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Background: There is limited evidence for the use of an intra-aortic balloon pump (IABP) in adult patients with a total cavopulmonary, or Fontan circulation., Case Summary: A patient in his twenties with a Fontan circulation presented with sepsis, pneumonia, and pulmonary oedema. He was born with a hypoplastic left ventricle, atrioventricular septal defect, and hypoplastic aortic arch, and a total cavopulmonary circulation had been established within his first years of life. Standard of care treatment with antibiotics, non-invasive ventilatory support, loop diuretics, and vasopressors was initiated. Due to persistent pulmonary congestion and increasing general fatigue, an IABP was placed via a femoral artery to offload the failing systemic ventricle. Secondary to IABP treatment, mean arterial pressure rose, and vasodilatory nitroprusside could be introduced. Over 4 days of IABP treatment, the patient's general condition and ventricular systolic function improved significantly., Discussion: This case suggests that IABP treatment was important in the recovery of our patient with a Fontan circulation, pneumonia, and heart failure. We propose that during IABP treatment, an increase in stroke volume and a reduction in ventricular filling pressure is achieved, thereby increasing the transpulmonary pressure gradient that is central to pulmonary blood flow in Fontan patients. More definitive evidence is necessary to confirm our hypotheses., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: The complement system and neutrophil extracellular traps (NETs) might contribute to ischemia-reperfusion injury in ST-elevation myocardial infarction (STEMI). We aimed to estimate associations between complement activation and NETs in STEMI, and their prognostic value on clinical endpoints., Methods: In this cohort study, 864 patients admitted for PCI during STEMI were included. Complement activation was analyzed by the terminal complement complex (TCC), while NETs were analyzed by myeloperoxidase-DNA, citrullinated histone 3 (CitH3) and dsDNA. The composite endpoint was reinfarction, unscheduled revascularization, stroke, hospitalization due to heart failure, or death, and the secondary endpoint was total mortality. The association between TCC and clinical endpoints was assessed by Cox regression and ROC curve analysis., Results: TCC was weakly correlated to dsDNA ( r  = 0.127, p  < 0.001) and CitH3 ( r  = 0.102, p  = 0.003). After a median follow-up time of 4.6 years, 184 (21.3 %) patients had reached a clinical endpoint. TCC was not associated with the composite endpoint, but with total mortality (HR: 1.673, 95 % CI: [1.014, 2.761], p  = 0.044). The significant association was lost when adjusting for CRP, NT-proBNP, LVEF and time from symptoms to PCI. In ROC curve analysis of total mortality, the AUC for TCC alone was 0.549 (95 % CI: [0.472, 0.625]), AUC for dsDNA alone was 0.653 (95 % CI: [0.579, 0.720]), while AUC for TCC and dsDNA combined was 0.660 (95 % CI: [0.590, 0.730])., Conclusions: In this STEMI cohort, TCC was not associated with the composite endpoint, but somewhat with total mortality. Combining TCC and dsDNA did not increase the prognostic value compared to dsDNA alone., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Objective: The role of neutrophil extracellular traps (NETs) in acute heart failure is unknown. We recently showed that interleukin 8, a putative NETs stimulator, was associated with myocardial recovery in acute heart failure complicating ST-elevation myocardial infarction (STEMI). In this exploratory post-hoc study, we aimed to investigate the role of NETs components in relation to myocardial function and interleukin 8 in STEMI patients with symptomatic acute heart failure., Methods: In 61 STEMI patients developing acute heart failure within 48 hours of successful revascularization, wall motion score index (WMSI), global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF) were assessed by echocardiography at baseline and on day 5. Blood drawn at baseline and days 1, 2 and 5 was used to quantify double-stranded DNA (dsDNA), myeloperoxidase-DNA complexes (MPO-DNA) and citrullinated histone 3 (CitH3). The area under the curve (AUC) of each NETs marker and interleukin 8 was approximated for the first 5 days., Results: dsDNAAUC and MPO-DNAAUC correlated significantly with change in WMSI from baseline to day 5 (rs = 0.28 for both, p≤0.05), whereas NETs AUCs did not correlate with changes in GLS and LVEF. dsDNAAUC was significantly correlated with interleukin 8AUC (r = 0.40, p = 0.003). However, mixed model regression could not identify a significant effect of the NETs components on myocardial function parameters., Conclusions: In this cohort with acute heart failure complicating STEMI, NETs components were partly correlated with myocardial function and interleukin 8 levels, yet no causal relationship between NETs components and myocardial recovery could be established., Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT00324766., Competing Interests: The authors have declared that no competing interests exist.

Complement activation and neutrophil extracellular traps (NETs) have both been suggested to drive atherosclerotic plaque progression. Although experimental studies suggest interplay between these two innate immunity components, the relevance in patients with coronary artery disease (CAD) is unclear. The aim of this study was to assess associations between complement activation and NETs in patients with stable CAD and examine the role of complement activation on clinical outcome. Blood samples from a cohort of patients with angiographically verified stable CAD ( n = 1001) were analyzed by ELISA for the terminal complement complex (TCC) and by relative quantification for gene expression of the C5a receptor 1 (C5aR1) as markers of complement activation. As markers of NETs, dsDNA was analyzed by fluorescent nucleic acid stain and myeloperoxidase-DNA (MPO-DNA) by ELISA. Clinical outcome was defined as unstable angina, nonhemorrhagic stroke, acute myocardial infarction (MI), or death ( n = 106, whereof 36 MI). Levels of TCC and C5aR1 were not significantly correlated to dsDNA (TCC: r = -0.045, p = 0.153; C5aR1: r = -0.060, p = 0.434) or MPO-DNA (TCC: r = 0.026, p = 0.414; C5aR1: r = 0.123, p = 0.107). When dividing TCC and C5aR1 levels into quartiles (Q), levels of MPO-DNA differed significantly across quartiles (TCC: p = 0.008, C5aR1: 0.049), while dsDNA did not (TCC: p = 0.181, C5aR1: p = 0.771). Patients with TCC levels in Q4 had significantly higher levels of MPO-DNA than Q1-3 ( p = 0.019), and C5aR1 levels in Q3-4 had significantly higher levels of MPO-DNA than Q1-2 ( p = 0.046). TCC levels did not differ between patients experiencing a clinical endpoint or not, but high levels were associated with increased risk of acute MI (OR. 1.97, 95% CI: 0.99-3.90, p = 0.053) during two-year follow up, also when adjusted for relevant covariates. In conclusion, TCC and C5aR1 were moderately associated with the NET marker MPO-DNA, and TCC levels were related to the risk of future MI in this cohort of patients with stable CAD., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Karsten E. Kluge et al.)

