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A new study uses a continuous wave electron beam to investigate energy flow, radiative decay and reaction rates in continuous wave rare gas-halogen systems.

A 1.73 micrometer xenon-iodide infrared laser is used to demonstrate the idea of using low-energy electron beams for pumping laser systems in dense gases to achieve high specific power deposition. SiNx ceramic foils of 300 nm-width were used as entrance window in a traverse geometry resulting in a configuration that permits several atmospheres in pressure differentials with only a minimum of energy being lost during the transmission.

Demonstrates that corona discharges in xenon gas can be an efficient source of excimer vacuum ultraviolet (VUV) radiation. Observed conversion efficiencies of electrical power into VUV light greater than 50 percent; Model describing the light production mechanism in the discharge region.

Studies show that the corona discharges in xenon gas can be used to generate vacuum ultraviolet (VUV) radiation with minimal ionization loses. Based on the results, a continuous wave large area Xe*2172nm excimer light source with 130mW/cm2 output and a possible wall plug efficiently close to 48% is recommended.

A stable discharge between two pin electrodes separated by several hundred micrometres in a high pressure rare gas (~900 mbar) halogen (~1 mbar) mixture is shown to yield continuous wave (CW) ultra violet (UV) and vacuum UV light sources. Lamps operating at 193 (ArF*) and 157 nm ( [inline image]) have been demonstrated. Total CW output power in the UV was measured to be 30 for ArF* and 20 mW for [inline image]. The brightness of the light sources is estimated to be of the order of several W cm-2 sr-1. With direct current excitation, electrode lifetimes are limited to a few minutes due to fluorine salt deposits. However, using a radio frequency (RF) field to drive the discharge, the lifetime of the lamps increased to hundreds of hours. A one-dimensional model of the RF micro-discharge explaining the increase in electrode lifetime is presented. The technology described can be adapted to many other wavelengths and promises even higher powers in future. [ABSTRACT FROM AUTHOR]

S100A8/A9 is an endogenous alarmin secreted by myeloid cells during many acute and chronic inflammatory disorders. Despite increasing evidence of the proinflammatory effects of extracellular S100A8/A9, little is known about its intracellular function. Here, we show that cytosolic S100A8/A9 is indispensable for neutrophil post-arrest modifications during outside-in signaling under flow conditions in vitro and neutrophil recruitment in vivo, independent of its extracellular functions. Mechanistically, genetic deletion of S100A9 in mice caused dysregulated Ca 2+ signatures in activated neutrophils resulting in reduced Ca 2+ availability at the formed LFA-1/F-actin clusters with defective β 2 integrin outside-in signaling during post-arrest modifications. Consequently, we observed impaired cytoskeletal rearrangement, cell polarization, and spreading, as well as cell protrusion formation in S100a9 -/- compared to wildtype (WT) neutrophils, making S100a9 -/- cells more susceptible to detach under flow, thereby preventing efficient neutrophil recruitment and extravasation into inflamed tissue., Competing Interests: MN, RI, IR, VL, JP, MG, AY, TV, JR, MS, SD, MS, CM, BW, MS, MP No competing interests declared, (© 2024, Napoli et al.)

