Fresh Frozen Plasma Resuscitation Provides Neuroprotection Compared to Normal Saline in a Large Animal Model of Traumatic Brain Injury and Polytrauma

We have previously shown that early treatment with fresh frozen plasma (FFP) is neuroprotective in a swine model of hemorrhagic shock (HS) and traumatic brain injury (TBI). However, it remains unknown whether this strategy would be beneficial in a more clinical polytrauma model. Yorkshire swine (42?50?kg) were instrumented to measure hemodynamic parameters, brain oxygenation, and intracranial pressure (ICP) and subjected to computer-controlled TBI and multi-system trauma (rib fracture, soft-tissue damage, and liver injury) as well as combined free and controlled hemorrhage (40% blood volume). After 2?h of shock (mean arterial pressure, 30?35?mm Hg), animals were resuscitated with normal saline (NS; 3?volume) or FFP (1?volume; n=6/group). Six hours postresuscitation, brains were harvested and lesion size and swelling were evaluated. Levels of endothelial-derived vasodilator endothelial nitric oxide synthase (eNOS) and vasoconstrictor endothelin-1 (ET-1) were also measured. FFP resuscitation was associated with reduced brain lesion size (1005.8 vs. 2081.9?mm3; p=0.01) as well as swelling (11.5% vs. 19.4%; p=0.02). Further, FFP-resuscitated animals had higher brain oxygenation as well as cerebral perfusion pressures. Levels of cerebral eNOS were higher in the FFP-treated group (852.9 vs. 816.4?ng/mL; p=0.03), but no differences in brain levels of ET-1 were observed. Early administration of FFP is neuroprotective in a complex, large animal model of polytrauma, hemorrhage, and TBI. This is associated with a favorable brain oxygenation and cerebral perfusion pressure profile as well as higher levels of endothelial-derived vasodilator eNOS, compared to normal saline resuscitation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140168/1/neu.2014.3535.pd

Eggs of the copepod Acartia tonsa Dana require hypoxic conditions to tolerate prolonged embryonic development arrest

Additional file 1. Raw data and calculations for all experiments as well as an overview of experiments in this study

Liraglutide for Weight Management in Children and Adolescents With Prader-Willi Syndrome and Obesity

CONTEXT: Prader-Willi syndrome (PWS) is characterized by lack of appetite control and hyperphagia, leading to obesity. Pharmacological options for weight management are needed. OBJECTIVE: To determine whether liraglutide treatment for weight management is superior to placebo/no treatment in pediatric individuals with PWS. METHODS: This was a multicenter, 52-week, placebo-controlled trial with a 16-week double-blinded period. Adolescents (n = 31, aged 12-17 years; Tanner stage 2-5) and children (n = 24, aged 6-11 years; Tanner stage <2) with PWS and obesity were included. Patients were randomized 2:1 to liraglutide 3.0 mg (or maximum-tolerated dose) or placebo for 16 weeks, after which placebo was stopped. Liraglutide was continued for 52 weeks. All patients followed a structured diet and exercise program throughout the trial. The coprimary endpoints were change in body mass index (BMI) standard deviation score (SDS) from baseline to 16 and 52 weeks. Secondary endpoints included other weight-related parameters, hyperphagia, and safety. RESULTS: Change in BMI SDS from baseline to weeks 16 and 52 was not significantly different between treatments in adolescents (estimated treatment difference: -0.07 at week 16 and -0.14 at week 52) and children (-0.06 and -0.07, respectively). Changes in other weight-related parameters between treatments were not significant. At week 52, hyperphagia total and drive scores were lower in adolescents treated with liraglutide vs no treatment. The most common adverse events with liraglutide were gastrointestinal disorders. CONCLUSION: Although the coprimary endpoints were not met, changes in hyperphagia total and drive scores in adolescents warrant further studies on liraglutide in this population

Differential effects of fresh frozen plasma and normal saline on secondary brain damage in a large animal model of polytrauma, hemorrhage and traumatic brain injury

