Exploring the Obesity Paradox in A Murine Model of Sepsis: Improved Survival Despite Increased Organ Injury in Obese Mice
The objective of this study was to test the existence of the obesity paradox in a murine model of cecal slurry (CS)-induced sepsis with insulin-resistant diet-induced obese mice. Male C57BL/6 mice were provided high-fat (HFD) or low-fat (LFD) diets for 20 weeks. HFD-fed mice experienced higher rates of survival compared to LFD-fed mice after septic challenge induced by CS injection (66% vs. 25%, P = 0.01, survival assessed for 14 days). Despite the survival advantage, HFD-fed mice had higher rates of positive bacterial cultures and increased markers of kidney injury. Circulating levels of IL-6, IL-1β, TNFα, and I...
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

Death-Associated Protein Kinase 1 Promotes Alveolar Epithelial Cell Apoptosis and Ventilator-Induced Lung Injury Through P53 Pathway
Conclusions: DAPK1 contributes to AEC apoptosis and the onset of VILI though P53 and its intrinsic pro-apoptotic pathway. Inhibition of DAPK1 or P53 alleviates high tidal volume ventilation-induced lung injury and AEC apoptosis. (Source: Shock)
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

Effects of Sodium Thiosulfate During Resuscitation From Trauma-and-Hemorrhage in Cystathionine Gamma Lyase (CSE) Knockout Mice
Background: Sodium thiosulfate (Na2S2O3) is a clinically established drug with antioxidant and sulphide-releasing properties. Na2S2O3 mediated neuro- and cardioprotective effects in ischemia/reperfusion models and anti-inflammatory effects in LPS-induced acute lung injury. Moreover, Na2S2O3 improved lung function during resuscitation from hemorrhagic shock in swine with pre-existing atherosclerosis, characterized by decreased expression of cystathionine γ-lyase (CSE), a major source of hydrogen sulfide (H2S) synthesis in the vasculature. Based on these findings, we investigated the effects of Na2S2O3 administration du...
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

MEF2D Participates in Microglia-Mediated Neuroprotection in Cerebral Ischemia-Reperfusion Rats
Conclusion: These results indicate that MEF2D is a necessary molecule for neuroinflammation regulation and neuronal injury in cerebral ischemia. (Source: Shock)
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research

Increased Plasma Hyaluronan Levels are Associated With Acute Traumatic Coagulopathy
Introduction: Acute traumatic coagulopathy (ATC) is an endogenous impairment in hemostasis that often contributes to early mortality after trauma. Endothelial glycocalyx damage is associated with trauma-induced coagulation abnormalities; however, the specific relationship between hyaluronan (HA), a key glycocalyx constituent, and ATC has not been evaluated. Methods: We performed a secondary analysis of prospectively collected data from a recent study in which trauma patients (>18 years) admitted to our Level I trauma center with an ABC Score≥2 were enrolled. Partial thromboplastin time (PTT), international n...
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Clinical Science Aspects Source Type: research

Shock-Induced Endothelial Dysfunction is Present in Patients With Occult Hypoperfusion After Trauma
Background: Shock-induced endothelial dysfunction, evidenced by elevated soluble thrombomodulin (sTM) and syndecan-1 (Syn-1), is associated with poor outcomes after trauma. The association of endothelial dysfunction and overt shock has been demonstrated; it is unknown if hypoperfusion in the setting of normal vital signs (occult hypoperfusion [OH]) is associated with endothelial dysfunction. We hypothesized that sTM and Syn-1 would be elevated in patients with OH when compared to patients with normal perfusion. Methods: A single-center study of patients requiring highest-level trauma activation (2012–2016) was...
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Clinical Science Aspects Source Type: research

Distinctive Biomarker Features in the Endotheliopathy of COVID-19 and Septic Syndromes
Background: Endotheliopathy is a key element in COVID-19 pathophysiology, contributing to both morbidity and mortality. Biomarkers distinguishing different COVID-19 phenotypes from sepsis syndrome remain poorly understood. Objective: To characterize circulating biomarkers of endothelial damage in different COVID-19 clinical disease stages compared with sepsis syndrome and normal volunteers. Methods: Patients with COVID-19 pneumonia (n = 49) were classified into moderate, severe, or critical (life-threatening) disease. Plasma samples were collected within 48 to 72 h of hospitalization to analyze endo...
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Clinical Science Aspects Source Type: research

Outcomes Associated With Early RBC Transfusion in Pediatric Severe Sepsis: A Propensity-Adjusted Multicenter Cohort Study
Conclusions: RBC transfusion is common in pediatric severe sepsis and may be associated with adverse outcomes. Future studies are needed to clarify these associations, to understand patient-specific transfusion risks, and to develop more precise transfusion strategies. (Source: Shock)
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Clinical Science Aspects Source Type: research

