SHOCK最新文献

Objective: The aim of this study is to compare laboratory parameters between incomplete Kawasaki disease (IKD) and sepsis, and to evaluate the predictive value of common laboratory parameters in distinguishing IKD from sepsis.

Methods: A retrospective analysis was conducted on medical records of patients diagnosed with Kawasaki disease or sepsis between January 2021 and December 2023. A total of 207 cases of IKD and 315 cases of sepsis were included in this study. Clinical data were analyzed to identify intergroup differences.

Results: Significant intergroup differences ( P  < 0.05) were observed in blood platelet (PLT) count, procalcitonin, aspartate aminotransferase, alanine aminotransferase (ALT), urea nitrogen, creatinine, C-reactive protein, fibrinogen (Fib), and D-dimer levels. Markers with statistically significant variations relevant to the diagnosis of IKD were identified using binary logistic regression analysis. Receiver operating characteristic curve analysis demonstrated areas under the curve of 0.771 for PLT, 0.800 for ALT, and 0.755 for Fib. A combined assessment of these markers resulted in improved sensitivity and specificity.

Conclusion: PLT, ALT, and Fib can serve as laboratory markers for distinguishing IKD from sepsis and offer diagnostic reference value. Their combined assessment may improve the predictive accuracy for IKD.

Objective: Sepsis is a life-threatening complication of infection in which a dysregulated host response precipitates multiorgan dysfunction. Neutrophil extracellular traps contribute to infection-induced immunothrombosis by releasing cell-free DNA (cfDNA), which provides a prothrombotic scaffold for blood clots. Although DNase I has therapeutic promise due to its ability to degrade cfDNA, its short plasma half-life (2 to 4 h) may necessitate multiple daily injections, potentially posing challenges for clinical use. This study investigates the efficacy of i.v. administration of PRX-119, a PEGylated recombinant human DNase I with an extended half-life of ~12 h.

Methods: Sepsis was induced in C57Bl/6 mice (10-12 weeks old) using the cecal ligation and puncture (CLP) model. The efficacy of i.v. PRX-119 (1 mg/kg) was tested in 72-h and 7-day survival studies, including clinically relevant supportive therapies (antibiotics, fluid resuscitation). We measured plasma levels of cfDNA, IL-6, IL-10, and thrombin-antithrombin (TAT) complexes. We assessed physiological parameters, bacterial burden, lung myeloperoxidase, and organ injury/function.

Results: Using both sexes, a single dose of PRX-119 (at T  = 8 h) or two doses (at T  = 4 and 24 h) improved survival at 72 h. Using male mice, we observed that three doses (at T  = 4, 20, and 36 post-CLP) provided a sustained protective effect at 7 days post-CLP. PRX-119 treatment reduced cfDNA, IL-6, TAT, lung myeloperoxidase, and bacterial load. PRX-119 treatment also reduced organ injury.

Conclusions: Intravenous delivery of PRX-119 improved survival and reduced immunothrombosis and organ injury, without the need for frequent injections.

Background: Frailty is an important determinant of outcomes in patients with cardiovascular disease; however, its impact on the management and prognosis of cardiogenic shock (CS) remains unclear. This study examined the association between frailty and in-hospital outcomes, focusing on sex-based differences in treatment and mortality.

Methods: We used the National Inpatient Sample from 2016 to 2019 to identify adult patients hospitalized with CS. Frailty was assessed using the Hospital Frailty Risk Score and categorized as low (<5), intermediate (5-15), or high risk of frailty (>15). Logistic regression was used to estimate the odds ratios (ORs) with their 95% confidence intervals (CIs).

