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Shock : Injury, Inflammation, and Sepsis : Laboratory and Clinical Approaches
Journal Prestige (SJR): 1.331  Citation Impact (citeScore): 3 Number of Followers: 12  Hybrid journal (It can contain Open Access articles)ISSN (Print) 1073-2322 - ISSN (Online) 1540-0514 Published by LWW Wolters Kluwer  [330 journals]
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- A MACHINE LEARNING MODEL DERIVED FROM ANALYSIS OF TIME-COURSE
GENE-EXPRESSION DATASETS REVEALS TEMPORALLY STABLE GENE MARKERS PREDICTIVE
OF SEPSIS MORTALITY-
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Authors: Huang; Min; Atreya, Mihir R.; Holder, Andre; Kamaleswaran, Rishikesan
Abstract:
Sepsis is associated with significant mortality and morbidity among critically ill patients admitted to intensive care units and represents a major health challenge globally. Given the significant clinical and biological heterogeneity among patients and the dynamic nature of the host immune response, identifying those at high risk of poor outcomes remains a critical challenge. Here, we performed secondary analysis of publicly available time-series gene-expression datasets from peripheral blood of patients admitted to the intensive care unit to elucidate temporally stable gene-expression markers between sepsis survivors and nonsurvivors. Using a limited set of genes that were determined to be temporally stable, we derived a dynamical model using a Support Vector Machine classifier to accurately predict the mortality of sepsis patients. Our model had robust performance in a test dataset, where patients' transcriptome was sampled at alternate time points, with an area under the curve of 0.89 (95% CI, 0.82–0.96) upon 5-fold cross-validation. We also identified 7 potential biomarkers of sepsis mortality (STAT5A, CX3CR1, LCP1, SNRPG, RPS27L, LSM5, SHCBP1) that require future validation. Pending prospective testing, our model may be used to identify sepsis patients with high risk of mortality accounting for the dynamic nature of the disease and with potential therapeutic implications.
PubDate: Sat, 23 Sep 2023 00:00:00 GMT-
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- CEBPD REGULATES OXIDATIVE STRESS AND INFLAMMATORY RESPONSES IN
HYPERTENSIVE CARDIAC REMODELING-
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Authors: Zhao; Jinghong; Hu, Jilin; Zhang, Rongyi; Deng, Jianping
Abstract:
Hypertension seems to inevitably cause cardiac remodeling, increasing the mortality of patients. This study aimed to explore the molecular mechanism of CCAAT/enhancer-binding protein delta (CEBPD)–mediated oxidative stress and inflammation in hypertensive cardiac remodeling. The hypertensive murine model was established through angiotensin-II injection, and hypertensive mice underwent overexpressed CEBPD vector injection, cardiac function evaluation, and observation of histological changes. The cell model was established by angiotensin-II treatment and transfected with overexpressed CEBPD vector. Cell viability and surface area and oxidative stress (reactive oxygen species/superoxide dismutase/lactate dehydrogenase/malondialdehyde) were assessed, and inflammatory factors (TNF-α/IL-1β/IL-6/IL-10) were determined both in vivo and in vitro. The levels of CEBPD, miR-96-5p, inositol 1,4,5-trisphosphate receptor 1 (IP3R), natriuretic peptide B, and natriuretic peptide A, collagen I, and collagen III in tissues and cells were determined. The binding relationships of CEBPD/miR-96-5p/IP3R 3′ untranslated region were validated. CEBPD was reduced in cardiac tissue of hypertensive mice, and CEBPD upregulation improved cardiac function and attenuated fibrosis and hypertrophy, along with reductions of reactive oxygen species/lactate dehydrogenase/malondialdehyde/TNF-α/IL-1β/IL-6 and increases in superoxide dismutase/IL-10. CEBPD enriched on the miR-96-5p promoter to promote miR-96-5p expression, whereas CEBPD and miR-96-5p negatively regulated IP3R. miR-96-5p silencing/IP3R overexpression reversed the alleviative role of CEBPD overexpression in hypertensive mice. In summary, CEBPD promoted miR-96-5p to negatively regulate IP3R expression to inhibit oxidative stress and inflammation, thereby alleviating hypertensive cardiac remodeling.
