Epidemiology and factors associated with mortality among pediatric major trauma patients in Nova Scotia: A 17-year retrospective analysis.

BACKGROUND: Major traumatic injury in the pediatric population requires further evaluation to improve patient outcomes. Relatively few Canadian studies have investigated pediatric trauma using population-based data. Our objectives were to describe the epidemiology of pediatric major trauma in Nova Scotia and identify factors associated with in-hospital mortality. METHODS: Retrospective cohort study of pediatric major trauma patients (age <18 years) injured in Nova Scotia over a 17-year period (April 2001-March 2018). Data were collected from the Nova Scotia Trauma Registry. Characteristics were compared between patient subgroups using t-tests, chi-square analyses and Fisher's exact test. Temporal trends were evaluated using the Mann-Kendall test. Incidence and mortality rates were mapped using ArcGIS Pro. A multivariate logistic regression model was created to assess for factors associated with in-hospital mortality. RESULTS: A total of 1258 injuries were observed over the 17-year study period. The incidence of pediatric major trauma was 41.7 per 100,000 person-years. Most patients were male (819/1258; 65.1 %) and resided in urban areas (764/1258; 60.7 %). Blunt trauma accounted for 86.2 % (1084/1258) of injuries, and motor vehicle collisions were the most common cause (448/1258; 35.6 %). Incidence and mortality rates were highest in the 15-17 year age group, with a trend towards increasing incidence among females (p = 0.011). Mortality was 17.2 % (217/1258) of patients; 10.9 % (137/1258) died pre-hospital. No trends were detected in mortality rates. The regression model showed increased odds of in-hospital mortality for every point increase in the ISS (OR 1.05; 95 % CI 1.02 to 1.09) and for every unit decrease in scene GCS (OR 0.63; 95 % CI 0.56-0.71). Rural patients were 2 times more likely to die in-hospital versus urban patients (OR 2.40; 95 % CI 1.01-5.69), and patients injured at home were 6 times more likely to die compared to those injured in other locations (OR 6.19; 95 % CI 1.01-38.11). CONCLUSION: Pediatric trauma remains a major public health issue in Canada and beyond. Greater efforts are required to expand our understanding of trauma epidemiology and develop targeted injury prevention strategies, especially for rural inhabitants.

Pre-hospital mortality among pediatric trauma patients in Nova Scotia.

OBJECTIVES: Limited data exist on pre-hospital pediatric trauma mortality in Canada. The Nova Scotia Trauma Registry is a provincial population-based registry that captures data from the Medical Examiner Service. This study examined the characteristics of pediatric trauma patient mortality in the pre-hospital and in-hospital settings. METHODS: We conducted a cohort study of major pediatric traumas recorded in our provincial database from April 1, 2001 to March 31, 2018. Characteristics of pre-hospital and in-hospital deaths were compared with t tests and Chi-square analyses. Multivariate regression modeling was used to identify predictors of pre-hospital mortality. The geographic distribution of pre-hospital trauma was assessed using choropleth maps. RESULTS: We identified 1,258 pediatric traumas, resulting in 217 deaths (137 pre-hospital, 80 in-hospital). Males accounted for 62.7% of fatalities. The 15-17 age group accounted for most deaths in both groups (pre-hospital 61.3%; in-hospital 41.3%). Injuries sustained in rural areas resulted in 74.7% of all deaths. For both groups, blunt trauma was the predominant injury type and motor vehicle collisions, the most prevalent injury mechanism. Patients who died pre-hospital had a higher mean age (13.3 vs. 10.7, p = 0.002) and a greater proportion were intentional injuries (23.4% vs. 15%; p = 0.02). Urban residency was more frequently observed in in-hospital deaths (57.5% vs. 36.5%, p < 0.001). Pre-hospital mortality was associated with increasing age (OR 1.1), higher injury severity score (OR 1.1), and intentional injury (OR 15.6). CONCLUSION: Over 10% of major pediatric traumas resulted in pre-hospital death, primarily from motor vehicle collisions in rural areas. Compared to in-hospital mortality, patients who died pre-hospital were older with more severe injuries and more likely to have intentionally injured themselves. These results underscore the importance for emergency physicians and EMS systems to consider geographic factors and injury patterns, advocate for improved injury prevention programs, mental health supports, and delivery of on-scene critical care services.

