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.

Energy calibration of high-resolution X-Ray TES microcalorimeters with 3 eV optical photons.

With the improving energy resolution of transitionedge sensor (TES) based microcalorimeters, performance verification and calibration of these detectors has become increasingly challenging, especially in the energy range below 1 keV where fluorescent atomic X-ray lines have linewidths that are wider than the detector energy resolution and require impractically high statistics to determine the gain and deconvolve the instrumental profile. Better behaved calibration sources such as grating monochromators are too cumbersome for space missions and are difficult to use in the lab. As an alternative, we are exploring the use of pulses of 3 eV optical photons delivered by an optical fiber to generate combs of known energies with known arrival times. Here, we discuss initial results of this technique obtained with 2 eV and 0.7 eV resolution X-ray microcalorimeters. With the 2 eV detector, we have achieved photon number resolution for pulses with mean photon number up to 133 (corresponding to 0.4 keV).

Rationale and design of the RECording COurses of vasculaR Diseases registry (RECCORD registry).

BACKGROUND: The prevalence of peripheral artery disease (PAD) is increasing worldwide. Revascularization procedures constitute a cornerstone of the therapy in PAD, not only in critical limb ischaemia but increasingly also in patients with intermittent claudication. The German Society of Angiology - Society for Vascular Medicine is establishing a nationwide, prospective, multicentre registry to address the lack of contemporary real life data regarding current practice of medical and interventional care in vascular patients and its subsequent long-term outcome. PATIENTS AND METHODS: The RECording COurses of vasculaR Diseases registry (RECCORD registry) is an observational, prospective, multicentre, all-comers registry platform. In the initial phase, patients referred for endovascular revascularization of PAD of the lower limbs will be prospectively included and followed up for at least one year. At baseline, data on patients' demographic characteristics, comorbidities, previous peripheral interventions, medication, and clinical stage of PAD (Rutherford category), haemodynamic parameters, and procedural data including complications will be assessed. Major adverse cardiac and limb events will be recorded at planned (at six and 12 months) and at any unplanned visits. The therapeutic management will be exclusively left to the discretion of the vascular specialists. RESULTS AND CONCLUSIONS: The RECCORD registry will provide a comprehensive dataset depicting the current real life practice and outcome of vascular care. The seven predefined quality indicators will be used for benchmarking the participating centres. Moreover, identifying factors promoting a favourable outcome might pave the way for an evidence-based therapeutic strategy and a dedicated therapeutic pathway for patients with PAD including patient-oriented best interventional approaches. In the future, the RECCORD registry may provide a general platform to study the courses of various defined vascular diseases in order to get detailed insights into the real life current practice of health care provided to vascular patients.

Differential impact of diabetes mellitus type II and arterial hypertension on collateral artery growth and concomitant macrophage accumulation.

BACKGROUND: Diabetes mellitus type II and arterial hypertension are major risk factors for peripheral arterial disease and have been considered to reduce collateral growth (arteriogenesis). Collateral growth proceeds through different stages. Vascular proliferation and macrophage accumulation are hallmarks of early collateral growth. MATERIAL AND METHODS: We here compare the impact of arterial hypertension and diabetes mellitus type II on collateral proliferation (Brdu incorporation) and macrophage accumulation (ED 2 staining) as well as collateral vessel function (collateral conductance) in a rat model of peripheral vascular disease (femoral artery occlusion), diabetes mellitus type II (Zucker fatty diabetic rats and Zucker lean rat controls) and arterial hypertension (induced via clip placement around the right renal arteriy). We furthermore tested the impact of monocyte chemoattractant protein-1 (MCP­1) on collateral proliferation and macrophage accumulation in these models RESULTS: Diabetic animals showed reduced vascular proliferation and macrophage accumulation, which however did not translate into a change of collateral conductance. Hypertensive animals on the contrary had reduced collateral conductances without altered macrophage accumulation and only a marginal reduction in collateral proliferation. Infusion of MCP­1 only enhanced vascular proliferation in diabetic animals. CONCLUSIONS: These findings illustrate that impaired monocyte/macrophage recruitment is responsible for reduced collateral growth under diabetic conditions but not in arterial hypertension suggesting that diabetes mellitus in particular affects early stages of collateral growth whereas hypertension has its impact on later remodeling stages. Successful pro-arteriogenic treatment strategies in a patient population that presents with diabetes mellitus and arterial hypertension need to address different stages of collateral growth and thus different molecular and cellular targets simultaneously.

[Interventional therapy of pulmonary embolism - update]. / Interventionelle Therapie der Lungenembolie ­ aktueller Stand.