PubDate: Mon, 18 Sep 2023 00:00:00 GMT-
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- METABOLOMIC AND PROTEOMIC CHANGES IN TRAUMA-INDUCED HYPOCALCEMIA
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Authors: Schaid; Terry R. Jr; LaCroix, Ian; Cohen, Mitchell J.; Hansen, Kirk C.; Moore, Ernest E.; Sauaia, Angela; Cralley, Alexis L.; Thielen, Otto; Hallas, William; Erickson, Christopher; Mitra, Sanchayita; Dzieciatkowska, Monika; Silliman, Christopher C.; D’Alessandro, Angelo
Abstract:
Background: Trauma-induced hypocalcemia is common and associated with adverse outcomes, but the mechanisms remain unclear. Thus, we aimed to characterize the metabolomic and proteomic differences between normocalcemic and hypocalcemic trauma patients to illuminate biochemical pathways that may underlie a distinct pathology linked with this clinical phenomenon. Methods: Plasma was obtained on arrival from injured patients at a Level 1 Trauma Center. Samples obtained after transfusion were excluded. Multiple regression was used to adjust the omics data for injury severity and arrival base excess before metabolome- and proteome-wide comparisons between normocalcemic (ionized Ca2+> 1.0 mmol/L) and hypocalcemic (ionized Ca2+ ≤ 1.0 mmol/L) patients using partial least squares-discriminant analysis. OmicsNet and Gene Ontology were used for network and pathway analyses, respectively. Results: Excluding isolated traumatic brain injury and penetrating injury, the main analysis included 36 patients (n = 14 hypocalcemic, n = 22 normocalcemic). Adjusted analyses demonstrated distinct metabolomic and proteomic signatures for normocalcemic and hypocalcemic patients. Hypocalcemic patients had evidence of mitochondrial dysfunction (tricarboxylic acid cycle disruption, dysfunctional fatty acid oxidation), inflammatory dysregulation (elevated damage-associated molecular patterns, activated endothelial cells), aberrant coagulation pathways, and proteolytic imbalance with increased tissue destruction. Conclusions: Independent of injury severity, hemorrhagic shock, and transfusion, trauma-induced hypocalcemia is associated with early metabolomic and proteomic changes that may reflect unique pathology in hypocalcemic trauma patients. This study paves the way for future experiments to investigate mechanisms, identify intervenable pathways, and refine our management of hypocalcemia in severely injured patients.
PubDate: Tue, 05 Sep 2023 00:00:00 GMT-
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- PREDICTIVE VALUE OF NEUTROPHIL EXTRACELLULAR TRAP COMPONENTS FOR 28-DAY
ALL-CAUSE MORTALITY IN PATIENTS WITH CARDIAC ARREST: A PILOT OBSERVATIONAL
STUDY-
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Authors: Li; Peijuan; Liang, Shuangshuang; Wang, Ling; Guan, Xiaolan; Wang, Jin; Gong, Ping
Abstract:
Background: Ischemia-reperfusion after cardiac arrest (CA) activates peptidyl arginine deiminase and citrullinated histone H3 (CitH3), which leads to the formation of neutrophil extracellular traps (NETs). This study attempted to determine the alterations in NET components in post-CA patients as well as analyze the association of NETs with 28-day all-cause mortality. Methods: In this study, 95 patients with restoration of spontaneous circulation (ROSC) after CA were included. They were categorized into the survivor group (n = 32) and the nonsurvivor group (n = 63) according to their 28-day survival statuses. The control group comprised 20 healthy individuals. The