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Objective: Postoperative renal dysfunction necessitating hemodialysis after implantation of ventricular assist devices presents a challenge with respect to establishment of hemodialysis access. Lack of pulsatile flow has led to concerns that arteriovenous fistulas will not mature. This study aims to evaluate arteriovenous fistula as a method of hemodialysis., Methods: Consecutive patients who underwent implantation of a ventricular assist device between 1988 and 2016 with a subsequent need for hemodialysis were identified. Retrospective data were collected for patients requiring hemodialysis through an arteriovenous fistula or arteriovenous graft. Access flow rates and duration of patency are reported., Results: Sixty-four patients were identified (10 required long-term hemodialysis, 5 via arteriovenous fistula, 1 via arteriovenous graft). All six patients receiving long-term hemodialysis access were on continuous-flow ventricular assist devices. Brachiocephalic arteriovenous fistulas were performed in all arteriovenous fistula patients, and the average preoperative vein diameter was 4.1 ± 0.9 mm. On 30-day follow-up, the average flow rate was 1262 ± 643 mL/min (880-2220). In arteriovenous fistula patients, one died at 30 days, one arteriovenous fistula required ligation for steal syndrome at 5 months, and one was abandoned after 10.7 months for low flow. Of remaining fistulas, one was converted to an arteriovenous graft at 1.7 years for malfunction (with 5.3 month patency), and one remains open at 4.0 years., Conclusion: Arteriovenous fistulas should be considered in selected patients with ventricular assist devices as a means of long-term hemodialysis access to avoid use of catheters. Maturation and usage of primary arteriovenous fistulas is possible despite lack of pulsatile flow.

Purpose of Review: To give an overview of recently published articles about the management of vasculo-Behcet's with particular emphasis on anticoagulation., Recent Findings: Biologic agents are emerging as a potential therapeutic option in refractory vasculo-Behcet with a good safety profile. Evidence further shows that following nonpulmonary aneurysm repair, there is a reduced risk of recurrent aneurysmal formation at the operative site in patients treated with immunosuppressants in addition to their surgery, than those undergoing surgical intervention alone., Summary: Behcet disease patients are at risk of developing multiple vascular complications including thrombosis and aneurysms. Treatment should focus on reducing inflammation; and the role of anticoagulation is still debatable.

Granulomas, organized aggregates of immune cells which form in response to Mycobacterium tuberculosis (Mtb), are characteristic but not exclusive of tuberculosis (TB). Despite existing investigations on TB granulomas, the determinants that differentiate host-protective granulomas from granulomas that contribute to TB pathogenesis are often disputed. Thus, the goal of this narrative review is to help clarify the existing literature on such determinants. We adopt the a priori view that TB granulomas are host-protective organelles and discuss the molecular and cellular determinants that induce protective granulomas and those that promote their failure. While reports about protective TB granulomas and their failure may initially seem contradictory, it is increasingly recognized that either deficiencies or excesses of the molecular and cellular components in TB granuloma formation may be detrimental to the host. More specifically, insufficient or excessive expression/representation of the following components have been reported to skew granulomas toward the less protective phenotype: (i) epithelioid macrophages; (ii) type 1 adaptive immune response; (iii) type 2 adaptive immune response; (iv) tumor necrosis factor; (v) interleukin-12; (vi) interleukin-17; (vii) matrix metalloproteinases; (viii) hypoxia in the TB granulomas; (ix) hypoxia inducible factor-1 alpha; (x) aerobic glycolysis; (xi) indoleamine 2,3-dioxygenase activity; (xii) heme oxygenase-1 activity; (xiii) immune checkpoint; (xiv) leukotriene A4 hydrolase activity; (xv) nuclear-factor-kappa B; and (xvi) transforming growth factor-beta. Rather, more precise and timely coordinated immune responses appear essential for eradication or containment of Mtb infection. Since there are several animal models of infection with Mtb , other species within the Mtb complex, and the surrogate Mycobacterium marinum – whether natural (cattle, elephants) or experimental (zebrafish, mouse, guinea pig, rabbit, mini pig, goat, non-human primate) infections – we also compared the TB granulomatous response and other pathologic lung lesions in various animals infected with one of these mycobacteria with that of human pulmonary TB. Identifying components that dictate the formation of host-protective granulomas and the circumstances that result in their failure can enhance our understanding of the macrocosm of human TB and facilitate the development of novel remedies – whether they be direct therapeutics or indirect interventions – to efficiently eliminate Mtb infection and prevent its pathologic sequelae. [ABSTRACT FROM AUTHOR]

Introduction: Behçet disease (BD) is an inflammatory multisystem disorder of unknown etiology, believed to be triggered by infection and environmental factors in genetically predisposed individuals. The significance of understanding BD lies in its impact on global health due to its diverse clinical manifestations and geographical distribution. Areas covered: This review discusses the epidemiology of BD, emphasizing its prevalence estimated at 10.3 (95% CI, 6.1, 17.7) per 100,000 population, with higher rates observed in regions historically linked to the Silk Route. The criteria for diagnosis are explored, focusing on clinical manifestations that guide healthcare professionals in identifying and managing BD. Additionally, the review encompasses treatment strategies, highlighting TNF-alpha inhibitors as pivotal biologics and newer agents like IL-1 inhibitors and Ustekinumab that broaden the therapeutic options for BD. Expert opinion: Our work provides insights into the evolving landscape of treatments for BD, emphasizing the expanding role of newer agents alongside established therapies like TNF-alpha inhibitors. [ABSTRACT FROM AUTHOR]

