Men with erectile dysfunction (ED) should be screened for cardiovascular risk factors - Cost-benefit considerations in Swiss men.

Background: Current evidence indicates that erectile dysfunction (ED) is an independent risk factor for future cardiovascular events. This study aimed to estimate the cost-effectiveness of screening and subsequent preventive treatment for cardiovascular risk factors among men newly diagnosed with ED from the Swiss healthcare system perspective. Methods: Based on known data on ED and cardiovascular disease (CVD) prevalence and incidence costs and effects of a screening intervention for cardiovascular risk including corresponding cardiovascular prevention in men with ED were calculated for the Swiss population over a period of 10 years. Results: Screening and cardiovascular prevention over a period of 10 years in Swiss men with ED of all seriousness degrees, moderate and severe ED only, or severe ED only can probably avoid 41,564, 35,627, or 21,206 acute CVD events, respectively. Number needed to screen (NNS) to prevent one acute CVD event is 30, 23, and 10, respectively. Costs for the screening intervention are expected to be covered at the seventh, the fifth, and the first year, respectively. Conclusion: Screening and intervention for cardiovascular risk factors in men suffering from ED is a cost-effective tool not only to strengthen prevention and early detection of cardiovascular diseases but also to avoid future cardiovascular events.

Long-Term Outcomes of Drug-Eluting Stent Implantation for Patients With Atherosclerotic Erectile Dysfunction not Responding to PDE-5-Inhibitors.

PURPOSE: Endovascular therapy of erection-related arteries was shown to be a promising treatment option for patients with severe erectile dysfunction. Purpose of this study was to assess the longer-term safety and clinical success rate of endovascular revascularization of erection-related arteries with the Angiolite BTK stent in patients with arteriogenic erectile dysfunction. MATERIALS AND METHODS: A total of 147 consecutive men (63.5±9.3 years) with erectile dysfunction due to 345 atherosclerotic lesions underwent endovascular revascularization. Patients received an International Index of Erectile Function (IIEF)-15 questionnaire at 30.3±7.2 months (follow-up [FU] period no less than 18 months) after stenting. An improvement by 4 points in the erectile function domain consisting of 6 questions (IIEF-6) was defined as minimal clinically important difference (MCID). RESULTS: Technical success was achieved in 99% of lesions. One major adverse event occurred after endovascular revascularization. Sixty-eight (46%) patients completed their latest FU at least 18 months following the last intervention. Minimal clinically important difference was achieved in 54% (37/68) of patients. CONCLUSIONS: In patients with arteriogenic erectile dysfunction not responding to phosphodiesterase-5-inhibitors (PDE-5-Is), endovascular therapy with a novel thin-strut sirolimus-eluting stent is a safe and effective treatment option during short- and longer-term FU. CLINICAL IMPACT: Patients with severe erectile dysfunction profit greatly from endovascular therapy of erection-related arteries. Stable clinical outcomes are seen beyond a 1-year timeframe. It is proven that, the drug-eluting stent therapy for atherosclerotic ED in patients who have not responded to PDE-5-I therapy is safe and effective during longer-term follow-up.

Role of Lp(a) in patients with erectile dysfunction undergoing angioplasty for symptomatic pelvic artery disease.

Background: Atherosclerotic disease of erection-related arteries is a major reason for erectile dysfunction (ED). Lp(a) has been implied in the pathophysiology of atherosclerosis in the coronary and lower limb arteries. Here, we investigated if Lp(a) plays a specific role in ED due with symptomatic pelvic artery atherosclerosis. Patients and methods: Out of 276 consecutive patients treated for ED with angioplasties on proximal (69%) and distal (31%, distal to Alcock channel) erection-related arteries, 236 patients (age: 62±10 years) of which Lp(a) values were available were retrospectively analyzed. Results: The baseline International Index of Erectile Function-15 (IIEF-15) score was 29±15 and significantly increased to 43±20 (increase: 14±21) after treatment at average follow up of 286±201 days. In 25%, Lp(a) values were elevated to more than 30 mg/dL. Hypercholesterolemia, coronary, lower extremity peripheral, and polyvascular disease were more common in patients with Lp(a) ≥60 mg/dl. Anatomic arterial lesion distribution (proximal/distal), improvement in IIEF-15 and clinically driven re-intervention rate (overall 7%) did not differ between patients with <30, 30-59, and ≥60 mg/dL Lp(a). Conclusions: While angioplasty is an effective therapy for ED of arterial origin in patients with obstruction of erection-related arteries, Lp(a) does not seem to play a major role for clinical outcomes in these patients.

