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      The Metabolic Stress Response to Burn Trauma: Current Understanding and Therapies

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          Summary

          Severe burns incur a profound stress response, which is unrivaled in terms of its magnitude and duration. Recent evidence suggests that the pathophysiological stress response to severe burns persists for several years post injury. Thus, there is a pressing need for novel strategies that mitigate this response and restore normal metabolic function in burn survivors.

          This is the first installment of a three-part series exploring the stress response to severe burn trauma. In this article we aim to distill the current knowledge pertaining to the stress response to burn trauma, highlighting recent developments and important knowledge gaps that need to be pursued in order to develop novel therapeutic strategies which improve outcomes in burn survivors.

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          Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.).

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            Long-Term Persistance of the Pathophysiologic Response to Severe Burn Injury

            Background Main contributors to adverse outcomes in severely burned pediatric patients are profound and complex metabolic changes in response to the initial injury. It is currently unknown how long these conditions persist beyond the acute phase post-injury. The aim of the present study was to examine the persistence of abnormalities of various clinical parameters commonly utilized to assess the degree hypermetabolic and inflammatory alterations in severely burned children for up to three years post-burn to identify patient specific therapeutic needs and interventions. Methodology/Principal Findings Patients: Nine-hundred seventy-seven severely burned pediatric patients with burns over 30% of the total body surface admitted to our institution between 1998 and 2008 were enrolled in this study and compared to a cohort non-burned, non-injured children. Demographics and clinical outcomes, hypermetabolism, body composition, organ function, inflammatory and acute phase responses were determined at admission and subsequent regular intervals for up to 36 months post-burn. Statistical analysis was performed using One-way ANOVA, Student's t-test with Bonferroni correction where appropriate with significance accepted at p<0.05. Resting energy expenditure, body composition, metabolic markers, cardiac and organ function clearly demonstrated that burn caused profound alterations for up to three years post-burn demonstrating marked and prolonged hypermetabolism, p<0.05. Along with increased hypermetabolism, significant elevation of cortisol, catecholamines, cytokines, and acute phase proteins indicate that burn patients are in a hyperinflammatory state for up to three years post-burn p<0.05. Conclusions Severe burn injury leads to a much more profound and prolonged hypermetabolic and hyperinflammatory response than previously shown. Given the tremendous adverse events associated with the hypermetabolic and hyperinflamamtory responses, we now identified treatment needs for severely burned patients for a much more prolonged time.
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              Metformin: an update.

              Metformin is an insulin-sensitizing agent with potent antihyperglycemic properties. Its efficacy in reducing hyperglycemia in type 2 diabetes mellitus is similar to that of sulfonylureas, thiazolidinediones, and insulin. Metformin-based combination therapy is often superior to therapy with a single hypoglycemic agent. The antihyperglycemic properties of metformin are mainly attributed to suppressed hepatic glucose production, especially hepatic gluconeogenesis, and increased peripheral tissue insulin sensitivity. Although the precise mechanism of hypoglycemic action of metformin remains unclear, it probably interrupts mitochondrial oxidative processes in the liver and corrects abnormalities of intracellular calcium metabolism in insulin-sensitive tissues (liver, skeletal muscle, and adipocytes) and cardiovascular tissue.
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                Author and article information

                Journal
                2985213R
                5470
                Lancet
                Lancet
                Lancet (London, England)
                0140-6736
                1474-547X
                17 December 2017
                01 October 2016
                04 January 2018
                : 388
                : 10052
                : 1417-1426
                Affiliations
                [1 ]Department of Surgery, University of Texas Medical Branch
                [2 ]Shriners Hospitals for Children – Galveston, Texas
                [3 ]Department of Surgery, Massachusetts General Hospital, Harvard Medical School – Boston, Massachusetts
                [4 ]Department of Kinesiology and Health, Rutgers University, New Brunswick, New Jersey
                [5 ]Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, New Jersey
                Author notes
                [*]

                Full Professor

                Article
                NIHMS927924
                10.1016/S0140-6736(16)31469-6
                5753602
                27707498
                a78de349-b83a-46af-bebc-2b9515e2eed6

                This manuscript version is made available under the CC BY-NC-ND 4.0 license.

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                Medicine
                Medicine

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