Background: Farm-dust mediated asthma protection in childhood was replicated in numerous epidemiological studies. Central immune mechanisms are not fully understood. This exploratory study aimed to disentangle underlying immunological regulation of farm-dust mediated protection in peripheral blood on a single-cell level., Methods: Single-cell protein expression of in vitro farm-dust stimulated and unstimulated cells from allergic asthmatics and healthy controls were measured using mass cytometry. Analysis of innate and adaptive cellular proportions (linear regression) and T-cell proliferation was performed. Functional marker intensity was investigated using Earth Mover's Distance and the Monte Carlo permutation test., Results: Farm-dust stimulation induced cell type-specific regulation: Key-features of farm-dust stimulation comprised opposing regulation of immune-cell frequencies (downregulated innate cell populations (monocytes/DCs (p < .001), NK-cells (p < .05)) and upregulated adaptive populations (B-cells, CD4 + T-cells (both p < .05)), reduced CD4 + CD25 - T-cell proliferation, and differential cell type-specific functional marker expression. Following stimulation, functional marker analysis revealed induced activation (CD25) in T-cells and NK-T-cells in both phenotypes even after correction for multiple testing. Cytotoxicity (GZMB) and inflammation (pERK1/2, pp38) related markers were reduced in T-cells exclusively in asthmatic children. Asthma-associated markers (Gata3, RORγ, and HLA-DR) were reduced in T- and innate- cell populations of asthmatics following stimulation. B-cells displayed a phenotypically independent increase of diverse functional markers upon farm-dust stimulation., Conclusions: This study mimicking in vivo environmental exposure identified a novel profile of immune-regulatory markers using mass cytometry demonstrating decreased asthma-associated markers following farm-dust stimulation. These findings may be key for further studies on asthma prevention in childhood., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Numerous children present with early wheeze symptoms, yet solely a subgroup develops childhood asthma. Early identification of children at risk is key for clinical monitoring, timely patient-tailored treatment, and preventing chronic, severe sequelae. For early prediction of childhood asthma, we aimed to define an integrated risk score combining established risk factors with genome-wide molecular markers at birth, complemented by subsequent clinical symptoms/diagnoses (wheezing, atopic dermatitis, food allergy)., Methods: Three longitudinal birth cohorts (PAULINA/PAULCHEN, n = 190 + 93 = 283, PASTURE, n = 1133) were used to predict childhood asthma (age 5-11) including epidemiological characteristics and molecular markers: genotype, DNA methylation and mRNA expression (RNASeq/NanoString). Apparent (ap) and optimism-corrected (oc) performance (AUC/R2) was assessed leveraging evidence from independent studies (Naïve-Bayes approach) combined with high-dimensional logistic regression models (LASSO)., Results: Asthma prediction with epidemiological characteristics at birth (maternal asthma, sex, farm environment) yielded an ocAUC = 0.65. Inclusion of molecular markers as predictors resulted in an improvement in apparent prediction performance, however, for optimism-corrected performance only a moderate increase was observed (upto ocAUC = 0.68). The greatest discriminate power was reached by adding the first symptoms/diagnosis (up to ocAUC = 0.76; increase of 0.08, p = .002). Longitudinal analysis of selected mRNA expression in PASTURE (cord blood, 1, 4.5, 6 years) showed that expression at age six had the strongest association with asthma and correlation of genes getting larger over time (r = .59, p < .001, 4.5-6 years)., Conclusion: Applying epidemiological predictors alone showed moderate predictive abilities. Molecular markers from birth modestly improved prediction. Allergic symptoms/diagnoses enhanced the power of prediction, which is important for clinical practice and for the design of future studies with molecular markers., (© 2024 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Background: Abdominal aortic aneurysm (AAA) rupture is still associated with a mortality rate of 80-90%. Imaging techniques or molecular fingerprinting for patient-specific risk stratification to identify pending rupture are still lacking. The chemokine (C-X-C motif) receptor (CXCR4) activation by CXCL12 ligand has been identified as a marker of inflammation and atherosclerosis, associated with AAA. Both are highly expressed in the aortic aneurysm wall. However, it is still unclear whether different expression levels of CXCR4 and CXCL12 can distinguish ruptured AAAs (rAAA) from intact AAAs (iAAA). Patients and methods: Abdominal aortic tissue samples (rAAA: n=29; iAAA: n=54) were excised during open aortic repair. Corresponding serum samples from these patients (n=9 from rAAAs; n=47 from iAAA) were drawn pre-surgery. Healthy aortic tissue samples (n=8) obtained from adult kidney donors during transplantation and serum samples from healthy adult volunteers were used as controls (n=5 each). Results: CXCR4 was mainly expressed in the media of the aneurysmatic tissue. Focal positive staining was also observed in areas of inflammatory infiltrates within the adventitia. In tissue lysates, no significant differences between iAAA, rAAA, and healthy controls were observed upon ELISA analysis. In serum samples, the level of CXCR4 was significantly increased in rAAA by 4-fold compared to healthy controls ( p =0.011) and 3.0-fold for rAAA compared to iAAA ( p <0.001). Furthermore a significant positive correlation between aortic diameter and serum CXCR4 concentration was found for both, iAAA and rAAA ( p =0.042). Univariate logistic regression analysis showed that increased CXCR4 serum concentrations were associated with AAA rupture (OR: 4.28, 95% CI: 1.95-12.1, p =0.001). Conclusions: CXCR4 concentration was significantly increased in serum of rAAA patients and showed a significant correlation with an increased aortic diameter. The level of CXCR4 in serum was associated with a more than 4-fold risk increase for rAAA and thus could possibly serve as a biomarker in the future. However, further validation in larger studies is required.