RéSUMé: OBJECTIFS: Il existe peu de données sur la mortalité liée aux traumatismes pédiatriques pré-hospitaliers au Canada. La Nouvelle-Écosse. Le registre des traumatismes est un registre provincial fondé sur la population qui saisit les données du Medical Examiner Service. Cette étude a examiné les caractéristiques des traumatismes pédiatriques la mortalité des patients en milieu pré-hospitalier et hospitalier. MéTHODES: Nous avons mené une étude de cohorte des traumatismes pédiatriques majeurs enregistrés dans notre province base de données du 1er avril 2001 au 31 mars 2018. Caractéristiques des services pré-hospitaliers et les décès hospitaliers ont été comparés aux tests-t et aux analyses du chi carré. La modélisation multivariée de régression a été utilisée pour identifier les prédicteurs de la mortalité pré-hospitalière. La répartition géographique des traumatismes pré-hospitaliers a été évaluée à l'aide de cartes choroplèthes. RéSULTATS: Nous avons identifié 1258 traumatismes pédiatriques, entraînant 217 décès (137 pré-hospitaliers, 80 hospitalier les hommes représentaient 62,7% des décès. Le groupe des 15 à 17 ans représentait la plupart des décès dans les deux groupes (avant l'hôpital 61,3%; à l'hôpital 41,3%). Blessures subies dans les régions rurales ont entraîné 74,7% de tous les décès. Pour les deux groupes, le traumatisme contondant était le type de blessure prédominant et les collisions de véhicules à moteur, les blessures les plus fréquentes. Les patients décédés avant l'hospitalisation avaient un âge moyen plus élevé (13,3 vs 10,7, p = 0,002) et une plus grande proportion étaient des blessures intentionnelles (23,4% contre 15%; p = 0,02). La résidence en milieu urbain était plus fréquemment observée dans les décès à l'hôpital (57,5% contre 36,5%, p < 0.001). La mortalité pré-hospitalière était associée à une augmentation de l'âge (CP 1.1) le score de gravité des blessures (CP 1.1) et les blessures intentionnelles (CP 15.6). CONCLUSIONS: Plus de 10% des traumatismes pédiatriques majeurs ont entraîné un décès avant l'hôpital, principalement à cause de troubles moteurs les collisions de véhicules dans les régions rurales. Comparativement à la mortalité à l'hôpital, les patients qui sont décédés avant. les établissements de soins palliatifs étaient plus âgés et plus susceptibles d'avoir intentionnellement subi des blessures plus graves. Ces résultats soulignent l'importance pour les médecins d'urgence et les systèmes de SMU pour tenir compte des facteurs géographiques et des tendances en matière de blessures, préconiser amélioration des programmes de prévention des blessures, du soutien en santé mentale et de la prestation sur place services de soins intensifs.

A Case of Septic Portal Vein Thrombosis in a 71-Year-Old Female.

Portal vein thrombosis (PVT) is a relatively rare condition that is characterized by partial or complete occlusion of the portal vein. The most common risk factors for developing PVT are a result of a low intra-hepatic vein flow or pro-thrombotic states, including underlying liver disease, coagulopathies, infection, and malignancy. Patients with PVT can present asymptomatically, while others are in profound shock. Clinical manifestations vary based on the location of the thrombus, degree of occlusion, and if it has become infected. Although an uncommon source of sepsis in the emergency department (ED), maintaining a high degree of clinical suspicion for septic PVT is critical as there are additional treatment considerations apart from early antibiotic therapy as in general sepsis. The following case report focuses on a 71-year-old woman with a septic PVT who presented to the ED with fever and hypotension in the absence of known risk factors. Current management guidelines and evidence regarding treatment strategies for septic PVT are also discussed in further detail.

Treatment-Resistant Wide-Complex Tachycardia in a Three-Year-Old Girl.