Neutrophil extracellular traps (NETs) have been implicated in atherothrombosis; however, their potential role as markers of risk is unclear. We investigated whether circulating NETs-related components associated with clinical outcome and hypercoagulability in ST-elevation myocardial infarction (STEMI). In this observational cohort study, STEMI patients admitted for PCI (n = 956) were followed for median 4.6 years, recording 190 events (reinfarction, unscheduled revascularization, stroke, heart failure hospitalization, or death). Serum drawn median 18 hours post-PCI was used to quantify double-stranded DNA (dsDNA) and the more specific NETs markers myeloperoxidase-DNA and citrullinated histone 3. Levels of the NETs markers did not differ significantly between groups with/without a primary composite endpoint. However, patients who died (n = 76) had higher dsDNA compared to survivors (p < 0.001). Above-median dsDNA was associated with an increased number of deaths (54 vs. 22, p < 0.001). dsDNA in the upper quartiles (Q) was associated with increased mortality (Q3 vs. Q1 + 2 adjusted HR: 1.89 [95% CI 1.03 to 3.49], p = 0.041 and Q4 vs. Q1 + 2 adjusted HR: 2.28 [95% CI 1.19 to 4.36], p = 0.013). dsDNA was weakly correlated with D-dimer (r s  = 0.17, p < 0.001). dsDNA levels associated with increased all-cause mortality, yet weakly with hypercoagulability in STEMI patients. The prognostic significance of potentially NETs-related markers requires further exploration.

Background: The relevance of neutrophil extracellular traps (NETs) in acute ST-elevation myocardial infarction (STEMI) is unclear. We explored the temporal profile of circulating NET markers and their associations to myocardial injury and function and to adverse clinical events in STEMI patients., Methods and Results: In 259 patients, blood samples were drawn before and after PCI, on day 1, and after 4 months. Double-stranded deoxyribonucleic acid (dsDNA) and myeloperoxidase-DNA (MPO-DNA) were measured in serum by a nucleic acid stain and ELISA. Cardiac magnetic resonance imaging assessed microvascular obstruction (MVO), area at risk, infarct size, myocardial salvage index, left ventricular ejection fraction (LVEF), and change in indexed left ventricular end-diastolic volume (LVEDVi). Clinical events were registered after 12 months. dsDNA and MPO-DNA levels were highest before PCI, with reduced levels thereafter (all p ≤ 0.02). Patients with high vs. low day 1 dsDNA levels (>median; 366 ng/ml) more frequently had MVO, larger area at risk, larger infarct size acutely and after 4 months, and lower myocardial salvage index (all p < 0.03). Moreover, they had lower LVEF acutely and after 4 months, and larger change in LVEDVi (all p ≤ 0.014). High day 1 dsDNA levels also associated with risk of having a large infarct size (>75th percentile) and low LVEF (≤49%) after 4 months when adjusted for gender, time from symptoms to PCI, and infarct localization (OR 2.3 and 3.0, both p < 0.021), and patients with high day 1 dsDNA levels were more likely to experience an adverse clinical event, also when adjusting for peak troponin T (hazard ratio 5.1, p = 0.012). No such observations were encountered for MPO-DNA., Conclusions: High day 1 dsDNA levels after STEMI were associated with myocardial infarct size, adverse left ventricular remodeling, and clinical outcome. Although the origin of dsDNA could be discussed, these observations indicate a potential role for dsDNA in acute myocardial ischemia. This trial is registered with S-08421d, 2008/10614 (Regional Committee for Medical Research Ethics in South-East Norway (2008))., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2019 Ragnhild Helseth et al.)

Neutrophil extracellular traps (NETs) are network-like structures released by activated neutrophils. They consist mainly of double-stranded DNA, histones, and neutrophil granule proteins. Continuous release of NETs in response to external stimuli leads to activation of surrounding platelets and monocytes/macrophages, resulting in damage to endothelial cells (EC) and vascular smooth muscle cells (VSMC). Some clinical trials have demonstrated the association between NETs and the severity and prognosis of atherosclerosis. Furthermore, experimental findings have shed light on the molecular mechanisms by which NETs contribute to atherogenesis. NETs play a significant role in the formation of atherosclerotic plaques. This review focuses on recent advancements in the understanding of the relationship between NETs and atherosclerosis. It explores various aspects, including the formation of NETs in atherosclerosis, clinical trials investigating NET-induced atherosclerosis, the mechanisms by which NETs promote atherogenesis, and the translational implications of NETs. Ultimately, we aim to propose new research directions for the diagnosis and treatment of atherosclerosis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background Neutrophil extracellular traps, comprising chromatin and granule proteins, have been implicated in atherothrombosis. Design and methods We investigated whether the circulating neutrophil extracellular traps markers, double-stranded DNA and myeloperoxidase-DNA were associated with clinical outcome and hypercoagulability in patients with stable coronary artery disease. Patients with angiographically verified stable coronary artery disease ( n = 1001) were included. Follow-up was 2 years, recording 106 clinical endpoints (unstable angina, non-haemorrhagic stroke, myocardial infarction or death). Serum collected at baseline was used to determine double-stranded DNA and myeloperoxidase-DNA levels. Results The neutrophil extracellular traps markers were weakly intercorrelated ( r = 0.103, P = 0.001). Patients with the highest quartile of double-stranded DNA had weakly but significantly elevated hypercoagulability markers (prothrombin fragment 1+2, D-dimer, free and total tissue factor pathway inhibitor ( P < 0.001 for all)). Men, smokers, patients with metabolic syndrome and patients with a previous myocardial infarction had significantly elevated double-stranded DNA levels ( P ≤ 0.002 for all). Significantly higher double-stranded DNA levels were observed in the group experiencing a clinical endpoint compared to the group without ( P = 0.019). When categorising double-stranded DNA into quartiles, a distinct cut-off between the lowest and upper three quartiles was observed. Adjusting for relevant covariates, patients in the upper three quartiles had an odds ratio of 2.01 (95% confidence interval 1.12, 3.58, P = 0.019) for experiencing a clinical endpoint. Myeloperoxidase-DNA was not significantly associated with clinical outcome or hypercoagulability. Conclusions Double-stranded DNA levels were significantly related to adverse clinical outcome after 2 years, but only weakly associated with hypercoagulability. These observations suggest that the detrimental effects of neutrophil extracellular traps in coronary artery disease might extend beyond those related to hypercoagulability.

