Hydrogen Sulphide Release via the Angiotensin Converting Enzyme Inhibitor Zofenopril Prevents Intimal Hyperplasia in Human Vein Segments and in a Mouse Model of Carotid Artery Stenosis.

OBJECTIVE: Hypertension is a major risk factor for intimal hyperplasia (IH) and re-stenosis following vascular and endovascular interventions. Preclinical studies suggest that hydrogen sulphide (H2S), an endogenous gasotransmitter, limits re-stenosis. While there is no clinically available pure H2S releasing compound, the sulfhydryl containing angiotensin converting enzyme inhibitor zofenopril is a source of H2S. Here, it was hypothesised that zofenopril, due to H2S release, would be superior to other non-sulfhydryl containing angiotensin converting enzyme inhibitors (ACEi) in reducing intimal hyperplasia. METHODS: Spontaneously hypertensive male Cx40 deleted mice (Cx40-/-) or wild type (WT) littermates were randomly treated with enalapril 20 mg or zofenopril 30 mg. Discarded human vein segments and primary human smooth muscle cells (SMCs) were treated with the active compound enalaprilat or zofenoprilat. IH was evaluated in mice 28 days after focal carotid artery stenosis surgery and in human vein segments cultured for seven days ex vivo. Human primary smooth muscle cell (SMC) proliferation and migration were studied in vitro. RESULTS: Compared with control animals (intima/media thickness 2.3 ± 0.33 µm), enalapril reduced IH in Cx40-/- hypertensive mice by 30% (1.7 ± 0.35 µm; p = .037), while zofenopril abrogated IH (0.4 ± 0.16 µm; p < .002 vs. control and p > .99 vs. sham operated Cx40-/- mice). In WT normotensive mice, enalapril had no effect (0.9665 ± 0.2 µm in control vs. 1.140 ± 0.27 µm; p > .99), while zofenopril also abrogated IH (0.1623 ± 0.07 µm; p < .008 vs. control and p > .99 vs. sham operated WT mice). Zofenoprilat, but not enalaprilat, also prevented IH in human vein segments ex vivo. The effect of zofenopril on carotid and SMCs correlated with reduced SMC proliferation and migration. Zofenoprilat inhibited the mitogen activated protein kinase and mammalian target of rapamycin pathways in SMCs and human vein segments. CONCLUSION: Zofenopril provides extra beneficial effects compared with non-sulfhydryl ACEi in reducing SMC proliferation and re-stenosis, even in normotensive animals. These findings may hold broad clinical implications for patients suffering from vascular occlusive diseases and hypertension.

Arterial and Mixed Venous Kinetics of Desflurane and Sevoflurane, Administered Simultaneously, at Three Different Global Ventilation to Perfusion Ratios in Piglets with Normal Lungs.

BACKGROUND: Previous studies have established the role of various tissue compartments in the kinetics of inhaled anesthetic uptake and elimination. The role of normal lungs in inhaled anesthetic kinetics is less understood. In juvenile pigs with normal lungs, the authors measured desflurane and sevoflurane washin and washout kinetics at three different ratios of alveolar minute ventilation to cardiac output value. The main hypothesis was that the ventilation/perfusion ratio (VA/Q) of normal lungs influences the kinetics of inhaled anesthetics. METHODS: Seven healthy pigs were anesthetized with intravenous anesthetics and mechanically ventilated. Each animal was studied under three different VA/Q conditions: normal, low, and high. For each VA/Q condition, desflurane and sevoflurane were administered at a constant, subanesthetic inspired partial pressure (0.15 volume% for sevoflurane and 0.5 volume% for desflurane) for 45 min. Pulmonary arterial and systemic arterial blood samples were collected at eight time points during uptake, and then at these same times during elimination, for measurement of desflurane and sevoflurane partial pressures. The authors also assessed the effect of VA/Q on paired differences in arterial and mixed venous partial pressures. RESULTS: For desflurane washin, the scaled arterial partial pressure differences between 5 and 0 min were 0.70 ± 0.10, 0.93 ± 0.08, and 0.82 ± 0.07 for the low, normal, and high VA/Q conditions (means, 95% CI). Equivalent measurements for sevoflurane were 0.55 ± 0.06, 0.77 ± 0.04, and 0.75 ± 0.08. For desflurane washout, the scaled arterial partial pressure differences between 0 and 5 min were 0.76 ± 0.04, 0.88 ± 0.02, and 0.92 ± 0.01 for the low, normal, and high VA/Q conditions. Equivalent measurements for sevoflurane were 0.79 ± 0.05, 0.85 ± 0.03, and 0.90 ± 0.03. CONCLUSIONS: Kinetics of inhaled anesthetic washin and washout are substantially altered by changes in the global VA/Q ratio for normal lungs.

