Effect of a pediatric trauma response team on emergency department treatment time and mortality of pediatric trauma victims

OBJECTIVE: Delay in the provision of definitive care for critically injured children may adversely effect outcome. We sought to speed care in the emergency department (ED) for trauma victims by organizing a formal trauma response system. DESIGN: A case-control study of severely injured children, comparing those who received treatment before and after the creation of a formal trauma response team. SETTING: A tertiary pediatric referral hospital that is a locally designated pediatric trauma center, and also receives trauma victims from a geographically large area of the Western United States. SUBJECTS: Pediatric trauma victims identified as critically injured (designated as "trauma one") and treated by a hospital trauma response team during the first year of its existence. Control patients were matched with subjects by probability of survival scores, and were chosen from pediatric trauma victims treated at the same hospital during the year preceding the creation of the trauma team. INTERVENTIONS: A trauma response team was organized to respond to pediatric trauma victims seen in the ED. The decision to activate the trauma team (designation of patient as "trauma one") is made by the pediatric emergency medicine (PEM) physician before patient arrival in the ED, based on data received from prehospital care providers. Activation results in the notification and immediate travel to the ED of a pediatric surgeon, neurosurgeon, emergency physician, intensivist, pharmacist, radiology technician, phlebotomist, and intensive care unit nurse, and mobilization of an operating room team. Most trauma one patients arrived by helicopter directly from accident scenes. OUTCOME MEASURES: Data recorded included identifying information, diagnosis, time to head computerized tomography, time required for ED treatment, admission Revised Trauma Score, discharge Injury Severity Score, surgical procedures performed, and mortality outcome. Trauma Injury Severity Score methodology was used to calculate the probability of survival and mortality compared with the reference patients of the Major Trauma Outcome Study, by calculation of z score. RESULTS: Patients treated in the ED after trauma team initiation had statistically shorter times from arrival to computerized tomography scanning (27 +/- 2 vs 21 +/- 4 minutes), operating room (63 +/- 16 vs 623 +/- 27 minutes) and total time in the ED (85 +/- 8 vs 821 +/- 9 minutes). Calculation of z score showed that survival for the control group was not different from the reference population (z = -0.8068), although survival for trauma-one patients was significantly better than the reference population (z = 2.102). CONCLUSION: Before creation of the trauma team, relevant specialists were individually called to the ED for patient evaluation. When a formal trauma response team was organized, time required for ED treatment of severe trauma was decreased, and survival was better than predicted compared with the reference Major Trauma Outcome Study population.     

Production of granulocyte colony-stimulating factor in vitro by monocytes from preterm and term neonates [see comments]

We postulated that defective generation of granulocyte colony- stimulating factor (G-CSF) by cells of newborn infants might underlie their deficiencies in upregulating neutrophil production and function during bacterial infection. To test this, we isolated monocytes from the blood of preterm neonates, term neonates, and adults and, after stimulation with various concentrations of interleukin-1 alpha (IL-1 alpha) or lipopolysaccharide (LPS), quantified G-CSF concentrations in cell supernatants and G-CSF mRNA in cell lysates. When stimulated with plateau concentrations of IL-1 alpha for 24 hours, G-CSF concentrations were higher in supernatants of adult cells (8,699 +/- 5,529 pg/10(6) monocytes) than in those from term infants (2,557 +/- 442 pg, P < .05) or from preterm infants (879 +/- 348 pg, P < .05 v adults). When stimulated with plateau concentrations of LPS, supernatants of monocytes from preterm neonates had less G-CSF than did those from term neonates or adults. G-CSF mRNA content was low in cells from preterm infants, higher in those from term infants, and highest in those from adults. On the basis of the in vitro studies, we speculated that serum G-CSF concentrations might be less elevated in neutropenic neonates than in neutropenic adults. Indeed, serum concentrations were relatively low in all nonneutropenic subjects; 92 +/- 34 pg/mL (mean +/- SEM) in 10 preterm neonates, 114 +/- 21 pg/mL in 16 term neonates, and 45 +/- 13 pg/mL in 11 healthy adults. Serum concentrations were not elevated in 7 neutropenic neonates (39 +/- 17 pg/mL) but were in 8 neutropenic adults (2101 +/- 942 pg/mL, P < .05 v healthy adults). Other studies suggested that the lower G-CSF production in neonates is not counterbalanced by a heightened sensitivity of G-CSF--responsive progenitors to G-CSF. Therefore, we speculate that newborn infants, particularly those delivered prematurely, generate comparatively low quantities of G-CSF after inflammatory stimulation, and that this might constitute part of the explanation for their defective upregulation of neutrophil production and function during infection.     