Objective: Endoscopic vein harvest (EVH) has been demonstrated to improve early morbidity when compared with conventional open vein harvest (OVH) technique for infrainguinal bypass surgery. However, recent literature suggests conflicting results regarding mid- and long-term patency with EVH. The purpose of this study is to compare graft patency between harvest techniques specifically in patients with critical limb ischemia., Methods: This retrospective study compared two groups of patients (EVH = 39 and OVH = 49) undergoing lower extremity revascularization from January 2009 to December 2011. Outcome measures included patency rates, postoperative complications, and wound infection. Graft patency was assessed using Kaplan-Meier curves., Results: Both groups were matched for demographics and indications for bypass (critical limb ischemia). Median follow-up was 22 months. There was a significant reduction in the incidence of wound infection at the vein harvest site in the EVH group (OVH = 20%; EVH = 0%; P < .001), nevertheless, the difference was not significant when only the anastomotic sites were included (OVH = 12.2%; EVH = 15.4%; P = .43). The hospital length of stay was comparable between the two groups (EVH = 8.73 ± 9.69; OVH = 6.35 ± 3.28; P = .26) with no significant difference in the recovery time. Primary graft patency rate was 43.2% in the EVH group and 69.4% in the OVH group (P = .007) at 3 years. The most common reason for loss of primary patency was graft occlusion (61.5%) in the OVH group and vein graft stenosis (54.5%) in the EVH group. The average number of vascular reinterventions per bypass graft was significantly lower in the OVH group compared with the EVH group (OVH = 0.37; EVH = 1.28; P < .001)., Conclusions: Our findings demonstrate inferior primary patency when using the technique of EVH. Additionally, we identified a significantly higher rate of reintervention in the EVH cohort as well as a higher rate of vein graft body stenosis. However, EVH was associated with a decreased rate of wound complications with similar limb salvage and secondary patency rates when compared to OVH. EVH should therefore be selectively utilized in patients at high risk for wound complications., (Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Unlabelled: Ischemia-reperfusion (I/R) injury is a process whereby an initial hypoxic insult and subsequent return of blood flow leads to the propagation of innate immune responses and organ injury. The necessity of the pattern recognition receptor, Toll-like receptor (TLR)4, for this innate immune response has been previously shown. However, TLR4 is present on various cell types of the liver, both immune and nonimmune cells. Therefore, we sought to determine the role of TLR4 in individual cell populations, specifically, parenchymal hepatocytes (HCs), myeloid cells, including Kupffer cells, and dendritic cells (DCs) subsequent to hepatic I/R. When HC-specific (Alb-TLR4(-/-) ) and myeloid-cell-specific (Lyz-TLR4(-/-) ) TLR4 knockout (KO) mice were subjected to warm hepatic ischemia, there was significant protection in these mice, compared to wild type (WT). However, the protection afforded in these two strains was significantly less than global TLR4 KO (TLR4(-/-) ) mice. DC-specific TLR4(-/-) (CD11c-TLR4(-/-) ) mice had significantly increased hepatocellular damage, compared to WT mice. Circulating levels of high-mobility group box 1 (HMGB1) were significantly reduced in Alb-TLR4(-/-) mice, compared to WT, Lyz-TLR4(-/-) , CD11c-TLR4(-/-) mice and equivalent to global TLR4(-/-) mice, suggesting that TLR4-mediated HMGB1 release from HCs may be a source of HMGB1 after I/R. HCs exposed to hypoxia responded by rapidly phosphorylating the mitogen-activated protein kinases, c-Jun-N-terminal kinase (JNK) and p38, in a TLR4-dependent manner; inhibition of JNK decreased release of HMGB1 after both hypoxia in vitro and I/R in vivo., Conclusion: These results provide insight into the individual cellular response of TLR4. The parenchymal HC is an active participant in sterile inflammatory response after I/R through TLR4-mediated activation of proinflammatory signaling and release of danger signals, such as HMGB1., (Copyright © 2013 American Association for the Study of Liver Diseases.)

Background: Atherosclerosis is an inflammatory disease in which interferon (IFN)-gamma, the signature cytokine of Th1 cells, plays a central role. We investigated whether interleukin (IL)-17, the signature cytokine of Th17 cells, is also associated with human coronary atherosclerosis., Methods and Results: Circulating IL-17 and IFN-gamma were detected in a subset of patients with coronary atherosclerosis and in referent outpatients of similar age without cardiac disease but not in young healthy individuals. IL-17 plasma levels correlated closely with those of the IL-12/IFN-gamma/CXCL10 cytokine axis but not with known Th17 inducers such as IL-1beta, IL-6, and IL-23. Both IL-17 and IFN-gamma were produced at higher levels by T cells within cultured atherosclerotic coronary arteries after polyclonal activation than within nondiseased vessels. Combinations of proinflammatory cytokines induced IFN-gamma but not IL-17 secretion. Blockade of IFN-gamma signaling increased IL-17 synthesis, whereas neutralization of IL-17 responses decreased IFN-gamma synthesis; production of both cytokines was inhibited by transforming growth factor-beta1. Approximately 10-fold fewer coronary artery-infiltrating T helper cells were IL-17 producers than IFN-gamma producers, and unexpectedly, IL-17/IFN-gamma double producers were readily detectable within the artery wall. Although IL-17 did not modulate the growth or survival of cultured vascular smooth muscle cells, IL-17 interacted cooperatively with IFN-gamma to enhance IL-6, CXCL8, and CXCL10 secretion., Conclusions: Our findings demonstrate that IL-17 is produced concomitantly with IFN-gamma by coronary artery-infiltrating T cells and that these cytokines act synergistically to induce proinflammatory responses in vascular smooth muscle cells.

Interleukin (IL) 1alpha produced by human endothelial cells (ECs), in response to tumor necrosis factor (TNF) or to co-culture with allogeneic T cells in a TNF-dependent manner, can augment the release of cytokines from alloreactive memory T cells in vitro. In a human-mouse chimeric model of artery allograft rejection, ECs lining the transplanted human arteries express IL-1alpha, and blocking IL-1 reduces the extent of human T cell infiltration into the artery intima and selectively inhibits IL-17 production by infiltrating T cells. In human skin grafts implanted on immunodeficient mice, administration of IL-17 is sufficient to induce mild inflammation. In cultured cells, IL-17 acts preferentially on vascular smooth muscle cells rather than ECs to enhance production of proinflammatory mediators, including IL-6, CXCL8, and CCL20. Neutralization of IL-17 does not reduce T cell infiltration into allogeneic human artery grafts, but markedly reduces IL-6, CXCL8, and CCL20 expression and selectively inhibits CCR6(+) T cell accumulation in rejecting arteries. We conclude that graft-derived IL-1 can promote T cell intimal recruitment and IL-17 production during human artery allograft rejection, and suggest that targeting IL-1 in the perioperative transplant period may modulate host alloreactivity.

Inflammation is associated with the pathogenesis of coronary atherosclerosis, although the mechanisms remain unclear. We investigated whether cytokine secretion by innate immune responses could contribute to the production of proarteriosclerotic Th1-type cytokines in human coronary atherosclerosis. Cytokines were measured by ELISA in the plasma of patients with coronary atherosclerosis undergoing cardiac catheterization. IL-18 was detected in all subjects, whereas a subset of patients demonstrated a coordinated induction of other IFN-gamma-related cytokines. Specifically, elevated plasma levels of IL-12 correlated with that of IFN-gamma and IFN-gamma-inducible chemokines, defining an IFN-gamma axis that was activated independently of IL-6 or C-reactive protein. Systemic inflammation triggered by cardiopulmonary bypass increased plasma levels of the IFN-gamma axis, but not that of IL-18. Activation of the IFN-gamma axis was not associated with acute coronary syndromes, but portended increased morbidity and mortality after 1-year follow-up. IL-12 and IL-18, but not other monokines, elicited secretion of IFN-gamma and IFN-gamma-inducible chemokines in human atherosclerotic coronary arteries maintained in organ culture. T cells were the principal source of IFN-gamma in response to IL-12/IL-18 within the arterial wall. This inflammatory response did not require, but was synergistic with and primed for TCR signals. IL-12/IL-18-stimulated T cells displayed a cytokine-producing, nonproliferating, and noncytolytic phenotype, consistent with previous descriptions of lymphocytes in stable plaques. In contrast to cognate stimuli, IL-12/IL-18-dependent IFN-gamma secretion was prevented by a p38 MAPK inhibitor and not by cyclosporine. In conclusion, circulating IL-12 may provide a mechanistic link between inflammation and Th1-type cytokine production in coronary atherosclerosis.

Due to the ability of γδ T cells to bridge adaptive and innate immunity, γδ T cells can respond to a variety of molecular cues and acquire the ability to induce a variety of cytokines such as IL-17 family, IFN-γ, IL-4, and IL-10. IL-17 + γδ T cells (γδ T17 cells) populations have recently received considerable interest as they are the major early source of IL-17A in many immune response models. However, the exact mechanism of γδ T17 cells is still poorly understood, especially in the context of cardiovascular disease (CVD). CVD is the leading cause of death in the world, and it tends to be younger. Here, we offer a review of the cardiovascular inflammatory and immune functions of γδ T17 cells in order to understand their role in CVD, which may be the key to developing new clinical applications., (©2022 Society for Leukocyte Biology.)

