinization, insulin/alkalinization, and rapid reductions in osmolality. Methyl-isobutyl-amiloride, a nonselective inhibitor of sodium-hydrogen exchangers (NHEs), reduced cell swelling in brain slices elicited with simulated DKA therapy (in vitro) and decreased brain water content in juvenile DKA mice administered insulin and rehydration therapy (in vivo). Specific pharmacological inhibition of the NHE1 isoform with cariporide also inhibited cell swelling, but only in the presence of the anion transport (AT) inhibitor 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid. DKA did not alter brain NHE1 isoform expression, suggesting that the cell swelling attributed to the NHE1 was activity dependent. In conclusion, our data raise the possibility that brain cell swelling can be elicited by DKA treatment factors and that it is mediated by NHEs and/or coactivation of NHE1 and AT.

Children with traumatic brain injury are reported to have deficits in performance monitoring, but the mechanisms underlying these deficits are not well understood. Four performance monitoring hypotheses were explored by comparing how 28 children with traumatic brain injury and 28 typically developing controls (matched by age and sex) performed on the stop-signal task. Control children slowed significantly more following incorrect than correct stop-signal trials, fitting the error monitoring hypothesis. In contrast, the traumatic brain injury group showed no performance monitoring difference with trial types, but significant group differences did not emerge, suggesting that children with traumatic brain injury may not perform the same way as controls.

Summary Sepsis is characterized by a severe systemic inflammatory response to infection that is associated with high morbidity and mortality despite optimal care. Invariant natural killer T (iNK T) cells are potent regulatory lymphocytes that can produce pro- and/or anti-inflammatory cytokines, thus shaping the course and nature of immune responses; however, little is known about their role in sepsis. We demonstrate here that patients with sepsis/severe sepsis have significantly elevated proportions of iNK T cells in their peripheral blood (as a percentage of their circulating T cells) compared to non-septic patients. We therefore investigated the role of iNK T cells in a mouse model of intra-abdominal sepsis (IAS). Our data show that iNK T cells are pathogenic in IAS, and that T helper type 2 (Th2) polarization of iNK T cells using the synthetic glycolipid OCH significantly reduces mortality from IAS. This reduction in mortality is associated with the systemic elevation of the anti-inflammatory cytokine interleukin (IL)-13 and reduction of several proinflammatory cytokines within the spleen, notably interleukin (IL)-17. Finally, we show that treatment of sepsis with OCH in mice is accompanied by significantly reduced apoptosis of splenic T and B lymphocytes and macrophages, but not natural killer cells. We propose that modulation of iNK T cell responses towards a Th2 phenotype may be an effective therapeutic strategy in early sepsis.

The role of flexible bronchoscopy and bronchoalveolar lavage (BAL) for the care of children with airway and pulmonary diseases is well established, with collected BAL fluid most often used clinically for microbiologic pathogen identification and cellular analyses. More recently, powerful analytic research methods have been used to investigate BAL samples to better understand the pathophysiological basis of pediatric respiratory disease. Investigations have focused on the cellular components contained in BAL fluid, such as macrophages, lymphocytes, neutrophils, eosinophils, and mast cells, as well as the noncellular components such as serum molecules, inflammatory proteins, and surfactant. Molecular techniques are frequently used to investigate BAL fluid for the presence of infectious pathologies and for cellular gene expression. Recent advances in proteomics allow identification of multiple protein expression patterns linked to specific respiratory diseases, whereas newer analytic techniques allow for investigations on surfactant quantification and function. These translational research studies on BAL fluid have aided our understanding of pulmonary inflammation and the injury/repair responses in children. We review the ethics and practices for the execution of BAL in children for translational research purposes, with an emphasis on the optimal handling and processing of BAL samples.