Effect of Adrenocorticotropic Hormone Stimulation During Simultaneous Bilateral Adrenal Vein Sampling in Primary Aldosteronism.

The aim of the study was to investigate the significance and influence of adrenocorticotropic hormone (ACTH) stimulation in primary aldosteronism (PA) patients with simultaneous bilateral adrenal vein sampling (AVS). All patients diagnosed with PA underwent simultaneous bilateral AVS with ACTH. In 95 patients, the post-ACTH SI significantly increased (p<0.001), and it gradually decreased from t10-t30 after ACTH stimulation (p<0.001). The unsuccessful catheterization decreased after ACTH stimulation. Time points within 20 min after ACTH stimulation were better for sampling, and the selectivity did not increase over longer periods. According to lateralization before and after ACTH stimulation, the patients could be divided into 3 groups (U, unilateral; B, bilateral): U/U , U/B or B/U, and B/B. Compared with the U/U group, in the U/B or B/U and B/B groups, the lateralization index (LI) was lower both at baseline and after ACTH stimulation (p<0.0001), the contralateral index (CLI) was higher after ACTH stimulation (p<0.003), the serum potassium level was higher (p<0.001), and the carbon dioxide combining power (CO2CP) and base excess (BE) levels were lower. In conclusion, in simultaneous bilateral AVS, ACTH stimulation had significant effects on increasing the catheterization selectivity. Lateralization change was observed after stimulation. After ACTH stimulation, fewer patients could be diagnosed with lateralized PA. Patients with consistent lateralized PA showed a more serious phenotype.

Adrenocorticotropic Hormone-Stimulated Adrenal Venous Sampling Underestimates Surgically Curable Primary Aldosteronism: A Retrospective Cohort Study and Review of Contemporary Studies.

[Figure: see text].

2,3,7,8-Tetrachlorodibenzo-p-dioxin exposure disrupts development of the visceral and ocular vasculature.

The aryl hydrocarbon receptor (AHR) has endogenous functions in mammalian vascular development and is necessary for mediating the toxic effects of a number of environmental contaminants. Studies in mice have demonstrated that AHR is necessary for the formation of the renal, retinal, and hepatic vasculature. In fish, exposure to the prototypic AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces expression of the AHR biomarker cyp1a throughout the developing vasculature and produces vascular malformations in the head and heart. However, it is not known whether the vascular structures that are sensitive to loss of AHR function are also disrupted by aberrant AHR activation. Here, we report that TCDD-exposure in zebrafish disrupts development of 1) the subintestinal venous plexus (SIVP), which vascularizes the developing liver, kidney, gut, and pancreas, and 2) the superficial annular vessel (SAV), an essential component of the retinal vasculature. Furthermore, we determined that TCDD exposure increased the expression of bmp4, a key molecular mediator of SIVP morphogenesis. We hypothesize that the observed SIVP phenotypes contribute to one of the hallmarks of TCDD exposure in fish - the failure of the yolk sac to absorb. Together, our data describe novel TCDD-induced vascular phenotypes and provide molecular insight into critical factors producing the observed vascular malformations.

Vascular uptake on 18F-sodium fluoride positron emission tomography: precursor of vascular calcification?

BACKGROUND: Microcalcifications cannot be identified with the present resolution of CT; however, 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) imaging has been proposed for non-invasive identification of microcalcification. The primary objective of this study was to assess whether 18F-NaF activity can assess the presence and predict the progression of CT detectable vascular calcification. METHODS AND RESULTS: The data of two longitudinal studies in which patients received a 18F-NaF PET-CT at baseline and after 6 months or 1-year follow-up were used. The target to background ratio (TBR) was measured on PET at baseline and CT calcification was quantified in the femoral arteries at baseline and follow-up. 128 patients were included. A higher TBR at baseline was associated with higher calcification mass at baseline and calcification progression (ß = 1.006 [1.005-1.007] and ß = 1.002 [1.002-1.003] in the studies with 6 months and 1-year follow-up, respectively). In areas without calcification at baseline and where calcification developed at follow-up, the TBR was .11-.13 (P < .001) higher compared to areas where no calcification developed. CONCLUSION: The activity of 18F-NaF is related to the amount of calcification and calcification progression. In areas where calcification formation occurred, the TBR was slightly but significantly higher.