OBJECTIVE: Clinical consultations with patients should be informed by the evidence-based and involve shared decision making (SDM). We aimed to determine the delivery of SDM by clinicians with patients referred for invasive treatment of cardiac electrical disease and to establish whether decisions made corresponded with patient and referring physician expectations. METHODS: Forty-nine outpatient consultations with two consultant cardiologists in one large tertiary centre were audio-recorded. Demographic data, diagnosis, reasons for referral and decision reached were compared directly with patient and referring physician expectations. The OPTION instrument was used to measure SDM. Patient expectations and satisfaction were elicited. RESULTS: Quality of SDM was good (mean OPTION score 49%) and there was broad patient satisfaction. While all patients were suitable for invasive treatment, and the majority (80%, n=39) had been explicitly referred for it, only 59% (n=29) opted to proceed. Consultation quality with respect to SDM was significantly greater for patients choosing a less invasive option. CONCLUSION: These consultations often change expected management. Where decision making in the consultation is of higher quality, patients were more likely to change to a less invasive option. PRACTICE IMPLICATIONS: Clinicians performing invasive cardiac treatment should be able to demonstrate high quality decision making. [ABSTRACT FROM AUTHOR]

In xenotransplantation, the vascular endothelium serves as the first point of contact between the recipient’s blood and the transplanted donor organ. The loss of the endothelium’s ability to control the plasma cascades plays a critical role in the dysregulation of the complement and coagulation systems, which greatly contribute to graft rejection and hinder long-term xenograft survival. Although it is known that an intact glycocalyx is a key feature of a resting endothelium that exhibits optimal anticoagulant and anti-inflammatory properties, the role of the endothelial glycocalyx in xenotransplantation is barely investigated so far. Here, we discuss the central role of endothelial cells and the sugar-rich endothelial glycocalyx in regulating the plasma cascades, and how the loss of these functions contributes to graft damage and rejection. We highlight the importance of preserving the regulatory functions of both endothelial cells and the glycocalyx as strategies to improve xenotransplantation outcomes. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is characterized by chronic non-recessive inflammation of the intestinal mucosa involving both innate and adaptive immune responses. Currently, new targeted therapies are urgently needed for UC, and neutrophil extracellular traps (NETs) are new therapeutic options. NETs are DNA-based networks released from neutrophils into the extracellular space after stimulation, in which a variety of granule proteins, proteolytic enzymes, antibacterial peptides, histones, and other network structures are embedded. With the deepening of the studies on NETs, their regulatory role in the development of autoimmune and autoinflammatory diseases has received extensive attention in recent years. Increasing evidence indicates that excess NETs exacerbate the inflammatory response in UC, disrupting the structure and function of the intestinal mucosal barrier and increasing the risk of thrombosis. Although NETs are usually assigned a deleterious role in promoting the pathological process of UC, they also appear to have a protective role in some models. Despite such progress, comprehensive reviews describing the therapeutic promise of NETs in UC remain limited. In this review, we discuss the latest evidence for the formation and degradation of NETs, focusing on their double-edged role in UC. Finally, the potential implications of NETs as therapeutic targets for UC will be discussed. This review aims to provide novel insights into the pathogenesis and therapeutic options for UC. [ABSTRACT FROM AUTHOR]

Introduction: Patients with systemic lupus erythematosus are prone to develop cardiovascular disease (CVD), and have increased morbidity and mortality. Methods: We conducted a retrospective analysis on lupus nephritis patients to assess the occurrence and predictors of major adverse cardiovascular events (MACE). Data were collected from patients who underwent kidney biopsy between 2005 and 2020. Statistical analysis was performed to unveil correlations. Results: 91 patients were analyzed in this period, with a mean age of 37.3 ± 12.3 years and 86% being female. The mean follow-up time was 62 ± 48 months. 15.38% of the patients underwent at least one MACE. Two patients deceased of CVD. Increased age (35.81 ± 11.14 vs 45.5 ± 15.11 years, p=0.012) entailed a higher occurrence of MACEs. Neutrophil count (5.15 ± 2.83 vs 7.3 ± 2.99 Giga/L, p=0.001) was higher, whereas diastolic blood pressure (DBP) was lower (89.51 ± 10.96 vs 78.43 ± 6.9 mmHg, p<0.001) at the time of the biopsy in patients with MACE. Age, neutrophil count, and DBP proved to be independent predictors of MACEs. We propose a new model (CANDE – Cardiovascular risk based on Age, Neutrophil count, and Diastolic blood pressure Estimation score) calculated from these variables, which predicts the probability of MACE occurrence. Conclusion: This study underscores the importance of actively screening for cardiovascular risks in this vulnerable patient population. Age, neutrophil count, and diastolic blood pressure have been established as independent risk factors for MACE in lupus nephritis. The CANDE score derived from these parameters may serve as a prompt, cost-effective, and easily accessible estimation tool for assessing the likelihood of major adverse cardiovascular risk. These findings emphasize the necessity for comprehensive management strategies addressing both immune dysregulation and cardiovascular risk factors in systemic lupus erythematosus to mitigate adverse outcomes. [ABSTRACT FROM AUTHOR]