Newborns are at high risk of developing neonatal sepsis, particularly if born prematurely. This has been linked to divergent requirements the immune system has to fulfill during intrauterine compared with extrauterine life. By transcriptomic analysis of fetal and adult neutrophils, we shed new light on the molecular mechanisms of neutrophil maturation and functional adaption during fetal ontogeny. We identified an accumulation of differentially regulated genes within the noncanonical NF-κB signaling pathway accompanied by constitutive nuclear localization of RelB and increased surface expression of TNF receptor type II in fetal neutrophils, as well as elevated levels of lymphotoxin α in fetal serum. Furthermore, we found strong upregulation of the negative inflammatory regulator A20 (Tnfaip3) in fetal neutrophils, which was accompanied by pronounced downregulation of the canonical NF-κB pathway. Functionally, overexpressing A20 in Hoxb8 cells led to reduced adhesion of these neutrophil-like cells in a flow chamber system. Conversely, mice with a neutrophil-specific A20 deletion displayed increased inflammation in vivo. Taken together, we have uncovered constitutive activation of the noncanonical NF-κB pathway with concomitant upregulation of A20 in fetal neutrophils. This offers perfect adaption of neutrophil function during intrauterine fetal life but also restricts appropriate immune responses particularly in prematurely born infants.

The hostile tumor microenvironment (TME) is a major challenge for the treatment of solid tumors with T-cell receptor (TCR)-modified T-cells (TCR-Ts), as it negatively influences T-cell efficacy, fitness, and persistence. These negative influences are caused, among others, by the inhibitory checkpoint PD-1/PD-L1 axis. The Preferentially Expressed Antigen in Melanoma (PRAME) is a highly relevant cancer/testis antigen for TCR-T immunotherapy due to broad expression in multiple solid cancer indications. A TCR with high specificity and sensitivity for PRAME was isolated from non-tolerized T-cell repertoires and introduced into T-cells alongside a chimeric PD1-41BB receptor, consisting of the natural extracellular domain of PD-1 and the intracellular signaling domain of 4-1BB, turning an inhibitory pathway into a T-cell co-stimulatory pathway. The addition of PD1-41BB to CD8+ T-cells expressing the transgenic PRAME-TCR enhanced IFN-γ secretion, improved cytotoxic capacity, and prevented exhaustion upon repetitive re-challenge with tumor cells in vitro without altering the in vitro safety profile. Furthermore, a single dose of TCR-Ts co-expressing PD1-41BB was sufficient to clear a hard-to-treat melanoma xenograft in a mouse model, whereas TCR-Ts without PD1-41BB could not eradicate the PD-L1-positive tumors. This cutting-edge strategy supports development efforts to provide more effective TCR-T immunotherapies for the treatment of solid tumors.