Objective: The objective of this study was to examine the relationship between systemic inflammation and long-term mortality in patients with hypertension., Methods: The study employed a retrospective cohort design. The study population was derived from the National Health and Nutrition Examination Survey (NHANES), and the mortality data for this population was acquired from the National Death Index (NDI) database. Systemic inflammation was quantified by the Systemic Immune Inflammation Index (SII) and the Systemic Inflammatory Response Index (SIRI), which were then categorized into four groups (Q1-Q4, with Q4 representing the highest level of SII or SIRI). Weighted Cox regression models were constructed to investigate the association between mortality and SII and SIRI, with hazard ratios (HRs) subsequently calculated., Results: A total of 7431 participants were included in the analysis. The highest quantile (Q4) of SII was associated with a higher risk of all-cause mortality (hazard ratio 1.36, 95% CI 1.1-1.69, P < 0.001). After adjustment for important covariates, the association remained significant (hazard ratio 1.70, 95% CI 1.27-2.30, P < 0.001). The highest quantile (Q4) of SIRI was also associated with the highest risk of mortality (hazard ratio 2.11, 95% CI 1.64-2.70, P < 0.001), and this association remained significant after adjustment for important covariates (hazard ratio 1.64, 95% CI 0.61-1.22, P = 0.001)., Conclusion: Both SII and SIRI scores were found to be associated with mortality rates in patients with hypertension. The findings suggest that these scores may serve as complementary biomarkers to the neutrophil-to-lymphocyte ratio (NLR) for assessing mortality risk in patients with hypertension. Further investigation is warranted to elucidate the underlying mechanisms that underpin this association., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To explore the role of interleukin (IL)‐17 in connective tissue disease‐associated pulmonary arterial hypertension (CTD‐PAH) and to investigate its possible mechanism on pulmonary artery smooth muscle cells (PASMCs). Methods: Enzyme‐linked immunosorbent assay (ELISA) were used to compare levels of serum IL‐17 in patients with CTD‐PAH and healthy controls (HCs). After treatment for 3 months, the serum IL‐17 levels were tested in CTD‐PAH. ELISA and immunohistochemistry were used to compare levels of serum IL‐17 and numbers of pulmonary artery IL‐17+ cells, respectively, in a rat model of monocrotaline‐induced PAH and untreated rats. Proliferation, migration, and inflammatory factors expression of PASMCs were assessed after stimulation with different concentrations of IL‐17 for various time periods. Proteins in the mitogen‐activated protein kinase (MAPK) pathway were examined by western blot. Results: Levels of IL‐17 were upregulated in patients with CTD‐PAH compared to HCs. After 3 months of treatment, serum IL‐17 levels were downregulated with pulmonary artery pressure amelioration. Moreover, serum IL‐17 levels and numbers of IL‐17+ cells infiltrating lung arterioles were increased in PAH model rats. IL‐17 could dose‐ and time‐dependently promote proliferation and migration of PASMCs as well as time‐dependently induce IL‐6 and intercellular cell adhesion molecule‐1 (ICAM‐1) expression. The levels of MKK6 increased after IL‐17 treatment. Inhibition of MAPK decreased proliferation of PASMCs. Conclusion: Levels of IL‐17 may increase in CTD‐PAH, and IL‐17 promotes proliferation, migration, and secretion of IL‐6 and ICAM in PASMCs, respectively, which likely involves the p‐38 MAPK pathway. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Behçet's disease should be suspected in young adults who present with heart failure and/or vascular lesions. Cardiac involvement and mesenteric artery aneurysm are rare but should be recognized because of their severity. [ABSTRACT FROM AUTHOR]

Application of endoscopic vein harvest (EVH) in infrainguinal bypass surgery generated mixed results. The purpose of this study was to compare outcomes between endoscopic vein harvest and open vein harvest (OVH) in femoral-to-popliteal artery bypass (FPB). Case series analysis that involved all patients undergoing femoral-to-popliteal artery bypass with single-segment great saphenous vein between January 2012 and December 2017. There were 170 femoral-to-popliteal artery bypasses performed in 168 patients who met the inclusion criteria; 25 (14.7%) in EVH group and 145 (85.3%) in OVH group. Chronic limb-threatening ischemia was an indication for surgery in 60% of EVH patients and 79% of OVH patients (15/25; 60% EVH vs 114/145; 79% OVH; p =.08). Mean follow-up was significantly longer for EVH group (65.71 months EVH vs 45.32 months OVH; p =.003). EVH group had a lower wound complication rate (4/25; 16% EVH vs 45/145; 31% OVH; p =.336), especially at the harvest incision site, despite higher rate of obesity amongst EVH patients (15/25; 60% EVH vs 35/145; 24% OVH; p <.001). The reintervention rate was higher in EVH group (10/25; 40% EVH vs 42/145; 29% OVH; p =.38). At 5 years, primary (69.1% EVH vs 67.0% OVH; p =.85), primary assisted (87.6% EVH vs 73.5% OVH; p =.18), and secondary patency rates (87.3% EVH vs 76.7% OVH; p =.25) did not demonstrate significant differences between the groups. Endoscopic vein harvest for femoral-to-popliteal artery bypass decreased the rate and severity of wound complications, but this difference was statistically insignificant. Obese patients are more suitable for endoscopic vein harvest, with relatively lower chances of developing wound infections. Despite the higher rate of reinterventions, endoscopic vein harvest patency rates were in line with those for the open vein harvest group in up to 5 years of follow-up. [ABSTRACT FROM AUTHOR]

Background: Immune and inflammatory responses have a pivotal role in the pathogenesis of rheumatoid arthritis (RA) and atherosclerotic cardiovascular disease (ASCVD). This study aims to explore the change of peripheral lymphocytes, especially the absolute and relative changes in peripheral T cells in RA patients with and without ASCVD. Hypothesis: The changes in the lymphocyte subsets were assessed to provide a novel insight in diagnosing and preventing ASCVD in patients with RA. Methods: A propensity score matching system (1:1) was conducted to perform a matched case–control study with 169 pairs RA‐ASCVD and RA participants. Univariate and multivariate analyses were performed to determine the association between peripheral lymphocytes and RA‐ASCVD. Result: Multivariate logistic regression analysis demonstrated that Th17 cell absolute, Th17 cell Ratio, Th17/Treg were associated with a significantly higher risk of ASCVD after model adjustment. Then we focused on Th17/Treg, multivariate logistic analyses in tri‐sectional Th17/Treg groups showed that the odds of ASCVD is gradually increasing with Th17/Treg rank's rising after model adjustment. Finally, the restricted cubic spline of Th17/Treg and odds ratio of RA‐ASCVD was conducted. Interestingly, we found a critical point of Th17/Treg (critical point = 0.2399). Th17/Treg shows a protective role in the odds of ASCVD when Th17/Treg < 0.2399. With smaller Th17/Treg, the protective efficiency is more obvious when Th17/Treg < 0.2399. Conclusions: Our study suggested that increasing absolute and percentage of Th17 cells in the peripheral blood of patients with RA was associated with the development of ASCVD. And Th17/Treg may be a promising biomarker for patients with RA in indicating comorbidity with ASCVD. Key Messages: Absolute and percentage of Th17 cells in peripheral blood of patients with rheumatoid arthritis‐atherosclerotic cardiovascular disease (RA‐ASCVD) is significantly higher. Elevated Th17/Treg may be a potential biomarker for RA patients in predicting comorbidity with ASCVD. The imbalance of Th17/Treg may be involved in the pathogenesis of ASCVD in rheumatoid arthritis. Downregulating Th17/Treg could be potential therapeutic targets for preventing RA patients from ASCVD. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic lipid-driven inflammatory response of the innate and adaptive immune systems, and it is responsible for several cardiovascular ischemic events. The present study aimed to determine immune infiltration-related biomarkers in carotid atherosclerotic plaques (CAPs). Gene expression profiles of CAPs were extracted from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between the CAPs and control groups were screened by the "limma" package in R software. Immune cell infiltration between the CAPs and control groups was evaluated by the single sample gene set enrichment analysis. Key infiltrating immune cells in the CAPs group were screened by the Wilcoxon test and least absolute shrinkage and selection operator regression. The weighted gene co-expression network analysis was used to identify immune cell-related genes. Hub genes were identified by the protein–protein interaction (PPI) network. Receiver operating characteristic curve analysis was performed to assess the gene's ability to differentiate between the CAPs and control groups. Finally, we constructed a miRNA-gene-transcription factor network of hub genes by using the ENCODE database. Eleven different types of immune infiltration-related cells were identified between the CAPs and control groups. A total of 1,586 differentially expressed immunity-related genes were obtained through intersection between DEGs and immune-related genes. Twenty hub genes were screened through the PPI network. Eventually, 7 genes (BTK, LYN, PTPN11, CD163, CD4, ITGAL, and ITGB7) were identified as the hub genes of CAPs, and these genes may serve as the estimable drug targets for patients with CAPs. [ABSTRACT FROM AUTHOR]