blood samples were collected from the patients on days 1, 3, and 7 after ROSC and from the control subjects at the time of enrollment. The serum cell-free DNA (cfDNA) level was determined using the fluorescent labeling method, and the serum concentrations of NET components, including CitH3, myeloperoxidase, neutrophil elastase, and nucleosomes, were estimated using the enzyme-linked immunosorbent assay. Results: Compared with the control group, the serum NET components were significantly increased in the patients 1 week after ROSC (all P < 0.05). These components were significantly higher in the nonsurvivor group than in the survivor group (all P < 0.05). Spearman correlational analysis revealed that the components were positively correlated with Acute Physiology and Chronic Health Evaluation II scores (both P < 0.05). Binary logistic regression analysis indicated that serum cfDNA, CitH3, and nucleosomes on days 1 and 3 after ROSC were independent predictors of 28-day all-cause mortality. Furthermore, these parameters on day 1 after ROSC had the biggest areas under the receiver operating characteristic curves (0.876, 0.862, and 0.861, respectively). Conclusions: Elevated serum levels of cfDNA, CitH3, myeloperoxidase, neutrophil elastase, and nucleosomes were positively correlated with disease severity after ROSC. However, only serum CitH3, cfDNA, and nucleosomes on day 1 after ROSC showed a good predictive value for 28-day all-cause mortality.
PubDate: Tue, 05 Sep 2023 00:00:00 GMT-
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- ENHANCED EFFICACY OF RESVERATROL-LOADED SILVER NANOPARTICLE IN ATTENUATING
SEPSIS-INDUCED ACUTE LIVER INJURY: MODULATION OF INFLAMMATION, OXIDATIVE
STRESS, AND SIRT1 ACTIVATION-
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Authors: Üstündağ; Hilal; Kalindemirtaş, Ferdane Danişman; Doğanay, Songül; Demir, Özlem; Kurt, Nezahat; Huyut, Mehmet Tahir; Özgeriş, Betül; Kariper, İshak Afşin
Abstract:
Sepsis-induced acute liver injury is a life-threatening condition involving inflammation, oxidative stress, and endothelial dysfunction. In the present study, the preventive effects of resveratrol (RV) alone and RV-loaded silver nanoparticles (AgNPs + RV) against sepsis-induced damage were investigated and compared in a rat model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Rats were divided into four groups: Sham, CLP, RV, and AgNPs + RV. Pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, presepsin, procalcitonin (PCT), 8-hydroxy-2′-deoxyguanosine (8-OHDG), vascular endothelial growth factor (VEGF), and sirtuin-1 (SIRT1) levels were assessed to determine the treatments' effects. AgNPs + RV treatment significantly reduced pro-inflammatory cytokines, NF-κB activation, presepsin, PCT, 8-OHDG, and VEGF levels compared with the CLP group, indicating attenuation of sepsis-induced liver injury. Both RV and AgNPs + RV treatments increased SIRT1 levels, suggesting a potential role of SIRT1 activation in mediating the protective effects. In conclusion, AgNPs + RV treatment demonstrated extremely enhanced efficacy in alleviating sepsis-induced liver injury by modulating inflammation, oxidative stress, and endothelial dysfunction, potentially mediated through SIRT1 activation. In this study, the effect of AgNPs + RV on sepsis was evaluated for the first time, and these findings highlight AgNPs + RV as a promising therapeutic strategy for managing sepsis-induced liver injury, warranting further investigation.