Extracorporeal cardiopulmonary resuscitation (ECPR) is emerging as a feasible and effective rescue strategy for prolonged cardiac arrest (CA). However, prolonged total body ischemia and reperfusion can cause microvascular occlusion that prevents organ reperfusion and recovery of function. One hypothesized mechanism of microvascular "no-reflow" is leukocyte adhesion and formation of neutrophil extracellular traps. In this study we tested the hypothesis that a leukocyte filter (LF) or leukocyte modulation device (L-MOD) could reduce NETosis and improve recovery of heart and brain function in a swine model of prolonged cardiac arrest treated with ECPR. Thirty-six swine (45.5 ± 2.5 kg, evenly distributed sex) underwent 8 min of untreated ventricular fibrillation CA followed by 30 min of mechanical CPR with subsequent 8 h of ECPR. Two females were later excluded from analysis due to CPR complications. Swine were randomized to standard care (Control group), LF, or L-MOD at the onset of CPR. NET formation was quantified by serum dsDNA and citrullinated histone as well as immunofluorescence staining of the heart and brain for citrullinated histone in the microvasculature. Primary outcomes included recovery of cardiac function based on cardiac resuscitability score (CRS) and recovery of neurologic function based on the somatosensory evoked potential (SSEP) N20 cortical response. In this model of prolonged CA treated with ECPR we observed significant increases in serum biomarkers of NETosis and immunohistochemical evidence of microvascular NET formation in the heart and brain that were not reduced by LF or L-MOD therapy. Correspondingly, there were no significant differences in CRS and SSEP recovery between Control, LF, and L-MOD groups 8 h after ECPR onset (CRS = 3.1 ± 2.7, 3.7 ± 2.6, and 2.6 ± 2.6 respectively; p = 0.606; and SSEP = 27.9 ± 13.0%, 36.7 ± 10.5%, and 31.2 ± 9.8% respectively, p = 0.194). In this model of prolonged CA treated with ECPR, the use of LF or L-MOD therapy during ECPR did not reduce microvascular NETosis or improve recovery of myocardial or brain function. The causal relationship between microvascular NETosis, no-reflow, and recovery of organ function after prolonged cardiac arrest treated with ECPR requires further investigation. [ABSTRACT FROM AUTHOR]

Activated neutrophils release a range of inflammatory products that represent potential biomarkers, and there is interest in the prognostic value of these in acute coronary syndrome (ACS) patients. We conducted a systematic review to examine neutrophil-enriched biomarkers and the occurrence of major adverse cardiovascular events (MACE) in patients with ACS. We identified twenty-seven studies including 17,831 patients with ACS. The most studied biomarkers were neutrophil gelatinase-associated lipocalin (NGAL) and myeloperoxidase (MPO). Meta-analyses showed that elevated NGAL was associated with higher MACE rates (unadjusted risk ratio (RR) 1.52, 95% CI 1.12–2.06, p = 0.006) as were elevated MPO levels (unadjusted RR 1.61, 95% CI 1.22–2.13, p = 0.01). There was limited data suggesting that increased levels of calprotectin, proteinase-3 and double-stranded DNA were also associated with MACE. These results suggest that higher levels of neutrophil-enriched biomarkers may be predictive of MACE in patients with ACS, although higher-quality studies are needed to confirm these observations. [ABSTRACT FROM AUTHOR]

Beta (β)-thalassemia and sickle cell disease (SCD) are characterized by a hypercoagulable state, which can significantly influence organ complication and disease severity. While red blood cells (RBCs) and erythroblasts continue to play a central role in the pathogenesis of thrombosis in β-thalassemia and SCD, additional factors such as free heme, inflammatory vasculopathy, splenectomy, among other factors further contribute to the complexity of thrombotic risk. Thus, understanding the role of the numerous factors driving this hypercoagulable state will enable healthcare practitioners to enhance preventive and treatment strategies and develop novel therapies for the future. We herein describe the pathogenesis of thrombosis in patients with β-thalassemia and SCD. We also identify common mechanisms underlying the procoagulant profile of hemoglobinopathies translating into thrombotic events. Finally, we review the currently available prevention and clinical management of thrombosis in these patient populations., (© 2024 Wiley Periodicals LLC.)

Systemic immune inflammation index (SII) is a global parameter that comprehensively reflects body inflammation, this study aims to assess the correlation between this index and erectile dysfunction (ED). This cross-sectional study incorporated 164 ED patients and 95 healthy adult males. The collection of general demographic information and pertinent hematological data from the participants enabled the computation of corresponding SII values. Statistical analysis, encompassing descriptive statistics as well as normality and logistic regression analyses, was carried out employing SPSS version 26. The findings of the univariate analysis revealed a noteworthy distinction in triglyceride levels (TG) (P = 0.017) and SII (P < 0.001) between ED patients and the healthy population. Subsequent multivariate logistic regression analysis unveiled a significant association between SII (odd ratio (OR):1.012, 95% confidence interval (CI):1.008-1.015; P < 0.001) and the occurrence of ED. Since the impact value is not clearly visible, SII/100 is utilized to magnify the effect value one hundredfold. The regression analysis results indicate that the OR value of SII/100 is 3.171, and the 95% CI is 2.339-4.298 (P < 0.001). The Receiver Operating Characteristic (ROC) curve analysis ascertained an AUC of 0.863 (P < 0.001) for SII, with a determined cut-off value of 391.53(10 9 /L), exhibiting a sensitivity of 81.7% and specificity of 83.2%. Moreover, when comparing patients with varying degrees of ED severity, both univariate (P < 0.001) and subsequent multivariate logistic regression analyses (OR: 1.007, 95% CI: 1.004-1.010; P < 0.001) underscored the significance of the SII value. At this point, SII/100 OR: 1.971, 95% CI: 1.508-2.576 (P < 0.001). The ROC curve analysis in this context demonstrated an AUC of 0.799 (P < 0.001), with a determined cut-off value of 746.63(10 9 /L), featuring a sensitivity of 60.6% and specificity of 91.6%. These discerned outcomes affirm a correlation between SII and ED, establishing its potential not only in predicting the onset of ED but also in differentiating among various levels of ED severity., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Acute urticaria is a prevalent inflammatory dermatosis characterized by fulminant wheals, often accompanied by severe pruritis. It may also cause nausea, vomiting, and abdominal pain. Numerous studies have substantiated the pivotal involvement of double-stranded DNA (dsDNA) in autoimmunity. However, the role of dsDNA in the pathogenesis of acute urticaria is unclear., Methods: We measured serum dsDNA levels in patients and controls. The relationship between dsDNA levels and environmental exposures (temperature, ultraviolet [UV] index, and season) was investigated by correlating disease onset dates with archived meteorological data. Finally, we used quantitative PCR to determine the expressions of genes encoding dsDNA receptors, single-stranded RNA (ssRNA) receptors, exosome formation, and type I interferon in the peripheral blood of patients and controls., Results: Serum dsDNA levels were significantly higher in patients with acute urticaria compared with controls (mean values 1.38 and 0.94 ng/ml, respectively, P < 0.001). dsDNA levels were higher in patients exposed to higher environmental temperatures and UV indices and were higher during the summer months. We also found that the expressions of genes encoding dsDNA receptors, ssRNA receptors, absent in melanoma factor 2 (AIM2)-related inflammatory factors, and interferon alpha were up-regulated in patients., Conclusions: We demonstrated that serum dsDNA levels are elevated in acute urticaria and are influenced by climatic factors such as temperature, ultraviolet index, and season. We also found that elevated dsDNA promotes the expression of AIM2-related factors and type I interferons. This study generates new hypotheses regarding the pathogenesis of acute urticaria and suggests novel therapeutic targets., (© 2024 the International Society of Dermatology.)