Wide-complex, monomorphic tachycardias represent a range of tachyarrhythmias. Such patients can present asymptomatically and hemodynamically stable, while others are in shock. The etiology of the rhythm can be difficult to determine in the emergency department, and although electrocardiogram findings may be helpful, a workup after stabilization may be necessary to determine the cause. Treatment is therefore dependent on hemodynamic status and follows a stepwise approach, as initial therapies may be ineffective. We present the case of a three-year-old girl with wide-complex tachycardia which was exceedingly refractory to preliminary treatments and required trials of multiple treatment approaches to achieve conversion to normal sinus rhythm.

Alteration in oxytocin levels induced by early social environment affects maternal behavior and estrogen receptor alpha in mandarin voles (Microtus mandarinus).

Many studies have shown that the early social environment exerts long-term effects on the brain and also the parental behavior of adults. Oxytocin (OXT) is one of the most important neurotransmitters that regulate social behavior; howerve, whether the early social environment affects parental behavior via OXT remains unclear. Using socially monogamous adult mandarin voles (Microtus mandarinus), the present study found that 1) both paternal deprivation and early social deprivation significantly decreased OXT expression in both the paraventricular hypothalamic nucleus (PVN) and the supraoptic nucleus (SON) of F2 generation offspring; 2) systemic neonatal OXT injection in naïve animals promoted maternal but not paternal behavior in adult F2 offspring; 3) systemic neonatal OXT injection significantly increased ERα expression in both the medial preoptic area (MPOA) and the ventro medial hypothalamic nucleus (VMH) in female but not in male mandarin voles; 4) systemic neonatal administration of an OXT antagonist significantly reduced ERα expression in the bed nucleus of the stria terminalis (BNST), VMH, and the arcuate hypothalamic nucleus (Arc) in females and in all examined brain regions in males. In summary, the obtained data demonstrate that the early social environment could affect OXT level, which in turn leads to long-term effects on ERα expression in relevant brain regions, consequently affecting maternal behavior but not paternal behavior.

2-Arachidonylglycerol Protects Primary Astrocytes Exposed to Oxygen-Glucose Deprivation Through a Blockade of NDRG2 Signaling and STAT3 Phosphorylation.

The human N-Myc downstream-regulated gene 2 (NDRG2) is expressed in astrocytes, and may be involved in the modulation of gliacyte function in the central nervous system. Our previous study found suppression of NDRG2 up-regulation in reactive astrocytes in cerebral ischemic tolerance. 2-Arachidonylglycerol (2-AG) can induce cerebral ischemic tolerance. However, the underlying mechanism of NDRG2 in cytoprotection induced by 2-AG in primary astrocytesis still unknown. In this study, we investigated the role of NDRG2 in cerebral ischemic tolerance induced by 2-AG after oxygen-glucose deprivation (OGD) in primary astrocytes. The results showed that primary astrocytes exposed to OGD resulted in marked increase of lactate dehydrogenase (LDH) release and decrease of methyl thiazolyl tetrazolium (MTT) reduction activity in comparison to control cultures. The levels of NDRG2 and phospho-signal transducer and activator of transcription 3 (pSTAT3) in the OGD group were comparably higher than those in the control group, and the up-regulation of NDRG2 and pSTAT3 was suppressed in NDRG2 siRNA group. The cell viability in the 2-AG group was higher than that in the OGD group, and transfecting the NDRG2 pSRL-CDH1-GFP vector reversed the protective effects of 2-AG. The levels of NDRG2 and pSTAT3 in the 2-AG group were lower than those in the OGD group. 2-AG suppressed STAT3 phosphorylation by decreased expression of NDRG2. In conclusion, 2-AG protects primary astrocytes exposed to oxygen-glucose deprivation through a blockade of NDRG2 signaling and STAT3 phosphorylation. These findings bring insight to the roles of NDRG2 in ischemic-hypoxic injury and provide novel potential targets for future potent clinical therapies on cerebral ischemia injury.

Cannabinoids & Stress: impact of HU-210 on behavioral tests of anxiety in acutely stressed mice.