Frequency and anatomic distribution of arterial obstructions in patients with vasculogenic erectile dysfunction not responding to intracavernous prostaglandin.

Background: The extent of arterial disease in patients with erectile dysfunction (ED) non-responsive to intracavernosal injection of Alprostadil is of importance for therapeutic options. However, published evidence, in particular angiographically validated is scarce. Here we investigated arterial lesion patterns in this specific patient cohort by selective angiography. Patients and methods: A cohort of 239 patients received a clinical and duplex-sonographic workup for ED of suspected vascular origin. Duplex ultrasound of the cavernosal arteries was performed after intracavernosal injection of 10 µg Alprostadil. Consequently, standardized workup included grading of the erectile and determination of peak systolic velocity (PSV) and end-diastolic velocity (EDV) in both cavernosal arteries. PSV-values below 30 cm/sec indicated reduced arterial flow, whereas EDV-values above 15 cm/sec indicated a venous leak of the pudendal veins. All patients with suspected arterial ED based on duplex sonography underwent contrast-enhanced computed tomography. Endovascular therapy was carried out in ED patients not responsive or with significant side effects to PDE-5-inhibitors or Alprostadil by selective angiographic depiction of erection-related arteries. Results: 54 patients with a mean age of 61.2 (±9.8) years underwent angioplasty of erectionr elated arteries. Out of these 48/54 (89%) patients presented with an erection considered insufficient for penetration (E0-E3) subsequent to intracavernous application of 10 µg Alprostadil. 14/48 (29%) patients had bilateral arterial obstructions and 34/48 (71%) had unilateral disease. Commonly affected was the internal pudendal artery (n = 31, 65%), followed closely by the common penile artery (n = 30, 64%). The least affected arteries were the dorsal penile (n = 6, 13%), hypogastric (n = 4, 8%), common iliac (n = 4, 8%), cavernosal (n = 4, 8%), and inferior gluteal (n = 1, 2%) arteries. Conclusions: Arterial obstructions amenable to endovascular revascularization are frequent in patients non-responsive to intracavernosal prostaglandin administration. Therapeutic strategies in ED patients non-responsive to conservative measures should therefore consider endovascular treatment opportunities.

Demographic and procedural characteristics in the RECording COurses of vasculaR Diseases (RECCORD) registry - the first 1000 patients.

Background: The RECcording COurses of vasculaR Diseases (RECCORD) registry established by the German Society of Angiology - Society for Vascular Medicine aimed to address the lack in contemporary real-world data regarding current practice of medical and interventional care in vascular patients. We herein report the demographic and procedural characteristics of the first 1000 patients undergoing endovascular revascularization (EVR) for symptomatic peripheral artery disease (PAD). Patients and methods: RECCORD is an observational, prospective, multicenter, all-comers registry. Only patients undergoing EVR for symptomatic PAD are included and followed up for at least 1 year. Demographic characteristics, comorbidities, previous peripheral vascular interventions, medication, clinical stage of lower extremity artery disease (Rutherford category), hemodynamic parameters, and procedural data including complications are recorded via an entirely web-based platform. Results: Of the first 1000 patients (mean age 70 ± 10 years, 35% female) with 1096 EVR at 1477 vascular segments of the lower extremities, 25.0% were at the stage of chronic limb threatening ischemia (CLTI) and 75.0% at non-CLTI. The femoropopliteal segment was the dominant target lesion site (61.0%), followed by iliac (26.4%) and below-the-knee EVR (10.3%). Only angioplasty was performed in 130 EVR (11.9%), adjunctive drug coated balloons (DCB) in 498 (45.4%), additional stenting in 633 (57.8%). Debulking devices were used in 106 (9.7%) EVR. Clinical (Rutherford categories) and hemodynamic parameters (ankle-brachial-index) as well as secondary preventive medication were significantly improved post EVR. Periprocedural complications occurred in 63 (5.7%) EVR with pseudoaneurysm as the leading complication type in 26 (2.4%) EVR. Conclusions: The baseline data of the first 1000 patients from the RECCORD registry representing the real-world setting illustrate that the majority of EVR are performed in patients with claudication. Adjunctive use of DCB and stenting are the dominant types of EVR, while periprocedural complications are at an acceptable low rate.