Atherosclerosis (AS) is a pathological process associated with various cardiovascular diseases. Upon different stimuli, neutrophils release reticular complexes known as neutrophil extracellular traps (NETs). Numerous researches have indicated a strong correlation between NETs and AS. However, its role in cardiovascular disease requires further investigation. By utilizing a machine learning algorithm, we examined the genes associated with NETs that were expressed differently in individuals with AS compared to normal controls. As a result, we identified four distinct genes. A nomogram model was built to forecast the incidence of AS. Additionally, we conducted analysis on immune infiltration, functional enrichment and consensus clustering in AS samples. The findings indicated that individuals with AS could be categorized into two groups, exhibiting notable variations in immune infiltration traits among the groups. Furthermore, to measure the NETs model, the principal component analysis algorithm was developed and cluster B outperformed cluster A in terms of NETs. Additionally, there were variations in the expression of multiple chemokines between the two subtypes. By studying AS NETs, we acquired fresh knowledge about the molecular patterns and immune mechanisms implicated, which could open up new possibilities for AS immunotherapy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: This study aims to describe the use of patient partnership, as defined by the Montreal Model, in emergency departments (EDs) in France and report the perception of patient partnership from both the practitioner and patient perspectives. Methods: This cross-sectional study was conducted between July 2020 and October 2020. First, a survey was sent to 146 heads of EDs in both teaching hospitals and non-teaching hospitals in France to assess the current practices in terms of patient partnership in service organization, research, and teaching. The perceived barriers and facilitators of the implementation of such an approach were also recorded. Then, semi-structured telephone interviews were carried out with patients involved in a service re-organization project. Results: A total of 48 answers (response rate 32.9%) to the survey were received; 33.3% of respondents involved patients in projects relating to service re-organization, 20.8% involved patients in teaching projects, and 4.2% in research projects. Overall, 60.4% of the respondents were willing to involve patients in re-organization or teaching projects. The main barriers mentioned for establishing patient partnership were difficulties regarding patient recruitment and lack of time. The main advantages mentioned were the improvement in patient/caregiver relationship and new ideas to improve healthcare. When interviewed, patients mentioned the desire to improve healthcare and the necessity to involve people with different profiles and backgrounds. A too important personal commitment was the most frequently raised barrier to their engagement. All the patients recognized their positive role, and more generally, the positive role of patient engagement in service re-organization. Conclusion: Although this preliminary study indicates a rather positive perception of patient partnership among heads of EDs in France and partner patients, this approach is still not widely applied in practice. [ABSTRACT FROM AUTHOR]

Background/Introduction: Cigarette smoking is a potent modifiable risk factor for coronary artery disease (CAD). However, little is known about alterations to prothrombotic state and platelet reactivity early after smoking cessation following percutaneous coronary interventions (PCI). Purpose: We investigated alterations to platelet reactivity, coagulation and markers of platelet, endothelial, inflammatory and coagulation activation in clopidogrel-treated patients with CAD after PCI before and after smoking cessation. Methods: Smoking patients aged 18 years or older at least 30 days after PCI were recruited and encouraged to quit the habit. At baseline and at 30 days, we measured platelet reactivity with VerifyNow system, thrombomodulin, P-selectin, platelet factor 4 (CXCL4/PF4), citrullinated histone H3 (H3cit) and cotinine level. Results: Among 117 patients, 84 patients (72%) at a median age of 60.5 years (40 [interquartile range 30–47] pack-years) completed a 30-day follow-up. At day 30, 30 (35.7%) patients stopped smoking with cotinine level < 50 ng/ml. Baseline characteristics were similar in both groups. In smoking quitters a change in platelet reactivity was larger (Δ platelet reactivity units (PRU) 19 [2, 43] vs. -6 [-32, 37], p = 0.018), along with a change in P-selectin concentration (-11.82 [-23.62, 1.34] vs. 7.19 [-14.24, 17.19] ng/ml, p = 0.005). Positive correlations was noticed between cotinine and both P-selectin (r = 0.23, p = 0.045) and CXCL4 (r = 0.27, p = 0.02). Conclusion: After smoking cessation in CAD patients following PCI an increase in platelet reactivity and a decrease in P-selectin levels were observed. The risk of thrombotic complications post PCI might be paradoxically enhanced among patients who stopped smoking. [ABSTRACT FROM AUTHOR]