PubDate: Tue, 05 Sep 2023 00:00:00 GMT-
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- SEPSIS LEADS TO IMPAIRED MITOCHONDRIAL CALCIUM UPTAKE AND SKELETAL MUSCLE
WEAKNESS BY REDUCING THE MICU1:MCU PROTEIN RATIO-
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Authors: Li; Xuexin; Sun, Bowen; Li, Jie; Ye, Wanlin; Li, Mingjuan; Guan, Fasheng; Wu, Songlin; Luo, Xuerong; Feng, Jianguo; Jia, Jing; Liu, Xueru; Li, Tao; Liu, Li
Abstract:
Purpose: Intensive care unit–acquired weakness (ICUAW) is a severe neuromuscular complication that frequently occurs in patients with sepsis. The precise molecular pathophysiology of mitochondrial calcium uptake 1 (MICU1) and mitochondrial calcium uniporter (MCU) in ICUAW has not been fully elucidated. Here, we speculate that ICUAW is associated with MICU1:MCU protein ratio–mediated mitochondrial calcium ([Ca2+]m) uptake dysfunction. Methods: Cecal ligation and perforation (CLP) was performed on C57BL/6J mice to induce sepsis. Sham-operated animals were used as controls. Lipopolysaccharide (LPS) (5 μg/mL) was used to induce inflammation in differentiated C2C12 myoblasts. Compound muscle action potential (CMAP) was detected using a biological signal acquisition system. Grip strength was measured using a grip-strength meter. Skeletal muscle inflammatory factors were detected using ELISA kits. The cross-sectional area (CSA) of the tibialis anterior (TA) muscle was detected by hematoxylin and eosin staining. Cytosolic calcium ([Ca2+]c) levels were measured using Fluo-4 AM. Adeno-associated virus (AAV) was injected into TA muscles for 4 weeks to overexpress MICU1 prophylactically. A lentivirus was used to infect C2C12 cells to increase MICU1 expression prophylactically. Findings: The results suggest that sepsis induces [Ca2+]m uptake disorder by reducing the MICU1:MCU protein ratio, resulting in skeletal muscle weakness and muscle fiber atrophy. However, MICU1 prophylactic overexpression reversed these effects by increasing the MICU1:MCU protein ratio. Conclusions: ICUAW is associated with impaired [Ca2+]m uptake caused by a decreased MICU1:MCU protein ratio. MICU1 overexpression improves sepsis-induced skeletal muscle weakness and atrophy by ameliorating the [Ca2+]m uptake disorder.
PubDate: Tue, 05 Sep 2023 00:00:00 GMT-
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- INITIATION TIMING OF VASOPRESSOR IN PATIENTS WITH SEPTIC SHOCK: A
SYSTEMATIC REVIEW AND META-ANALYSIS-
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Authors: Ye; Enci; Ye, Hui; Wang, Shengyao; Fang, Xiangming
Abstract:
Background: Vasopressor plays a crucial role in septic shock. However, the time for vasopressor initiation remains controversial. We conducted a systematic review and meta-analysis to explore its initiation timing for septic shock patients. Methods: PubMed, Cochrane Library, Embase, and Web of Sciences were searched from inception to July 12, 2023, for relevant studies. Primary outcome was short-term mortality. Meta-analysis was performed using Stata 15.0. Results: Twenty-three studies were assessed, including 2 randomized controlled trials and 21 cohort studies. The early group resulted in lower short-term mortality than the late group (OR [95% CI] = 0.775 [0.673 to 0.893], P = 0.000, I2 = 67.8%). The significance existed in the norepinephrine and vasopressin in subgroup analysis. No significant difference was considered in the association between each hour’s vasopressor delay and mortality (OR [95% CI] = 1.02 [0.99 to 1.051], P = 0.195, I2 = 57.5%). The early group had an earlier achievement of target MAP (P < 0.001), shorter vasopressor use duration (P < 0.001), lower serum lactate level at 24 h (P = 0.003), lower incidence of kidney injury (P = 0.001), renal replacement therapy use (P = 0.022), and longer ventilation-free days to 28 days (P < 0.001). Conclusions: Early initiation of vasopressor (1–6 h within septic shock onset) would be more beneficial to septic shock patients. The conclusion needs to be further validated by more well-designed randomized controlled trials.