Results: Among 640,595 admissions, frailty was strongly associated with increased mortality (high vs. low risk: OR 2.15, 95% CI 2.03-2.27) and major bleeding (high vs. low risk: OR 6.18, 95% CI 5.53-6.92). Women had higher in-hospital mortality than men, but only at low (OR 1.30, 95% CI 1.22-1.39) and intermediate frailty risk (OR 1.16, 95% CI 1.13-1.20). Women had lower use of pulmonary artery catheterization, intra-aortic balloon pump, and percutaneous ventricular assist device compared to men, at any level of frailty risk. The odds of major bleeding in women versus men varied according to frailty risk. Renal replacement therapy was higher in women versus men with intermediate or high risk of frailty.

Conclusions: Frailty independently predicted higher mortality and lower use of mechanical circulatory support in patients with CS. Women have worse outcomes with less invasive treatment, highlighting sex disparities in CS care.

Background: Cardiogenic shock requiring mechanical circulatory support is a life-threatening complication of cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to determine the role of myoglobin in predicting the occurrence of postoperative cardiogenic shock requiring mechanical circulatory support within 14 days.

Methods: A total of 4,610 patients undergoing cardiac surgery with CPB were included and analyzed. Mechanical circulatory support included the form of intra-aortic balloon pump and extracorporeal membrane oxygenation. Cox regression with a natural cubic spline was used to assess the relationship between postoperative myoglobin levels and the 14-day risk of mechanical circulatory support for cardiogenic shock.

Results: Of 4,610 patients, 279 (6.1%) required mechanical circulatory support within 14 days after surgery. The 14-day risk of using mechanical circulatory support increased with the postoperative peak myoglobin levels. Among the patients who underwent aortic surgery, the threshold myoglobin level measured within 1 day after surgery, associated with an adjusted hazard ratio greater than 1.00 for using mechanical circulatory support within 14 days, was 1,568 ng/mL (95% confidence interval [CI], 195-6,040). Among the patients who underwent non-aortic surgery, the corresponding threshold myoglobin level was 419 ng/mL (95% CI, 180-452).

Conclusions: Postoperative myoglobin levels are closely related to the 14-day risk of using mechanical circulatory support after cardiac surgery. When postoperative myoglobin exceeds certain thresholds, the 14-day risk of using mechanical circulatory support after surgery starts to increase with the myoglobin level. Myoglobin has potential value in predicting postoperative cardiogenic shock requiring mechanical circulatory support within 14 days after cardiac surgery.

Sudden cardiac arrest (CA) is associated with high mortality and morbidity rates, largely due to detrimental effects of global ischemia on every organ. Notably, clinical evidence indicates that gastrointestinal tract damage is frequently observed in successfully resuscitated CA patients and suggests that this damage has a negative impact on prognosis. However, experimental CA studies have rarely examined this clinically relevant pathologic change, and as such, little is known about the underlying mechanisms. Here, we provide the first evidence that mast cells (MCs) play a critical role in gut damage after CA. Our data first showed notable activation of intestinal MCs and evidence of disrupted gut integrity following CA in a mouse model. Then, using both pharmacologic and genetic tools, we found that treatment with the MC activator C48/80 significantly increased gut permeability, whereas gut function was better preserved in MC-deficient mice compared to wild-type mice. Together, our results identified MC activation as a critical pathologic process driving post-CA gut damage.