Objective Exogenously administered CO interferes with PMN recruitment to the inflamed organs. The mechanisms of CO-dependent modulation of vascular proadhesive phenotype, a key step in PMN recruitment, are unclear. Methods We assessed the effects/mechanisms of CO liberated from a water-soluble CORM-3 on modulation of the proadhesive phenotype in hCMEC/D3 in an in vitro model of endotoxemia. To this end, hCMEC/D3 were stimulated with LPS (1 μg/mL) for six hours. In some experiments hCMEC/D3 were pretreated with CORM-3 (200 μmol/L) before LPS-stimulation. PMN rolling/adhesion to hCMEC/D3 were assessed under conditions of laminar shear stress (0.7 dyn/cm2). In parallel, expression of adhesion molecules E-selectin, ICAM-1, and VCAM-1 (qPCR), activation of transcription factors, NF-κB and AP-1 (ELISA), and MAPK-signaling (expression/phosphorylation of p38, ERK1/2, and JNK1/2; western blot) were assessed. Results The obtained results indicate that CORM-3 pretreatment reduces PMN rolling/adhesion to LPS-stimulated hCMEC/D3 (p

Subarachnoid hemorrhage (SAH) is an independent prognostic indicator of outcome in adult severe traumatic brain injury (sTBI). There is a paucity of investigations on SAH in pediatric sTBI. The goal of this study was to determine in pediatric sTBI patients SAH prevalence, associated factors, and its relationship to short-term outcome. We retrospectively analyzed 171 sTBI patients (pre-sedation GCS ≤8 and head MAIS ≥4) who underwent CT head imaging within the first 24 h of hospital admission. Data were analyzed with both univariate and multivariate techniques. SAH was found in 42 % of sTBI patients (n = 71/171), and it was more frequently associated with skull fractures, cerebral edema, diffuse axonal injury, contusion, and intraventricular hemorrhage (p

Previous work has demonstrated that carbon monoxide releasing molecules (CORMs) suppress inflammation, however, the mechanisms are not well understood. Neutrophil (PMN)-derived myeloperoxidase (MPO...

BACKGROUND: The objective of this study was to describe the epidemiology of concussions presenting to the emergency department (ED). METHODS: A retrospective cohort of concussions for pediatric (age G 18 years) patients treated in the ED of a regional pediatric Level 1 trauma center from 2006 to 2011 was examined. Descriptive and geographic analyses were completed, with comparisons by age groups and residence (urban/rural). RESULTS: There were a total of 2,112 treated pediatric concussions. Two thirds of the concussions occurred in males (67%), with a median age of 13 years (interquartile range [IQR], 6). Nearly half of the pediatric concussions were sports related (48%); 36% of these concussions were from hockey. Significant differences were found in the distribution of the mechanism of injury across age groups (p G 0.001). Falls were most prevalent among young children, and sports concussions, for children 10 years and older. Two fifths of concussions occurred during winter months. Discharge disposition significantly differed by age ( p G 0.001), with home discharge increasing with age up to 14 years. There were a total of 387 rural (19%) and 1,687 urban (81%) concussed patients, for a mean ED concussion visit rate of 2.2 per 1,000 and 3.5 per 1,000, respectively. Rural patients were older (14 [IQR, 6] vs. 13 [IQR, 6], p = 0.019] and sustained 2.5 times more concussions from a motor vehicle crash compared with urban youth patients ( p G 0.001). CONCLUSION: Males in early adolescence are at highest risk for concussion, particularly from sport-related activities. Urban and rural children have differences in their etiology and severity of concussions. Concussions are predictable, and their prevention should be targeted based on epidemiologic and environmental data.

The corticotropin releasing hormone (CRH) system has been suggested to initiate seizure activity in the developing brain. However, human data to support this theory is lacking. In this study, we have demonstrated that the expression of CRH, CRH-binding protein, and CRH-R1 (a CRH membrane receptor) were significantly elevated in cortical tissue obtained from 6 children with generalized epilepsy (mean age 8.2+/-1.5 years) relative to age-matched controls (mean age 7.8+/-1.4 years). In contrast, no significant difference in the expression of CRH-R2 was observed. The advent of CRH-R1 receptor antagonists may prove useful as novel anticonvulsants.