Tumor immunity is a growing field of research that involves immune cells within the tumor microenvironment. Neutrophil extracellular traps (NETs) are neutrophil-derived extracellular web-like chromatin structures that are composed of histones and granule proteins. Initially discovered as the predominant host defense against pathogens, NETs have attracted increasing attention due to they have also been tightly associated with tumor. Excessive NET formation has been linked to increased tumor growth, metastasis, and drug resistance. Moreover, through direct and/or indirect effects on immune cells, an abnormal increase in NETs benefits immune exclusion and inhibits T-cell mediated antitumor immune responses. In this review, we summarize the recent but rapid progress in understanding the pivotal roles of NETs in tumor and anti-tumor immunity, highlighting the most relevant challenges in the field. We believe that NETs may be a promising therapeutic target for tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Neutrophil extracellular traps (NETs) may be associated with the development of thrombosis. Experimental studies have confirmed the presence of NETs in thrombi specimens and potential role of NETs in the mechanisms of thrombosis. Clinical studies also have demonstrated significant changes in the levels of serum or plasma NETs biomarkers, such as citrullinated histones, myeloperoxidase, neutrophil elastase, nucleosomes, DNA, and their complexes in patients with thrombosis. This paper aims to comprehensively review the currently available evidence regarding the change in the levels of NETs biomarkers in patients with thrombosis, summarize the role of NETs and its biomarkers in the development and prognostic assessment of venous thromboembolism, coronary artery diseases, ischemic stroke, cancer-associated thromboembolism, and coronavirus disease 2019-associated thromboembolism, explore the potential therapeutic implications of NETs, and further discuss the shortcomings of existing NETs biomarkers in serum and plasma and their detection methods. [ABSTRACT FROM AUTHOR]

Although significant progress has been made in the study of gastric cancer (GC), clinicians lack reliable protein markers for accurate diagnosis and tumor stratification. Neutrophil extracellular traps (NETs) are networks of extracellular fibers composed of DNA from neutrophils. We have previously reported that abundant NETs are deposited in GC, damaging human umbilical vein endothelial cells (HUVECs) and triggering the release of tissue factors, leading to a hypercoagulable state in GC. However, the specific effects of NETs on HUVECs are unclear. We aimed to explore the functional changes caused by NETs on HUVECs, providing evidence that NETs may fuel GC progression. Through quantitative proteomics, we identified 6182 differentially expressed proteins in NET-stimulated HUVECs by TMT. The reliability of the TMT technique was confirmed by parallel reaction monitoring (PRM) analysis of 17 differentially expressed proteins. Through bioinformatics analysis, we found that NETs upregulate ANGPT2 in HUVECs. We comprehensively analyzed the prognosis, biological function, immune response, and therapeutic value of ANGPT2 in GC. We found that overexpression of ANGPT2 in GC is associated with poor prognosis and potentially regulates multiple biological functions. At the same time, ANGPT2 also predicted immunotherapeutic and chemotherapeutic responses in GC. In conclusion, NETs promoted ANGPT2 overexpression in the GC microenvironment. In the future, the neutrophil/NETs-ANGPT2 axis may provide a new target for the treatment of GC. [ABSTRACT FROM AUTHOR]

Bactericidal/permeability-increasing protein (BPI) exhibits a number of important characteristics. RNA-seq analysis revealed that the BPI expression was increased in platelets of (non)ST-elevated myocardial infarction (NSTEMI/STEMI) patients. Activated platelets can induce NETosis which may be accompanied by the release of myeloperoxidase-DNA (MPO-DNA) and S100A8/A9. This study investigated the plasma BPI levels in myocardial infarction patients and its correlation with MPO-DNA and S100A8/A9. This prospective study recruited 80 control individuals, as well as 63 NSTEMI and 59 STEMI patients who were admitted to the First Affiliated Hospital of Bengbu Medical College for coronary angiography (CAG) and/or percutaneous coronary intervention (PCI) between May 1, 2020 and August 31, 2020. Demographic and clinical characteristics, clinical indicators, hs-CRP, IL-1β, MPO-DNA (a circulated marker of NETs), circulating levels of S100A8/A9 and BPI were measured from each individual. The severity of coronary lesions was evaluated by the Gensini score, based on the results of the CAG. Pearson's or spearman's correlation was used to examine the correlation between BPI and the above-mentioned parameters, as well as the severity of coronary artery disease. Linear regression analysis was applied to identify the independent predictive factors of BPI. Received operating characteristic (ROC) curve analysis was used to evaluate the diagnostic efficacy of plasma BPI for MI. The plasma BPI levels increased by 8.76 times in the STEMI group and 5.38 times in the NSTEMI group compared to the control group. The plasma level of hs-CRP and IL-1β in both STEMI and NSTEMI groups were also significantly higher than the control group. In addition, the plasma levels of MPO-DNA and S100A8/A9 in the STEMI and NSTEMI groups were significantly higher than the control group. Plasma levels of BPI were positively correlated with IL-1β, hs-CRP, MPO-DNA and S100A8/A9. The correlation between BPI and the severity of coronary artery disease was also significant. The optimal cutoff value of plasma BPI was 35.1705 ng/ml for MI patients from the ROC curve analysis. Plasma BPI levels are increased in myocardial infarction patients and positively correlated with MPO-DNA and S100A8/A9. Plasma BPI level may serve as a potential biomarker of myocardial infarction. [ABSTRACT FROM AUTHOR]

Aims Extracellular chromatin and deoxyribonuclease (DNase) have been identified as important players of thrombosis, inflammation, and homeostasis in a murine model. We previously demonstrated that activated neutrophils release neutrophil extracellular traps (NETs) at the culprit site in ST-elevation myocardial infarction (STEMI), which significantly contribute to extracellular chromatin burden, and are associated with larger infarcts. To understand the correlation between neutrophil activation, extracellular chromatin, and infarct size (IS), we investigated these parameters in a porcine myocardial infarction model, and at different time points and sites in a prospective STEMI trial with cardiac magnetic resonance (CMR) endpoints. Methods and results In a prospective STEMI trial (NCT01777750), 101 STEMI patients were included and blood samples were obtained from first medical contact until 6 months after primary percutaneous coronary intervention (pPCI) including direct sampling from the culprit site. CMR was performed 4 ± 2 days and 6 months after pPCI. Neutrophil counts, markers of extracellular chromatin, and inflammation were measured. Double-stranded deoxyribonucleic acid (dsDNA), citrullinated histone 3, nucleosomes, myeloperoxidase, neutrophil elastase, and interleukin (IL)-6 were significantly increased, while DNase activity was significantly decreased at the culprit site in STEMI patients. High neutrophil counts and dsDNA levels at the culprit site correlated with high microvascular obstruction (MVO) and low ejection fraction (EF). High DNase activity at the culprit site correlated with low MVO and high EF. In correspondence, dsDNA correlated with IS in the porcine myocardial infarction model. In porcine infarcts, neutrophils and extracellular chromatin were detected in congested small arteries corresponding with MVO. Markers of neutrophil activation, extracellular chromatin, DNase activity and CMR measurements correlated with markers of systemic inflammation C-reactive protein and IL-6 in patients. Conclusions NETs and extracellular chromatin are important determinants of MVO in STEMI. Rapid degradation of extracellular chromatin by DNases appears to be crucial for microvascular patency and outcome. [ABSTRACT FROM AUTHOR]