Background: While childhood asthma prevalence is rising in Westernized countries, farm children are protected. The mitogen-activated protein kinase (MAPK) pathway with its negative regulator dual-specificity phosphatase-1 (DUSP1) is presumably associated with asthma development., Objectives: We aimed to investigate the role of MAPK signaling in childhood asthma and its environment-mediated protection, including a representative selection of 232 out of 1062 children from two cross-sectional cohorts and one birth cohort study., Methods: Peripheral blood mononuclear cells (PBMC) from asthmatic and healthy children were cultured upon stimulation with farm-dust extracts or lipopolysaccharide. In subgroups, gene expression was analyzed by qPCR (PBMCs, cord blood) and NanoString technology (dendritic cells). Protein expression of phosphorylated MAPKs was measured by mass cytometry. Histone acetylation was investigated by chromatin immunoprecipitation., Results: Asthmatic children expressed significantly less DUSP1 (p = .006) with reduced acetylation at histone H4 (p = .012) compared with healthy controls. Farm-dust stimulation upregulated DUSP1 expression reaching healthy levels and downregulated inflammatory MAPKs on gene and protein levels (PBMCs; p ≤ .01). Single-cell protein analysis revealed downregulated pMAPKs upon farm-dust stimulation in B cells, NK cells, monocytes, and T-cell subpopulations., Conclusion: Lower DUSP1 baseline levels in asthmatic children and anti-inflammatory regulation of MAPK in several immune cell types by farm-dust stimulation indicate a regulatory function for DUSP1 for future therapy contributing to anti-inflammatory characteristics of farming environments., (© 2021 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Acute abdominal aortic occlusion (AAO) is a rare vascular emergency associated with high morbidity and mortality. In the present study, we analyzed the clinical management and outcomes for a consecutive patient series during a 16-year period., Methods: We included all patients with an acute AAO and bilateral acute limb ischemia who had been treated between 2004 and 2019. Patients with dissection, aneurysm rupture, or chronic occlusive disease were excluded. The patient characteristics, surgical procedures, and outcomes were extracted retrospectively from a prospective aortic database, electronic patient files, and outpatient examination records. The extent of ischemia was classified according to the TASC II (Inter-Society Consensus for the Management of Peripheral Arterial Disease) section on acute limb ischemia. The primary endpoints were 30-day mortality (safety endpoint) and the combined 6-month amputation and/or death rate (efficacy endpoint). The follow-up outcomes, amputation rates, and 30-day complications were evaluated as secondary endpoints. The patient cohort was divided into four 4-year groups (2004-2007, 2008-2011, 2012-2015, 2016-2019) to assess the outcome changes over time. Statistical analysis included χ 2 tests and univariate and linear regression analyses., Results: A total of 74 patients (57% male; median age, 64.5 years) with an acute AAO were identified. Arterial thrombosis was the most common etiology (66%). The extent of ischemia was TASC I, IIa, IIb, and III in 7%, 39%, 40%, and 14%, respectively. The patient numbers had increased significantly over time (P = .016). Of the patients, 42% had undergone open transfemoral recanalization (including hybrid procedures), 35% open aortic surgery, 15% extra-anatomic bypass surgery, and 5% (four patients) endovascular therapy alone. The overall 30-day mortality rate was 23%, and the 6-month amputation and/or death rate was 43%. The 30-day mortality rate had declined significantly from 54% for 2004 to 2007 to 10% for 2011 to 2015 (odds ratio [OR], 0.10; 95% confidence interval [CI], 0.001-0.52) and 20% for 2016 to 2019 (OR, 0.21; 95% CI, 0.05-0.90), a statistically nonsignificant trend showing that the relative decline in the use of open aortic procedures was associated with decreased 30-day mortality (P = .06). Univariate analysis indicated that elevated serum lactate on admission (OR, 3.33; 95% CI, 1.06-10.48) and an advanced stage of limb ischemia (OR, 4.33), were strongly associated with an increased 30-day mortality rate. The incidence of severe postoperative systemic complications also indicated a greater incidence of both primary endpoints. The 6-month amputation and/or mortality rates were also affected by the presence of atrial fibrillation (OR, 3.63; 95% CI, 1.34-9.79) and increased patient age (OR, 3.96; 95% CI, 1.49-10.53)., Conclusions: Acute AAO remains a life-threatening emergency. Immediate transfemoral open or endovascular techniques should be preferred, if technically possible and proper intraoperative imaging is available., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: This is a description of the German healthcare landscape regarding carotid artery disease, assessment of hospital incidence time courses for carotid endarterectomy (CEA) and carotid artery stenting (CAS), and simulation of potential effects of minimum hospital caseload requirements for CEA and CAS., Methods: The study is a secondary data analysis of diagnosis related group statistics data (2005-2016), provided by the German Federal Statistical Office. Cases encoded by German operation procedure codes for CEA or CAS and by International Classification of Diseases (ICD-10) codes for carotid artery disease were included. Hospitals were categorised into quartiles according to annual caseloads. Linear distances to the closest hospital fulfilling hypothetical caseload requirements were calculated., Results: A total of 132 411 and 33 709 patients treated with CEA and CAS from 2012 to 2016 were included. CEA patients had lower rates of myocardial infarction (1.4% vs. 1.8%) and death (1.2% vs. 4.0%), and CAS patients were more often treated after emergency admission (38.1% vs. 27.1%). Age standardised annual hospital incidences were 67.2 per 100 000 inhabitants for CEA and 16.3 per 100 000 inhabitants for CAS. The incidence for CEA declined from 2005 to 2016, with CAS rising again until 2016 after having declined from 2010 to 2013. Regarding distance from home to hospital, centres offering CEA are distributed more homogeneously across Germany, compared with those performing CAS. Hypothetical introduction of minimum annual caseloads (> 20 for CEA; > 10 for CAS) imply that 75% of the population would reach their hospital after travelling 45 km for CEA and 70 km for CAS., Conclusion: Differences in spatial distribution mean that statutory minimum annual caseloads would have a greater impact on CAS accessibility than CEA in Germany. Presumably because of a decline in carotid artery disease and a transition towards individualised therapy for asymptomatic patients, hospital incidence for CEA has been declining., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Introduction: In Germany, the regional settlement structure is heterogenous, ranging from densely populated cities with a tight network of vascular health care to large regions in which access to health care is limited in terms of space and time. Therefore, the aim of this secondary data analysis was to investigate the association between the settlement structure of the patient's home district (KT), and the hospital incidence, type of therapy, and mortality of non-ruptured abdominal aortic aneurysms (nrAAA)., Methods: The microdata of the DRG statistics of the Federal Statistical Office for the years 2005-2014 were evaluated. All patients with nrAAA (ICD-10 Code I71.4) who were admitted to a German hospital and treated by open surgery and endovascular repair were included. Classification of treatment was based on the German Operation and Procedure Code. Patients were grouped according to the settlement structure of their home district defined by the Federal Institute for Research on Building, Urban Affairs and Spatial Development (KT1 independent city, KT2 urban district, KT3 rural district, KT4 sparsely populated region). The age-, sex- and risk-adjusted association between the type of settlement structure and in-hospital mortality was analysed using a multivariable multi-level regression model. The Elixhauser co-morbidity score validated for administrative data was used for risk adjustment., Results: Of 95,452 cases included, 88 % were men. Mean age was 72 years. There were 28,970 (30 %) patients in KT1, 37,759 (40 %) in KT2, 14,442 (15 %) in KT3 and 14,281 (15 %) in KT4. The hospital incidence was 12.4 per 100,000 inhabitants in KT1, 11.8 in KT2, 10.8 in KT3 and 11.2 in KT4 (p <0.001, falling trend). The proportion of EVAR treatment was 56 % in KT1, 54 % in KT2, 57 % KT3, and 59 % in KT4 (p <0.001, increasing trend). The raw hospital mortality of patients from KT1 to KT4 was 3.4 %, 3.4 %, 3.2 % and 3.6 %, respectively (p=0.553 for trend). The multivariable regression analysis revealed no statistically significant association between the KT and hospital mortality (KT1=reference, RR KT2=0.97 [95% CI 0.79-1.15], RR KT3=0.98 [0.81-1.14], RR KT4=0.98 [0.86-1.11])., Conclusions: The study shows that both the hospital incidence and the type of therapy (endovascular vs. open) differed between the settlement structural district types, but there is no urban-rural gap regarding in-hospital mortality of treated nrAAA., (Copyright © 2021. Published by Elsevier GmbH.)