Treatment of the antiphospholipid syndrome with direct oral anticoagulantsPosition statement of German societies.

The antiphospholipid-syndrome (APS) is one of the most severe forms of thrombophilia, which may not only lead to recurrent venous but also to arterial thromboembolic events (TE), and to severe pregnancy complications, respectively. APS is defined by clinical symptoms and specific laboratory findings: 1. Lupus anticoagulant (LA), 2. anticardiolipin-antibodies (ACA), and 3. ß2-Glycoprotein I-antibodies (ß2GPI-Ab). All test results have to be confirmed after at least 12 weeks. The thrombotic risk is highest, if all 3 test groups are positive. It must be pointed out that the presence of UFH, VKA or DOACs may lead to false positive LA-test results; the addition of a specific absorber after blood sampling may provide reliable results in the presence of DOACs. A prospective randomized controlled trial comparing warfarin and rivaroxaban (TRAPS-trial) including only high-risk patients with triple positive APS was terminated early because of an increased rate of TE in patients treated with rivaroxaban [19 %, mostly arterial, compared to 3 % with warfarin (HR 7.4;1.7-32.9)]. Subsequently, a warning letter was issued by the pharmaceutical manufacturers of DOACs, including a warning of DOAC use in APS-patients, particularly in triple-positive high-risk patients. Conclusions: 1. Clinical suspicion of APS requires careful diagnostic testing. Because of inadequate diagnostic workup, many patients may not even have an APS, and these patients could be adequately treated with a DOAC. 2. Patients with single or double positive antiphospholipid antibodies but without positive LA may have a comparably low thrombotic risk and may also be treated with a DOAC in venous TE - sufficient evidence for that conclusion is not yet available but is suggested by the results of meta-analyses. 3. Triple positive patients or those with APS who suffered from arterial thromboembolism have a very high recurrence risk of thrombosis; the TRAPS-Study shows that these patients should be treated with VKA instead of a DOAC.

Endothelial progenitor cells as a biological marker of peripheral artery disease.

The role of endothelial progenitor cells (EPCs) in peripheral artery disease (PAD) remains unclear. We hypothesized that EPC mobilization and function play a central role in the development of endothelial dysfunction and directly influence the degree of atherosclerotic burden in peripheral artery vessels. The number of circulating EPCs, defined as CD34(+)/KDR(+) cells, were assessed by flow cytometry in 91 subjects classified according to a predefined sample size of 31 non-diabetic PAD patients, 30 diabetic PAD patients, and 30 healthy volunteers. Both PAD groups had undergone endovascular treatment in the past. As a functional parameter, EPC colony-forming units were determined ex vivo. Apart from a broad laboratory analysis, a series of clinical measures using the ankle-brachial index (ABI), flow-mediated dilatation (FMD) and carotid intima-media thickness (cIMT) were investigated. A significant reduction of EPC counts and proliferation indices in both PAD groups compared to healthy subjects were observed. Low EPC number and pathological findings in the clinical assessment were strongly correlated to the group allocation. Multivariate statistical analysis revealed these findings to be independent predictors of disease appearance. Linear regression analysis showed the ABI to be a predictor of circulating EPC number (p=0.02). Moreover, the functionality of EPCs was correlated by linear regression (p=0.017) to cIMT. The influence of diabetes mellitus on EPCs in our study has to be considered marginal in already disease-affected patients. This study demonstrated that EPCs could predict the prevalence and severity of symptomatic PAD, with ABI as the determinant of the state of EPC populations in disease-affected groups.

Venous thrombosis following endovenous laser ablation with and without thromboprophylaxis.