Calf Vein Thrombosis Comparison of Outcomes for Axial and Muscular Venous Thrombosis.

BACKGROUND: The objective of this study was to characterize clinical features and outcomes among patients with calf deep vein thrombosis (DVT) limited to the muscular veins compared with axial veins. METHODS: Consecutive patients with ultrasound confirmed acute DVT involving the calf veins (January 1, 2016-August 1, 2018) were identified from the Gonda Vascular Center ultrasound database. Patients were divided into axial or muscular groups based on thrombus location. Demographics, management, and outcomes were compared. RESULTS: Over the study period, there were 647 patients with calf DVT equally distributed between axial (n = 321) and muscular (n = 326) locations. Within these groups, peroneal and soleal veins were most commonly involved. Nearly all cases were provoked (97%). Synchronous pulmonary embolism (PE) were more common for axial (30.8%) compared to muscular groups (20.2%; p = 0.001); nearly one-third had no pulmonary symptoms. Anticoagulation for a median of 3 months was initiated for 85.5% of both groups. Venous thromboembolism (VTE) recurrence was more common in the axial group (15.9% vs. 7.1%, p = 0.0015) including more frequent DVT propagation (9.4% vs. 3.1%; p = 0.0017) and PE (3.4% vs. 0.6%; p = 0.0168). Major bleeding, clinically relevant nonmajor bleeding, and mortality rates did not differ between groups. Withholding anticoagulation led to more frequent thrombus propagation in the axial group (3.4% vs. 0.9%; p = 0.029). CONCLUSION: Several important features distinguish muscular from axial DVT. Axial DVT are more likely to have an associated PE and are more likely to experience recurrent VTE, particularly if anticoagulation is withheld.

Sclerotherapy treatment of a large venous malformation invading the bladder wall related to Klippel-Trenaunay syndrome.

We report the case of a 35-year-old woman who presented with recurrent macroscopic haematuria and known diagnosis of Klippel-Trenaunay syndrome. Imaging and cystoscopy identified an extensive venous malformation involving a large area of the bladder wall. Holmium laser therapy was ineffective at obtaining symptom control. Following a multidisciplinary team meeting, transvenous sclerotherapy with sodium tetradecyl sulphate was performed under image guidance. A reduction in venous density was observed on cystoscopy and the patient has had complete resolution of symptoms within 6 weeks and continued to be asymptomatic up to 24-month follow-up. We propose that transvenous sclerotherapy is considered first-line treatment in this clinical setting.

Effectiveness and Safety of Ethanol for the Treatment of Venous Malformations: A Meta-Analysis.

BACKGROUND: Venous malformations (VM) are common vascular malformations. Percutaneous injection of sclerosants into the lesion has become mainstream therapy. The most commonly used sclerosants are ethanol, polidocanol, bleomycin, and the like. But few articles have reported that sclerosants are more effective and safer. METHODS: We performed a search on Cochrane, Embase, PubMed, China National Knowledge Infrastructure, CBM, and Wan Fang databases of Controlled Trials (from January 1, 2010, launch up to April 10, 2019) reporting outcome of intralesional ethanol, polidocanol, and bleomycin injections in patients with VM (n ≥ 20). A meta-analysis was conducted using Rev-man 5.3 software. RESULTS: A total of 9 articles, 632 participants and 676 lesions were included. Quality of evidence was generally low. Meta-analysis showed that absolute ethanol treatment was better than polidocanol in treating VM (p = .001), and absolute ethanol elicited a better response than bleomycin (p = .01). Ethanol therapeutic effect was not statistically significant compared with ethanol alone (p = .07), but the combination effect was better than polidocanol (p = .04). Ethanol treatment showed significantly more adverse reactions than polidocanol and combination therapy. CONCLUSION: Absolute ethanol combined with polidocanol is more effective in treating VM and has fewer adverse reactions.