The gut microbiome and its metabolites are increasingly implicated in several cardiovascular diseases, but their role in human myocardial infarction (MI) injury responses have yet to be established. To address this, we examined stool samples from 77 ST-elevation MI (STEMI) patients using 16 S V3-V4 next-generation sequencing, metagenomics and machine learning. Our analysis identified an enriched population of butyrate-producing bacteria. These findings were then validated using a controlled ischemia/reperfusion model using eight nonhuman primates. To elucidate mechanisms, we inoculated gnotobiotic mice with these bacteria and found that they can produce beta-hydroxybutyrate, supporting cardiac function post-MI. This was further confirmed using HMGCS2-deficient mice which lack endogenous ketogenesis and have poor outcomes after MI. Inoculation increased plasma ketone levels and provided significant improvements in cardiac function post-MI. Together, this demonstrates a previously unknown role of gut butyrate-producers in the post-MI response. Here, Chen et. al. characterize the relationship between the gut microbiota and plasma metabolite changes in the context of ST-elevation myocardial infarction (STEMI), unveiling a role of butyrate-producing bacteria and their ketogenesis in post-STEMI cardiac repair, a finding validated in nonhuman primate and mouse models. They show that butyrate supplementation reduces myocardial infarction severity in mice, underscoring the significance of butyrate-producing bacteria and beta-hydroxybutyrate in improving post-MI outcomes. [ABSTRACT FROM AUTHOR]

Adipose tissue inflammation has been implicated in various chronic inflammatory diseases and cancer. Perivascular adipose tissue (PVAT) surrounds the aorta as an extra layer and was suggested to contribute to atherosclerosis development. PVAT regulates the function of endothelial and vascular smooth muscle cells in the aorta and represent a reservoir for various immune cells which may participate in aortic inflammation. Recent studies demonstrate that adipocytes also express various cytokine receptors and, therefore, may directly respond to inflammatory stimuli. Here we will summarize current knowledge on immune mechanisms regulating adipocyte activation and the crosstalk between myeloid cells and adipocytes in pathogenesis of atherosclerosis. [ABSTRACT FROM AUTHOR]

The liver is one of the pivotal organs in the human body and is fundamentally responsible for detoxification and metabolism. Various disorders such as non-alcoholic fatty liver disease, fibrosis, cirrhosis, hepatocellular carcinoma, and hepatitis are associated with improper functions of the liver. Hence, biomarkers are needed to determine the severity. Further, many liver enzymes, including the cascade of aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), and total bilirubin (TBIL), are conventional liver biomarkers. They are not, however, unique to the liver; hence, efforts are being made to identify the precise biomarkers for liver illness that can target liver diseases. HMGB1, cytokeratin 18 (K18), glutathione-S-transferase-α (GST-α), glutamate dehydrogenase (GLDH), malate dehydrogenase (MDH), and microRNAs (miRNA) are a few examples of developing biomarkers used to detect many liver diseases. Hence, the review has highlighted various novel biomarkers of the liver so that various pathophysiological pathways and treatments can be made easier. [ABSTRACT FROM AUTHOR]

Aims Atherosclerosis is driven by multiple processes across multiple body systems. For example, the innate immune system drives both atherogenesis and plaque rupture via inflammation, while coronary artery-occluding thrombi formed by the coagulation system cause myocardial infarction and death. However, the interplay between these systems during atherogenesis is understudied. We recently showed that coagulation and immunity are fundamentally linked by the activation of interleukin-1α (IL-1α) by thrombin, and generated a novel knock-in mouse in which thrombin cannot activate endogenous IL-1α [IL-1α thrombin mutant (IL-1αTM)]. Methods and results Here, we show significantly reduced atherosclerotic plaque formation in IL-1αTM/ Apoe −/− mice compared with Apoe −/− and reduced T-cell infiltration. However, IL-1αTM/ Apoe −/− plaques have reduced vascular smooth muscle cells, collagen, and fibrous caps, indicative of a more unstable phenotype. Interestingly, the reduced atherogenesis seen with thrombin inhibition was absent in IL-1αTM/ Apoe −/− mice, suggesting that thrombin inhibitors can affect atherosclerosis via reduced IL-1α activation. Finally, bone marrow chimeras show that thrombin-activated IL-1α is derived from both vessel wall and myeloid cells. Conclusions Together, we reveal that the atherogenic effect of ongoing coagulation is, in part, mediated via thrombin cleavage of IL-1α. This not only highlights the importance of interplay between systems during disease and the potential for therapeutically targeting IL-1α and/or thrombin, but also forewarns that IL-1 may have a role in plaque stabilization. [ABSTRACT FROM AUTHOR]

