A proposal for a revision of the phlebographic classification of congenital venous malformations.

Background: Venous malformation (VM) is the most frequent type of congenital vascular malformation. In terms of functional outcome local sclerotherapy remains the most important therapeutic tool. For planning and correct estimation and prevention of complications, an exact anatomical classification of the VM is crucial. Not only the drainage, as assessed in the established classification, but also the phlebographic aspect of the internal VM structure itself plays a decisive role. In order to integrate this aspect, we aim to validate a proposal for a revised phlebographic VM classification distinguishing non-lacunar (a) and lacunar (b) types. Methods: We retrospectively analyzed all patients with VM in whom a direct puncture phlebography was performed in our clinic between 2009 and 2018 to assess morphology and flow characteristics. Phlebographic assessment included: (I) differentiation of non-lacunar vs. lacunar type; (II) drainage assignment according to the existing classification; (III) adjusted classification combining both. Inter-reader agreement was measured in percentage as well as by the Cohen's kappa coefficient (κ). Results: Overall 26 patients were classified as non-lacunar (a) and 41 patients as lacunar (b) VM. For this categorization, inter-reader agreement was 96% (κ=0.91). Classical Puig classification into types I, II, III and IV showed 87% inter-reader agreement (κ=0.78). For the adjusted classification adding the non-lacunar or lacunar characteristic to type I-IV an agreement of 82% (κ=0.77) was achieved. Conclusions: Phlebographic differentiation into non-lacunar and lacunar VM is feasible and reliable to distinguish phenotypic subgroups of patients with VM. We therefore propose to integrate this parameter of the internal VM structure into the existing classification.

The TOPOS study.

Background: We aimed to study the long-term safety and efficacy of oblique venous stents for post-thrombotic syndrome (PTS) with iliac vein compression. Patients and methods: In the multinational, prospective, single-arm TOPOS study, PTS patients scheduled for endovascular therapy with the sinus-Obliquus® stent and optional distal extension with the sinus-Venous® or sinus-XL Flex® stent were enrolled at eight European vascular centres between October 2016 and December 2020. The primary outcome was primary stent patency at 24 months, and secondary outcomes included the clinical course of PTS (Villalta score, revised Venous Clinical Severity Score [rVCSS], Visual Analog Scale [VAS] of pain), quality of life changes (Chronic Venous Insufficiency Quality of Life Questionnaire, CIVIQ-20), and device-related complications. Results: We enrolled 60 patients (mean age 46±15 years, 68% women, 13% active ulcers): 80% required stent extension (70% below the inguinal ligament). The primary patency rate at 24 months was 80.7% (95%CI 68.1-90.0%); it was higher in patients without vs. those with stent extension (90.9% vs. 78.3%, p=.01). Compared to baseline, the Villalta, rVCSS, pain VAS, and CIVIQ-20 decreased by a median of 8 (interquartile range (IQR): 4-11), 5 (IQR: 3-7), 3 (IQR: 2-5), and 17 (IQR: 6-22) points, respectively; p<.001 for all parameters. Overall, 9 events of acute stent occlusion, 4 symptomatic stent stenosis, and 1 pulmonary embolism occurred. We did not observe major bleeding events or contralateral thrombosis. Conclusions: Endovascular treatment with the oblique stent and optional stent extension was safe and resulted in high patency rates at 24 months. The reduction in PTS severity was substantial and persisted over 2-year follow-up.

A cost-effective sequencing method for genetic studies combining high-depth whole exome and low-depth whole genome.

Whole genome sequencing (WGS) at high-depth (30X) allows the accurate discovery of variants in the coding and non-coding DNA regions and helps elucidate the genetic underpinnings of human health and diseases. Yet, due to the prohibitive cost of high-depth WGS, most large-scale genetic association studies use genotyping arrays or high-depth whole exome sequencing (WES). Here we propose a cost-effective method which we call "Whole Exome Genome Sequencing" (WEGS), that combines low-depth WGS and high-depth WES with up to 8 samples pooled and sequenced simultaneously (multiplexed). We experimentally assess the performance of WEGS with four different depth of coverage and sample multiplexing configurations. We show that the optimal WEGS configurations are 1.7-2.0 times cheaper than standard WES (no-plexing), 1.8-2.1 times cheaper than high-depth WGS, reach similar recall and precision rates in detecting coding variants as WES, and capture more population-specific variants in the rest of the genome that are difficult to recover when using genotype imputation methods. We apply WEGS to 862 patients with peripheral artery disease and show that it directly assesses more known disease-associated variants than a typical genotyping array and thousands of non-imputable variants per disease-associated locus.