Background: Specific allergy sensitization pattern, using "component-resolved diagnosis" (CRD), is a central component of allergy and asthma in childhood. Besides this, allergic asthma has been characterized by a Th2-shifted endotype with elevation of classical Th2 cytokines. Recently, other endotypes with distinct mechanisms focusing on cytokine regulation evolved, yet those pathways are still not well understood., Objective: (a) To define reproducible immunological endotypes using cytokine expression in an asthma cohort and (b) to characterize their sensitization profile and clinical phenotype., Methods: Supernatants from PBMCs of 234 children (median age 10 years) of an asthma cohort were analysed for cytokine expressions. The children were split into a training (n = 49) and validation (n = 185) group. The training group was used to identify immunological endotypes by clustering cytokine expressions, which were then assessed regarding clinical characteristics and specific IgE of recombinant allergen components. Next, our findings were validated in the validation group., Results: We identified novel endotypes based on primarily unstimulated cytokine expression. One endotype showed an IFN-γ/Interleukin (IL)-17/IL-5 predominance, a different sensitization pattern (high in birch/apple; p < .01), and inferior lung function (p < .01). A second endotype grouped young children with food allergy and reduced lung function. Our findings were reproducible in the validation group., Conclusion and Clinical Relevance: We identified two novel clinical asthma endotypes via cytokine expression pattern with distinct sensitization patterns. These novel findings are critical for clinical guidance and open avenues for identifying underlying mechanisms and more patient-specific therapies., (© 2021 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Background: The German quality assurance guideline on abdominal aortic aneurysm (AAA) was implemented by the Joint Federal Committee (Gemeinsamer Bundesausschuss, G-BA) in 2008. The aims of this study were to verify the association between hospital case volume and outcome and to assess the hypothetical effect of minimum caseload requirements., Methods: The German diagnosis-related groups statistics for the years 2012 to 2016 were scrutinized for AAA (ICD-10 GM I71.3/4) with procedure codes for endo - vascular or open surgical treatment. The primary endpoint was in-hospital mortality. Logistic regression models were used for risk adjustment, and odds ratios (OR) were calculated as a function of the annual hospital-level case volume of AAA. In a hypo - thetical approach, the linear distances for various minimum caseloads (MC) were evaluated to assess accessibility., Results: The mortality of intact AAA (iAAA) was 2.7% (men [M] 2.4%, women [W] 4.2%); ruptured AAA (rAAA), 36.9% (M 36.9%, F 37.5%). An inverse relationship between annual hospital case volume of AAA and mortality was confirmed (iAAA/rAAA: from 3.9%/51% [<10 cases/year] through 3.3%/37% [30-39 cases/year] to 1.9%/28% [≥ 75 cases/year]). For a reference category of 30 AAA procedures/year, the following significant OR were found: 10 AAA cases/year, OR 1.21 (95% confidence interval [1.20; 1.21]); 20 cases, OR 1.09 [1.09; 1.09]; 50 cases, OR 0.89 [0.89; 0.89]; 75 cases, OR 0.82 [0.82; 0.82]. In a hypothetical centralization scenario with assumed MC of 30/year, 86% of the population would have to travel less than 100 km to the nearest hospital; with an MC of 40, this would apply to only 50% (without redistribution effects)., Conclusion: In the observed period, a significant correlation was confirmed between high annual case volume and low in-hospital mortality. A minimum caseload requirement of 30 AAA operations/year seems reasonable in view of the accessibility of hospitals. Cite this.