Background: Neutrophil extracellular traps NETs have been linked to glucose and the pathogenesis of type 1 diabetes mellitus (T1DM). NETs also play a role in vascular inflammation and the development of coronary artery disease (CAD). The role of NETs in CAD progression in patients with long-term T1DM is unclear. We aimed to 1) investigate whether levels of circulating NETs markers were elevated in long-term T1DM subjects compared to controls, and 2) explore whether levels of NETs were related to the presence of CAD. Material and Methods: 102 patients with > 45 years of T1DM and 75 age-matched controls were enrolled in a cross-sectional study. Median age was 62 years. Computed tomography coronary angiography (CTCA) was performed in 148 subjects without established coronary heart disease. For the current study, CAD was defined as a coronary artery stenosis >50%. Double-stranded deoxyribonucleic acid (dsDNA) was measured by a nucleic acid stain, myeloperoxidase-DNA (MPO-DNA), citrullinated histone 3 (H3Cit) and peptidylarginine deiminase 4 (PAD4) by ELISAs, while gene expression of PAD4 was measured in leukocytes from PAXgene tubes. Results: Circulating MPO-DNA levels were significantly lower in patients with T1DM than in controls (0.17 vs 0.29 OD, p<0.001), while dsDNA, H3Cit, PAD4 and gene expression of PAD4 did not differ with respect to the presence of T1DM. There were no significant associations between NETs markers and HbA1c in the T1DM group. None of the NETs markers differed according to the presence of CAD in patients with T1DM. While all circulating NETs markers correlated significantly with circulating neutrophils in the control group (r=0.292-393, p<0.014), only H3Cit and PAD4 correlated with neutrophils in the T1DM group (r= 0.330-0.449, p ≤ 0.001). Conclusions: In this cross-sectional study of patients with long-term T1DM and age-matched controls, circulating NETs levels were not consistently associated with the presence of T1DM or glycemic status, and did not differ according to the presence of CAD in patients with T1DM. Our results entail the possibility of altered neutrophil function and reduced NETosis in T1DM. This warrants further investigation. [ABSTRACT FROM AUTHOR]

Neutrophil extracellular traps (NETs), a web-like structures containing chromatin, have a significant role in assisting the capture and killing of microorganisms by neutrophils during infection. The specific engagement of cell-surface receptors by extracellular signaling molecules activates diverse intracellular signaling cascades and regulates neutrophil effector functions, including phagocytosis, reactive oxygen species release, degranulation, and NET formation. However, overproduction of NETs is closely related to the occurrence of inflammation, autoimmune disorders, non-canonical thrombosis and tumor metastasis. Therefore, it is necessary to understand neutrophil activation signals and the subsequent formation of NETs, as well as the related immune regulation. In this review, we provide an overview of the immunoreceptor-mediated regulation of NETosis. The pathways involved in the release of NETs during infection or stimulation by noninfectious substances are discussed in detail. The mechanisms by which neutrophils undergo NETosis help to refine our views on the roles of NETs in immune protection and autoimmune diseases, providing a theoretical basis for research on the immune regulation of NETs. [ABSTRACT FROM AUTHOR]

The benefits of remote ischaemic conditioning (RIC) have been difficult to translate to humans, when considering traditional outcome measures, such as mortality and heart failure. This paper reviews the recent literature of the anti-inflammatory effects of RIC, with a particular focus on the innate immune response and cytokine inhibition. Given the current COVID-19 pandemic, the inflammatory hypothesis of cardiac protection is an attractive target on which to re-purpose such novel therapies. A PubMed/MEDLINE™ search was performed on July 13th 2020, for the key terms RIC, cytokines, the innate immune system and inflammation. Data suggest that RIC attenuates inflammation in animals by immune conditioning, cytokine inhibition, cell survival and the release of anti-inflammatory exosomes. It is proposed that RIC inhibits cytokine release via a reduction in nuclear factor kappa beta (NF-κB)-mediated NLRP3 inflammasome production. In vivo, RIC attenuates pro-inflammatory cytokine release in myocardial/cerebral infarction and LPS models of endotoxaemia. In the latter group, cytokine inhibition is associated with a profound survival benefit. Further clinical trials should establish whether the benefits of RIC in inflammation can be observed in humans. Moreover, we must consider whether uncomplicated MI and elective surgery are the most suitable clinical conditions in which to test this hypothesis. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between physician-patient treatments shared decision making (SDM), patient satisfaction, and adoption of a new health technology.Methods: A cross-sectional study was conducted from July 2016 to October 2016 in Fujian Province and Shanghai, in Eastern China. A total of 542 physicians and 619 patients in eleven hospitals were surveyed. Patients and their treating physicians completed self-reported questionnaires on patient-physician SDM, satisfaction with treatment decision making and adoption of a new health technology. Correlation analysis, multivariate logistic regression and multivariate linear regression were performed.Results: The majority (68.20 percent) of patients preferred SDM. Involvement of patients in SDM was positively associated with their satisfaction with treatment decision making (p < .001) and adoption of a new health technology (p < .05). Better concordance between their preference and actual SDM was positively associated with patients' adoption behavior (p < .05), but no statistically significant association was found between concordance and satisfaction.Conclusion: SDM was the most important predictor of patients' satisfaction with decision making and adoption of a new health technology. Therefore, better communication between physicians and patients is recommended to improve their SDM, increase patient satisfaction and to assist with the adoption of new technologies. Training healthcare provider and teaching communication skills in working with patients in the initial stage of technology diffusion is required. [ABSTRACT FROM AUTHOR]