Association of sex and cardiovascular risk factors with atherosclerosis distribution pattern in lower extremity peripheral artery disease.

Objective: Atherosclerosis expression varies across not only coronary, cerebrovascular, and peripheral arteries but also within the peripheral vascular tree. The underlying pathomechanisms of distinct atherosclerosis phenotypes in lower extremity peripheral artery disease (PAD) is poorly understood. We investigated the association of cardiovascular risk factors (CVRFs) and atherosclerosis distribution in a targeted approach analyzing symptomatic patients with isolated anatomic phenotypes of PAD. Methods: In a cross-sectional analysis of consecutive patients undergoing first-time endovascular recanalization for symptomatic PAD, data of patients with isolated anatomic phenotypes of either proximal (iliac) or distal (infrageniculate) atherosclerosis segregation were extracted. We performed a multivariable logistic regression model with backward elimination to investigate the association of proximal and distal PAD with CVRFs. Results: Of the 637 patients (29% females) with endovascular recanalization, 351 (55%) had proximal and 286 (45%) had distal atherosclerosis. Female sex [odds ratio (OR) 0.33, 95% confidence interval (CI) 0.20-0.54, p = 0.01], active smoking (OR 0.16, 95% CI 0.09-0.28, p < 0.001), and former smoking (OR 0.33, 95% CI 0.20-0.57, p < 0.001) were associated with proximal disease. Diabetes mellitus (DM) (OR 3.25, 95% CI 1.93-5.46, p < 0.001), chronic kidney disease (CKD) (OR 1.18, 95% CI 1.08-1.28, p < 0.001), and older age (OR 1.31, 95% CI 1.06-1.61, p = 0.01) were associated with distal disease. Conclusion: Female sex, particularly in the context of smoking, is associated with clinically relevant, proximal atherosclerosis expression. Our additional findings that distal atherosclerosis expression is associated with DM, CKD, and older age suggest that PAD has at least two distinct atherosclerotic phenotypes with sex-specific and individual susceptibility to atherogenic risk factors.

NETs-Induced Thrombosis Impacts on Cardiovascular and Chronic Kidney Disease.

Arterial and venous thrombosis constitute a major source of morbidity and mortality worldwide. Association between thrombotic complications and cardiovascular and other chronic inflammatory diseases are well described. Inflammation and subsequent initiation of thrombotic events, termed immunothrombosis, also receive growing attention but are still incompletely understood. Nevertheless, the clinical relevance of aberrant immunothrombosis, referred to as thromboinflammation, is evident by an increased risk of thrombosis and cardiovascular events in patients with inflammatory or infectious diseases. Proinflammatory mediators released from platelets, complement activation, and the formation of NETs (neutrophil extracellular traps) initiate and foster immunothrombosis. In this review, we highlight and discuss prominent and emerging interrelationships and functions between NETs and other mediators in immunothrombosis in cardiovascular disease. Also, with patients with chronic kidney disease suffering from increased cardiovascular and thrombotic risk, we summarize current knowledge on neutrophil phenotype, function, and NET formation in chronic kidney disease. In addition, we elaborate on therapeutic targeting of NETs-induced immunothrombosis. A better understanding of the functional relevance of antithrombotic mediators which do not increase bleeding risk may provide opportunities for successful therapeutic interventions to reduce thrombotic risk beyond current treatment options.

Sex-specific and hormone-related differences in vascular remodelling in atherosclerosis.