Background: Revascularization strategies for chronic mesenteric ischemia (CMI) include open (OR) and endovascular (ER) modalities. The primary objective of this study was to analyze the safety and effectiveness of OR and ER and the impact of clinical and morphological variables on early and midterm outcomes in a consecutive series of CMI patients in a tertiary referral center., Patients and Methods: From 2004 to 2017, all CMI patients treated with OR and ER were retrospectively identified. Patient records, preoperative imaging, as well as peri- and postoperative outcomes were analyzed. Univariable and multivariable analysis was performed to identify clinical or morphological variables affecting reintervention rates within 2 years., Results: In total, 63 patients (33% male; mean age 71, range 60-76 years) were treated by ER (41 patients) or OR (22 patients) for CMI. Mean follow-up was 26 (10-71) months. 30-day mortality was 0.0% after ER and 4.5% after OR (p = 0.069); 30-day morbidity was 9.8% vs. 31.8%, respectively (p = 0.030). Length of stay was significantly longer after OR (14 vs. 4 days; p < 0.001). Freedom from reintervention rate after 2 years was 82% after OR and 73% after ER (p = 0.14). Overall survival did not differ after 2 years (OR 85% vs. ER 86%; p = 0.35). Multivariable analysis revealed that smoking was associated with higher risk of reintervention (hazard ratio, HR: 4.14; 95% confidence interval, CI 1.11-15.53; p = 0.03). Additionally, a nonsignificant trend of lower reintervention rates after OR was detected (HR 0.23 95% CI 0.05-1.08; p = 0.06)., Conclusion: Due to a lower invasiveness, despite the higher reintervention rate, an "endovascular first" strategy is justified and recommended.