OBJECTIVE: Venous thromboembolism (VTE) occurs infrequently after endovenous laser ablation (EVLA). The purpose of this study was to assess the incidence of VTE after EVLA with and without pharmacologic prophylaxis. METHODS: From October 2019 to March 2020, a series of consecutive patients from the prospectively maintained VEINOVA (vein occlusion with various techniques) registry was retrospectively analyzed. All the patients underwent EVLA with and without postoperative thromboprophylaxis. A 1470-nm laser wavelength with a radial fiber was used for EVLA. Concomitant phlebectomy or sclerotherapy of insufficient tributaries was allowed. Perivenous tumescence was applied with 1% Rapidocaine (lidocaine hydrochloride monohydrate; Sintetica SA). Ablation of varicose veins was performed by continuously drawing back the laser fiber at a power of 10 W, aiming for a linear endovenous energy delivery of 60 to 90 J/cm. Compression stockings were applied postoperatively, and the patients were advised to wear them for 1 week. Duplex ultrasound was performed at the 1- and 4-week follow-up visits to determine the occlusion rate and the occurrence of EHIT and VTE. RESULTS: Overall, 249 patients were identified from the registry. Of the 249 patients, 26 were omitted because of treatment of recurrent varicose veins. Finally, 223 consecutive patients with 223 legs and 227 saphenous veins (159 great saphenous veins, 49 small saphenous veins, and 19 anterior accessory saphenous veins) were included in the final analysis. Their mean age was 58.1 ± 13.8 years, and 167 patients (73.1%) were women. The clinical CEAP (clinical, etiology, anatomy, pathophysiology) classification was C2 for 11 legs (4.9%), C3 for 123 legs (55.2%), C4a or C4b for 86 legs (38.6%), and C5 to C6 for 3 legs (1.4%). Thromboprophylaxis was given to 132 patients (59.2%) for 3 days (rivaroxaban 10 mg once daily to 130 patients [98.5%] and low-molecular-weight heparin to 2 patients [1.5%]). No thromboprophylaxis was administered to 91 patients (40.8%) after EVLA. The average treatment length was 34.2 ± 19.3 cm and the average diameter was 5.0 ± 1.3 mm. At 1 week of follow-up, no thrombotic event had occurred in either group. At 4 weeks of follow-up, one case of EHIT class 2 (1.1%) and one case of pulmonary embolism (1.1%) had occurred in the group without thromboprophylaxis. In the thromboprophylaxis group, one deep vein thrombosis (0.8%) event had occurred (adjusted P = .135). At 1 and 4 weeks of follow-up, the treated varicose veins remained occluded in both groups. CONCLUSIONS: Endovenous ablation of truncal varicose veins appears to be safe with a low thrombotic event rate with or without pharmacologic thromboprophylaxis. However, more data are needed before a final recommendation regarding the best thromboprophylaxis treatment option can be given.

Infrapopliteal lesion morphology in patients with critical limb ischemia: implications for the development of anti-restenosis technologies.

PURPOSE: To angiographically evaluate infrapopliteal arterial lesion morphology in a consecutive series of patients presenting with critical limb ischemia (CLI) and undergoing infrapopliteal angioplasty. METHODS: A prospective analysis was undertaken of a consecutive series of CLI patients undergoing endovascular therapy in a tertiary referral center in the year 2011. Morphological assessment of baseline angiograms obtained prior to revascularization included lesion length, assessment of calcification using a semi-quantitative scoring system, and reference vessel diameter (RVD) measurement. Delta RVDs were assessed subtracting distal RVDs from proximal RVDs. A total of 197 infrapopliteal lesions in 105 CLI patients (n=106 limbs) were assessed. Of these, 136 lesions were treated by endovascular means. RESULTS: The average length of treated lesions was 87.1±43.8 mm in stenoses and 124.0±78.3 mm in chronic occlusions (p<0.001). Mean RVD proximal to the lesions was 1.88 mm whereas it was 1.66 mm distal to the lesions (p≤0.03). Mean arterial calcification was 1.15. CONCLUSION: This prospective angiographic series underlines the complex nature and extensive longitudinal involvement of infrapopliteal lesions in CLI patients. These findings should be taken into consideration for anti-restenosis concepts in this challenging subgroup of peripheral artery disease patients.

Erectile dysfunction: role of computed tomography cavernosography in the diagnosis and treatment planning of venous leak.

