RESUMO
OBJECTIVE: The aim of this study was to identify a mortality benefit with the use of whole blood (WB) as part of the resuscitation of bleeding trauma patients. BACKGROUND: Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with WB emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality. METHODS: We performed a 14-center, prospective observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score. All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included acute kidney injury, deep vein thrombosis/pulmonary embolism, pulmonary complications, and bleeding complications. RESULTS: A total of 1623 [WB: 1180 (74%), BCT: 443(27%)] patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs 0.83), more comorbidities, and more blunt MOI (all P <0.05). After controlling for center, age, sex, MOI, and injury severity score, we found no differences in the rates of acute kidney injury, deep vein thrombosis/pulmonary embolism or pulmonary complications. WB patients were 9% less likely to experience bleeding complications and were 48% less likely to die than BCT patients ( P <0.0001). CONCLUSIONS: Compared with BCT, the use of WB was associated with a 48% reduction in mortality in trauma patients. Our study supports the use of WB use in the resuscitation of trauma patients.
Assuntos
Injúria Renal Aguda , Hemostáticos , Trombose Venosa , Ferimentos e Lesões , Transfusão de Sangue , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Ressuscitação , Ferimentos e Lesões/complicações , Ferimentos e Lesões/terapiaRESUMO
The human leukocyte antigen (HLA) system is a highly polymorphic family of genes involved in immunity and responsible for identifying self versus non-self. HLA typing is essential for solid organ and bone marrow transplantation as well as in non-transplant settings such as disease association and pharmacogenomics. Typing of HLA genes differs from most molecular testing as, rather than evaluating differences from an accepted "wild-type" gene, it must distinguish between thousands of similar, but distinct alleles. This article will describe the HLA system and nomenclature. We will then discuss clinical uses of HLA typing including solid organ transplantation, hematopoietic stem cell transplantation, evaluation of platelet refractory patients, disease association, and pharmacogenetics. Finally, we describe common molecular methods of HLA typing.
Assuntos
Antígenos HLA/classificação , Antígenos HLA/genética , Teste de Histocompatibilidade/métodos , Alelos , Genótipo , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Laboratórios , Patologia Molecular/métodos , Análise de Sequência de DNA/métodosRESUMO
IL-13 has a prominent role in host defense against the gastrointestinal nematode Nippostrongylus brasiliensis; however, the role of IL-13Ralpha2 in the immune and functional response to enteric infection is not known. In the current study, we investigated changes in smooth muscle and epithelial cell function as well as alterations in gene expression of IL-13 and IL-4 and their receptors using laser-capture microdissection of specific cell types in the small intestine of N. brasiliensis-infected mice. An infection-induced up-regulation of IL-13Ralpha2 gene expression was confined to smooth muscle and was dependent on STAT6 and IL-13, but not on IL-4. In contrast, expression of IL-13Ralpha1 was reduced, indicating that changes in IL-13alpha2 expression serve to limit the biological effects of IL-13. The increased availability of IL-13 in IL-13Ralpha2(-/-) mice resulted in marked changes in constitutive epithelial and smooth muscle function. In addition, maximal changes in smooth muscle hypercontractility and epithelial cell resistance peaked earlier after infection in IL-13Ralpha2(-/-) compared with wild-type mice. This did not coincide with an earlier Th2 immune response as expression of IL-4 and IL-13 was attenuated in IL-13Ralpha2(-/-) mice and worm expulsion was similar to that of wild-type mice. These data show that IL-13Ralpha2 plays an important role in nematode infection by limiting the availability of IL-13 during infection, thereby regulating both the immune and biological effects of IL-13.
Assuntos
Subunidade alfa2 de Receptor de Interleucina-13/imunologia , Nippostrongylus/imunologia , Infecções por Strongylida/imunologia , Animais , Regulação da Expressão Gênica/imunologia , Imunidade , Interleucina-13 , Interleucina-4 , Camundongos , Camundongos Endogâmicos BALB C , Músculo Liso/metabolismo , Fator de Transcrição STAT6RESUMO
Infection with gastrointestinal nematodes exerts profound effects on both immune and physiological responses of the host. Helminth infection induces a hypercontractility of intestinal smooth muscle that is dependent on the Th2 cytokines, IL-4 and IL-13, and may contribute to worm expulsion. Protease-activated receptors (PARs) are expressed throughout the gut, and activation of PAR-1 was observed in asthma, a Th2-driven pathology. In the current study we investigated the physiologic and immunologic regulation of PAR-1 in the murine small intestine, specifically 1) the effect of PAR-1 agonists on small intestinal smooth muscle contractility, 2) the effects of Nippostrongylus brasiliensis infection on PAR-1 responses, 3) the roles of IL-13 and IL-4 in N. brasiliensis infection-induced alterations in PAR-1 responses, and 4) the STAT6 dependence of these responses. We demonstrate that PAR-1 activation induces contraction of murine intestinal smooth muscle that is enhanced during helminth infection. This hypercontractility is associated with an elevated expression of PAR-1 mRNA and protein. N. brasiliensis-induced changes in PAR-1 function and expression were seen in IL-4-deficient mice, but not in IL-13- or STAT6-deficient mice, indicating the dependence of IL-13 on the STAT6 signaling pathway independent of IL-4.