Shock

Trauma, burn injury, sepsis and ischemia lead to acute and chronic loss of skeletal muscle mass and function. Healthy muscle is essential for eating, posture, respiration, reproduction, and mobility, as well as for appropriate function of the senses including taste, vision, and hearing. Beyond providing support and contraction, skeletal muscle also exerts essential roles in temperature regulation, metabolism, and overall health. As the primary reservoir for amino acids, skeletal muscle regulates whole-body protein and glucose metabolism by providing substrate for protein synthesis and supporting hepatic gluconeogenesis during illness and starvation...

INTRODUCTION: In human sepsis, little is known about the relationships between complement activation and the clinical characteristics of sepsis, including disseminated intravascular coagulation (DIC), interventions, and prognosis. MATERIALS AND METHODS: Adult patients with sepsis admitted from November 2016 to December 2018 were included. We used the plasma levels of soluble C5b-9 (SC5b-9) as a marker of complement activation. We compared the clinical characteristics and complement components between patients with and without DIC...

BACKGROUND: Trauma and hemorrhagic shock trigger mobilization of hematopoietic progenitor cells (HPC) from bone marrow to peripheral blood. Hepatocyte growth factor (HGF), tyrosine-protein kinase Met (c-Met), matrix metallopeptidase 9 (MMP-9), and corticosterone regulate this mobilization process. We hypothesized that beta-blockade with propranolol and sympathetic outflow inhibition with clonidine following trauma and chronic stress would decrease hematopoietic progenitor cell mobilization...

OBJECTIVE: This study is to evaluate the effects of the Adenoviral βARKct (Adv. βARKct) myocardial gene transfection following cardioplegic arrest on cardiopulmonary bypass (CPB) in a swine model. METHODS: Swine models of cardioplegic arrest on CPB were established after 5 days of myocardial injection of Adv. βARKct or Adv. luciferase. The pigs were randomized into Adv. βARKct, Control, and Sham groups. Invasive hemodynamics, cardiac function, biomarkers and tissue morphology were assessed...

BACKGROUND: This study aimed to assess the severity of acute lung injury after mild or severe hemorrhagic shock and resuscitation, and to examine the therapeutic effects of suberoylanilide hydroxamic acid (SAHA) on lung injury. METHODS: Mild and severe hemorrhagic shock were induced by total blood volume loss of 20% or 40%, respectively, which was maintained for 60 min. Then, resuscitation was performed by autologous blood and SAHA or a vehicle solution accordingly...

PURPOSE: Lipopolysaccharides (LPS) are presumed to contribute to the inflammatory response in sepsis. We investigated if extracorporeal Alteco® LPS Adsorber for LPS removal in early Gram-negative septic shock was feasible and safe. Also, effect on endotoxin level, inflammatory response and organ function were assessed. METHODS: A pilot, double-blinded, randomized, Phase IIa, feasibility clinical investigation was undertaken in six Scandinavian intensive care units aiming to allocate thirty-two septic shock patients with abdominal or urogenital focus to LPS Adsorber therapy or a Sham Adsorber, therapy without active LPS-binding...

OBJECTIVE: Diaphragm dysfunction often occurs in patients with prolonged mechanical ventilation (MV) after resuscitation. Mild hypothermia (MHT) is a classical treatment to improve the outcomes of cardiac arrest (CA), however, the effect of MHT on diaphragm function remains unclear. In the present study, we aim to investigate the effect of MHT on diaphragmatic microcirculation and function using a murine cardiopulmonary resuscitation model. METHODS: Thirty-two rats were randomly assigned into a resuscitation normothermia group (RNT), an intra-resuscitation hypothermia group (IRH), a post-resuscitation hypothermia group (PRH), or a sham control group...

BACKGROUND: Circulating complement C3 fragments released during septic shock might contribute to the development of complications such as profound hypotension and disseminated intravascular coagulation. The role of C3 in the course of septic shock varies in the literature, possibly because circulating C3 exists in different forms indistinguishable via traditional ELISA-based methods. We sought to test the relationship between C3 forms, measured by Western blotting with its associated protein size differentiation feature, and clinical outcomes...

Surfactant protein B (SP-B) is essential for life and plays critical roles in host defense and lowering alveolar surface tension. A single nucleotide polymorphism (SNP rs1130866) of human SP-B (hSP-B) alters the N-linked glycosylation, thus presumably affecting SP-B function. This study has investigated the regulatory roles of hSP-B genetic variants on lung injury in pneumonia-induced sepsis. METHODS: Wild-type (WT) FVB/NJ and humanized transgenic SP-B-T and SP-B-C mice (expressing either hSP-B C or T allele without mouse SP-B gene) were infected intratracheally with 50 μl (4 × 10 CFUs/mouse) Pseudomonas aeruginosa Xen5 or saline, then sacrificed 24 hrs or 48 hrs after infection...