Atherosclerosis, a lipid-driven inflammatory disease, is the main underlying cause of cardiovascular diseases (CVDs) both in men and women. Sex-related dimorphisms regarding CVDs and atherosclerosis were observed since more than a decade ago. Inflammatory mediators such as cytokines, but also endothelial dysfunction, vascular smooth muscle cell migration and proliferation lead to vascular remodelling but are differentially affected by sex. Each year a greater number of men die of CVDs compared with women and are also affected by CVDs at an earlier age (40-70 years old) while women develop atherosclerosis-related complications mainly after menopause (60+ years). The exact biological reasons behind this discrepancy are still not well-understood. From the numerous animal studies on atherosclerosis, only a few include both sexes and even less investigate and highlight the sex-specific differences that may arise. Endogenous sex hormones such as testosterone and oestrogen modulate the atherosclerotic plaque composition and the frequency of such plaques. In men, testosterone seems to act like a double-edged sword as its decrease with ageing correlates with an increased risk of atherosclerotic CVDs, while testosterone is also reported to promote inflammatory immune cell recruitment into the atherosclerotic plaque. In premenopausal women, oestrogen exerts anti-atherosclerotic effects, which decline together with its level after menopause resulting in increased CVD risk in ageing women. However, the interplay of sex hormones, sex-specific immune responses and other sex-related factors is still incompletely understood. This review highlights reported sex differences in atherosclerotic vascular remodelling and the role of endogenous sex hormones in this process.

Criteria to predict midterm outcome after stenting of chronic iliac vein obstructions (PROMISE trial).

BACKGROUND: Endovenous stent placement has become a first-line approach to prevent post-thrombotic syndrome in patients with chronic post-thrombotic obstruction (PTO) or nonthrombotic iliac vein lesions if conservative management fails. This study aims to identify factors associated with loss of patency to facilitate patient selection for endovenous stenting. METHODS: We retrospectively analyzed 108 consecutive patients after successful endovenous stenting for chronic vein obstruction performed at a single institution from January 2008 to July 2020. Using multivariable logistic regression, we explored potential predictive factors for loss of stent patency, including baseline demographics, post-thrombotic changes, and peak flow velocities measured in the common femoral vein (CFV), deep femoral vein, and femoral vein (FV) using duplex ultrasound examination. RESULTS: The mean follow-up duration was 41 ± 26 months, and participants had a mean age of 47.4 ± 15.4 years with 46.3% women. Ninety (83.3%) patients had PTO and 18 (16.7%) had nonthrombotic iliac vein lesions, predominantly due to May-Thurner syndrome. Loss of patency occurred in 20 (18.5%) patients, all treated for PTO. Comorbidities, side of intervention, and sex did not differ between patients with occluded and patent stents. Stent occlusion was more common with increasing number of stents implanted (P < .001) and with distal stent extension into and beyond the CFV (P < .001). Preinterventional predictive factors for stent occlusion were lower duplex ultrasound peak velocity in the CFV (odds ratio [OR]: 7.52, 95% confidence interval [CI]: 2.54-22.28; P < .001) and FV (OR: 10.75, 95% CI: 2.07-55.82; P < .005), and post-thrombotic changes in the deep femoral vein (OR: 4.51, 95% CI: 1.53-13.25; P = .006) and FV (OR: 3.62: 95% CI: 1.11-11.84; P = .033). Peak velocities of ≤7 cm/s (interquartile range: 0-20 cm/s) in the CVF and ≤8 cm/s (interquartile range: 5-10 cm/s) in the FV were significantly associated with loss of patency. CONCLUSIONS: Insufficient venous inflow as assessed by low peak velocities in the CFV and FV as well as post-thrombotic findings represent reliable risk predictors for stent occlusions, warranting their inclusion into the decision-making process for invasive treatment of PTO.

Efficacy of a Drug-Eluting Stent Versus Bare Metal Stents for Symptomatic Femoropopliteal Peripheral Artery Disease: Primary Results of the EMINENT Randomized Trial.