BACKGROUND: Venous leak appears to be the most common cause of vasculogenic erectile dysfunction (ED), which can be treated with venous embolization. Traditionally, conventional cavernosography was used for the diagnosis and treatment planning of venous leak. Recently, computed tomography (CT) cavernosography was introduced as a novel cross-sectional imaging method proposed to be advantageous over conventional cavernosography. We created a novel management algorithm for diagnosing venous leak including CT cavernosography as an imaging modality. In order to provide a broader basis for our management algorithm, a systematic literature review was conducted. MAIN BODY: In this article we systematically review relevant literature on using CT cavernosography for the diagnosis and treatment planning in ED patients with venous leak following the PRISMA selection process. Nine full-text articles were included in the review and assigned a level of evidence grade (all grade II). Two studies (2/9) compared the results of conventional cavernosography with those of CT cavernosography which was superior for site-specific venous leak identification (19.4% vs. 100%, respectively). CT cavernosography is a more detailed imaging method that is faster to perform, exposes the patient to less radiation, and requires less contrast material. In one study (1/9), CT cavernosography was used for diagnostic purposes only. Eight studies (8/9) cover both, diagnostic imaging and treatment planning including embolization (1/9) and sclerotherapy (2/9) of venous leak in patients with venogenic ED. Three studies (3/9) describe anatomical venous leak classifications that were established based on CT cavernosography findings for accurate mapping of superficial and/or deep venous leak and identification of mixed or more complex forms of venous leak present in up to 84% of patients. In addition to treatment planning, one study (1/9) used CT cavernosography also for follow-up imaging post treatment. CONCLUSION: CT cavernosography is superior to conventional cavernosography for diagnosis and treatment planning in patients with ED caused by venous leak (grade II levels of evidence). Consequently, CT cavernosography should be included in management algorithms for ED patients with suspected venous leak.

Streptococcus pneumoniae serotype 1 capsular polysaccharide induces CD8CD28 regulatory T lymphocytes by TCR crosslinking.

Zwitterionic capsular polysaccharides (ZPS) of commensal bacteria are characterized by having both positive and negative charged substituents on each repeating unit of a highly repetitive structure that has an alpha-helix configuration. In this paper we look at the immune response of CD8(+) T cells to ZPSs. Intraperitoneal application of the ZPS Sp1 from Streptococcus pneumoniae serotype 1 induces CD8(+)CD28(-) T cells in the spleen and peritoneal cavity of WT mice. However, chemically modified Sp1 (mSp1) without the positive charge and resembling common negatively charged polysaccharides fails to induce CD8(+)CD28(-) T lymphocytes. The Sp1-induced CD8(+)CD28(-) T lymphocytes are CD122(low)CTLA-4(+)CD39(+). They synthesize IL-10 and TGF-beta. The Sp1-induced CD8(+)CD28(-) T cells exhibit immunosuppressive properties on CD4(+) T cells in vivo and in vitro. Experimental approaches to elucidate the mechanism of CD8(+) T cell activation by Sp1 demonstrate in a dimeric MHC class I-Ig model that Sp1 induces CD8(+) T cell activation by enhancing crosslinking of TCR. The expansion of CD8(+)CD28(-) T cells is independent, of direct antigen-presenting cell/T cell contact and, to the specificity of the T cell receptor (TCR). In CD8(+)CD28(-) T cells, Sp1 enhances Zap-70 phosphorylation and increasingly involves NF-kappaB which ultimately results in protection versus apoptosis and cell death and promotes survival and accumulation of the CD8(+)CD28(-) population. This is the first description of a naturally occurring bacterial antigen that is able to induce suppressive CD8(+)CD28(-) T lymphocytes in vivo and in vitro. The underlying mechanism of CD8(+) T cell activation appears to rely on enhanced TCR crosslinking. The data provides evidence that ZPS of commensal bacteria play an important role in peripheral tolerance mechanisms and the maintenance of the homeostasis of the immune system.

Basic control of reperfusion effectively protects against reperfusion injury in a realistic rodent model of acute limb ischemia.