Biomarker Analysis for Combination Therapy of Vitamin C and Thiamine in Septic Shock: A Post-Hoc Study of the ATESS Trial
Conclusion: Vitamin C and thiamine administration during the early phase of septic shock did not significantly change prognostic biomarker levels of IL-6, IL-10, AP2, and S100β. Trial registration: NCT, ClinicalTrials.gov NCT03756220, ATESS. Registered 28 November 2018, https://clinicaltrials.gov/ct2/show/NCT03756220. (Source: Shock)
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Clinical Science Aspects Source Type: research

Vitamin C, Hydrocortisone, and the Combination Thereof Significantly Inhibited Two of Nine Inflammatory Markers Induced by Escherichia Coli But Not by Staphylococcus Aureus – When Incubated in Human Whole Blood
Vitamin C combined with hydrocortisone is increasingly being used to treat septic patients, even though this treatment regimen is based on questionable evidence. When used, a marked effect on key players of innate immunity would be expected, as sepsis is featured by a dysregulated immune response. Here, we explored the effect of vitamin C and hydrocortisone alone and combined, in an ex vivo human whole-blood model of Escherichia coli- or Staphylococcus aureus-induced inflammation. Inflammatory markers for activation of complement (terminal C5b-9 complement complex [TCC]), granulocytes (myeloperoxidase), platelets (β-th...
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Clinical Science Aspects Source Type: research

Potential Value of Presepsin Guidance in Shortening Antibiotic Therapy in Septic Patients: a Multicenter, Prospective Cohort Trial
In this study, we investigated an emerging biomarker presepsin-guided strategy, which can be used to evaluate the shortening of antibiotic treatment in patients with sepsis without risking a worse outcome. Methods: In this multicenter prospective cohort trial, patients were assigned to the presepsin or control groups. In the presepsin group, antibiotics were ceased based on predefined cut-off ranges of presepsin concentrations. The control group stopped antibiotics according to international guidelines. The primary endpoints were the number of days without antibiotics within 28 days and mortality at 28 and 90 da...
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Clinical Science Aspects Source Type: research

Impact of Clinical Sepsis Phenotypes on Mortality and Fluid Status in Critically Ill Patients
Background: Sepsis is associated with high rates of in-hospital mortality, despite being the focus of medical research and public health initiatives for several years. The primary objective of this study was to determine the influence of septic phenotypes on rates of in-hospital mortality throughout intensive care unit (ICU) admission. Patients and Methods: Retrospective, single-center cohort study. Medical ICU of an academic medical center. Medical ICU patients admitted between January 2016 and August 2019 with a “sepsis alert” were screened for admitting diagnosis of “sepsis” or “septic shock.” Pat...
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Clinical Science Aspects Source Type: research

A New Time-Window Prediction Model For Traumatic Hemorrhagic Shock Based on Interpretable Machine Learning
Early warning prediction of traumatic hemorrhagic shock (THS) can greatly reduce patient mortality and morbidity. We aimed to develop and validate models with different stepped feature sets to predict THS in advance. From the PLA General Hospital Emergency Rescue Database and Medical Information Mart for Intensive Care III, we identified 604 and 1,614 patients, respectively. Two popular machine learning algorithms (i.e., extreme gradient boosting [XGBoost] and logistic regression) were applied. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the performance of the models. By analyzin...
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Clinical Science Aspects Source Type: research

Elevated Plasma Levels of Matrix Metalloproteinase-3 and Tissue-Inhibitor of Matrix Metalloproteinases-1 Associate With Organ Dysfunction and Mortality in Sepsis
Conclusion: Elevated plasma concentrations of TIMP-1 associate with organ dysfunction and mortality in sepsis. Higher plasma levels of MMP-3 associate with shock and mortality. Plasma MMP and TIMP-1 may warrant further investigation as emerging sepsis theragnostic biomarkers. (Source: Shock)
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Clinical Science Aspects Source Type: research

Laboratory Markers of Acidosis and Mortality in Cardiogenic Shock: Developing a Definition of Hemometabolic Shock
Background: Acidosis and higher lactate predict worse outcomes in cardiogenic shock (CS) patients. We sought to determine whether overall acidosis severity on admission predicted in-hospital mortality in CS patients. Methods: This retrospective descriptive analysis included CS patients admitted to a single academic tertiary cardiac intensive care unit from 2007 to 2015. Admission arterial pH, base excess, and anion gap values were used to generate a Composite Acidosis Score (range 0–5, with a score ≥2 defining Severe Acidosis). Adjusted in-hospital mortality was analyzed using multivariable logistic regressi...
Source: Shock - December 17, 2021 Category: Emergency Medicine Tags: Clinical Science Aspects Source Type: research