Background : Since the prevalence of abdominal aortic aneurysms (AAA) in Europe has declined to about 2.5%, general screening programs of elderly men are being called into question. On the other hand, other vascular diseases (e.g. coronary heart disease, CHD) are associated with a higher prevalence of AAA. This might have an impact on future targeted AAA screening programs. This study aimed to reevaluate the current prevalence of AAA in male patients with CHD, in order to assess whether CHD patients should be offered a targeted AAA ultrasound screening program. Patients and methods : The SCAN (Screening Cardiovascular Patients for Aortic Aneurysms) study prospectively evaluated the AAA prevalence in 1000 consecutive male CHD patients (70.1 ± 11.2 years) requiring any coronary intervention at an university hospital. All patients received transverse and longitudinal ultrasound scans of the abdominal aorta. Aortic diameter was assessed using the outer-to-outer measurement-technique. Primary endpoint was the prevalence of AAA. Secondary outcomes included stratification in 1-, 2-, or 3-vessel CHD. Results : AAA was detected in 85 patients (median diameter 38 mm, range 30-80 mm), corresponding to an overall prevalence of 8.5%. AAA prevalence was significantly associated with CHD severity: 5.6% in 1-vessel, 7.1% in 2-vessel, and 10.8% in 3-vessel CHD (P  = 0.037). The multivariable analysis showed, that age per 10 years increase (OR 1.5, 95% CI 1.2-1.9, P  = 0.001) and hyperlipidemia (OR 2.2, 95% CI 1.3-3.8, P  = 0.003) were significantly associated with an AAA. The likelihood to be diagnosed with an AAA was significantly lower in non-smokers (OR 0.24, 95% CI, P < 0.001). Conclusions : This study confirms that CHD requiring any type of coronary intervention is strongly associated with AAA in male patients. AAA prevalence increases with CHD severity. Since the AAA prevalence is still significantly higher than in the general population, targeted ultrasound screening should be considered for all CHD patients.

Development and homeostasis of blood vessels critically depend on the regulation of endothelial cell-cell junctions. VE-cadherin (VEcad)-based cell-cell junctions are connected to the actin cytoskeleton and regulated by actin-binding proteins. Coronin 1B (Coro1B) is an actin binding protein that controls actin networks at classical lamellipodia. The role of Coro1B in endothelial cells (ECs) is not fully understood and investigated in this study. Here, we demonstrate that Coro1B is a novel component and regulator of cell-cell junctions in ECs. Immunofluorescence studies show that Coro1B colocalizes with VEcad at cell-cell junctions in monolayers of ECs. Live-cell imaging reveals that Coro1B is recruited to, and operated at actin-driven membrane protrusions at cell-cell junctions. Coro1B is recruited to cell-cell junctions via a mechanism that requires the relaxation of the actomyosin cytoskeleton. By analyzing the Coro1B interactome, we identify integrin-linked kinase (ILK) as new Coro1B-associated protein. Coro1B colocalizes with α-parvin, an interactor of ILK, at the leading edge of lamellipodia protrusions. Functional experiments reveal that depletion of Coro1B causes defects in the actin cytoskeleton and cell-cell junctions. Finally, in matrigel tube network assays, depletion of Coro1B results in reduced network complexity, tube number and tube length. Together, our findings point toward a critical role for Coro1B in the dynamic remodeling of endothelial cell-cell junctions and the assembly of endothelial networks., (Copyright © 2020 Werner, Weckbach, Salvermoser, Pitter, Cao, Maier-Begandt, Forné, Schnittler, Walzog and Montanez.)