The study objective was to describe the epidemiology of serious concomitant injuries and their effects on outcome in pediatric severe traumatic brain injury (sTBI).A retrospective cohort of all severely injured (Injury Severity Score [ISS] ≥ 12) pediatric patients (18 years) admitted to our pediatric intensive care unit, between 2000 and 2011, after experiencing an sTBI (Glasgow Coma Scale [GCS] score ≤ 8 and head Abbreviated Injury Scale [AIS] ≥ 4) were included. Two groups were compared based on the presence of serious concomitant injuries (maximum AIS score ≥ 3). Multivariate logistic regression was undertaken to determine variable associations with mortality.Of the 180 patients with sTBI, 113 (63%) sustained serious concomitant injuries. Chest was the most commonly injured extracranial body region (84%), with lung being the most often injured. Patients with serious concomitant injuries had increased age, weight, and injury severity (p0.001) and were more likely injured in a motor vehicle collision (91% vs. 48%, p0.001). Those with serious concomitant injuries had worse sTBI, based on lower presedation GCS (p = 0.031), higher frequency of fixed pupils (p = 0.006), and increased imaging abnormalities (SAH and DAI, p ≤ 0.01). Non-neurosurgical operations and blood transfusions were more frequent in the serious concomitant injury group (p0.01). The differences in mortality for the two groups failed to reach statistical significant (p = 0.053), but patients with serious concomitant injuries had higher rates of infection and acute central diabetes insipidus, fewer ventilator-free days, and greater length of stays (p0.05). Multivariate analyses revealed fixed pupillary response (odd ratio [OR], 63.58; p0.001), presedation motor GCS (OR, 0.23; p = 0.001), blood transfusion (OR, 5.80; p = 0.008), and hypotension (OR, 4.82; p = 0.025) were associated with mortality, but serious concomitant injuries was not (p = 0.283).Head injury is the most important prognostic factor in mortality for sTBI pediatric patients, but the presence of serious concomitant injuries does contribute to greater morbidity, including longer stays, more infections, fewer ventilator-free days, and a higher level of care required on discharge from hospital.Prognostic and epidemiologic study, level III.

To systematically review the literature on brain injury biomarkers, defined as any injury biomarker detected in cerebrospinal fluid (CSF) or blood injury biomarkers primarily expressed in the brain parenchyma, to determine outcome prediction in pediatric severe traumatic brain injury (sTBI).A search of MEDLINE(®), EMBASE(®), PsycINFO(®), Pubmed(®), and the Cochrane Database, as well as grey literature sources, personal contacts, hand searches, and reference lists. The search terms used were traumatic brain injury, biomarkers, prognosis, and children. No language, publication type, or publication date restrictions were imposed. All articles were critically reviewed by two clinicians independently.A total of 7,150 articles were identified initially with 16 studies identified for review. Eighteen different biomarkers were examined; 11 in CSF and 7 in blood. Outcomes assessed included either in-hospital mortality or functional state (hospital discharge, 3-months or 6-months; Glasgow Outcome Scale or Pediatric Cerebral Performance Category). Significant correlations were established between sTBI outcomes and various biomarkers in CSF (IL-6, IL-8, IL-1β, S100β, NGF, NSE, DCX, ET-1, HMGB-1, cytochrome C) and blood (GFAP, NF-H, UCH-L1, SBDP-145, leptin). Mixed results were obtained for blood S100β. Outcome did not correlate with several biomarkers in either CSF (BDNF, GDNF, α-Syn) or blood (NSE, MBP). The Class of Evidence was considered II in 1 study and III in the remaining 15 studies.Based on the status of current sTBI biomarker research, we recommend that future research should be directed at both novel biomarker discovery and validation of biomarker panels in large, well-designed longitudinal studies.

Study design:A retrospective registry review.Objectives:To determine the incidence of cervical spine (CS) injuries and collar complications in severely injured paediatric trauma patients.Setting:Regional Trauma Centre, Children's Hospital.Methods:A retrospective review of 365 paediatric severe trauma patients (0-17 years), defined as an Injury Severity Score (ISS)≥12, admitted to the paediatric intensive care unit (PICU).Results:Clinically significant CS injuries occurred in 5% (n=18/365) of trauma patients, in 9% (n=13/149) of traumatic brain injury (TBI) patients and in 11% (n=6/56) of in-hospital trauma deaths. CS injuries were suspected before imaging in 33% (n=6/18) of patients based on either motor/sensory impairment or shock. CS injuries were deemed unstable in 61% (n=11/18) of patients. Patients with CS injuries had higher ISS, and longer PICU and hospital stays (P

