FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3048791348> ?p ?o ?g. }

• W3048791348 endingPage "279" @default.
• W3048791348 startingPage "277" @default.
• W3048791348 abstract "This issue of Shock contains 16 outstanding manuscripts which advance our knowledge in the fields of shock, sepsis, inflammation, and organ dysfunction. While the study designs and areas of interest are wide-ranging, there is an underlying theme in the issue of advancements in basic and translational science. Each article has the potential to improve precision medicine models through a variety of disease sates. The issue begins with an intriguing systematic review article by Komaru et al. (1) exploring the incidence of acute kidney injury (AKI) in intensive care units (ICUs). In their analysis, they included 76 large cohort studies with over 500,000 patients and analyzed the correlation of AKI incidence with patient mortality. Somewhat surprisingly, they found that between individual centers/studies, as the incidence of AKI increases the mortality of patients with AKI decreases, even after stratification by AKI severity. The authors postulate that institutions with higher incidence of AKI may have increased AKI awareness and evidenced-based protocol care, leading to early and comprehensive management improving outcomes. The first clinical science manuscript in this month's issue was composed by Weiss et al. (2), who performed a prospective cohort study of 161 pediatric septic patients, investigating associations of mitochondrial dysfunction, immunoparalysis, and systemic inflammation. Evaluating blood samples over serial timepoints, they performed multiple tests including peripheral blood mononuclear cell mitochondrial respiration, whole blood immune function [through lipopolysaccharide (LPS) stimulation of tumor necrosis factor alpha (TNFα) and HLA-DR expression], and numerous inflammatory cytokine levels. They were able to demonstrate that mitochondrial respiration was lower in septic children with immunoparalysis compared with those that were not, offering intriguing opportunities for development of future novel therapies. Continuing the theme of prognostication in sepsis, Garnacho-Montero et al. (3) evaluated the inflammasome in sepsis, focusing on temporal associations and outcomes. They examined both transcriptional expression (of nucleotide-binding domain, leucine-rich repeat-containing receptor, pyrin domain-containing-3 [NLRP3]) and circulating protein (of interleukin [IL]-1β and caspase-1, 3) levels over a 1-week period in septic and non-septic critically ill patients. Their results revealed that prolonged inflammasome activation through NLRP3 upregulation may be protective in sepsis, and that sepsis survivors (versus nonsurvivors) have differences in caspase protein expression patterns. The mechanistic and temporal observations of the inflammasome in septic patients found in this study hold promise for future therapeutic research. Mitochondrial dysfunction is a common occurrence in sepsis. Huang et al. (4) sought to determine the prognostic value of the mitochondrial membrane protein uncoupling protein-2 (UCP2) as a biomarker in sepsis, measuring serum UCP2 levels of septic and critically-ill non-septic patients at ICU admission. They found that UCP2 concentrations were higher in septic patients, increased with sepsis severity, and outperformed clinical parameters such as sequential organ failure assessment scores in identifying both sepsis and septic shock. Additionally, they found that patients with higher UCP2 levels at ICU admission had increased 28-day mortality. The authors proposed UCP2 may have both early diagnostic and prognostic value as a sepsis biomarker. The importance of AKI in sepsis was previously highlighted in the opening review article. The article by Beunders et al. (5) points out that our ability to diagnose renal dysfunction is tied to creatine clearance, which has its shortcomings. In their manuscript, they performed a pilot study evaluating a novel serum biomarker, proenkephalin, as a means of estimating glomerular filtration rate (GFR) in a cohort of septic patients. They compared this novel biomarker and more commonly used creatinine-based methods to the gold standard (but clinically tedious) laboratory method of GFR iodhexol clearance. They found that creatinine-based methods tended to overestimate GFR, while proenkephalin showed strong inverse correlation (R2 = 0.90) with GFR-iodhexol. They proposed that this feasible biomarker shows promise in determining non-steady-state kidney function. Another important clinical topic of interest was studied by de Roquetaillade et al. (6), who evaluated the effect of chronic antihypertensive usage on septic shock outcomes. They evaluated over 700 septic patients requiring vasopressor support, and found that on multivariate analysis prior antihypertensive usage did not increase total early (<24 h) vasopressor requirement, and was not associated with higher ICU mortality. Importantly, they performed subgroup analysis of antihypertensive categories, also finding no differences. The authors suggest that these findings argue against the commonly perceived notion that chronic antihypertensives may worsen early hemodynamic failure in sepsis. As with other promising studies possibly shaping future therapeutic interventions in sepsis, Chen et al. (7) explored the possibility of using histone deacetylase inhibitors (HDACi's) to manipulate platelet activation and the formation of neutrophil extracellular traps (NETs). Through a series of in vitro experiments, they established a method of patient platelet and neutrophil isolation, followed by appropriate platelet activation and induction