BACKGROUND: A clear patency benefit of a drug-eluting stent (DES) over bare metal stents (BMSs) for treating peripheral artery disease of the femoropopliteal segment has not been definitively demonstrated. The EMINENT study (Trial Comparing Eluvia Versus Bare Metal Stent in Treatment of Superficial Femoral and/or Proximal Popliteal Artery) was designed to evaluate the patency of the Eluvia DES (Boston Scientific, Marlborough, MA), a polymer-coated paclitaxel-eluting stent, compared with BMSs for the treatment of femoropopliteal artery lesions. METHODS: EMINENT is a prospective, randomized, controlled, multicenter European study with blinded participants and outcome assessment. Patients with symptomatic peripheral artery disease (Rutherford category 2, 3, or 4) of the native superficial femoral artery or proximal popliteal artery with stenosis ≥70%, vessel diameter of 4 to 6 mm, and total lesion length of 30 to 210 mm were randomly assigned 2:1 to treatment with DES or BMS. The primary effectiveness outcome was primary patency at 12 months, defined as independent core laboratory-assessed duplex ultrasound peak systolic velocity ratio ≤2.4 in the absence of clinically driven target lesion revascularization or surgical bypass of the target lesion. Primary sustained clinical improvement was a secondary outcome defined as a decrease in Rutherford classification of ≥1 categories compared with baseline without a repeat target lesion revascularization. Health-related quality of life and walking function were assessed. RESULTS: A total of 775 patients were randomly assigned to treatment with DES (n=508) or commercially available BMSs (n=267). Baseline clinical, demographic, and lesion characteristics were similar between the study groups. Mean lesion length was 75.6±50.3 and 72.2±47.0 mm in the DES and BMS groups, respectively. The 12-month incidence of primary patency for DES treatment (83.2% [337 of 405]) was significantly greater than for BMS (74.3% [165 of 222]; P<0.01). Incidence of primary sustained clinical improvement was greater among patients treated with the DES than among those who received a BMS (83.0% versus 76.6%; P=0.045). The health-related quality of life dimensions of mobility and pain/discomfort improved for the majority of patients in both groups (for 66.4% and 53.6% of DES-treated and for 64.2% and 58.1% of BMS-treated patients, respectively) but did not differ significantly. At 12 months, no statistical difference was observed in all-cause mortality between patients treated with the DES or BMS (2.7% [13 of 474] versus 1.1% [3 of 263]; relative risk, 2.4 [95% CI, 0.69-8.36]; P=0.15). CONCLUSIONS: By demonstrating superior 1-year primary patency, the results of the EMINENT randomized study support the benefit of using a polymer-based paclitaxel-eluting stent as a first-line stent-based intervention for patients with symptomatic peripheral artery disease attributable to femoropopliteal lesions. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02921230.

Upside-down positioning of a peri-interventional cava filter during endovascular thrombectomy of a septic superior vena cava thrombosis.

A 43-year-old male patient with advanced colon carcinoma presented with disseminated staphylococcus aureus bacteremia and central venous catheter associated septic thrombosis of the superior vena cava. Despite appropriate antimicrobial therapy and surgical debridement of distant foci, bacteremia persisted, so an endovascular thrombectomy was performed. Contrary to the usual application, the Capturex® peri-interventional cava filter was positioned upside down, in the direction of the blood flow, in the superior vena cava to prevent septic embolism during mechanical thrombectomy. The wall-adherent septic thrombus was mechanically detached using a RAT fragmentation basket® followed by Aspirex® rotational thrombectomy. Final phlebography showed complete thrombus removal. Small thrombus fragments could be demonstrated in the filter after retrieval. The adapted technique of a reverse positioning of the Capturex® filter in the superior vena cava seems feasible and effective.

Cone-Beam CT-assisted navigation for endovascular treatment of erection-related artery stenosis in patients with erectile dysfunction.

BACKGROUND: Angioplasty and stenting have emerged as endovascular treatment options for arteriogenic erectile dysfunction over the past few years. Considerable anatomical variation of the erection related pelvic arteries can be challenging during these procedures, leading to time-consuming repetitive super-selective angiograms for navigation. TECHNIQUE: We report a novel technique of using C-arm Cone-Beam CT and vessel navigation software to facilitate super-selective catheterization. CONCLUSION: Cone-Beam CT-guided navigation for vascular assessment of arteriogenic ED is an optional approach compared to exclusive angiographic assessment. Compared to CT angiography, C-arm Cone-Beam CT offers benefits regarding usage of contrast media and radiation exposure. It has the advantage to combine imaging with endovascular procedures in a single session, reduces time to target navigation in complex pelvic arteries anatomy and may increase therapy safety in endovascular treatment of ED.

Preoperative Factors Associated with Target Lesion Revascularization following Endovascular Therapy of the Superficial Femoral Artery.