Comparison of the Safety and Efficacy of Foam Sclerotherapy With 1: 2 Polidocanol to Air Ratio Versus 1: 4 Ratio for the Treatment of Reticular Veins of the Lower Extremities.

BACKGROUND: Foam sclerotherapy is a common treatment of lower extremity reticular veins. The effect of different liquid-gas ratios on foam stability and efficacy has been controversial. OBJECTIVE: To evaluate the use of 2 different polidocanol (POL) to air ratios for the treatment of reticular veins of the lower extremities. METHODS AND MATERIALS: Patients with lower extremity reticular veins were randomized to foam sclerotherapy with POL mixed with 4 mL of room air for one lower extremity or 2 mL for the other lower extremity. All telangiectasias were treated with glycerin immediately after treatment of the reticular veins. Adverse events (AEs) and efficacy were evaluated by both subject and blinded investigator. RESULTS: Thirty subjects completed the study. No statistically significant difference was seen in AEs between the 2 different POL to air ratios by subject questionnaire and blinded investigator scores at all time points. Subjects and blinded investigator reported a mean improvement between 0% and 50% at Day 21 and 26% to 75% at Day 90, which was not significantly different between groups. CONCLUSION: Two different POL to air ratios, 1:2 versus 1:4, were similarly safe and efficacious for the treatment reticular veins of the lower extremities.

A Novel Compound Sclerosant: Polidocanol-Bleomycin Foam.

BACKGROUND: Foam sclerotherapy is an effective treatment strategy for venous malformations. Both polidocanol (POL) and bleomycin are effective sclerosants; however, no studies have reported POL-bleomycin foam. OBJECTIVE: To introduce a method for producing POL-bleomycin foam and evaluate the stability of POL-bleomycin foam with bleomycin concentrations. MATERIALS AND METHODS: Group A: 2 mL of 1% POL + 8 mL of air; Group B: 2 mL of 1% POL + 3 U bleomycin + 8 mL of air; Group C: 2 mL of 1% POL + 6 U bleomycin + 8 mL of air; Group D: 2 mL of 1% POL + 12 U bleomycin + 8 mL of air. Tessari method was used for foam generation. The foam half-life time (FHT) was used to evaluate foam stability. Five recordings were made for each group. RESULTS: The FHT was 148.6 ± 2.9 seconds in Group A, 148.8 ± 4.0 seconds in Group B, 148.4 ± 2.6 seconds in Group C, and 148.8 ± 1.6 seconds in Group D. The FHT in different groups showed no significant differences. CONCLUSION: The POL-bleomycin foam was prepared successfully and its FHT was as long as the POL foam.

Drug-eluting Vein Graft with Acetylsalicylic Acid-Ticagrelor-Unfractionated Heparin Complex Inhibits Early Graft Thrombosis

Background: Bypass graft surgery remains to be an important treatment option for left main and multivessel coronary artery disease. Approximately 2% of saphenous vein grafts are lost immediately after the coronary artery bypass graft operations and 12% in the first month due to thrombosis. Aims: To administer one anticoagulant and two antiplatelet agents in a way that locally affects the vein graft before the bypass operation and to thereby analyse their effects on early graft thrombosis. Study Design: Animal experimentation. Methods: Since ticagrelor was used locally for the first time in this study, its efficacy in combination with other drugs (acetylsalicylic acid, acetylsalicylic acid and ticagrelor, and acetylsalicylic acid + ticagrelor + unfractionated heparin) was examined on rats including control (untreated) and sham (pluronic gel) group (n=14 for each group). Before the tunica adventitia layer of the femoral veins was bypassed to the femoral artery, it was coated with the drug-eluting pluronic F-127 gel. The presence or absence of thrombus in the vein graft samples was recorded under light microscopy. In vein graft preparations where thrombus was detected, the thrombus area (µm2) was calculated using the Axiovision software. Immunohistochemical staining was performed with the anti-rat von Willebrand factor polyclonal antibody kit. Results: The number of preparations containing thrombus was significantly lower in the acetylsalicylic acid + ticagrelor + unfractionated heparin group than in the acetylsalicylic acid, control, and sham groups, according to the comparisons made on the 1st and 3rd days (p=0.001 and 0.02, respectively). von Willebrand factor staining was significantly lower in the acetylsalicylic acid + ticagrelor + unfractionated heparin group than in the other groups on the 3rd day (p=0.005). Conclusion: Locally effective acetylsalicylic acid-ticagrelor-unfractionated heparin complex has been shown to significantly reduce thrombus formation in vein grafts in this experimental model. Local administration of these drugs, which are routinely administered orally just before stent implantations, on the vein graft before the bypass is performed can prevent the loss of vein grafts due to thrombus, thereby reducing the mortality and morbidity of these patients.