of NET formation. Once these were established, they were able to demonstrate that HDACi's attenuated the activated platelet induction of NET formation. This complex set of experiments both expands our mechanistic understanding of NET induction, while offering a future target for intervention in NET-related organ injury. Building on their previous work, Otani et al. (8) performed a series of experiments to elucidate the mechanisms behind how prevention of gut epithelial apoptosis improves survival in septic mice, behind this. Following sepsis induction through cecal ligation and puncture (CLP) on both wild-type mice and transgenic mice overexpressing the antiapoptotic protein Bcl-2 in gut epithelium, the authors were able to demonstrate that transgenic mice had decreased intestinal apoptosis, reduced intestinal permeability following sepsis, and numerous differences in tight junction mRNA and protein expression. The authors propose that these in vivo results indicate tight junction alterations may partially explain the survival benefit of Bcl-2 overexpression previously shown in septic mice. Fang et al. (9) studied the cardioprotective effect of genistein, a naturally found flavonoid with numerous pharmacologic effects, on burn-induced myocardial injury. Using a mouse burn model, the authors were able to show that genistein ameliorated burn-induced myocardial injury as treated mice had preserved ejection fraction, lower markers of myocardial necrosis, and reduced levels of oxidative stress. Most importantly, they were able to give mechanistic insight into this protection, as genistein-treated mice had increased expression of Notch1 pathway proteins, but in Notch1 knockout mice the cardioprotective effect of genistein (in both functional testing and oxidative stress) was abolished. The authors proposed more research in this pathway may lead to novel therapeutics in post-burn myocardial injury. Sepsis-associated encephalopathy (SAE) is a common complication in sepsis that is difficult to distinguish from encephalopathies of other causes. This is in part due to the fact that serum biomarkers are difficult to identify due to limitations of crossing the blood–brain barrier. Visitchanakun et al. (10) present thought-provoking work on identifying serum microRNAs (miRNA) in SAE. Following induction of mouse encephalopathy through CLP sepsis or nephrectomy-induced uremia, brain and plasma samples were analyzed for miRNA expression patterns. The authors found a specific miRNA, miR-370-3p, which was elevated in SAE but not uremic encephalopathy, and subsequently showed human SAE patients had increased levels of this miRNA compared to healthy controls. They propose this plasma miRNA as a biomarker candidate for SAE in future studies. Permissive hypotension has become a standard of care for traumatic resuscitation in certain injuries. In addition, there has been a shift toward early whole blood administration to maintain hypotensive resuscitation (HR) in military settings. However, this is not always feasible in civilian prehospital settings. Kheirabadi et al. (11) present intriguing work comparing albumin solution versus whole blood or fresh frozen plasma for early HR (for 2 h) in a rabbit hemorrhagic shock model, prior to full resuscitation and surgical repair. The authors determined that while whole blood resuscitation required less volume, there were no other clinically significant differences in the groups apart from increased bleeding time in the albumin group, with no differences in long-term organ dysfunction or survival. The findings suggest that 5% albumin resuscitative solutions may be a viable alternative in prehospital resuscitation in hemorrhagic shock when whole blood is not readily available. While literature involving the gut microbiome (GM) has increased tremendously in previous years, the effect of the GM in burn patients is less well understood. McIntyre et al. (12) present a study on the effects of fluid resuscitation on the GM in a porcine burn model. Following 40% burns, subjects were randomized to varying volumes of resuscitation, with serial fecal swabs taken and intestinal harvest following euthanasia. They found that overall burns produced a significant shift in GM β-diversity, but variations in fluid resuscitation altered (in a dose-dependent manner) several phyla, as well as protein expression in the small intestine. The authors propose that this is the first study to show alterations in porcine GM following large burn injury, and given the widely debated topic of fluid resuscitation strategies in burn care, further study into the post-burn GM could provide useful insights into burn physiology and burn resuscitation. Vascular endothelial glycocalyx (EG) injury plays a key role in circulatory system regulation during shock, with EG damage contributing to vascular permeability and microvascular tone. Building on their previous work showing hydrogen gas (H2) stabilizes hemodynamics in hemorrhagic shock, Tamura et al. (13) provide further mechanistic insight in a rat hemorrhagic shock and resuscitation model. Along with H2 inhalation effect on mean arterial pressure, they studied two distinct pathways by treating with either xanthine oxidoreductase (XOR) inhibitors or anti-TNFα antibodies. They showed that H2 effect on hemodynamics was independent of XOR activity, but does suppress TNFα release and EG degradation. These led them to propose that H2 may be useful for reducing inflammatory cytokines and endothelial dysfunction in hemorrhagic shock. Disruption of EG occurs in other inflammatory and shock states, including sepsis. The next manuscript by Fukuta et al. (14) sought to determine if myocardial injury in sepsis