Ischemia-reperfusion (I/R) injury remains a major contributor to myocardial damage, significantly impacting cardiovascular morbidity and mortality. This study identifies key genes and pathways involved in I/R-induced myocardial injury through differential gene expression analysis and weighted gene co-expression network analysis. Functional enrichment analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Disease Ontology, highlight the involvement of immune response and oxidative stress pathways in I/R injury. Machine learning approaches, such as LASSO, Support Vector Machine Recursive Feature Elimination, and Random Forest, were employed to identify feature genes predictive of I/R progression, with Ifi204 emerging as a critical factor. The role of interferon-induced protein 204 (Ifi204) in myocardial protection during I/R injury was further explored using a heart-specific Ifi204 knockout mouse model. The effects of Ifi204 deficiency on myocardial injury, inflammation, and oxidative stress were assessed. Notably, heart-specific Ifi204 knockout mice demonstrated reduced myocardial infarct size, improved heart function, and lower serum markers of myocardial injury, including creatine kinase, lactate dehydrogenase, and cardiac troponin T. These mice also exhibited attenuated oxidative stress and suppressed NF-κB signaling, as evidenced by reduced malondialdehyde levels and increased superoxide dismutase activity. Furthermore, overexpression of Ifi204 in primary cardiomyocytes enhanced the inflammatory response via NF-κB activation, leading to increased secretion of proinflammatory cytokines, such as TNF-α and IL-6. These effects were mitigated by NF-κB inhibition, suggesting that Ifi204 modulates inflammation through NF-κB signaling. This study provides new insights into the molecular mechanisms underlying myocardial I/R injury and positions Ifi204 as a potential therapeutic target for cardiovascular diseases.

Background: Accurate assessment of tissue perfusion is challenging. Commonly used markers like lactate levels and central venous oxygen saturation are indirect, intermittent, and provide a global picture of circulatory status which may not reflect perfusion at the organ level. The Urethral Perfusion Index (UPi), measured through a specialized urinary catheter, is a novel technique that offers continuous, real-time monitoring of perfusion in a central tissue bed, potentially providing more immediate and targeted clinical information.

Objectives: 1. The aims of the study were (1) to assess the correlation between changes to left ventricular outflow tract velocity time integral (LVOT VTi) and UPi following a fluid challenge and (2) To assess the relationship between UPi and other markers of tissue perfusion.

Design: Interventional, feasibility pilot study.

Setting: Single-center, study conducted at a tertiary-level institution in the United Kingdom. All patients were mechanically ventilated adults, whom the primary clinical team thought would benefit from a fluid challenge.

Intervention: A fluid challenge (FC) was defined as a 250 mL bolus of crystalloid solution.

Main outcome measures: Focused transthoracic echocardiogram measured LVOT VTi and UPi, measured before and after FC.

Results: There were no reported complications associated with device use or insertion. Mean duration of data recorded was 19 h and the Signal Quality Index of the UPi trace was high (93%). There was a moderate positive correlation between the time matched values of UPi and LVOT VTi (Spearman r = 0.55, P  < 0.0001), R 2 value of 0.272. However, there was no discernible correlation seen between change in UPi and VTi following fluid (Spearman r = 0.24, P  = 0.14). Patients with below-average UPi at baseline had evidence of poorer systemic tissue perfusion, as measured by lactate concentration and capillary refill time, and received more vasoactive drugs.

Conclusion: UPi may be a marker of tissue perfusion in a diverse group of critically ill patients. With further evaluation it may, therefore, present a future therapeutic target. Although there is some relationship between LVOT VTi and UPi, it is not precise enough to be used as a marker of fluid responsiveness.

Trial registration: London Southeast Research and Ethics Committee (22/LO/0911).

Background: Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, goes along with a complex and not yet fully understood host response. Despite many different biomarkers, optimal screening tools to identify patients with sepsis are still needed. In a previous, single-center clinical trial with well-defined and well-separated patient cohorts, a new biophotonic marker based on the Raman spectroscopic characterization of leukocytes showed added value to stratify patients and identify infection and sepsis.

Results: In the INTELLIGENCE studies, 279 patients from six centers in two countries were analyzed, and the Raman spectra of ~1500 leukocytes per patient were measured within only 1 hour. This marks a huge step from bench to bedside regarding usability and technology readiness level of Raman spectroscopy in multicentre clinical trials. With a discriminatory power comparable to individual conventional biomarkers (C-reactive protein, procalcitonin, interleukin-6, and soluble urokinase-type plasminogen activator receptor), the Raman score of leukocytes could not provide added value to the clinical discrimination of sepsis in the INTELLIGENCE-1 study cohorts of intensive care patients with infections. When translating the classification model from INTELLIGENCE-1 to the heterogeneous patient cohort recruited at the emergency department of the double-blinded INTELLIGENCE-2 trial, the Raman score failed to provide added value.