BACKGROUND: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) may improve Systolic Blood Pressure (SBP) in hypovolemic shock. It has, however, not been studied in patients with impending traumatic cardiac arrest (ITCA). We aimed to study the feasibility and clinical outcome of REBOA in patients with ITCA using data from the ABOTrauma Registry. METHODS: Retrospective and prospective data on the use of REBOA from 16 centers globally were collected...

STUDY OBJECTIVE: The quick sequential organ failure assessment (qSOFA) was proposed to identify infected patients at risk for mortality, an indication of sepsis, in non-intensive care unit settings. This study tests whether qSOFA improves physician prediction of mortality among infected Emergency Department (ED) patients. METHODS: We performed a secondary analysis of a prospective, observational study of potentially septic ED patients, conducted between two urban, academic medical centers, from July 2016 - December 2017...

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Sepsis is one of the most important causes of maternal mortality. In our previous work, we established a polymicrobial sepsis (caecal ligation and puncture, [CLP]) model in murine pregnancy and found that pregnant mice had a greater susceptibility to septic shock. In this model, mortality appeared to be associated with the development of early haemodynamic dysfunction and although circulating cytokine levels were similar, "off target" lung inflammatory cell numbers were greater in pregnant mice.Here, we have used the same CLP model to test the hypothesis that inhibiting the metabolism of the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine would improve the outcome of sepsis in pregnancy...

The impact of diabetes mellitus on outcomes in trauma patients continues to attract interest, but data regarding the impact of longer term glycemic control are still lacking. This study evaluated the effect of long-term glycemic control on outcomes. Trauma patients presenting to the University of Alabama at Birmingham Hospital, between 2011 and 2018, were stratified into 4 groups, based on admission HbA1C level. A Poisson regression with robust error variance was used to estimate risk ratios and associated confidence intervals for the association between HbA1C and specific outcomes...

Changing demographic trends have led to an increase in the overall geriatric trauma patient volume. Furthermore, the intersection of aging and injury can be problematic because geriatric patients have multiple comorbidities, geriatric-specific syndromes, and reduced physiological reserve. Despite mounting evidence that frail geriatric patients have inferior outcomes following trauma, very few studies have examined the effect of aging on the biological response to injury. In the present article, we review the current literature and explore the pathophysiological rationale underlying observed data, available evidence, and future directions on this topic...

BACKGROUND: Circulatory shock is a life-threatening disorder that is associated with high mortality, with a state of systemic and tissue hypoperfusion that can lead to organ failure, including the brain, where altered mental state is often observed. We hypothesized that cerebral autoregulation (CA) is impaired in patients with circulatory shock. METHODS: Adult patients with circulatory shock and healthy controls were included. Cerebral blood flow velocity (CBFV, transcranial Doppler ultrasound) and arterial blood pressure (BP, Finometer or intra-arterial line) were continuously recorded during 5-minutes in both groups...

BACKGROUND: Reduced B cell numbers plays a critical role in sepsis immunosuppression. The role of B-cell maturation regulated by T follicular helper (Tfh) cells in reduced B cell numbers during sepsis remains unclear. We tested the hypothesis that impaired B-cell maturation contributes to reduced B cell numbers. DESIGN: Retrospective study and observational prospective cohort study. SETTINGS: Critical care units. METHODS: To identify the exact lymphocyte counts that affect the prognosis of sepsis, we firstly conducted a retrospective study...

BACKGROUND: The peptidylarginine deiminase (PAD) family converts arginine into citrulline through protein citrullination. PAD2 and PAD4 inhibitors can improve survival in hemorrhagic shock (HS). However, the impact of isoform specific PAD inhibition in improving survival has not been studied. In this study, we utilize selective Pad2 knockout (KO) mice to elucidate loss of function of PAD2 leads to pro-survival effect in HS. METHODS: HS: Pad2 and wild type (WT) mice (n = 5/group) were subjected to lethal HS (55% volume hemorrhage)...

OBJECTIVE: Immune dysregulation is a defining feature of sepsis, but the role for mitochondria in the development of immunoparalysis in pediatric sepsis is not known. We sought to determine if mitochondrial dysfunction measured in peripheral blood mononuclear cells (PBMCs) is associated with immunoparalysis and systemic inflammation in children with sepsis. DESIGN: Prospective observational study SETTING:: Single academic pediatric intensive care unit (PICU) PATIENTS:: 161 children with sepsis/septic shock and 18 non-infected PICU controls MEASUREMENTS AND MAIN RESULTS:: Mitochondrial respiration in PBMCs, markers of immune function, and plasma cytokines were measured on days 1-2 (T1), 3-5 (T2), and 8-14 (T3) after sepsis recognition, and once for controls...