results from EG changes caused by neutrophil elastase (NE) activation. Through an LPS injection model comparing wild-type and granulocyte-colony stimulating factor (G-CSF) knockout mice, they were able to show that myocardial injury and EG structural damage were attenuated in G-CSF knockout mice. Subsequently, they compared NE inhibitor treated mice to controls in their LPS model, and found that NE inhibitor-treated mice had less myocardial damage, and preserved EG structure. The authors concluded that NE inhibition may provide a means of attenuating endotoxin-mediated myocardial damage. Prostaglandin E2 (PGE2) and its producing enzyme cyclooxygenase-2 (COX-2) have been known to play roles in both intestinal protection and injury, but the mechanisms behind these complex associations have not been fully elucidated. Golden et al. (15) examined the role of PGE2 receptors (EP1, EP2) in gut inflammatory processes using both cell cultures, and three separate mouse models of sepsis (LPS, CLP, necrotizing enterocolitis [NEC]). They were able to demonstrate that blocking EP2 prevents positive feedback regulation of COX-2 (and subsequent PGE2 production) during intestinal inflammation, and EP2 antagonism led to decreased NEC intestinal injury. The authors suggested that EP2 receptor modulation may have therapeutic benefit in the treatment of barrier failure during NEC. Finally, Yang et al. (16) present their work exploring the role of airway epithelial hepcidin in pneumonia. Building on previous knowledge that liver produced hepcidin downregulates iron and protects against infection, they used hepcidin knockout mice to show that lack of hepcidin in airway epithelium worsened pneumonia survival and increased bacterial burden. They were also able to show through macrophage ferroportin knockout mice, that hepcidin does not interact with bacteria directly, but rather through the macrophage protein. Additionally, through increased local hepcidin expression they were able to rescue mice from lethal bacteria pneumonia. Taken in concert, the authors proposed manipulating airway epithelial cell hepcidin may provide an alternative method to combat bacterial pneumonia. In summary, this issue of Shock contains a plethora of compelling manuscripts covering a variety of basic, translational, and clinical research. Regardless of topic, the respective authors enhance our understanding of shock. Whether gaining insight into pathologic mechanisms, offering new prognostic markers, or suggesting future novel therapeutics, these studies have the potential to guide future research and potentially improve patient care." @default.
• W3048791348 created "2020-08-18" @default.
• W3048791348 creator A5015888087 @default.
• W3048791348 creator A5031214939 @default.
• W3048791348 creator A5090126800 @default.
• W3048791348 date "2020-09-01" @default.
• W3048791348 modified "2023-09-27" @default.
• W3048791348 title "What's New in Shock, September 2020?" @default.
• W3048791348 cites W2971601761 @default.
• W3048791348 cites W2981055527 @default.
• W3048791348 cites W2981311241 @default.
• W3048791348 cites W2981442662 @default.
• W3048791348 cites W2982060984 @default.
• W3048791348 cites W2983327703 @default.
• W3048791348 cites W2985529083 @default.
• W3048791348 cites W2989221369 @default.
• W3048791348 cites W2991130979 @default.
• W3048791348 cites W2991495142 @default.
• W3048791348 cites W3002606730 @default.
• W3048791348 cites W3003027350 @default.
• W3048791348 cites W3005624538 @default.
• W3048791348 cites W3006607865 @default.
• W3048791348 cites W3006674130 @default.
• W3048791348 cites W3008395887 @default.
• W3048791348 doi "https://doi.org/10.1097/shk.0000000000001588" @default.
• W3048791348 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7678040" @default.
• W3048791348 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32796495" @default.
• W3048791348 hasPublicationYear "2020" @default.
• W3048791348 type Work @default.
• W3048791348 sameAs 3048791348 @default.
• W3048791348 citedByCount "0" @default.
• W3048791348 crossrefType "journal-article" @default.
• W3048791348 hasAuthorship W3048791348A5015888087 @default.
• W3048791348 hasAuthorship W3048791348A5031214939 @default.
• W3048791348 hasAuthorship W3048791348A5090126800 @default.
• W3048791348 hasBestOaLocation W30487913481 @default.
• W3048791348 hasConcept C126322002 @default.
• W3048791348 hasConcept C2781300812 @default.
• W3048791348 hasConcept C71924100 @default.
• W3048791348 hasConceptScore W3048791348C126322002 @default.
• W3048791348 hasConceptScore W3048791348C2781300812 @default.
• W3048791348 hasConceptScore W3048791348C71924100 @default.
• W3048791348 hasIssue "3" @default.
• W3048791348 hasLocation W30487913481 @default.
• W3048791348 hasLocation W30487913482 @default.
• W3048791348 hasLocation W30487913483 @default.
• W3048791348 hasLocation W30487913484 @default.
• W3048791348 hasOpenAccess W3048791348 @default.
• W3048791348 hasPrimaryLocation W30487913481 @default.
• W3048791348 hasRelatedWork W1506200166 @default.
• W3048791348 hasRelatedWork W1995515455 @default.
• W3048791348 hasRelatedWork W2048182022 @default.
• W3048791348 hasRelatedWork W2080531066 @default.
• W3048791348 hasRelatedWork W2604872355 @default.
• W3048791348 hasRelatedWork W2748952813 @default.
• W3048791348 hasRelatedWork W2899084033 @default.
• W3048791348 hasRelatedWork W3031052312 @default.
• W3048791348 hasRelatedWork W3032375762 @default.
• W3048791348 hasRelatedWork W3108674512 @default.
• W3048791348 hasVolume "54" @default.
• W3048791348 isParatext "false" @default.
• W3048791348 isRetracted "false" @default.
• W3048791348 magId "3048791348" @default.
• W3048791348 workType "article" @default.