BACKGROUND: Reperfusion injury is insufficiently addressed in current clinical management of acute limb ischemia. Controlled reperfusion carries an enormous clinical potential and was tested in a new reality-driven rodent model. METHODS AND RESULTS: Acute hind-limb ischemia was induced in Wistar rats and maintained for 4 hours. Unlike previous tourniquets models, femoral vessels were surgically prepared to facilitate controlled reperfusion and to prevent venous stasis. Rats were randomized into an experimental group (n=7), in which limbs were selectively perfused with a cooled isotone heparin solution at a limited flow rate before blood flow was restored, and a conventional group (n=7; uncontrolled blood reperfusion). Rats were killed 4 hours after blood reperfusion. Nonischemic limbs served as controls. Ischemia/reperfusion injury was significant in both groups; total wet-to-dry ratio was 159+/-44% of normal (P=0.016), whereas muscle viability and contraction force were reduced to 65+/-13% (P=0.016) and 45+/-34% (P=0.045), respectively. Controlled reperfusion, however, attenuated reperfusion injury significantly. Tissue edema was less pronounced (132+/-16% versus 185+/-42%; P=0.011) and muscle viability (74+/-11% versus 57+/-9%; P=0.004) and contraction force (68+/-40% versus 26+/-7%; P=0.045) were better preserved than after uncontrolled reperfusion. Moreover, subsequent blood circulation as assessed by laser Doppler recovered completely after controlled reperfusion but stayed durably impaired after uncontrolled reperfusion (P=0.027). CONCLUSIONS: Reperfusion injury was significantly alleviated by basic modifications of the initial reperfusion period in a new in vivo model of acute limb ischemia. With this model, systematic optimizations of according protocols may eventually translate into improved clinical management of acute limb ischemia.

Cell-based therapy facilitates venous thrombus resolution.

Endothelial progenitor cells (EPC) are involved in many healing processes in cardiovascular diseases and can be found in spontaneously resolving venous thrombi. The purpose of the present study was to investigate whether the therapeutic administration of EPC might enhance the resolution of venous thrombi. For this purpose, venous thrombosis was induced in the infrarenal inferior vena cava (IVC) in 28 athymic nude rats. Culture expanded EPC derived from human peripheral blood mononuclear cells were injected intravenously two and four days after thrombus induction. Recanalisation of the IVC and thrombus organisation were assessed by laser Doppler measurements of the blood flow and immunohistochemical detection of endothelialised luminal structures in the thrombus. EPC transplantation resulted in significantly enhanced thrombus neovascularisation (capillary density: 186.6 +/- 26.7/HPF vs. 78 +/- 12.3/HPF, p<0.01; area covered by capillaries: 8.9 +/- 1.7 microm(2) vs. 2.5 +/- 1.3 microm(2), p<0.01) and was accompanied by a substantial increase in intra-thrombus blood flow (perfusion ratio: 0.7 +/- 0.07 vs. 0.3 +/- 0.08, p<0.02). These results were paralleled by augmented macrophage recruitment into resolving thrombi in the animals treated with EPC (39.4 +/- 4.7/HPF vs. 11.6 +/- 1.9/HPF, p<0.01). Our data suggest that EPC transplantation might be of clinical value to facilitate venous thrombus resolution in cases where current therapeutic options have limited success.

Lack of extended venous thromboembolism prophylaxis in high-risk patients undergoing major orthopaedic or major cancer surgery. Electronic Assessment of VTE Prophylaxis in High-Risk Surgical Patients at Discharge from Swiss Hospitals (ESSENTIAL).

Extended pharmacological venous thromboembolism (VTE) prophylaxis beyond discharge is recommended for patients undergoing high-risk surgery. We prospectively investigated prophylaxis in 1,046 consecutive patients undergoing major orthopaedic (70%) or major cancer surgery (30%) in 14 Swiss hospitals. Appropriate in-hospital prophylaxis was used in 1,003 (96%) patients. At discharge, 638 (61%) patients received prescription for extended pharmacological prophylaxis: 564 (77%) after orthopaedic surgery, and 74 (23%) after cancer surgery (p < 0.001). Patients with knee replacement (94%), hip replacement (81%), major trauma (80%), and curative arthroscopy (73%) had the highest prescription rates for extended VTE prophylaxis; the lowest rates were found in patients undergoing major surgery for thoracic (7%), gastrointestinal (19%), and hepatobiliary (33%) cancer. The median duration of prescribed extended prophylaxis was longer in patients with orthopaedic surgery (32 days, interquartile range 14-40 days) than in patients with cancer surgery (23 days, interquartile range 11-30 days; p<0.001). Among the 278 patients with an extended prophylaxis order after hip replacement, knee replacement, or hip fracture surgery, 120 (43%) received a prescription for at least 35 days, and among the 74 patients with an extended prophylaxis order after major cancer surgery, 20 (27%) received a prescription for at least 28 days. In conclusion, approximately one quarter of the patients with major orthopaedic surgery and more than three quarters of the patients with major cancer surgery did not receive prescription for extended VTE prophylaxis. Future effort should focus on the improvement of extended VTE prophylaxis, particularly in patients undergoing major cancer surgery.