Anxiety disorders are one of the most prevalent classes of mental disorders affecting the general population, but current treatment strategies are restricted by their limited efficacy and side effect profiles. Although the cannabinoid system is speculated to be a key player in the modulation of stress responses and emotionality, the vast majority of current research initiatives had not incorporated stress exposure into their experimental designs. This study was the first to investigate the impact of exogenous cannabinoid administration in an acutely stressed mouse model, where CD1 mice were pre-treated with HU-210, a potent CB1R agonist, prior to acute stress exposure and subsequent behavioral testing. Exogenous cannabinoid administration induced distinct behavioral phenotypes in stressed and unstressed mice. While low doses of HU-210 were anxiolytic in unstressed subjects, this effect was abolished when mice were exposed to an acute stressor. The administration of higher HU-210 doses in combination with acute stress exposure led to severe locomotor deficits that were not previously observed at the same dose in unstressed subjects. These findings suggest that exogenous cannabinoids and acute stress act synergistically in an anxiogenic manner. This study underlies the importance of including stress exposure into future anxiety-cannabinoid research due to the differential impact of cannabinoid administration on stressed and unstressed subjects.

Combination of HBO and Memantine in Focal Cerebral Ischemia: Is There a Synergistic Effect?

Hyperbaric oxygen (HBO) therapy and memantine, a non-competitive NMDA antagonist, are both promising treatment strategies for improving stroke prognosis. However, HBO's narrow therapeutic time window (<6 h post-stroke) and the adverse effect of high-dose MEM administration limits the use of these therapeutic interventions. In this study, we investigated whether or not MEM could prolong the narrow therapeutic window of HBO treatment. Transient focal cerebral ischemia was induced in male Sprague-Dawley rats by middle cerebral artery occlusion (MCAO) for 120 min. MCAO produced neurobehavioral deficits, increased infarction volume, increased Evans blue (EB) content and levels of pro-inflammatory factors, as well as depleted glutathione (GSH), and reduced catalase (CAT) and superoxide dismutase (SOD) activity in the ischemic ipsilateral hemisphere. The combination of 5 mg/kg MEM treatment 15 min after the onset of ischemic event and HBO therapy 12 h post-reperfusion significantly restored neurologic scores, EB concentration and IL-10 levels, as well as significantly decreased infarct volume and increased antioxidant activity. These results imply that the combination of MEM and HBO therapy not only prolongs the therapeutic window of HBO treatment, but also lowers the dosage requirement of MEM. The mechanism underlying the neuroprotective effects of the combined treatment may lie in alleviated blood-brain barrier (BBB) permeability, inhibited inflammatory response, and up-regulation of the antioxidant enzyme activity.

Electroacupuncture attenuates reference memory impairment associated with astrocytic NDRG2 suppression in APP/PS1 transgenic mice.

Electroacupuncture (EA) has demonstrated therapeutic potential for the treatment of Alzheimer's disease (AD). A previous study reported that N-myc downstream-regulated gene 2 (NDRG2) was upregulated in the brain of patients with AD. In the present study, we investigated the effects of repeated EA administration on reference memory impairment and the role of NDRG2 in an amyloid precursor protein (APP)/presenilin-1 (PS1) double transgenic mouse model. Age-matched wild-type and transgenic mice were treated with EA (once per day for 30 min) for 4 weeks (four courses of 5 days EA administration and 2 days rest) beginning at 10 months of age. At seven and ten postnatal months of age and following a 4-week EA treatment regime, mice received training in the Morris water maze (MWM) and a probe test. Brain tissue was analyzed via Western blot and double-label immunofluorescence. Beginning at 7 months of age, APP/PS1 mice began to exhibit deficits in reference memory in the MWM test, an impairment associated with upregulation of glial fibrillary acidic protein (GFAP) and NDRG2. Four weeks of EA administration significantly ameliorated cognitive impairments and suppressed GFAP and NDRG2 upregulation. In conclusion, our findings demonstrated that EA administration can alleviate reference memory deficits and suppress NDRG2 upregulation in an AD transgenic mouse model. This study provides supportive evidence for EA as an effective therapeutic intervention for AD, as well as NDRG2 as a novel target for AD treatment.