Objectives: In patients with symptomatic peripheral arterial occlusive disease (PAOD), endovascular revascularization of the superficial femoral artery (SFA) is the most frequent intervention. A major drawback of endovascular procedures is clinically driven target lesion revascularization (CD-TLR), which may cause recurrence of symptoms, re-hospitalizations, and re-interventions. Outcome studies comparing endovascular modalities are heterogeneous and focus more on intraoperative rather than preoperative aspects. Studies have not examined potential risk factors in patients' phenotype before an intervention to prevent CD-TLR. Design: Monocentric, retrospective cohort study of 781 patients with symptomatic PAOD referred to an endovascular intervention of the SFA between 2000 and 2018. Methods: The study aim was to identify risk factors and phenotypes leading to symptomatic PAOD in patients with de novo lesions of the SFA and ≥1 CD-TLR within 12 months post-index procedure. Two groups were differentiated: patients without CD-TLR and with ≥1 CD-TLR. Patient phenotype was compared for cardiovascular (CV) risk factors, age, gender, and renal function. Results: 662 patients (84.8%) (age 73.5 ± 11.2 years; 243 women (36.7%)) with no CD-TLR were compared to 119 patients (15.2%) with ≥1 CD-TLR (age 70.9 ± 12.4 years; 55 women (46.2%)). Women, as well as subjects with dyslipidemia, had each a 1.8-time higher odds ratio of receiving multiple interventions within one year than men or subjects without dyslipidemia. Older subjects (per decade) had a lower odds ratio (0.7) for multiple interventions. Subjects with an eGFR (estimated glomerular filtration rate) <30 mL/min had 3.8 times higher and subjects with eGFR ≥30 and <60 mL/min had a 2.4 higher odds ratio of receiving multiple interventions than subjects with eGFR values ≥90 mL/min. Conclusion: Our data indicate that younger women, patients with dyslipidemia, or those with renal insufficiency are at risk for recurrent midterm CD-TLR after endovascular therapy of the SFA.

Inflammatory Mediators in Atherosclerotic Vascular Remodeling.

Atherosclerotic vascular disease remains the most common cause of ischemia, myocardial infarction, and stroke. Vascular function is determined by structural and functional properties of the arterial vessel wall, which consists of three layers, namely the adventitia, media, and intima. Key cells in shaping the vascular wall architecture and warranting proper vessel function are vascular smooth muscle cells in the arterial media and endothelial cells lining the intima. Pathological alterations of this vessel wall architecture called vascular remodeling can lead to insufficient vascular function and subsequent ischemia and organ damage. One major pathomechanism driving this detrimental vascular remodeling is atherosclerosis, which is initiated by endothelial dysfunction allowing the accumulation of intimal lipids and leukocytes. Inflammatory mediators such as cytokines, chemokines, and modified lipids further drive vascular remodeling ultimately leading to thrombus formation and/or vessel occlusion which can cause major cardiovascular events. Although it is clear that vascular wall remodeling is an elementary mechanism of atherosclerotic vascular disease, the diverse underlying pathomechanisms and its consequences are still insufficiently understood.

Catheter-Directed Thrombolysis for Postpartum Deep Venous Thrombosis.

Venous thromboembolism is a major concern during pregnancy as well as in the postpartum period. In acute proximal deep venous thrombosis, endovascular recanalization with locally administered thrombolytic agents has evolved as therapeutic alternative to anticoagulation alone. However, data on the bleeding risk of thrombolysis in the postpartum period is limited. We addressed the key clinical question of safety outcomes of catheter-directed thrombolysis (CDT) in the peri- and postpartum period. Therefore, we performed a non-exhaustive literature review and illustrated the delicate management of a patient with postpartum acute iliofemoral thrombosis treated with CDT and endovascular revascularization with thrombectomy, balloon angioplasty and stenting.

