With improvements in personnel and vehicular body armor,robust casualty evacuation capabilities,and damage control resuscitation strategies,more combat casualties are surviving to reach higher levels of care throughou...With improvements in personnel and vehicular body armor,robust casualty evacuation capabilities,and damage control resuscitation strategies,more combat casualties are surviving to reach higher levels of care throughout the casualty evacuation system.As such,medical centers are becoming more accustomed to managing the deleterious late consequences of combat trauma related to the dysregulation of the immune system.In this review,we aim to highlight these late consequences and identify areas for future research and therapeutic strategies.Trauma leads to the dysregulation of both the innate and adaptive immune responses,which places the injured at risk for several late consequences,including delayed wound healing,late onset sepsis and infection,multi-organ dysfunction syndrome,and acute respiratory distress syndrome,which are significant for their association with the increased morbidity and mortality of wounded personnel.The mechanisms by which these consequences develop are complex but include an imbalance of the immune system leading to robust inflammatory responses,triggered by the presence of damage associated molecules and other immune-modifying agents following trauma.Treatment strategies to improve outcomes have been difficult to develop as the immunophenotype of injured personnel following trauma is variable,fluid and difficult to determine.As more information regarding the triggers that lead to immune dysfunction following trauma is elucidated,it may be possible to identify the immunophenotype of injured personnel and provide targeted treatments to reduce the late consequences of trauma,which are known to lead to significant morbidity and mortality.展开更多
While conservative management such as fluid,bowel rest,and antibiotics is the mainstay of current acute pancreatitis management,there is a lot of promise in pharmacologic therapies that target various aspects of the p...While conservative management such as fluid,bowel rest,and antibiotics is the mainstay of current acute pancreatitis management,there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis.Extensive review of preclinical studies,which include assessment of therapies such as anti-secretory agents,protease inhibitors,anti-inflammatory agents,and anti-oxidants are discussed.Many of these studies have shown therapeutic benefit and improved survival in experimental models.Based on available preclinical studies,we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis.To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies.Despite these discouraging clinical studies,there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients.Better understanding of acute pancreatitis pathophysiology and lessons learnedfrom past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis.展开更多
The aim of this study was to explore the effects of parenteral supplementation with ω-3 fish oil emulsion （Omegaven） on systemic inflammatory response syndrome （SIRS） during the initial stage of severe acute panc...The aim of this study was to explore the effects of parenteral supplementation with ω-3 fish oil emulsion （Omegaven） on systemic inflammatory response syndrome （SIRS） during the initial stage of severe acute pancreatitis （SAP）. In a prospective, randomized and controlled trial, 60 patients with SAP were randomized either to treat with conventional therapy （Con group, n=30） or conventional therapy plus intravenous supplementation with ω-3 fish oil emulsion 0.2 g/kg every day （FO group, n=30）. The effects were analyzed by the SIRS-related indexes. The results showed that APACHE-Ⅱ scores in FO group were significantly lower, and the gap increased much farther after the 4th day than those in Con group （P〈0.05）. Fluid equilibrium time became shorter markedly in FO group than in Con group （5.1±2.2 days vs 8.4±2.3 days）. In FO group, SIRS scores were markedly decreased and the SIRS state vanished after the 4th day; Plasma level of TNF-α was significantly reduced, while IL-10 decreased markedly, most prominently between the 4th and 7th day, and the ratio of IL-10/TNF-α raised as compared with Con group （P〈0.05）. During the initial stage of SAP, parenteral supplementation with ω-3 fish oil emulsion could efficiently lower the magnitude and persistence time of the SIRS, markedly retrieve the unbalance of the pro-/anti-inflammatory cytokines, improve severe condition of illness and may provide a new way to regulate the SIRS.展开更多
基金RJS was supported by National Institutes of Health grants,K08-GM117367.
文摘With improvements in personnel and vehicular body armor,robust casualty evacuation capabilities,and damage control resuscitation strategies,more combat casualties are surviving to reach higher levels of care throughout the casualty evacuation system.As such,medical centers are becoming more accustomed to managing the deleterious late consequences of combat trauma related to the dysregulation of the immune system.In this review,we aim to highlight these late consequences and identify areas for future research and therapeutic strategies.Trauma leads to the dysregulation of both the innate and adaptive immune responses,which places the injured at risk for several late consequences,including delayed wound healing,late onset sepsis and infection,multi-organ dysfunction syndrome,and acute respiratory distress syndrome,which are significant for their association with the increased morbidity and mortality of wounded personnel.The mechanisms by which these consequences develop are complex but include an imbalance of the immune system leading to robust inflammatory responses,triggered by the presence of damage associated molecules and other immune-modifying agents following trauma.Treatment strategies to improve outcomes have been difficult to develop as the immunophenotype of injured personnel following trauma is variable,fluid and difficult to determine.As more information regarding the triggers that lead to immune dysfunction following trauma is elucidated,it may be possible to identify the immunophenotype of injured personnel and provide targeted treatments to reduce the late consequences of trauma,which are known to lead to significant morbidity and mortality.
基金Supported by Robert Wood Johnson Foundation grant(to Habtezion A)National Institutes of Health Grant DK092421(to Habtezion A)American College of Gastroenterology(to Park W)
文摘While conservative management such as fluid,bowel rest,and antibiotics is the mainstay of current acute pancreatitis management,there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis.Extensive review of preclinical studies,which include assessment of therapies such as anti-secretory agents,protease inhibitors,anti-inflammatory agents,and anti-oxidants are discussed.Many of these studies have shown therapeutic benefit and improved survival in experimental models.Based on available preclinical studies,we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis.To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies.Despite these discouraging clinical studies,there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients.Better understanding of acute pancreatitis pathophysiology and lessons learnedfrom past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis.
文摘The aim of this study was to explore the effects of parenteral supplementation with ω-3 fish oil emulsion （Omegaven） on systemic inflammatory response syndrome （SIRS） during the initial stage of severe acute pancreatitis （SAP）. In a prospective, randomized and controlled trial, 60 patients with SAP were randomized either to treat with conventional therapy （Con group, n=30） or conventional therapy plus intravenous supplementation with ω-3 fish oil emulsion 0.2 g/kg every day （FO group, n=30）. The effects were analyzed by the SIRS-related indexes. The results showed that APACHE-Ⅱ scores in FO group were significantly lower, and the gap increased much farther after the 4th day than those in Con group （P〈0.05）. Fluid equilibrium time became shorter markedly in FO group than in Con group （5.1±2.2 days vs 8.4±2.3 days）. In FO group, SIRS scores were markedly decreased and the SIRS state vanished after the 4th day; Plasma level of TNF-α was significantly reduced, while IL-10 decreased markedly, most prominently between the 4th and 7th day, and the ratio of IL-10/TNF-α raised as compared with Con group （P〈0.05）. During the initial stage of SAP, parenteral supplementation with ω-3 fish oil emulsion could efficiently lower the magnitude and persistence time of the SIRS, markedly retrieve the unbalance of the pro-/anti-inflammatory cytokines, improve severe condition of illness and may provide a new way to regulate the SIRS.