Estrogen-mediated endothelial progenitor cell biology and kinetics for physiological postnatal vasculogenesis.

Estrogen has been demonstrated to promote therapeutic reendothelialization after vascular injury by bone marrow (BM)-derived endothelial progenitor cell (EPC) mobilization and phenotypic modulation. We investigated the primary hypothesis that estrogen regulates physiological postnatal vasculogenesis by modulating bioactivity of BM-derived EPCs through the estrogen receptor (ER), in cyclic hormonally regulated endometrial neovascularization. Cultured human EPCs from peripheral blood mononuclear cells (PB-MNCs) disclosed consistent gene expression of ER alpha as well as downregulated gene expressions of ER beta. Under the physiological concentrations of estrogen (17beta-estradiol, E2), proliferation and migration were stimulated, whereas apoptosis was inhibited on day 7 cultured EPCs. These estrogen-induced activities were blocked by the receptor antagonist, ICI182,780 (ICI). In BM transplanted (BMT) mice with ovariectomy (OVX) from transgenic mice overexpressing beta-galactosidase (lacZ) regulated by an endothelial specific Tie-2 promoter (Tie-2/lacZ/BM), the uterus demonstrated a significant increase in BM-derived EPCs (lacZ expressing cells) incorporated into neovasculatures detected by CD31 immunohistochemistry after E2 administration. The BM-derived EPCs that were incorporated into the uterus dominantly expressed ER alpha, rather than ER beta in BMT mice from BM of transgenic mice overexpressing EGFP regulated by Tie-2 promoter with OVX (Tie-2/EGFP/BMT/OVX) by ERs fluorescence immunohistochemistry. An in vitro assay for colony forming activity as well as flow cytometry for CD133, CD34, KDR, and VE-cadherin, using human PB-MNCs at 5 stages of the female menstrual-cycle (early-proliferative, pre-ovulatory, post-ovulatory, mid-luteal, late-luteal), revealed cycle-specific regulation of EPC kinetics. These findings demonstrate that physiological postnatal vasculogenesis involves cyclic, E2-regulated bioactivity of BM-derived EPCs, predominantly through the ER alpha.

In vitro generation of murine myeloid dendritic cells from CD34-positive precursors.

Dendritic cells (DCs) link the innate and adaptive immune system. Currently, murine DCs for cell biology investigations are developed from MHC class II-negative bone marrow (BM) precursor cells, non-depleted BM cells or BM monocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Here we demonstrate an isolation procedure of functionally intact myeloid CD11c(+) CD11b(+) DCs derived from murine CD34-positive precursors. DCs derived from CD34(+) cells show functional internalization, maturation, cytokine secretion, MHC-restricted antigen presentation, and MHCII retrograde transport of antigens from the lysosomes to the cell surface. In comparison to the established method, the advantages of this isolation procedure are a shorter cultivation period, a superior transfection efficiency, the yield of a purer and more homogeneous population of immature DCs, and less consumption of cell culture medium and GM-CSF. The new isolation procedure and the functional quality of CD34(+) cell-derived murine myeloid DCs make them ideally suited for immunology and cell biology studies.

Incidental findings during computed tomographic angiography diagnostic work-up in patients with arteriogenic erectile dysfunction.

AIM: To analyse the incidental findings during computed tomographic angiography (CTA) diagnostic work-up in patients with arteriogenic erectile dysfunction (ED). PATIENTS AND METHODS: The medical records of all patients with suspected arteriogenic ED were entered into a database. Risk factors and underlying comorbidities were also collected. Pathological CTA findings were extracted from the CT readings and entered into the database. Incidental findings on CTA were classified as those requiring immediate medical treatment, requiring deferred medical treatment or of no clinical importance. RESULTS: A total of 200 patients underwent CTA for suspected arteriogenic ED. Mean patient age was 59.6 ± 11.7 years. Of these, 181 patients (90.5%) had obstructions of erection-related arteries. In 168 patients (84.0%), CTA showed multiple incidental pathological findings. Eighty-five of 200 patients (42.5%) exhibited incidental findings requiring immediate further medical workup and/or treatment: coronary artery calcification was diagnosed in 75/200 (37.5%), aorto-iliac aneurysms in 8/200 (4%) of patients and incidentally detected embolism in 1/200 patient. Pancreatic and liver tumours were less frequent (incidence 1.5% and 1%, respectively). Incidental findings requiring deferred medical workup and/or treatment were detected in 175/200 patients (87.5%). The findings with the highest prevalence were liver steatosis followed by colon diverticulosis and prostate hyperplasia. Findings of little to no clinical importance were reported in 117 (58.5%) patients. These included uncomplicated renal cysts, spinal degeneration and renal vascular anomalies. Almost every second patient presenting with ED had an incidental finding which required immediate treatment. CONCLUSIONS: Incidental findings not directly related to ED were common among patients undergoing CTA scans for suspected arterial obstructions. Coronary artery calcification was the leading finding requiring further medical workup and/or treatment. Thus, the benefit of CTA investigations extends beyond the anatomic description of arterial obstructions of erection-related arteries.