Conclusions: In theory, Raman assessment of leukocytes might still be a promising tool for sepsis diagnosis and patient stratification, but there is more basic, translational, and clinical research needed to refine its usability and clinical role, probably also taking questions of the pathophysiology of the dysregulated host response for a phenotype stratification into account.

Background: Care for massively bleeding patients has seen a return of focus to the use of cold stored whole blood (WB) as the primary resuscitation treatment. Nonhuman primates (NHP) are the ideal trauma animal model for preclinical hemostatic research as they are most physiologically akin to humans, yet study designs use autologous shed WB which does not fully recapitulate what occurs in human medicine. We sought to evaluate effects of prolonged 4°C storage of NHP WB.

Methods: WB was collected from 10 anesthetized male rhesus macaques and 5 male cynomolgus macaques into 10% CPDA-1 in 300 mL storage bags. WB units were tested at baseline prior to storage at 4°C and aseptically sampled daily for the first 4 days, then weekly at day 7 through day 28 of storage. Biochemical, hematologic, and hemostatic function parameters were assayed. Data were analyzed using a mixed effects analysis with multiple comparisons if significant.

Results: In both species, red cell, hemoglobin and hematocrit counts remained stable through day 28, while lactate and potassium levels significantly increased as sodium and pH decreased significantly. Hemostatic function significantly declined for both species from day 7 onward.

Conclusion: This study describes a viable method of manufacture of NHP stored WB and characterizes the storage lesion in both rhesus and cynomolgus macaques. Observationally, no overt differences were seen between species. Future resuscitation studies utilizing NHP models could improve translational relevance using stored allogenic WB.

Background: Septic shock (SS) is deadly. Sepsis-immune response transitions from an endotoxin-sensitive, hyper-inflammatory phase to an endotoxin-tolerant hypo-inflammatory phase. In mice, we implicated sirtuin 2 (SIRT2) for prolonged hypo-inflammation using leukocyte adhesion, the earliest in vivo inflammatory response to cytokine, chemokine, and metabolite stimuli. The role of SIRT2 in human sepsis remains unknown. We hypothesized that: 1. Peripheral blood mononuclear cells (PBMCs) adhesion response can be used as a physiological biomarker of hypo-inflammation, and 2. SIRT2 regulates the functions of PBMCs and macrophages during the hypo-inflammatory phase of human sepsis.

Methods: We stimulated control and SS-whole blood and PBMCs ± lipopolysaccharide (LPS) and investigated plasma cytokines, PBMC cell adhesion to ICAM-1 coated plates, adhesion molecule CD18 activation, SIRT2 expression, and cytokine response. In adhesion/endotoxin-tolerant PBMCs and THP-1 cells treated ± SIRT2 inhibitor AK-7, we analyzed cell adhesion, CD18 activation, and transmigration ± LPS. In monocyte-derived macrophages (MDMs) from SS vs. controls ± AK-7, we analyzed phagocytosis.

Results: We found: 1. Muted plasma TNF and IL-1β-response to LPS in SS vs. control (endotoxin-tolerance) 2. Endotoxin-tolerant SS-PBMCs exhibit high SIRT2 expression, and muted adhesion (adhesion-tolerance), CD18 activation, and transmigration with LPS. 3. SIRT2 inhibitor AK-7 reverses endotoxin and adhesion-tolerance in SS-PBMCs via CD18 activation, reverses the defective transmigration of endotoxin-tolerant PBMCs and improves phagocytosis in MDMs from SS patients.

Conclusion: PBMC adhesion, a physiological biomarker, can be used to detect hypo-inflammation. Defective PBMC and macrophage function in septic shock patients occur via high SIRT2 expression. SIRT2 inhibition is a potential therapeutic strategy for treating sepsis-associated hypo-inflammation.