CEAP clinical classes C0S-C4: differences, similarities and role of Ruscus + HMC + vitamin C in patients with chronic venous disease.

Since the publication of the CEAP classification, new research has enriched our knowledge; notably on the heritability of CVD and the genetic and environmental factors involved in this condition, as well as the symptoms apparent within the spectrum of the CEAP clinical classes and the benefits of medical treatment. Using the CEAP classification as a special theme, a symposium with the same title as the present paper was held at the annual meeting of the 2019 European Venous Forum. The lectures presented much valuable information, from which some key points can be extracted. The influence of environmental factors was demonstrated, and the fact that a large amount of information can be obtained from comprehensive history taking. There is robust evidence for heritability. Many candidate genes/loci have been identified, potentially offering new targets for treatment. More research is needed, notably using genome-wide association studies and also on microbiota, which may play a role in CVD through the inflammation pathway. Ruscus + HMC + vitamin C acts by increasing venous and lymphatic tone, protecting microcirculation, and reducing inflammation. It improves quality of life in C0S to C3 CVD patients, while a review of clinical studies and a meta-analysis have confirmed its clinical efficacy across a wide spectrum of CVD clinical classes: C0S, C1S, C2, C3 and C4. It has been awarded a Grade 1A recommendation by the international guidelines.

Prolonged Hyperoxygenation Treatment Improves Vein Graft Patency and Decreases Macrophage Content in Atherosclerotic Lesions in ApoE3*Leiden Mice.

Unstable atherosclerotic plaques frequently show plaque angiogenesis which increases the chance of rupture and thrombus formation leading to infarctions. Hypoxia plays a role in angiogenesis and inflammation, two processes involved in the pathogenesis of atherosclerosis. We aim to study the effect of resolution of hypoxia using carbogen gas (95% O2, 5% CO2) on the remodeling of vein graft accelerated atherosclerotic lesions in ApoE3*Leiden mice which harbor plaque angiogenesis. Single treatment resulted in a drastic decrease of intraplaque hypoxia, without affecting plaque composition. Daily treatment for three weeks resulted in 34.5% increase in vein graft patency and increased lumen size. However, after three weeks intraplaque hypoxia was comparable to the controls, as were the number of neovessels and the degree of intraplaque hemorrhage. To our surprise we found that three weeks of treatment triggered ROS accumulation and subsequent Hif1a induction, paralleled with a reduction in the macrophage content, pointing to an increase in lesion stability. Similar to what we observed in vivo, in vitro induction of ROS in bone marrow derived macrophages lead to increased Hif1a expression and extensive DNA damage and apoptosis. Our study demonstrates that carbogen treatment did improve vein graft patency and plaque stability and reduced intraplaque macrophage accumulation via ROS mediated DNA damage and apoptosis but failed to have long term effects on hypoxia and intraplaque angiogenesis.

CGRP in rat mesenteric artery and vein - receptor expression, CGRP presence and potential roles.