The present study evaluated the use of endocan, interleukin-17 (IL-17), and thrombospondin-4 (TSP-4) blood levels as potential biomarkers for the diagnosis and follow-up of peripheral arterial disease (PAD). Patients with PAD (Rutherford categories I, II, and III) who were admitted between March 2020 and March 2022 for cardiovascular surgery or outpatient clinic follow-up were included. The patients (n = 60) were divided into 2 groups: medical treatment (n = 30) and surgical treatment (n = 30). In addition, a control group (n = 30) was created for comparison. Endocan, IL-17, and TSP-4 blood levels were measured at the time of diagnosis and at the first month after treatment. Endocan and IL-17 values were found to be significantly higher in both groups that underwent medical (259.7 ± 46 pg/mL, 63.7 ± 16.6 pg/mL) and surgical (290.3 ± 84.5 pg/mL, 66.4 ± 19.6 pg/mL) treatment than the control group (187.4 ± 34.5 pg/mL, 56.5 ± 7.2 pg/mL P <.001). Tsp-4 value was found to be significantly higher only in the surgical treatment group (15 ± 4.3 ng/mL) than the control group (12.9 ± 1.4 ng/mL P <.05). The decreases in endocan, IL-17, and TSP-4 levels at the first month of treatment in both groups were also significant (P <.001). A combination of classical and these new biomarkers could be included in PAD screening, early diagnosis, severity determination, and follow-up protocols in order to provide effective assessment in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Cytokines are key players in the development of both type 1 diabetes (T1D) and cardiovascular disease (CVD). Offspring of women with T1D are known to have an increased risk of early-onset CVD. We studied whether an increased risk of CVD can be observed in the cytokine profile among young adult offspring of women with T1D. Methods: This cross-sectional case–control study included 67 offspring of women with T1D (cases) and 79 control participants (controls). At an age of 18–23 years, they participated in a clinical assessment including laboratory tests and questionnaires. Cytokine levels were analyzed from venous blood samples after 10 h fasting using Quansys biosciences Q-Plex™ High Sensitivity Human Cytokine Array. Results: Circulating cytokine levels were in general similar between the groups. The circulating levels of interferon-γ (1.78 [IQR 1.20, 2.36] pg/mL versus 2.57 [IQR 1.50, 3.89] pg/mL) (p = 0.006) were lower in cases than controls. Conclusion: The findings did not support our hypothesis that serum cytokine profile, determined in early adulthood, was associated with a more adverse CVD risk profile in offspring of women with T1D. Further studies are warranted to find out whether cytokines could serve as early biomarkers of CVD development or whether changes in the cytokine levels over years could be used to monitor CVD progression in offspring of women with T1D. [ABSTRACT FROM AUTHOR]

Background: Behçet's disease (BD) is a rare form of systemic vasculitis that affects small to large vessels. It is characterized by mucocutaneous, pulmonary, cardiovascular, gastrointestinal, and neurological manifestations. Large vessel involvement may occur in a third of cases. Veins are usually more affected than arteries. Furthermore aneurysms are the most frequent arterial complication. Case presentation: A 41-year-old man presented with multiple arterial aneurysms. He had previous medical history of a right popliteal aneurysm treated with a reversed femoro-popliteal venous bypass, long-term steroids and immunosuppressive treatment. On admission, diagnostic computed tomography angiography revealed multiple aneurysms, including an 87 mm aneurysm of the femoro-popliteal bypass and an abdominal aortic and left common iliac artery aneurysm. He received an intensification of medical treatment with methylprednisolone and infliximab intravenous infusion. Aorto iliac artery aneurysms were treated by infrarenal bifurcated stent graft implantation. The aneurysm of the venous femoro-popliteal bypass was treated by explantation and prosthetic repair. One month later, he presented with acute right limb ischemia related to occlusion of the right limb of the stent graft despite anticoagulation which was treated by mechanical thrombectomy. Conclusions: Vascular BD can worsen the vascular outcome after surgery. Except in an urgent context, BD must be controlled before surgery. This case report illustrates the importance of combined medical and surgical management, with first BD activity control with corticosteroids and immunosuppressive treatment, then surgical or endovascular treatment. [ABSTRACT FROM AUTHOR]

Background: We investigated the efficacy and safety of bronchial artery embolization (BAE) using a 5F JL4 catheter in patients with hemoptysis and a bronchial artery opening in the inferior wall of the aortic arch. Methods: This was a single-center retrospective study. Seventeen patients underwent BAE using 5F JL4. We then evaluated technical success (TS), clinical success (CS), incidence of complications, and hemoptysis recurrence rate (RR). Results: The TS rate of microcatheter superselective catheterization and CS rate after surgery were 100%, and the incidence of severe complications and postoperative RR were 17.6%. Conclusions: Bronchial artery embolization for hemoptysis with a BA opening in the inferior wall of the aortic arch using the 5F JL4 catheter could be a safe method. The short- and medium-term results were excellent. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is considered one of the most common heart disorders. Recent studies suggest that injections of amniotic membrane stem cells (AMSC) can improve heart function. Therefore, the current study investigated the effect of intra-myocardial injection of human amniotic membrane-derived stem cells (hAMCs) on inflammatoryrelated cytokines like IL-10 and IL-17 in the HF model of rats. Twenty-eight male Wistar rats were categorized into four groups: control, HF, culture medium injection group, and hAMCs injection group. After 60 days, blood samples were taken from the animals, and the expression levels of interleukins 10 and 17 were measured by the ELISA technique. The results showed that injection of hAMCs into male rats with HF caused down-regulation of IL-17 inflammatory cytokine and over-expression of IL-10 anti-inflammatory cytokine. Based on the results of this study and previous ones, we concluded that hAMCs could be considered one of the candidates in future studies on reducing inflammation in HF treatment by adjusting some inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Objectives: Behçet's disease (BD) is a multisystem inflammatory disorder with unknown etiology, and its aneurysmal lesions are associated with high mortality due to the high risk of rupture. This study intended to further explore the longterm safety and efficacy of endovascular therapy for BD-related aortic pseudoaneurysm (BAP). Methods: From January 2009 to May 2021, 17 BAP patients who underwent endovascular repair were retrospectively identified and enrolled. Adequate immunosuppressive treatment was instituted before and after endovascular treatment unless emergency surgery was required. The patients were followed up at 3, 6, and 12 months and yearly after the primary endovascular intervention by computed tomography angiography (CTA) examination. Results: Nineteen BAPs were identified among 17 patients. BAPs located at the aortic arch were found in three patients (17.6%), descending thoracic aorta in 5 (29.4%), and abdominal aorta in 10 (58.8%; suprarenal abdominal aorta in 2 [11.8%], and infrarenal abdominal aorta in 8 [47.1%]). The mean ESR during admission was 56.5 ± 24.9 mm/h (range = 30.0-120.0 mm/h), which fell to 22.7 ± 18.4 mm/h (range = 2.0-74.0 mm/h) before the endovascular intervention (p < 0.001). The rate of favorable immunosuppressive control before intervention is 76.5% (13/17). Technical success was achieved in all patients. Median follow-up time was 57.0 months (interquartile range [IQR] = 21.3-67.3 months). Pseudoaneurysm recurrence was observed in four patients, type I endoleak in one, pseudoaneurysms sac dilation in one, and external iliac artery occlusion in 1. Two patients died of pseudoaneurysm rupture. Five-year accumulated overall rate, recurrence-free rate, and reintervention-free survival rate of BAP patients were 92.8%, 75.4%, and 71.8%, respectively. Conclusion: Endovascular treatment in BAP patients seemed to be associated with long-term safety and efficacy with a 5-year overall survival rate of 92.8%. Adequate immunosuppressive treatment was essential for BAP patients to prevent aortic pseudoaneurysm recurrence and improve the prognosis. [ABSTRACT FROM AUTHOR]

T cells are the common type of lymphocyte to mediate allograft rejection, remaining long-term allograft survival impeditive. However, the heterogeneity of T cells, in terms of differentiation and activation status, the effector function, and highly diverse T cell receptors (TCRs) have thus precluded us from tracking these T cells and thereby comprehending their fate in recipients due to the limitations of traditional detection approaches. Recently, with the widespread development of single-cell techniques, the identification and characterization of T cells have been performed at single-cell resolution, which has contributed to a deeper comprehension of T cell heterogeneity by relevant detections in a single cell - such as gene expression, DNA methylation, chromatin accessibility, surface proteins, and TCR. Although these approaches can provide valuable insights into an individual cell independently, a comprehensive understanding can be obtained when applied joint analysis. Multi-omics techniques have been implemented in characterizing T cells in health and disease, including transplantation. This review focuses on the thesis, challenges, and advances in these technologies and highlights their application to the study of alloreactive T cells to improve the understanding of T cell heterogeneity in solid organ transplantation. [ABSTRACT FROM AUTHOR]