BACKGROUND This study was initiated was initiated to describe pediatric rear-occupant motor vehicle collision (MVC) injuries, including injury patterns and outcomes as well as characteristics associated with severe injury to the head and abdomen. METHODS A retrospective cohort of severely injured (Injury Severity Score [ISS] > 12) pediatric (age

Our aim is to report the consequences of epinephrine toxicity leading to cardiac failure in a child and the successful management with dopamine and milrinone. A previously healthy 13-year-old girl undergoing a left tympanomastoidectomy was inadvertently administered 10 mL of 1:1000 epinephrine subcutaneously (0.175 mg/kg) on the left post auricular region in lieu of lidocaine. She developed sudden supraventricular tachycardia, hypertension and flash pulmonary edema. She was initially treated with propofol, nitrogycerin and increased peak end-expiratory pressure. Within 4 h, she remained tachycardic, but was hypotensive with an increased central venous pressure. Electrocardiogram and echocardiogram investigations showed ST changes indicative of myocardial ischemia and globally reduced function, respectively. Dopamine infusion was administered, together with milrinone, resulting in a gradual improvement of cardiac function within 3 days. She was transitioned to enalapril and discharged home. This case highlights the clinical features of high dose epinephrine toxicity secondary to iatrogenic subcutaneous overdose followed by hypotension and pulmonary edema as a possible late effect of epinephrine and the successful management of secondary cardiac failure with administration of dopamine, milrinone and enalapril. © 2012 - IOS Press and the authors.

Objective To determine if the DKA-induced inflammation in juvenile mice provokes activation and dysfunction of CVECs. Methods DKA in juvenile mice was induced with administration of STZ and ALX. Blood from DKA mice was assessed for cytokines and soluble cell adhesion proteins, and either DKA plasma or exogenous compounds were applied to immortalized bEND3. Results DKA increased circulating levels of IL-6, IL-8(KC), MCP-1, IL-10, sE-selectin, sICAM-1, and sVCAM-1. Stimulation of bEND3 with DKA plasma caused cellular activation (increased ROS and activation of NF-κΒ), upregulation of a proadhesive phenotype (E-selectin, ICAM-1, and VCAM-1), and increased leukocyte-bEND3 interaction (leukocyte rolling/adhesion). TEER, a measure of bEND3 monolayer integrity, was decreased by DKA plasma. Activation and dysfunction of bEND3 with DKA plasma were suppressed by plasma heat treatment (56°C, 1 hour) and replicated with the application of DKA recombinant cytomix (IL-6, IL-8[KC], MCP-1, and IL-10), implicating circulating inflammatory protein(s) as mediators. Treatment of bEND3 with β-OH-butyrate, the main ketone elevated in DKA, failed to mimic the DKA plasma–induced activation and dysfunction of bEND3. Conclusions DKA elicits systemic inflammation associated with CVEC activation and dysfunction, possibly contributing to DKA-associated intracranial microvascular complications.

This study aimed to identify the causes and contributing factors, neurologic presentation, and outcomes of central pontine and extrapontine myelinolysis and to examine any trends in the presentation and course of these disorders over the past 50 years. Seventy-six pediatric cases were identified in the literature. Age, sex, decade of diagnosis, neurologic presentation, outcome, and attributed causes were extracted. The results showed that the diagnosis, course, and outcomes of central pontine and extrapontine myelinolysis clearly have changed over the past few decades. Early cases generally were diagnosed at autopsy as opposed to computed tomography or magnetic resonance imaging more recently. Ninety-four percent of cases prior to 1990 and only 7% of cases from 1990 onward resulted in patient mortality. The decade in which the case was reported was the strongest predictor of outcome (P < .001), followed by sodium dysregulation (P = .045) and dehydration (P = .07).

Given their relative hemodynamic stability, ketamine and etomidate are commonly chosen anesthetic agents for sedation during the endotracheal intubation of critically ill patients. As the use of etomidate has come into question particularly in patients with sepsis, due to its effect of adrenal suppression, there has been a shift in practice with more reliance on ketamine. However, as ketamine relies on a secondary sympathomimetic effect for its cardiovascular stability, cardiovascular and hemodynamic compromise may occur in patients who are catecholamine depleted. We present 2 critically ill patients who experienced cardiac arrest following the administration of ketamine for rapid sequence intubation (RSI). The literature regarding the use of etomidate and ketamine for RSI in critically ill patients is reviewed and options for sedation during endotracheal intubation in this population are discussed.