In vitro cell growth in neonates with Down's syndrome and transient myeloproliferative disorder

Bone marrow and peripheral blood cells from three newborns with Down's syndrome and transient myeloproliferative disorders were cultured in vitro. In the methylcellulose semiliquid system, normal colony formation with maturation and differentiation into granulocytes and monocyte-macrophages were observed in all three patients. This is different from the growth pattern usually seen in acute nonlymphocytic leukemia. A maternal serum inhibitor of both normal allogeneic GM-CFU and blast cell growth was also demonstrated, but its role in pathogenesis is uncertain. Normal in vitro granulopoiesis may help to differentiate the transient myeloproliferative syndrome from congenital leukemia in newborns with Down's syndrome.     

Reduced lysosomal clearance of autophagosomes promotes survival and colonization of Helicobacter pylori

Evasion of autophagy is key for intracellular survival of bacteria in host cells, but its involvement in persistent infection by Helicobacter pylori, a bacterium identified to invade gastric epithelial cells, remains obscure. The aim of this study was to functionally characterize the role of autophagy in H. pylori infection. Autophagy was assayed in H. pylori‐infected human gastric epithelium and the functional role of autophagy was determined via genetic or pharmacological ablation of autophagy in mouse and cell line models of H. pylori infection. Here, we showed that H. pylori inhibited lysosomal function and thereby promoted the accumulation of autophagosomes in gastric epithelial cells. Importantly, inhibiting autophagosome formation by pharmacological inhibitors or genetic ablation of BECN1 or ATG5 reduced H. pylori intracellular survival, whereas inhibition of lysosomal functions exerted an opposite effect. Further experiments demonstrated that H. pylori inhibited lysosomal acidification and the retrograde trafficking of mannose‐6‐phosphate receptors, both of which are known to positively regulate lysosomal function. We conclude that H. pylori subverts autophagy into a pro‐survival mechanism through inhibition of lysosomal clearance of autophagosomes. Disruption of autophagosome formation offers a novel strategy to reduce H. pylori colonization in human stomachs. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Circumvention of multi-drug resistance of cancer cells by Chinese herbal medicines

Multi-drug resistance (MDR) of cancer cells severely limits therapeutic outcomes. A proposed mechanism for MDR involves the efflux of anti-cancer drugs from cancer cells, primarily mediated by ATP-binding cassette (ABC) membrane transporters including P-glycoprotein. This article reviews the recent progress of using active ingredients, extracts and formulae from Chinese medicine (CM) in circumventing ABC transporters-mediated MDR. Among the ABC transporters, Pgp is the most extensively studied for its role in MDR reversal effects. While other MDR reversal mechanisms remain unclear, Pgp inhibition is a criterion for further mechanistic study. More mechanistic studies are needed to fully establish the pharmacological effects of potential MDR reversing agents.     

迷迭香提取物的抗乳腺癌活性研究

目的 :　研究天然香料迷迭香提取物 ( rosemary extract)及其主要抗氧化组分的抗乳腺癌活性。方法 :　采用常规的 MTT法 ,考察迷迭香提取物及其主要抗氧化组分鼠尾草酸( carnosic acid) ,鼠尾草酚 ( carnosol) ,rosmanol和迷迭香酸 ( rosmarinic acid)等对扩散型大鼠乳腺癌细胞 F3II和人乳腺癌细胞 MCF- 7增殖的抑制活性。结果 :　 ( 1 )鼠尾草酚和 rosmanol对乳腺癌细胞增殖抑制较强 ,鼠尾草酸和迷迭香提取物对乳腺癌细胞增殖抑制较弱 ,而迷迭香酸在该实验条件下基本上对增殖无抑制活性。 ( 2 )鼠尾草酚是一个选择性很高的乳腺癌细胞增殖抑制剂 ,其对乳腺癌细胞呈现较强的抑制活性 ,而对正常乳腺细胞增殖则基本上无抑制活性或抑制活性很低。结论 :　迷迭香主要抗氧化组份鼠尾草酚和 rosmanol对乳腺癌细胞增殖呈现较强的抑制活性 ,其中鼠尾草酚的抑制活性具有良好的选择性 ,是一个极有希望的乳腺癌增殖抑制剂 ,值得进一步研究