Background: Neutrophil extracellular traps (NETs) have recently been identified as mediators in atherothrombosis. Although NETosis in general has been suggested to be glucose dependent, the transferability to patients with acute ST-elevation myocardial infarction (STEMI) is unclear. We assessed whether the NETs markers double-stranded deoxyribonucleid acid (dsDNA) and myeloperoxidase-DNA (MPO-DNA) associated with plasma glucose and the glucometabolic status in the acute phase and 3 months after a STEMI. We also explored whether an acute glucose load resulted in upregulated NETosis by assessment of peptidylarginine deiminase 4 (PAD4) gene expression.Methods: In total, 224 STEMI patients were prospectively enrolled and underwent blood sampling acutely (median 16.5 h after PCI) and after 3 months. Glucometabolic status was defined based on the results of an oral glucose tolerance test (OGTT) as normal glucose regulation (NGR), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or type 2 diabetes (T2DM). dsDNA and MPO-DNA were measured in serum, while PAD4 mRNA was measured in circulating leukocytes by RT-PCR.Results: dsDNA levels were significantly correlated to plasma glucose both acutely and after 3 months (r = 0.12 and r = 0.17, both p < 0.02), whereas MPO-DNA was not. No associations with the glucometabolic status were encountered for dsDNA and MPO-DNA acutely, but after 3 months dsDNA levels were elevated in patients with IFG and T2DM vs. NGR (428 vs. 371 ng/ml and 408 vs. 371 ng/ml, both p < 0.045). During the acute glucose load after 3 months, dsDNA and MPO-DNA remained unchanged while PAD4 mRNA increased significantly (RQ 0.836 vs. 0.920, p = 0.02).Conclusions: In this cohort of STEMI patients, levels of dsDNA associated with plasma glucose both in the acute and stable condition. The glucometabolic status was not substantially related to the selected NETs markers, however, an acute glucose load by OGTT performed after 3 months resulted in increased PAD4 expression, suggestive of enhanced NETosis in the aftermath of STEMI.Trial Registration: www.clinicaltrials.gov, NCT00926133 . Registered June 23, 2009. [ABSTRACT FROM AUTHOR]

This editorial refers to 'Rapid neutrophil mobilization by VCAM-11 endothelial cell-derived extracellular vesicles', by N. Akbar I et al i . https://doi.org/10.1093/cvr/cvac012. While single-cell RNA sequencing has certainly highlighted many different neutrophil subsets simplistically, there is likely an anti-microbial and a repair neutrophil subset. [Extracted from the article]

Background: Higher levels of patient activation for self-managing health are associated with positive clinical and health care utilization outcomes. Identifying a patient's activation level can guide clinicians to tailor interventions to improve their health. Effective self-management of atrial fibrillation (AF) requires patient activation to participate in treatment decisions, prevent complications, and manage risk factors. Yet, little is known about activation in patients with AF. The purpose of this descriptive study was to identify patient activation levels and factors associated with activation in patients with AF. Methods: Patients (N=123), 66% male, with a mean (SD) age of 59.9 (11.3) years seeking treatment for AF at an arrhythmia clinic completed the Patient Activation Measure (PAM), Atrial Fibrillation Severity Scale, Knowledge about Atrial Fibrillation test, Hospital Anxiety Depression Scale, Godin Leisure-Time Exercise Questionnaire, and Patient Assessment of Chronic Illness Care. Sociodemographic and clinical data were obtained from medical records. PAM scores were categorized into Levels 1–4. Associations among patient-reported outcomes, sociodemographic, and clinical variables were analyzed using Fisher's exact tests and Kruskal–Wallis procedures. Results: The PAM scores of nearly half (45.5%) of the patients were at Level 3, while the scores of 38% were at Level 4. Male sex (P=0.02), higher education (P=0.004), being employed (P=0.005), lower body mass index (P=0.03), tobacco abstinence (P=0.02), less AF symptom burden (P=0.006), less depression (P≤0.0001) and anxiety (P=0.006), greater knowledge of AF (P=0.01), and higher levels of physical activity (P=0.02) were associated with higher activation levels. Conclusion: Higher levels of patient activation in those with AF were associated with a more positive health status and educational attainment. Additional research to describe activation in patients with AF is warranted to identify patients at risk for low activation and to tailor interventions to activation level. [ABSTRACT FROM AUTHOR]

Abstract: The Apollo heat flow experiment (HFE) was conducted at landing sites 15 and 17. On Apollo 15, surface and subsurface temperatures were monitored from July 1971 to January 1977. On Apollo 17, monitoring took place from December 1972 to September 1977. The investigators involved in the HFE examined and archived only data from the time of deployment to December 1974. The present authors recovered and restored major portions of the previously unarchived HFE data from January 1975 through September 1977. The HFE investigators noted that temperature of the regolith well below the reach of insolation cycles (~1 m) rose gradually through December 1974 at both sites. The restored data showed that the subsurface warming continued until the end of observations in 1977. Simultaneously, the thermal gradient decreased, because the warming was more pronounced at shallower depths. The present study has examined potential causes for the warming. Recently acquired images of the Lunar Reconnaissance Orbiter Camera over the two landing sites show that the regolith on the paths of the astronauts turned darker, lowering the albedo. We suggest that, as a result of the astronauts' activities, solar heat intake by the regolith increased slightly on average, and that resulted in the observed warming. Simple analytical heat conduction models with constant regolith thermal properties can show that an abrupt increase in surface temperature of 1.6 to 3.5 K at the time of probe deployment best duplicates the magnitude and the timing of the observed subsurface warmings at both Apollo sites. [ABSTRACT FROM AUTHOR]

Despite effective therapeutic and preventive strategies, atherosclerosis and its complications still represent a substantial health burden. Leukocytes and inflammatory mechanisms are increasingly recognized as drivers of atherosclerosis. Neutrophil granulocytes within the circulation were recently shown to undergo neutrophil extracellular trap (NET) formation, linking innate immunity with acute complications of atherosclerosis. In this chapter, we summarize mechanisms of NET formation, evidence for their involvement in atherosclerosis and thrombosis, and potential therapeutic regimens specifically targeting NET components., (© 2020. The Author(s).)