Objectives To investigate the association between the degree of patient dehydration on presentation with diabetic ketoacidosis (DKA) and clinical and laboratory parameters obtained on admission. Design Prospective descriptive study. Setting A tertiary care children9s hospital. Patients Thirty-nine paediatric patients (1 month–16 years) presenting with 42 episodes of DKA. Intervention Clinical and biochemical variables were collected on admission. Dehydration was calculated by measuring acute changes in body weight during the period of illness. All patients were treated according to a previously established protocol. Main outcome measures Magnitude of dehydration, defined as % loss of body weight (LBW), was determined by the difference in body weight obtained at presentation and at discharge. The relationship between the magnitude of dehydration and the clinical assessment and biochemical parameters was examined. Results The median (25th–75th centiles) magnitude of dehydration at presentation was 5.7% (3.8–8.3%) (mean±SD 6.8±5%). Neither the initial clinical assessment nor the comprehensive biochemical profile at admission correlated with the magnitude of dehydration. Despite considerable variation in the degree of dehydration and biochemical disequilibrium, all patients recovered from DKA within 24 h with a standardised therapeutic approach. Furthermore, the rapidity of patient recovery did not correlate with the magnitude of dehydration on presentation or the amount of fluid administered (median (25th–75th centiles) 48.8 ml/kg (38.5–60.3)) in the first 12 h. Conclusion The magnitude of dehydration in DKA is not reflected by either clinical or biochemical parameters. These findings need confirmation in larger studies.

Inflicted traumatic brain injury associated with Shaken Baby Syndrome (SBS) is a leading cause of injury mortality and morbidity in infants. A triple-dose SBS prevention program was implemented with the aim to reduce the incidence of SBS. The objectives of this study were to describe the epidemiology of SBS, the triple-dose prevention program, and its evaluation. Descriptive and spatial epidemiologic profiles of SBS cases treated at Children's Hospital, London Health Sciences Centre, from 1991 to 2010 were created. Dose 1 (in-hospital education): pre-post impact evaluation of registered nurse training, with a questionnaire developed to assess parents' satisfaction with the program. Dose 2 (public health home visits): process evaluation of additional education given to new parents. Dose 3 (media campaign): a questionnaire developed to rate the importance of factors on a 7-point Likert scale. These factors were used to create weights for statistical modeling and mapping within a geographic information system to target prevention ads. Forty-three percent of severe infant injuries were intentional. A total of 54 SBS cases were identified. The mean age was 6.7 months (standard deviation, 10.9 months), with 61% of infant males. The mean Injury Severity Score was 26.3 (standard deviation, 5.5) with a 19% mortality rate. Registered nurses learned new information on crying patterns and SBS, with a 47% increase in knowledge posttraining (p < 0.001). Over 10,000 parents were educated in-hospital, a 93% education compliance rate. Nearly all parents (93%) rated the program as useful, citing "what to do when the crying becomes frustrating" as the most important message. Only 6% of families needed to be educated during home visits. Locations of families with a new baby, high population density, and percentage of lone parents were found to be the most important factors for selecting media sites. The spatial analysis revealed six areas needed to be targeted for ad locations. SBS is a devastating intentional injury that often results in poor outcomes for the child. Implementing a triple-dose prevention program that provides education on crying patterns, coping strategies, and the dangers of shaking is key to SBS prevention. The program increased knowledge. Parents rated the program as useful. The media campaign allowed us to extend the primary prevention beyond new parents to help create a cultural change in the way crying, the primary trigger for SBS, is viewed. Targeting our intervention increased the likelihood that our message was reaching the population in greatest need.