PubDate: Sat, 02 Sep 2023 00:00:00 GMT-
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- EXPLORING THE ROLE OF CENTRAL VENOUS OXYGEN SATURATION IN THE EVALUATION
AND MANAGEMENT OF SEVERE HYPOXEMIA IN MECHANICALLY VENTILATED PATIENTS-
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Authors: Kanj; Amjad N.; Rovati, Lucrezia; Castillo Zambrano, Claudia; Marquez, Alberto; Robbins, Kellie; Cortes Puentes, Gustavo; Gallo De Moraes, Alice; Gajic, Ognjen
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Background: Although central venous oxygen saturation (ScvO2) has been used as an endpoint for the treatment of circulatory shock, its role in guiding the evaluation and treatment of patients with severe hypoxemia remains to be assessed. The aim of this study was to assess the incidence of low ScvO2 in a cohort of hypoxemic patients and the association of this finding with differences in clinical management and patient outcomes. Methods: Retrospective review of data from adult intensive care unit patients with hypoxemia who required invasive mechanical ventilation for over 24 h and had at least one ScvO2 measured within 6 h of a PaO2/FiO2 ratio
PubDate: Sat, 02 Sep 2023 00:00:00 GMT-
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- HOW SHOULD TRANEXAMIC ACID BE ADMINISTERED IN HEMORRHAGIC SHOCK'
CONTINUOUS SERUM CONCENTRATION MEASUREMENTS IN A SWINE MODEL-
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Authors: Lynghaug; Trine; Bakke, Håkon Kvåle; Fuskevåg, Ole Martin; Nielsen, Erik Waage; Dietrichs, Erik Sveberg
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Background: Tranexamic acid (TXA) reduces mortality in trauma patients. Intramuscular (IM) administration could be advantageous in low-resource and military settings. Achieving the same serum concentration as intravenous (IV) administration is important to achieve equal mortality reduction. Therefore, we aimed to investigate whether dividing an IM dose of TXA between two injection sites and whether an increase in dose would lead to serum concentrations comparable to those achieved by IV administration. Methods: Norwegian landrace pigs (n = 29) from a course in hemostatic emergency surgery were given TXA 1 h after start of surgery. Blood samples were drawn at 0, 5, 10, 15, 20, 25, 35, 45, 60, and 85 min. The samples were centrifuged and serum TXA concentrations quantified with liquid chromatography-tandem mass spectrometry. The use of two injection sites was compared with distributing the dose on one injection site, and a dose of 15 mg/kg was compared with a dose of 30 mg/kg. All IM groups were compared with IV administration. Results: The groups were in a similar degree of shock. Increasing the IM dose from the standard of 15 mg/kg to 30 mg/kg resulted in significantly higher serum concentrations of TXA, comparable to those achieved by IV administration. Distributing the IM dose on two injection sites did not affect drug uptake, as shown by equal serum concentrations. Conclusions: For IM administration of TXA, 30 mg/kg should be the standard dose. With a short delay, IM administration will provide equal serum concentrations as IV administration, above what is considered necessary to inhibit fibrinolysis.
PubDate: Sat, 02 Sep 2023 00:00:00 GMT-
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- DEXMEDETOMIDINE AMELIORATES ACUTE BRAIN INJURY INDUCED BY MYOCARDIAL
ISCHEMIA-REPERFUSION VIA UPREGULATING THE HIF-1 PATHWAY-
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Authors: Yang; Xue; Wu, Jianjiang; Cheng, Hu; Chen, Siyu; Wang, Jiang
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Objective: Neurological complications after myocardial ischemia/reperfusion (IR) injury remain high and seriously burden patients and their families. Dexmedetomidine (Dex), an α2 agonist, is endowed with analgesic-sedative and anti-inflammatory effects. Therefore, our study aims to explore the mechanism and effect of Dex on brain damage after myocardial IR injury. Methods C57BL/6 mice were randomly divided into sham, IR, and IR + Dex groups, and myocardial IR models were established. The impact of Dex on brain injury elicited by myocardial IR was assessed via ELISA for inflammatory factors in serum and brain; Evans blue for blood-brain barrier permeability; hematoxylin-eosin staining for pathological injury in brain; immunofluorescence for microglia activation in brain; Morris water maze for cognitive dysfunction; western blot for the expression level of HIF-1α, occludin, cleaved caspase-3, NF-κB p65, and p-NF-κB p65 in the brain. In addition, HIF-1α knockout mice were used to verify whether the neuroprotective function of Dex is associated with the HIF-1 pathway. Results: Dex was capable of reducing myocardial IR-induced brain damage including inflammatory factor secretion, blood-brain barrier disruption, neuronal edema, microglial activation, and acute cognitive dysfunction. However, the protective role of Dex was attenuated in HIF-1α knockout mice. Conclusion: Dex protects against myocardial IR-induced brain injury, and the neuroprotection of Dex is at least partially dependent on the activation of the HIF-1 pathway.
