Anaphylaxis, the most serious and life-threatening allergic reaction, produces the release of inflammatory mediators by mast cells and basophils. Regulator of calcineurin 1 (Rcan1) is a negative regulator of mast-cell degranulation. The action of mediators leads to vasodilation and an increase in vascular permeability, causing great loss of intravascular volume in a short time. Nevertheless, the molecular basis remains unexplored on the vascular level. We investigated Rcan1 expression induced by histamine, platelet-activating factor (PAF), and epinephrine in primary human vein (HV)-/artery (HA)-derived endothelial cells (ECs) and human dermal microvascular ECs (HMVEC-D). Vascular permeability was analyzed in vitro in human ECs with forced Rcan1 expression using Transwell migration assays and in vivo using Rcan1 knockout mice. Histamine, but neither PAF nor epinephrine, induced Rcan1-4 mRNA and protein expression in primary HV-ECs, HA-ECs, and HMVEC-D through histamine receptor 1 (H1R). These effects were prevented by pharmacological inhibition of calcineurin with cyclosporine A. Moreover, intravenous histamine administration increased Rcan1 expression in lung tissues of mice undergoing experimental anaphylaxis. Functional in vitro assays showed that overexpression of Rcan1 promotes barrier integrity, suggesting a role played by this molecule in vascular permeability. Consistent with these findings, in vivo models of subcutaneous and intravenous histamine-mediated fluid extravasation showed increased response in skin, aorta, and lungs of Rcan1-deficient mice compared with wild-type animals. These findings reveal that endothelial Rcan1 is synthesized in response to histamine through a calcineurin-sensitive pathway and may reduce barrier breakdown, thus contributing to the strengthening of the endothelium and resistance to anaphylaxis. These new insights underscore its potential role as a regulator of sensitivity to anaphylaxis in humans.

only a minority of patients operated on for CLI were receiving adequate cardiovascular risk factor modification.

CDT of iliofemoral DVT is a safe procedure. The patients can stay in a clinical vascular ward. The long-term efficacy is still durable in producing competent veins as concluded in our earlier published results.

In this observational study of CDT for ilio-femoral DVT it was demonstrated that symptom duration less than 2 weeks, absence of chronic post-thrombotic lesions and use of the pulse-spray technique for CDT resulted in better primary patency including normal valve function in the long term.

Catheter-directed thrombolysis for deep venous thrombosis is considered the basic treatment modality for intrathrombus removal. This method is preferably used in patients with iliofemoral deep venous thrombosis due to poor spontaneous recanalization in this segment, especially on the left side. The method was published almost 25 years ago and has gained ground in the treatment because of poor results from systemic thrombolysis and because of the possibility of stenting any underlying iliac obstruction during the procedure. However, the publications of catheter-directed thrombolysis reveal a great heterogeneity concerning catheter-directed thrombolysis technique and the lack of high quality evidence about monitoring as a tool to minimize the risk of bleeding and pulmonary embolism. Strict inclusion and exclusion criteria, correct composition and infusion of thrombolysis agent, imaging thrombus clearance during catheter-directed thrombolysis, ensuring flow enhancement during the bedridden situation, careful evaluation of indication for stenting based on imaging, and sufficient conversion to anticoagulation treatment following catheter-directed thrombolysis are essential. The aim of this paper is to discuss different treatment aspects of catheter-directed thrombolysis for iliofemoral thrombosis and to suggest a monitoring model for future treatment.

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The majority (66.7%; N = 96) of the identified 144 patients with CLI (mean age 71.2 years; median follow-up 99 weeks) underwent revascularisation within 6 weeks of diagnosis. Deferred invasive treatment was provided in 18.1% (N = 26) patients and 22 patients (15.3%) were treated permanently conservatively. AFS and OS did not differ significantly between the three groups (BresloweWilcoxon P = .16 for AFS and P = .09 for OS). Age, chronic obstructive pulmonary disease (COPD), and heart disease were significant independent predictors of AFS. Age, COPD, and hypertension were significant independent predictors of OS. Treatment was not a significant predictor of either AFS or OS.Conclusions: Not all patients with CLI require revascularisation to achieve an AFS that is similar to patients undergoing revascularisation, although the efficacy of conservative versus invasive treatment in CLI patients is still unclear. Further prospective studies should determine subgroups of patients in whom revascularisation may be omitted.

Purpose Spectral Doppler ultrasound (SDUS) is used for quantifying reflux in lower extremity varicose veins. The technique is angle-dependent opposed to the new angle-independent Vector Flow Imaging (VFI) method. The aim of this study was to compare peak reflux velocities obtained with VFI and SDUS in patients with chronic venous disease, i. e., pathological retrograde blood flow caused by incompetent venous valves. Materials and Methods 64 patients with chronic venous disease were scanned with VFI and SDUS in the great or the small saphenous vein, and reflux velocities were compared to three assessment tools for chronic venous disease. A flow rig was used to assess the accuracy and precision of the two methods. Results The mean peak reflux velocities differed significantly (VFI: 47.4 cm/s vs. SDUS: 62.0 cm/s, p<0.001). No difference in absolute precision (p=0.18) nor relative precision (p=0.79) was found. No correlation to disease severity, according to assessment tools, was found for peak reflux velocities obtained with either method. In vitro, VFI was more accurate but equally precise when compared to SDUS. Conclusion Both VFI and SDUS detected the pathologic retrograde flow in varicose veins but measured different reflux velocities with equal precision. VFI may play a role in evaluating venous disease in the future.