Introduction Trauma is a major cause of paediatric morbidity and mortality, yet knowledge of fluid resuscitation is limited. Our objectives were to determine current practises in resuscitation volume (RV) administered to paediatric non-haemorrhagic (NH) blunt trauma patients and to identify fluid related complications. Methods We examined data from 139 trauma patients 1–17 years of age with an injury severity score ≥12 resuscitated at a Trauma-designated Children's Hospital. Patients were separated into discreet groups based on ATLS age-dependent vital functions: toddler/preschooler (1–5 years), school age (6–12 years) and adolescent (13–17 years). Results The median RV (total fluid intake − maintenance fluid intake) in ml/kg over the first 24 h from the time of trauma by age was: 24 (IQR = 19–47; 1–5 years); 26 (IQR = 15–36; 6–12 years); and 22 (IQR = 14–42; 13–17 years). The differences in RV/kg/24 h following NH trauma was not significantly different between age groups ( p = 0.41). Urine output over the 24 h ranged from 2.5 (IQR = 1.9–3.3; lower age group) to 1.8 (IQR = 1.2–2.4; upper age group) ml/kg/h; greater than the ATLS recommended age-dependent targets. Haematocrit was the only significant independent predictor of RV/kg/24 h ( p n = 17/139) of patients, and included ascites (8%; n = 11/139) and/or pleural effusion(s) (9%; n = 13/139). Patients with fluid-related complications received significantly more RV in ml/kg/24 h (42, IQR = 27–76) than those without complications (22, IQR = 14–36; p = 0.001). Conclusions The range of median RV administered to paediatric NH blunt trauma patients with ISS ≥ 12 was 22–26 ml/kg/24 h. The RV administered was excessive based on high urine outputs and the presence of fluid-related complications. Further evaluation of RV triggers and endpoints used by paediatric traumatologists is required.

Neonatal microvillus inclusion disease (MID) is a congenital secretory diarrhea diagnosed by morphological enterocyte abnormalities on histology. The secretory diarrhea associated with MID occurs within the first few hours of birth and is exacerbated by enteral feeding. Affected newborns will die of dehydration and acid-base disturbances if MID is not rapidly recognized and treated with massive intravenous fluid replacement and gut rest. We report a case of a 4-day-old neonate presenting with 18% weight loss, hypernatremic dehydration and metabolic acidosis. Despite aggressive fluid resuscitation (206 ml/kg for the first 24 h), the dehydration and metabolic acidosis were only minimally improved. The diapers were found soaked with clear, non-odorous fluid on repeated examinations. Persistent secretory diarrhea was suspected. Stool electrolytes analyses showed a high NaCl content typical of secretory diarrhea and intestinal biopsy with electron microscopy was diagnostic of MID.

Background: Southwestern Ontario largely comprises rural farming districts and is home to numerous Old-Order Anabaptist settlements. Our objective was to describe the injuries sustained by rural children, both Old-Order Anabaptist and non-Anabaptist, to better target injury prevention programs. Methods: We retrospectively examined injury data of rural children in Southwestern Ontario with injury severity scores ≥12 obtained from hospital and trauma databases (1997–2007). Results: A total of 422 rural children were included in this study: 7.8% Anabaptist (n = 33) and 92.2% non-Anabaptist (n = 389). The age of injured Anabaptist children (median, 7 years; interquartile range = 10) was younger than non-Anabaptist children (median, 14 years; interquartile range = 7; p < 0.001). Anabaptist children were most frequently injured on their property (48.5%; n = 16 of 33; p < 0.001). Non-Anabaptist children were mostly injured on roads (56.8%; n = 221 of 389; p < 0.05) and by motor vehicle collisions (MVCs; 40.1%; n = 156 of 389; p = 0.02). Frequent causes of injury among Anabaptist children were falls (24.2%; n = 8 of 33; p = 0.02), animals (15.2%; n = 5 of 33; p = 0.004), and buggies (9.1%; n = 3 of 33). Approximately half of both groups injured in MVCs did not use seat belts. There were no significant differences between cohorts in sex, injury severity scores, hospitalization days, rates of complications, interventions, comorbidities, or mortality rates. Conclusions: Injuries to Anabaptist children occur at a young age, primarily on their property, and exhibit a unique spectrum of mechanisms. In contrast, injuries to non-Anabaptist children occur at an older age, primarily on roads, and in MVCs. The use of protective devices was low among all rural children. Development of collaborative injury prevention programs targeted to distinct rural communities, including Anabaptist and non-Anabaptist, are needed for reducing injuries among rural children.