Atherosclerosis, a common age-related disease, is characterized by intense immunological activity. Atherosclerotic plaque is composed of endothelial cells, vascular smooth muscle cells (VSMCs), lipids and immune cells infiltrating from the blood. During progression of the disease, VSMCs undergo senescence within the plaque and secrete SASP (senescence-associated secretory phenotype) factors that can actively modulate plaque microenvironment. We demonstrated that senescent VSMCs secrete increased number of extracellular vesicles (senEVs). Based on unbiased proteomic analysis of VMSC-derived EVs and of the soluble fraction of SASP (sSASP), more than 900 proteins were identified in each of SASP compartments. Comparison of the composition of VMSC-derived EVs with the SASP atlas revealed several proteins, including Serpin Family F Member 1 (SERPINF1) and Thrombospondin 1 (THBS1), as commonly upregulated components of EVs secreted by senescent VSMCs and fibroblasts. Among soluble SASP factors, only Growth Differentiation Factor 15 (GDF15) was universally increased in the secretome of senescent VSMCs, fibroblasts, and epithelial cells. Bioinformatics analysis of EV proteins distinguished functionally organized protein networks involved in immune cell function regulation. Accordingly, EVs released by senescent VSMCs induced secretion of IL-17, INFγ, and IL-10 by T cells and of TNFα produced by monocytes. Moreover senEVs influenced differentiation of monocytes favoring mix M1/M2 polarization with proinflammatory characteristics. Altogether, our studies provide a complex, unbiased analysis of VSMC SASP and prove that EVs derived from senescent VSMCs influence the cytokine milieu by modulating immune cell activity. Our results strengthen the role of senescent cells as an important inducer of inflammation in atherosclerosis. [ABSTRACT FROM AUTHOR]

Psoriasis and coronary artery disease (CAD) are related comorbidities that are well established, but whether a genetic basis underlies this is not well studied. We apply trans-disease meta-analysis to 11,024 psoriasis and 60,801 CAD cases, along with their associated controls, identifying one opposing and three shared genetic loci, which are confirmed through colocalization analysis. Combining results from Bayesian credible interval analysis with independent information from genomic, epigenomic, and spatial chromatin organization, we prioritize genes (including IFIH1 and IL23A) that have implications for common molecular mechanisms involved in psoriasis and CAD inflammatory signaling. Chronic systemic inflammation has been associated with CAD and myocardial infarction, and Mendelian randomization analysis finds that CAD as an exposure can have a significant causal effect on psoriasis (OR = 1.11; p = 3×10−6) following adjustment for BMI and waist-hip ratio. Together, these findings suggest that systemic inflammation which causes CAD can increase the risk of psoriasis. Coronary artery disease (CAD) and psoriasis are established comorbidities, however their molecular relationship remains unclear. Here, the authors performed trans-disease meta-analysis, highlighting four genetic loci with evidence of colocalization, and prioritized genes based on multiomic data integration. [ABSTRACT FROM AUTHOR]

Objective The aim of this observational cohort study was to assess the effectiveness and safety of the IL-6-receptor inhibitor tocilizumab (TCZ) in Behçet's syndrome (BS) with refractory arterial involvement. Methods Ten patients admitted to the Rheumatology and Immunology Department of Peking University People's Hospital between January 2014 and December 2019 were enrolled. The enrolled patients met the BS international criteria and exhibited severe arterial impairments. Refractory arterio-BS was diagnosed based on objective vascular symptoms unexplainable by other known illnesses, and resistance to traditional immunosuppressants and glucocorticoids after 12 weeks. Patients received 8 mg/kg TCZ infusions every 4 weeks for ≥24 weeks, with simultaneous continuation of immunosuppressants and glucocorticoids. Clinical and imaging data were assessed before and after TCZ treatment. Results The enrolled patients were men aged 44.3 (10.5) years; the median disease duration was 186.5 (45.7) months, and the average age of arterial impairment onset was 38.7 (12.9) years. The following trends were observed: improvement and maintenance of symptoms after the 26.8 (7.2)-month follow-up, n  = 9; complete remission, n  = 6; partial response, n  = 3; immunosuppressant dose reduction, n  = 4; radiologic improvement of arterial lesions, n  = 4; and TCZ discontinuation owing to enlarged abdominal aortic aneurysm relapse, n  = 1. The average daily glucocorticoid dose reduced from 54.5 (20.6) to 8.3 (3.6) mg/d (P  < 0.001), while the median ESR and CRP values reduced from 50 (2–82) mm/h and 32.9 (2.1–62.3) mg/dl to 4 (1–10) mm/h and 2.9 (0.2–12.1) mg/dl, respectively (P  < 0.001). No TCZ-associated side effects were noted. Conclusion TCZ proved to be safe and effective for refractory arterial lesions in BS, with a steroid- and immunosuppressant-sparing benefit. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) often features extensive cardiovascular (CV) comorbidity and patients with SLE are at significantly increased risk of CV event occurrence and CV-related mortality. While the specific mechanisms leading to this increased cardiovascular disease (CVD) risk remain to be fully characterized, this heightened risk cannot be fully explained by traditional CV risk factors and is likely driven by immunologic and inflammatory features of SLE. Widespread innate and adaptive immune dysregulation characterize SLE, and factors including excessive type I interferon burden, inappropriate formation and ineffective clearance of neutrophil extracellular traps, and autoantibody formation have been linked to clinical and metabolic features impacting CV risk in SLE and may represent pathogenic drivers of SLE–related CVD. Indeed, functional and phenotypic aberrations in almost every immune cell type are present in SLE and may impact CVD progression. As understanding of the contribution of SLE–specific factors to CVD in SLE improves, improved screening and monitoring of CV risk alongside development of therapeutic treatments aimed at prevention of CVD in SLE patients are required and remain the focus of several ongoing studies and lines of inquiry. [ABSTRACT FROM AUTHOR]

Background: The use of the traditional method for saphenous vein harvesting is associated with wound complications and not on-time patient mobilization. This has caused the improvement of minimally invasive vein harvesting techniques, together with general bridging. This study was designed to compare the therapeutic results of large saphenous vein harvesting with conventional and standard bridging techniques for lower extremity vascular reconstruction in patients with chronic lower extremity ischemia. Methods: In this randomized clinical trial study, 66 patients with chronic lower extremity ischemia were randomly divided into two groups: large saphenous vein harvesting by conventional technique (continuous longitudinal incision) (n=30) and standard Bridging technique (small and multiple incisions) (n=36). Pain score (VAS), graft patency, wound complications, surgery results and patient satisfaction was recorded. The follow-up period was six months. (IRCT20190511043562N1). Results: Graft patency (P=0.353), and Amputation-free Survival (P=0.397) did not show a significant difference between the two groups. Changes in pain score at rest (P=0.846) and movement (P=0.380) at different times did not show a significant difference between the two groups. One week after the operation, the incidence of infection in the bridging technique showed a significant decrease (P=0.045). During the six months of follow-up, the wound healing rate, ischemic pain relief, and claudication improvement were better in the bridging technique but did not show a significant difference with the conventional technique (P<0.05). Patient satisfaction was higher in the bridging technique but did not show a significant difference between the two groups (P<0.05). Conclusion: It seems that the use of the bridging technique in venous resection large saphenous vein harvesting is associated with reducing wound complications and pain, reducing the length of hospital stay, increasing the speed of wound healing, and improving patient satisfaction. The duration of graft patency and Amputation-free Survival were similar in the two groups. We believe that each technique has advantages and disadvantages that should be considered by the patient and surgeon when choosing a surgical procedure. [ABSTRACT FROM AUTHOR]