Cost-effectiveness analysis of alternative anticoagulation in suspected heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a life-threatening complication associated with high medical costs. Factor Xa inhibitors gradually replace approved treatment with intravenous direct thrombin inhibitors despite their off-label indication, because of easier management and favorable economic profile. Whether they are cost-effective remains unclear. We evaluated the cost-effectiveness of approved and off-label anticoagulants in patients with suspected HIT, based on census data from the largest Swiss hospital between 2015 and 2018. We constructed a decision tree model that reflects important clinical events associated with HIT. Relevant cost data were obtained from the finance department or estimated based on the Swiss-wide cost tariff. We estimated averted adverse events (AEs) and incremental cost-effectiveness ratio as primary outcome parameters. We performed deterministic and probabilistic sensitivity analyses with 2000 simulations to assess the robustness of our results. In the base-case analysis, the total cost of averting 1 AE was 49 565 Swiss francs (CHF) for argatroban, 30 380 CHF for fondaparinux, and 30 610 CHF for rivaroxaban; after adjusting for 4Ts score: 41 152 CHF (argatroban), 27 710 CHF (fondaparinux), and 37 699 CHF (rivaroxaban). Fondaparinux and rivaroxaban were more clinically effective than argatroban, with AEs averted of 0.820, 0.834, and 0.917 for argatroban, fondaparinux, and rivaroxaban, respectively. Treatment with fondaparinux resulted in less cost and more AEs averted, hence dominating argatroban. Results were most sensitive to AE rates and prolongation of stay. Monte Carlo simulations affirmed our base-case analysis. This is the first cost-effectiveness analysis comparing argatroban with fondaparinux and rivaroxaban using primary data. Fondaparinux and rivaroxaban resulted in more averted AEs, but fondaparinux had greater cost savings. Fondaparinux could be a viable alternative to argatroban.

Comprehensive review with pooled analysis on external and internal jugular vein aneurysm.

OBJECTIVE: The aim of the present comprehensive review was to present an overview of the clinical presentation and treatment options for external (EJVAs) and internal jugular vein aneurysms (IJVAs) to help clinicians in evidence-based decision making. METHODS: A systematic literature search was conducted in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) statement and included MEDLINE, Embase, Cochrane Library, Scopus, WHO (World Health Organization) trial register, ClinicalTrials.gov, and the LIVIVO search portal. The inclusion criteria were studies of patients who had presented with IJVAs or EJVAs. The exclusion criteria were animal and cadaver studies and reports on interventions using the healthy jugular vein for access only (ie, catheterization). Analysis of the pooled data from all eligible case reports was performed. RESULTS: From 1840 identified reports, 196 studies were eligible. A total of 256 patients with JVAs were reported, with 183 IJVAs and 73 EJVAs. IJVAs were reported to occur in 66% on the right side compared with the left side (P = .011). The patients with IJVAs were mostly children (median age, 12 years; interquartile range, 5.8-45.2 years). The patients with EJVAs were young adults (median age, 30 years; interquartile range, 11.0-46.5 years). EJVAs were more frequently reported in women and IJVAs in men (P = .008). Most of the patients were asymptomatic. Pulmonary embolization in association with thrombosed EJVAs was only reported for one patient. A report of the outcomes after surgery and conservative management was missing for ∼50% of the patients. No relevant complications were reported after ligation of the EJVA without reconstruction. Intracranial hypertension after ligation of the right-sided IJVA was reported in three children; in one of them, a pontine infarction was observed. CONCLUSIONS: JVAs are a disease of the younger population but can occur at any age. It seems to be safe to observe patients with nonthrombosed JVAs. However, in the presence of thrombus or pulmonary embolization, surgical treatment should be considered. A reconstruction technique of the IJVA with venous patency preservation should be preferred.

Clinical presentation of simple and combined or syndromic arteriovenous malformations.

OBJECTIVE: Arteriovenous malformations of the lower extremities (AVMLE) can present as simple or complex combined or syndromic forms (eg, Parkes Weber Syndrome). We aimed to characterize the differences in clinical presentation and natural history of these potentially life- and limb-threatening congenital vascular malformations. METHODS: We conducted a retrospective analysis of a consecutive series of patients with AVMLE who presented to a tertiary referral center in Switzerland between 2008 and 2018. Clinical baseline characteristics, D-dimer level, and course were summarized and differences between simple, non-syndromic and combined or syndromic AVMLE determined. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. RESULTS: Overall, 506 patients were prospectively enrolled in the Bernese Congenital Vascular Malformation Registry, 31 (6%) with AVMLE. There were 16 women and 15 men, with a mean age of 18 years at first diagnosis (range, 1 month to 72 years). Simple AVMLE was present in 22 (71%) and combined or syndromic AVMLE with limb overgrowth in 9 patients (29%), respectively. Common symptoms and signs were pain (n = 25; 81%), swelling (n = 21; 68%), and soft tissue hypertrophy (n = 13; 42%). Among combined or syndromic patients, three patients died from wound infection with sepsis or disseminated intravascular coagulation with bleeding complications (intracranial hemorrhage and bleeding from extensive leg ulcers). Combined or syndromic patients presented more often with bleeding (67% vs 5%; P < .001), malformation-related infection (44% vs 5%; P = .017) and leg length difference (56% vs 14%; P = .049). D-dimer levels were elevated (mean, 17,256 µg/L; range, 1557-80,000 µg/L) and angiographic appearance showed complex, mixed type of AVMs, including interstitial type IV, in all patients with combined or syndromic AVMLE. CONCLUSIONS: Patients with congenital simple AVMLE most often present with benign clinical features and rarely with complications related to hemodynamic changes. Patients with combined or syndromic AVMLE often face serious outcomes dominated by complications other than direct high-flow-related heart failure.