CGRP is a potent dilator of arteries and despite rich perivascular CGRP immunoreactivity in both arteries and veins the role of CGRP in veins remains unknown. The aim of the current study was to compare perivascular CGRP immunoreactivity and expression of CGRP receptor mRNA and CGRP receptor immunoreactivity in rat mesenteric arteries and veins. Furthermore, potential vasomotor effects of CGRP were explored in veins. Immunohistochemical studies reproduced rich perivascular CGRP innervation in arteries and in veins. Further, the presence of mRNA encoding the CGRP receptor subunits, CLR and RAMP1, were demonstrated in both arteries and veins using qPCR. Before comparing the vasoactive effects of CGRP in arteries and veins, we aimed to identify an experimental setting where vasomotor responses could be detected. Therefore, a length-tension study was performed in artery and vein segments. Whereas the arteries showed the characteristic monophasic curve with an IC/IC100 value of 0.9, surprisingly the veins showed a biphasic response with two corresponding IC/IC100 values of 0.7 and 0.9, respectively. There was no significant difference between fresh and cultured vasculature segments. To investigate whether a potential tension-dependent CGRP-induced dilation of veins caused the decline between the two IC/IC100 peaks, a second study was performed, with the CGRP receptor antagonist, BIBN4096BS (olcegepant) and the sensory nerve secretagogue, capsaicin. No significant vascular role of endogenous perivascular CGRP in mesenteric veins could be concluded, and a potential role of the rich perivascular CGRP and CGRP receptor abundancy in veins remains unknown.

Ultrasound Aspects and Recanalization Rates in Patients with Lower-Limb Deep Venous Thrombosis Treated with Rivaroxaban.

BACKGROUND: In this article, we report the ultrasound aspects and recanalization rates of patients with deep venous thrombosis (DVT) in the lower limbs treated with the rivaroxaban, focusing on the recanalization rate and the ultrasonographic aspects. METHODS: This was a prospective and consecutive cohort study of patients admitted with DVT who were submitted to treatment with rivaroxaban for 6 months at the Division of Vascular and Endovascular Surgery, Hospital do Servidor Público Estadual, São Paulo, Brazil, between March 2016 and July 2018. RESULTS: Fifty-one patients with DVT were admitted to the Vascular Surgery Department and received rivaroxaban for 6 months. The follow-up time was 360 days. Analyses were performed at 180 and 360 days. The rate of total venous recanalization at 360 days was 76.4% (39 patients). The incidence of partial venous recanalization was 23.5% (12 patients). At the first month, 11 patients (21.7%) continued with total occlusion of the vein, with 4 patients (6.5%) with no residual thrombi. However, at 6 months, only 2 patients (2.2%) continued with total occlusion of the vein, with 26 patients (47.8%) with no residual thrombi. At 12 months, there were 39 patients (76.4%) with no residual thrombi. Univariate and multivariate logistic regression identified the following factors related to total venous recanalization: the absence of popliteal vein reflux (odds ratio [OR], 0.386; P = 0.007), no residual thrombi (OR, 3.213; P = 0.008), femoropopliteal clot length at 1 month (OR, 3.021; P = 0.016), femoropopliteal clot length at 6 months (OR, 2.234; P = 0.008). The incidence of post-thrombotic syndrome (PTS) at 12 months was 8.3%. CONCLUSIONS: In this study, patients who received oral rivaroxaban displayed satisfactory total vein recanalization rate after 6 months and 12 months. The factors associated with better total recanalization rates were the absence of popliteal vein reflux, the absence of residual thrombi in the veins, femoropopliteal clot length at 1 month (OR, 3.021; P = 0.016), and femoropopliteal clot length at 6 months (OR, 2.234; P = 0.008). Moreover, the incidence of PTS at 12 months was 8.3%.

Activation of bradykinin-sensitive pericardial afferents increases systemic venous tone in conscious rats.

Our understanding of reflex regulation of veins lags behind that of the arterial system. While the cardiac sympathetic afferent reflex (CSAR) exerts control over sympathetic outflow, its effect on venous tone is not known. We tested the hypothesis that activation of pericardial bradykinin sensitive afferents elicits systemic venoconstriction. Male and female Sprague Dawley rats were chronically instrumented for measurement of arterial pressure and mean circulatory filling pressure, an index of venous tone, and with an indwelling pericardial catheter. Mean arterial pressure, heart rate and mean circulatory filling pressure responses were assessed in conscious rats in response to graded pericardial injections of bradykinin (1.5-20 µg/kg) before and after ganglionic blockade, and to intravenous norepinephrine (0.05-0.8 µg/kg). Bradykinin B2 receptor was assessed by Western blot. Pericardial bradykinin injections caused graded increases in mean arterial pressure, heart rate and mean circulatory filling pressure. These responses were markedly attenuated after autonomic blockade. The increments in mean circulatory filling pressure were attenuated in female rats. There were no differences in the venoconstrictor responses to norepinephrine or ventricular bradykinin receptor expression between male and females. We interpret these findings to indicate that activation of bradykinin sensitive pericardial afferents elicits a sexually dimorphic, autonomically mediated systemic venoconstrictor response. Differences in venous smooth muscle responses to norepinephrine or ventricular bradykinin receptor expression do not account for the sexual dimorphism. We conclude that systemic venoconstriction contributes to the overall hemodynamic response to activation of the cardiac sympathetic afferent reflex and that this effect is sexually dimorphic.