Coronary artery bypass graft (CABG) surgery remains a pivotal cornerstone, offering established symptomatic alleviation and prognostic advantages for patients grappling with complex multivessel and left main coronary artery diseases. Despite the lucid guidance laid out by contemporary guidelines regarding the choice between CABG and percutaneous coronary intervention (PCI), a notable hesitation persists among certain patients, characterized by psychological reservations, knowledge gaps, or individual beliefs that sway their inclination toward surgical intervention. This comprehensive review critically synthesizes the prevailing guidelines, modern practices, and outcomes pertaining to CABG surgery, delving into an array of techniques and advancements poised to enhance both short-term and enduring surgical outcomes. The exploration encompasses advances in on-pump and off-pump procedures, conduit selection strategies encompassing the bilateral utilization of internal mammary artery and radial artery conduits, meticulous graft evaluation methodologies, and the panorama of minimally invasive approaches, including those assisted by robotic technology. Furthermore, the review navigates the terrain of hybrid coronary revascularization, shedding light on the pivotal roles of shared decision-making and the heart team in shaping treatment pathways. As a comprehensive compendium, this review not only navigates the intricate landscape of CABG surgery but also aligns it with contemporary practices, envisioning its trajectory within the evolving currents of healthcare dynamics., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Previous studies have shown an increase of T cells and chemokines in vascular lesions of patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, detailed characterization of these T cells is still lacking, nor have treatment effects been evaluated. Methods: We included 41 treatment-naive CTEPH patients at diagnosis, 22 patients at 1-year follow-up, and 17 healthy controls (HCs). Peripheral blood T cells were characterized by flow cytometry for subset distribution, cytokine expression and activation marker profile. We used multiplex immunofluorescence to identify CCR6+ T cells in endarterectomy tissue from 25 patients. Results: At diagnosis, proportions of CCR6+ CD4+ T cells were increased in CTEPH patients compared with HCs. Patients displayed a significantly reduced production capacity of several cytokines including TNFα, IFNγ, GM-CSF and IL-4 in CD4+ T cells, and TNFα and IFNγ in CD8+ T cells. CD4+ and CD8+ T cells showed increased expression of the immune checkpoint protein CTLA4. Multivariate analysis separated CTEPH patients from HCs, based on CCR6 and CTLA4 expression. At 1-year follow-up, proportions of CCR6+CD4+ T cells were further increased, IFNγ and IL-17 production capacity of CD4+ T cells was restored. In nearly all vascular lesions we found substantial numbers of CCR6+ T cells. Conclusion: The observed increase of CCR6+ T cells and modulation of the IFNγ and IL-17 production capacity of circulating CD4+ T cells at diagnosis and 1-year follow-up – together with the presence of CCR6+ T cells in vascular lesions - support the involvement of the Th17-associated CCR6+ T cell subset in CTEPH. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, systemic, immune-mediated inflammatory disorder that is associated with a significantly increased risk of cardiovascular disease (CVD). Studies have shown that psoriasis often coexists with atherosclerosis, a chronic inflammatory disease of large and medium-sized arteries, which is a major cause of CVD. Although the molecular mechanisms underlying this comorbidity are not fully understood, clinical studies have shown that when interleukin (IL)-17A inhibitors effectively improve psoriatic lesions, atherosclerotic symptoms are also ameliorated in patients with both psoriasis and atherosclerosis. Also, IL-17A levels are highly expressed in the psoriatic lesions and atherosclerotic plaques. These clinical observations implicit that IL-17A could be a crucial link for psoriasis and atherosclerosis and IL-17A-induced inflammatory responses are the major contribution to the pathogenesis of comorbid psoriasis and atherosclerosis. In this review, the current literature related to epidemiology, genetic predisposition, and inflammatory mechanisms of comorbidity of psoriasis and atherosclerosis is summarized. We focus on the immunopathological effects of IL-17A in both diseases. The goal of this review is to provide the theoretical base for future preventing or treating psoriasis patients with atherosclerosis comorbidity. The current evidence support the notion that treatments targeting IL-17 seem to be hold some promise to reduce cardiovascular risk in patients with psoriasis. [ABSTRACT FROM AUTHOR]

Background: To explore the role and clinical significance of serum adiponectin and leptin levels in patients with psoriasis accompanied by atherosclerosis. Methods: Eighty patients diagnosed with psoriasis in our dermatology department and 40 healthy people in our physical examination centre were included as the study group and control group, respectively. All the included patients underwent fasting blood and serum tests. Levels of adiponectin, leptin, and the blood lipid content; colour Doppler ultrasonography of both common carotid arteries, internal carotid and external carotid arteries; and intimal-medial thickness (IMT) and carotid plaque were evaluated. Results: In the study group, the leptin level increased, and the serum adiponectin level decreased; these levels were statistically significantly different compared with those in the control group (t = 6.774, P < 0.001 and t = –3.511, P < 0.05, respectively). IMT was negatively correlated with adiponectin levels (r = –0.378, P < 0.001) and positively correlated with leptin levels (r = 0.581, P < 0.001). Conclusions: The imbalanced expression of serum and adiponectin levels will aggravate psoriasis and promote the occurrence of atherosclerosis. Serum levels can be used to assess the disease severity, detect vascular lesions early, and prevent the development of psoriasis to cardiovascular disease. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the 2-year safety and effectiveness of the PQ Bypass DETOUR system as a percutaneous femoropopliteal bypass. Materials and Methods: Seventy-eight patients with 82 long-segment femoropopliteal lesions were enrolled in this prospective, single-arm, multicenter study. The DETOUR system deployed Torus stent grafts directed through a transvenous route. Eligible patients included those with lesions of >10 cm and average of 371±55 mm. Key safety endpoints included major adverse events (MAEs) and symptomatic deep venous thrombosis in the target limb. Effectiveness endpoints included primary patency defined as freedom from ≥50% stenosis, occlusion, or clinically-driven target vessel revascularization (CD-TVR), primary assisted, and secondary patency. Results: Chronic total occlusions and severe calcium occurred in 96% and 67% of lesions, respectively. Core laboratory-assessed total lesion length averaged 371±51 mm with a mean occlusion length of 159±88 mm. The rates of technical and procedural success were 96%, with satisfactory delivery and deployment of the device without in-hospital MAEs in 79/82 limbs. The MAE rate was 22.0%, with 3 unrelated deaths (4%), 12 CD-TVRs (16%), and 1 major amputation (1%). Deep venous thrombosis developed in 2.8% of target limbs, and there were no reported pulmonary emboli. Primary, assisted primary, and secondary patency rates by the Kaplan–Meier analysis were 79±5%, 79±5%, and 86±4%, respectively. Conclusions: The PQ Bypass DETOUR system is a safe and effective percutaneous alternative to femoropopliteal open bypass with favorable results through 2 years. The DETOUR system provides a durable alternative to conventional endovascular modalities and open surgery for patients with long, severely calcified, or occluded femoropopliteal lesions. [ABSTRACT FROM AUTHOR]

A case study of a 34-year-old patient with multiple failed treatments over two years, whose lesions healed completely post-Rituximab treatment for a year. It reviews Behcet's disease phenotypes, treatments like immunosuppressives and biologicals, emphasizing altered antigen response in B cells and the role of Rituximab in managing the disease's recalcitrant symptoms.