PubDate: Tue, 29 Aug 2023 00:00:00 GMT-
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- TIME-DEPENDENT CHANGES IN PROINFLAMMATORY MEDIATORS ARE ASSOCIATED WITH
TRAUMA-RELATED VENOUS THROMBOEMBOLISM-
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Authors: Mankame; Atharwa R.; Sanders, Kelly E.; Cardenas, Jessica C.
Abstract:
Background: Tissue trauma and hemorrhage result in pronounced activation of the innate immune system. Given known crosstalk between inflammation and coagulation, soluble inflammatory mediators could be associated with venous thromboembolisms (VTEs) after major trauma. Objectives: This study aimed to identify plasma inflammatory mediators that are independent predictors of VTE risk in trauma patients. Methods: We performed a secondary analysis of the Pragmatic Randomized Optimal Platelets and Plasma Ratios (PROPPR) study. Plasma levels of 27 cytokines/chemokines were measured by Bio-Plex at admission and 2, 4, 6, 12, 24, 48, and 72 h later. Patients who died from exsanguination or within 24 h were excluded. Mann-Whitney tests were performed to assess no-VTE and VTE groups at each time point. Multivariable logistic regression was used to determine the adjusted effects of inflammatory mediators on VTE risk. Results: Eighty-six of the 575 patients (15%) included developed VTE. Interleukin (IL)-1ra, IL-6, IL-8, IL-10, eotaxin, granulocyte colony-stimulating factor, interferon-γ–inducible protein, monocyte chemoattractant protein 1 (MCP-1), and chemokine ligand 5 (regulated on activation, normal T cell expressed and secreted) were all significantly increased among VTE patients. Multivariable analyses demonstrated that IL-6, IL-8, interferon-γ–inducible protein, and MCP-1 were independently associated with VTE. Cox proportional hazards modeling identified IL-6, IL-8, and MCP-1 as independent predictors of accelerated VTE development. We identified significant correlations between inflammation and markers of coagulation and endothelial activation. Conclusion: Sustained systemic inflammation is a key driver of VTE risk after major trauma. Therapeutics targeting innate immune activation should be considered for development of future multimodal strategies to augment current VTE prophylaxis.
PubDate: Sat, 26 Aug 2023 00:00:00 GMT-
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- Recent Study Showing Rapidly Decreasing Levels of LPS Using the Efferon
LPS Using LAL Assay But Is LAL Assay Reliable to Detect Endotoxin'-
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Authors: Honore; Patrick M.; Perriens, Emily; El Ouahidi, Wissal; El Bachti, Amina; Tondeur, Aliyah; Blackman, Sydney
Abstract: No abstract available
PubDate: Mon, 07 Aug 2023 00:00:00 GMT-
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- If EAA Test Versus LAL Test is Always Clinically Better and Whether Any
Test Always Relates to the Therapeutic Value of Hemoperfusion in Septic
Shock Patients'-
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Authors: Pisarev; Vladimir M.; Rey, Sergei I.; Kulabukhov, Vladimir V.; Popov, Alexander Yu.
Abstract: No abstract available
PubDate: Mon, 07 Aug 2023 00:00:00 GMT-
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