Oxidized low density lipoprotein impairs endothelial progenitor cell function by downregulation of E-selectin and integrin alpha(v)beta5.

BACKGROUND: Oxidized low density lipoprotein (oxLDL) has been shown to induce apoptosis and senescence of endothelial progenitor cells (EPC). In the present study, we hypothesized that even sub-apoptotic concentrations of oxLDL impair the angiogenic potential of EPC and investigated if this effect is mediated by affecting adhesion and incorporation. METHODS: A co-culture system of human microvascular endothelial cells and EPC was used to study the effect of sub-apoptotic concentrations of native (nLDL) and oxLDL on cell-cell interaction. The expression and the functional role of angiogenic adhesion molecules and integrins was monitored by FACS and neutralizing assay, respectively. RESULTS: We observed an inhibition of tube formation and impairment of EPC integration into the vascular network of mature endothelial cells by oxLDL. In contrast, nLDL did not affect angiogenic properties of EPC. Incubation of EPC with sub-apoptotic oxLDL concentrations significantly decreased E-selectin and integrin alpha(v)beta(5) expression (37.6% positive events vs. 71.5% and 24.3% vs. 49.9% compared to control culture media without oxLDL). Interestingly, expression of alpha(v)beta(3), VE-cadherin and CD31 remained unchanged. Blocking of E-selectin and integrin alpha(v)beta(5) by neutralizing antibody effectively inhibited adhesion of EPC to differentiated endothelial cells (56.5% and 41.9% of control; p<0.001). CONCLUSION: In conclusion, oxidative alteration of LDL impairs angiogenic properties of EPC at sub-apoptotic levels by downregulation of E-selectin and integrin alpha(v)beta(5), both substantial mediators of EPC-endothelial cell interaction.

Impaired endothelial progenitor cell function predicts age-dependent carotid intimal thickening.

OBJECTIVES: We investigated whether qualitative or quantitative alterations of the endothelial progenitor cell (EPC) pool predict age-related structural vessel wall changes. BACKGROUND: We have previously shown that age-related endothelial dysfunction is accompanied by qualitative rather than quantitative changes of EPCs. Animal studies suggest that impaired EPC functions lead to accelerated arterial intimal thickening. METHODS: Intima-media thickness (IMT) was measured in the common carotid artery in our previously published groups of younger (25 +/- 1 years, n = 20) and older (61 +/- 2 years, n = 20) healthy non-smoking volunteers without arterial hypertension, hypercholesterolemia, and diabetes mellitus. Endothelial progenitor cells (EPCs, KDR(+)/CD34(+) and KDR(+)/CD133(+)) were counted in peripheral blood using flow cytometry. In ex vivo expanded EPCs, the function was determined as chemotaxis to VEGF, proliferation, and survival. RESULTS: We observed thicker IMT in older as compared to younger subjects (0.68 +/- 0.03 mm Vs. 0.48 +/- 0.02 mm, P < 0.001). Importantly, there were significant inverse univariate correlations between IMT, EPC chemotaxis, and survival (r = -0.466 P < 0.05; r = -0.463, P < 0.01). No correlation was observed with numbers of circulating EPCs. Multivariate regression analysis revealed that age, mean arterial pressure and migration of EPCs were independent predictors of IMT (R (2 )= 0.58). CONCLUSION: Impaired EPC function may lead to accelerated vascular remodeling due to chronic impairment of endothelial maintenance.