Ionic and non-ionic intravenous X-ray contrast media: antibacterial agents?

X-ray contrast media have been reported to have inhibitory effects on bacterial growth. Despite its potentially beneficial effect on patients, these features of contrast media have received relatively little attention in the medical literature in the past decades. The aim of this review is to evaluate the literature concerning the bactericidal and bacteriostatic effects of X-ray contrast media, specifically if there is a known difference concerning these effects between ionic and non-ionic contrast media. Systematic literature review was performed for the years of publication between 1911 and 2019. Since the publication of Grossich in 1911, the effect of iodine on the treatment of superficial infections in surgical procedures has been established clinical knowledge. Bacteriostatic and bactericidal effects of ionic X-ray contrast media are well established. However, non-ionic contrast agents have been the subject of little research in this respect. In past decades, the hypothesis emerged in the literature that mainly the concentration of free iodine might be responsible for any bacteriostatic or bactericidal effect of ionic X-ray contrast media. Nowadays, however, only non-ionic contrast media are used. The question regarding the mechanism and magnitude of bacteriostatic or bactericidal effects of these, non-ionic contrast media, could not be answered conclusively from this review. Non-ionic contrast media could be used intentionally when a local antibacterial effect is intended (e.g. in percutaneous abscess drainage), as well as to reduce the overall dose of antibiotics administered to a patient. Thus, this question remains relevant and might constitute the area of future research.

Neutrophil Extracellular Traps Affecting Cardiovascular Health in Infectious and Inflammatory Diseases.

Neutrophil extracellular traps (NETs) are web-like structures of decondensed extracellular chromatin fibers and neutrophil granule proteins released by neutrophils. NETs participate in host immune defense by entrapping pathogens. They are pro-inflammatory in function, and they act as an initiator of vascular coagulopathies by providing a platform for the attachment of various coagulatory proteins. NETs are diverse in their ability to alter physiological and pathological processes including infection and inflammation. In this review, we will summarize recent findings on the role of NETs in bacterial/viral infections associated with vascular inflammation, thrombosis, atherosclerosis and autoimmune disorders. Understanding the complex role of NETs in bridging infection and chronic inflammation as well as discussing important questions related to their contribution to pathologies outlined above may pave the way for future research on therapeutic targeting of NETs applicable to specific infections and inflammatory disorders.

Capillary-venule malformation is a microfistulous variant of arteriovenous malformation.

OBJECTIVE: To describe typical clinical presentation of patients with microfistular, capillary-venule (CV) malformation as a variant form of arteriovenous malformations (AVM). METHODS: A retrospective clinical analysis of 15 patients with CV-AVM confirmed by a computational flow model enrolled in a prospective database of patients with congenital vascular malformation between January 2008 and May 2018. RESULTS: The mean age of the patients at first time of presentation was 30 years with balanced sex ratio. Presentation was dominated by soft tissue hypertrophy (n = 12 [80.0%]) and atypical varicose veins (n = 11 [73.3%]). The anatomic location of enlarged varicose veins gave no uniform pattern and did not correspond with the typical picture of primary varicose vein disease. Most often, symptomatic CV-AVM was found at the lower extremities in this series of unselected patients. The most frequent compartment affected was the subcutis (n = 14 [93.3%]), involvement of muscle was recorded in one-third and cutis in one-fourth of patients. CONCLUSIONS: A high grade of clinical suspicion is needed to recognize CV-AVM and to prevent inadequate therapy owing to missed diagnosis.