Introduction: Human decidua basalis mesenchymal stem cells (DBMSCs) are potential therapeutics for the medication to cure inflammatory diseases, like atherosclerosis. The current study investigates the capacity of DBMSCs to stay alive and function in a harmful inflammatory environment induced by high levels of lipopolysaccharide (LPS). Methods: DBMSCs were exposed to different levels of LPS, and their viability and functional responses (proliferation, adhesion, and migration) were examined. Furthermore, DBMSCs' expression of 84 genes associated with their functional activities in the presence of LPS was investigated. Results: Results indicated that LPS had no significant effect on DBMSCs' adhesion, migration, and proliferation (24 h and 72 h) (p > 0.05). However, DBMSCs' proliferation was significantly reduced at 10 μg/mL of LPS at 48 h (p < 0.05). In addition, inflammatory cytokines and receptors related to adhesion, proliferation, migration, and differentiation were significantly overexpressed when DBMSCs were treated with 10 μg/mL of LPS (p < 0.05). Conclusion: These results indicated that DBMSCs maintained their functional activities (proliferation, adhesion, and migration) in the presence of LPS as there was no variation between the treated DBMSCs and the control group. This study will lay the foundation for future preclinical and clinical studies to confirm the appropriateness of DBMSCs as a potential medication to cure inflammatory diseases, like atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Parenchymal neuro‐Behçet's disease involvement is the most serious complication of Behçet's disease, and no sufficient data on its treatment exists. This study aims to investigate the efficacy and safety of infliximab treatment in neuro‐Behçet's disease patients with parenchymal involvement. Materials and Methods: Patients who were diagnosed with Behçet's disease with parenchymal neurological involvement and underwent infliximab treatment for at least 12 months were included in the study. Demographic, clinical, and radiological data of the patients were accessed through the electronic database of our hospital. Results: This study comprises 19 patients who were diagnosed with neuro‐Behçet's disease and used infliximab: 12 male and 7 female patients. The mean age of the patients was 36.5 ± 11.7 years, and the diagnostic age was 26.3 ± 10.8 years. The duration of treatment with infliximab was 32.3 months (minimum 11, max 79). In the 19 patients receiving infliximab treatment, 11 (58%) patients achieved remission (complete disappearance of neurological symptoms) and 7 (37%) patients achieved disease stability (no new neurological findings); steroid treatments were discontinued for these 18 patients. In addition, only 5 patients were concomitantly taking immunosuppressive drugs with the infliximab. Infliximab was discontinued after the development of a new parenchymal attack in the 9th month of infliximab treatment. Conclusion: In conclusion, parenchymal neurological involvement in Behçet's disease is an important cause of disability, and no sufficient data exists in literature on its treatment. The results of our study suggest that infliximab treatment was effective and safe in neuro‐Behçet's disease parenchymal involvement for preventing long‐term neurological attacks and discontinuing corticosteroid treatment. [ABSTRACT FROM AUTHOR]

Severe trauma is the principal cause of death among young people worldwide. Hemorrhagic shock is the leading cause of death after severe trauma. Traumatic hemorrhagic shock (THS) is a complex phenomenon associating an absolute hypovolemia secondary to a sudden and significant extravascular blood loss, tissue injury, and, eventually, hypoxemia. These phenomena are responsible of secondary injuries such as coagulopathy, endotheliopathy, microcirculation failure, inflammation, and immune activation. Collectively, these dysfunctions lead to secondary organ failures and multi-organ failure (MOF). The development of MOF after severe trauma is one of the leading causes of morbidity and mortality, where immunological dysfunction plays a central role. Damage-associated molecular patterns induce an early and exaggerated activation of innate immunity and a suppression of adaptive immunity. Severe complications are associated with a prolonged and dysregulated immune–inflammatory state. The current challenge in the management of THS patients is preventing organ injury, which currently has no etiological treatment available. Modulating the immune response is a potential therapeutic strategy for preventing the complications of THS. Mesenchymal stromal cells (MSCs) are multipotent cells found in a large number of adult tissues and used in clinical practice as therapeutic agents for immunomodulation and tissue repair. There is growing evidence that their efficiency is mainly attributed to the secretion of a wide range of bioactive molecules and extracellular vesicles (EVs). Indeed, different experimental studies revealed that MSC-derived EVs (MSC-EVs) could modulate local and systemic deleterious immune response. Therefore, these new cell-free therapeutic products, easily stored and available immediately, represent a tremendous opportunity in the emergency context of shock. In this review, the pathophysiological environment of THS and, in particular, the crosstalk between the immune system and organ function are described. The potential therapeutic benefits of MSCs or their EVs in treating THS are discussed based on the current knowledge. Understanding the key mechanisms of immune deregulation leading to organ damage is a crucial element in order to optimize the preparation of EVs and potentiate their therapeutic effect. [ABSTRACT FROM AUTHOR]

Background and Aim: Coronary artery disease (CAD) poses a worldwide health threat. Compelling evidence shows that pericardial adipose tissue (PAT), a brown-like adipose adjacent to the external surface of the pericardium, is associated with CAD. However, the specific molecular mechanisms of PAT in CAD are elusive. This study aims to characterize human PAT and explore its association with CAD. Methods: We acquired samples of PAT from 31 elective cardiac surgery patients (17 CAD patients and 14 controls). The transcriptome characteristics were assessed in 5 CAD patients and 4 controls via RNA-sequencing. Cluster profile R package, String database, Cytoscape were applied to analyze the potential pathways and PPI-network key to DEGS, whereas the hubgenes were predicted via Metascape, Cytohubba, and MCODE. We use Cibersort, ENCORI, and DGIDB to predict immunoinfiltration, mRNA-miRNA target gene network, and search potential drugs targeting key DEGs. The predictable hubgenes and infiltrating inflammatory cells were validated in 22 patients (12 CAD samples and 10 control samples) through RT-qPCR and immunohistochemistry. Results: A total of 147 different genes (104 up-regulated genes and 43 down-regulated genes) were identified in CAD patients. These different genes were associated with immunity and inflammatory dysfunction. Cibersort analysis showed monocytes and macrophages were the most common subsets in immune cells, whereas immunohistochemical results revealed there were more macrophages and higher proportion of M1 subtype cells in PAT of CAD patients. The PPI network and module analysis uncovered several crucial genes, defined as candidate genes, including Jun, ATF3, CXCR4, FOSB, CCl4, which were validated through RT-qPCR. The miRNA-mRNA network implicated hsa-miR-185-5p as diagnostic targets and drug-gene network showed colchicine, fenofibrate as potential therapeutic drugs, respectively. Conclusion: This study demonstrates that PAT is mainly associated with the occurrence of CAD following the dysfunction of immune and inflammatory processes. The identified hubgenes, predicted drugs and miRNAs are promising biomarkers and therapeutic targets for CAD. [ABSTRACT FROM AUTHOR]