Expert consensus on the conservative management of patients with chronic venous disease in CEAP clinical classes C0s-C3 in Italy.

OBJECTIVES: To define a consensual approach for the conservative treatment of patients C0s-C3. METHOD: The project was structured into two phases. The first one involved a group of Italian specialists in angiology and/or vascular surgery with the aim to compare their therapeutic choices in the management of patients in CEAP C0s-C3. The second phase used a Delphi consensus in order to elaborate practical statements on the conservative management of these patients. RESULTS: The first phase involved a group of 166 Italian specialists while the second phase involved a Steering Committee of 6 specialists and a panel of 20 specialists. At the end of the third round, a consensus >80% was reached on seven assertions. CONCLUSION: Seven statements have been drafted by a group of Italian specialists to provide physicians with practical guidance for the conservative treatment of C0s-C3 patients. Outstanding issues on the management of these patients were identified, confirming the urgent need of further research.

Extra-cardiac endovascular infections in the critically ill.

Vascular infections are associated with high complication rates and mortality. While there is an extensive body of literature surrounding cardiac infections including endocarditis, this is less so the case for other endovascular infections. The objective of this narrative review is to summarize the epidemiology, clinical features, and selected management of severe vascular infections exclusive of those involving the heart. Endovascular infections may involve either the arterial or venous vasculature and may arise in native vessels or secondary to implanted devices. Management is complex and requires multi-disciplinary involvement from the outset. Infective arteritis or device-related arterial infection involves removal of the infected tissue or device. In cases where complete excision is not possible, prolonged courses of antimicrobials are required. Serious infections associated with the venous system include septic thrombophlebitis of the internal jugular and other deep veins, and intracranial/venous sinuses. Source control is of paramount importance in these cases with adjunctive antimicrobial therapy. The role of anticoagulation is controversial although recommended in the absence of contraindications. An improved understanding of the management of these infections, and thus improved patient outcomes, requires multi-center, international collaboration.

[Effect of vascular changes on prognosis after induced chemotherapy for advanced hypopharyngeal carcinoma].

Objective: To analyze the clinical characteristics of two groups(vascular classification declines or not in narrow band imaging (NBI) of patients with advanced hypopharyngeal carcinoma after induced chemotherapy, to follow-up and compare the survival differences between the two groups, and to explore the effect of vascular changes on clinical prognosis after induced chemotherapy in patients with advanced hypopharyngeal carcinoma. Methods: Clinical data of 56 patients with advanced hypopharyngeal carcinoma from August 2014 to September 2016 in Beijing Tongren Hospital, Capital Medical University were collected. The patients were divided into two groups according to NBI vascular classification declines or not after induced chemotherapy. The survival of patients and the impact of different factors on the prognosis were retrospectively analyzed. SPSS 24.0 statistical software was used for analysis. Frequency data were compared between the two groups using χ(2) test. Kaplan-Meier method and Cox regression analysis were employed for survival analysis and Log-Rank test was used for inter-group comparison, P<0.05 was statistically significant. Results: There was significant difference in overall survival rate(OS) between two groups of patients with advanced hypopharyngeal carcinoma after induced chemotherapy (P<0.05). Multivariate analysis showed that NBI vascular classification changes after induced chemotherapy was the impact factor for prognosis of advanced hypopharyngeal carcinoma after induced chemotherapy. Conclusion: In addition to recurrence and metastasis, NBI vascular classification changes is the important impact factor for prognosis of advanced hypopharyngeal carcinoma after induced chemotherapy. Patients with NBI vascular classification declines have significant survival benefit. The patients with advanced hypopharyngeal carcinoma should be checked with NBI examination before and after induced chemotherapy. NBI should be included in the routine screening indicators for prognosis of advanced hypopharyngeal carcinoma.