We have previously shown that the extent of traumatic brain injury (TBI) in large animal models can be reduced with early infusion of fresh frozen plasma (FFP), but the precise mechanisms remain unclear. In this study, we investigated whether resuscitation with FFP or normal saline differed in their effects on cerebral metabolism and excitotoxic secondary brain injury in a model of polytrauma, TBI, and hemorrhagic shock. Yorkshire swine (n = 10) underwent Grade III liver injury, rib fracture, standardized TBI, and volume-controlled hemorrhage, (40% ± 5%) and were randomly resuscitated with either FFP or normal saline. Hemodynamic parameters and brain oxygenation were continuously monitored, while microdialysis was used to measure the brain concentrations of pyruvate, lactate, glutamate, and glycerol at baseline; 1 hour and 2 hours after shock; immediate postresuscitation (PR); as well as 2, 4, and 6 hours PR. Cells from the injured hemisphere were separated into mitochondrial and cytosolic fractions and analyzed for activity of the pyruvate dehydrogenase complex (PDH). There were no baseline differences in cerebral perfusion pressure, brain oxygenation, as well as concentrations of pyruvate, lactate, glutamate, and glycerol between the groups. At 2 hours and 4 hours PR, the FFP group had significantly higher cerebral perfusion pressures (52 [5] mm Hg vs. 43 [2] mm Hg, p = 0.016; and 50 [7] mm Hg vs. 37 [1] mm Hg, p = 0.008, respectively). There was a sustained and significant (p < 0.05) drop in the glutamate and glycerol levels in the FFP group, implying a decrease in excitotoxicity and brain damage, respectively. Mitochondrial PDH activity was significantly higher (2,666.2 [638.2] adjusted volume INT × mm vs. 1,293.4 [88.8] adjusted volume INT × mm, p = 0.008), and cytosolic PDH activity was correspondingly lower (671.4 [209.2] adjusted volume INT × mm vs. 3070.7 [484.3] adjusted volume INT × mm, p < 0.001) in the FFP group, suggesting an attenuation of mitochondrial dysfunction and permeability. In this model of TBI, polytrauma, and hemorrhage, FFP resuscitation confers neuroprotection by improving cerebral perfusion, diminishing glutamate-mediated excitotoxic secondary brain injury and reducing mitochondrial dysfunction

Achieving consensus on the language of obesity: a modified Delphi studyResearch in context

Summary: Background: Obesity is recognized by the World Health Organization as a chronic disease. As such, it should be referred to using the language of chronic diseases, with correct and established terminology and definitions. This study was designed to map the current language used to discuss obesity and to compare this with the standard language used for chronic disease. Methods: We performed a modified Delphi study to identify the language of chronic disease that is being used in the context of obesity, and to identify discrepancies and potential use of inadequate language with respect to the standard language used for chronic diseases. Participants (n = 24) were identified from relevant stakeholder groups and desk research, and included patients, healthcare professionals, policymakers, researchers, industry, and payers (social insurers) of 18 nationalities/regions in Europe, North/South America, and South Africa. Participants were enrolled between 20.10.2020 and 30.10.2020. The study comprised two rounds of qualitative surveys. In Round 1, participants responded to six open-ended questions. Round 2 comprised 38 statements based on key terms/themes identified in Round 1 and covered the definition, causes, progression, treatment, management, and complications of obesity. Consensus was defined as ≥70% participant agreement on a statement. Findings: All participants completed Round 1 and 23 participants completed Round 2. In Round 2, consensus was reached for 28 of the 38 statements. Participants reached a consensus regarding the use of statements that acknowledge the heterogeneous nature of obesity, but not on the use of statements that: defined obesity based on body mass index; regarded psychological, physical, or physiological factors among the main causes of obesity; or implied that weight loss should be the aim of obesity treatment. Interpretation: This study uses expert consensus to provide insight into the language used to describe obesity as a chronic disease, and forms the basis for a unified language of obesity. Funding: Innovative Medicines Initiative, Novo Nordisk A/S