Mechanical ventilation (MV) strategies are continuously evolving in an effort to minimize adverse events. The objective of this study was to determine the complications associated with MV in children.Prospective observational study. Over a period of 10 consecutive months, 150 patients (median age 0.8 years, IQR 4.4, 59% male) were enrolled in this study.The median duration of MV was 3.1 days (IQR 3.9). A total of 85 complications were observed in 60 (40%) patients (114 complications per 1,000 ventilation days). 16.7% of patients developed atelectasis, 13.3% post-extubation stridor, 9.3% failed extubation, 2.0% pneumothorax, 3.3% accidental extubation, 2.7% nasal or perioral tissue damage and 1.9% ventilator associated pneumonia. Atelectasis occurred most often in the left lower lobe (36%) or in the right upper lobe (26%). The incidence of atelectasis in children1 year of age was 12% (31 episodes per 1,000 days of ventilation) compared to 18% (57 episodes per 1,000 days of ventilation) in children ≥ 1 year of age (P0.05). Patients that failed extubation were ventilated for a median of 8.5 (IQR 8.8) days compared to 2.9 days (IQR, 3.8) in patients that were successfully extubated (P0.01). The absence of an air leak prior to extubation did not correlate with failed extubation. Accidental extubation was limited to orally intubated patients.MV complications occurred in 40% of patients and most often consisted of atelectasis and post-extubation stridor. Further studies are needed to examine associated risk factors and strategies to reduce their occurrence.

The role of CO in the modulation of antioxidant enzyme function has not been investigated, yet. In this study we assessed the effects and potential mechanisms of the ruthenium-based water-soluble CO-releasing molecule CORM-3 in the modulation of superoxide dismutase (SOD) activity/binding in vascular endothelial cells (HUVECs). To this end, HUVECs were treated with CORM-3 (100 μM) and assessed for total SOD activity in cell lysates (cell-associated SOD activity) and cell culture supernatants (soluble SOD). In parallel, release/binding of extracellular SOD (SOD-3) in the absence or presence of heparin (1-10 IU/ml), a key factor regulating SOD-3 cell-surface binding, was investigated. In addition, the effects of CORM-3 on the modulation of purified SOD-1 and SOD-2 activity in a cell-free system were also assessed. The results obtained indicate that CORM-3 effectively suppresses the activity of both purified SOD-1 and SOD-2. These findings were accompanied by CORM-3-dependent attenuation of total cell-associated SOD activity (without affecting SOD-1/SOD-2 protein expression) and a subsequent increase in ROS production (DHR123 oxidation) in HUVECs. In parallel, a concomitant increase in soluble-SOD activity (due to increased SOD-3 release from the cell surface) was observed in the cell culture supernatants. However, in the presence of heparin, total cell-associated SOD activity was significantly increased by CORM-3, because of increased binding of SOD-3 to HUVECs. Taken together these findings indicate for the first time that CORM-3 modulates both the activity of intracellular SOD (i.e., SOD-1 and SOD-2) and the binding of extracellular SOD (SOD-3) to the cell surface.

Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are dire neurological disorders, characterized by severe damage to the myelin sheath of neurons, which typically result from rapid correction or overcorrection of systemic hyponatremia. For many years, both conditions have been considered universally fatal, though survivors have been reported more recently. Pediatric cases are rare. We present a 13-year-old boy with panhypopituitarism secondary to repair of a nasofrontal encephalocele in infancy, managed on long-term corticosteroid, deamino arginine vasopressin and thyroid hormone. He presented with severe hyponatremia (116 mEq/l), which during correction rapidly and unexpectedly increased to 176 mEq/l, resulting in profoundly impaired consciousness. Brain imaging revealed multiple bilateral changes in the basal ganglia, thalamus, pons and cerebral white matter, consistent with both CPM and EPM. Malignant cerebellar edema necessitated emergent suboccipital craniectomy, with subsequent improvement in level of consciousness and imaging postoperatively. However, he succumbed to acute cardiorespiratory arrest 8 weeks later. Nine similar cases from the literature are reviewed.