Several catheter-based systems have been developed for interventional recanalization of pulmonary embolism. These include local ultrasound assisted thrombolysis (EKOS), in-toto-thrombectomy via retriever and aspiration system (FlowTriever) and the Indigo mechanical aspiration system. Safety and efficacy in the removal of thrombus have been demonstrated for all systems. Interventional recanalization strategies for high- and intermediate-high risk pulmonary embolism are potentially more effective in the removal of thrombus and restoration of right heart function than systemic thrombolysis with a lower risk of major bleeding complications. Preliminary data from registries and observational studies are very promising whereas the evidence for systemic thrombolysis treatment in high and intermediate-high risk pulmonary embolism is low. Randomized controlled clinical trials are currently performed comparing catheter based interventional therapies to systemic thrombolysis for the treatment of intermediate-high risk pulmonary embolisms. Primary outcome measurements include mortality, hemodynamic collapse, and major bleedings. Results are expected in 2025. The introduction of interventional therapies for pulmonary embolism was accompanied by an increased awareness of the complexity of pulmonary embolism management. The need for specialized interdisciplinary pulmonary embolism response teams (PERT-teams) and a well-structured approach including a PDCA cycle was recognized.

Acceleration of collateral development by carcinoembryonic antigen-related cell adhesion molecule 1 expression on CD11b/⁺Gr-1⁺ myeloid cells--brief report.

OBJECTIVE: Previously, we demonstrated the relevance for endothelial carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) expression in collateral formation. However, a proarteriogenic role for CEACAM1(+) myeloid cells is unknown. Here, we investigated the contribution of CEACAM1(+) myeloid cells on collateral formation. METHODS AND RESULTS: Collateral growth and vascular remodeling were analyzed in CEACAM1-competent and CEACAM1 null mice after femoral artery ligation in hindlimb ischemia. Reperfusion of the adductor muscles was evaluated by Laser Doppler measurements and microcomputed tomography imaging. In CEACAM1 null mice, poor reperfusion and reduced collateral formation were observed, accompanied by reduction in arterial diameters. Using flow cytometry, we identified an increase of the muscle-resident CD11b(+)/granulocyte receptor-1+ (Gr-1+) population in CEACAM1 null mice only, pointing toward a CEACAM1-dependent functional deviation. Direct and reciprocal bone marrow transplantations between CEACAM1-competent and CEACAM1 null mice, and antibody-mediated depletion of the CD11b(+)/Gr-1(+) population, confirmed the requirement of CEACAM1 expression on the CD11b(+)/Gr-1(+) population for reestablishment of perfusion after arterial occlusion. CONCLUSIONS: CEACAM1 expression on CD11b(+)/Gr-1(+) myeloid cells is a prerequisite for adequate collateral formation.

Description of a new Tiger Snake (Colubridae, Telescopus) from south-western Africa.

Telescopus finkeldeyi sp. nov. is described from western central to northern Namibia and south-western Angola. Its maximum size is less than that of the other three taxa occurring in southern Africa. It is further distinguished by its fairly variable colour pattern. Although the number of ventrals and the undivided anal scale are similar to that of T. beetzii, the presence of 19 scale rows around the middle differs from the 21 rows of T. beetzii.

Unexpected outcome of a sigmoid lesion believed to be malignant.

A 69-year-old male with a past medical history of an Olfactory nerve meningioma and left-sided Bell's palsy presented with 6 weeks of lower abdominal pain and weight loss of 4 kg in 6 months. His current medications included acetylsalicylic acid 80 mg once daily, Amlodipine 5 mg once daily and Allopurinol 300 mg once daily. Physical examination was benign without signs of acute abdomen. The abdomen was nondistended and soft but tender to palpation over the left lower quadrant. Laboratory studies showed no acute outliers. The patient was followed up by his pulmonologist because of thoracic lesions which required a PET-CT for further evaluation. This PET-CT revealed a focal zone of oedematous rectosigmoid colon with a strong suspicion of a semi-circular sigmoid neoplasia with continuation to the bladder (Figure 1a). A presumptive diagnosis of a primary colonic malignancy was made. Colonoscopy was performed and visualised a foreign linear object lodged in both walls of the diverticular sigmoid with surrounding inflammation, but otherwise normal mucosa (Figure 1b). No arguments could be made endoscopically to support the diagnosis of an underlying primary colonic malignancy.

CEACAM1+ myeloid cells control angiogenesis in inflammation.

Local inflammation during cutaneous leishmaniasis is accompanied by accumulation of CD11b(+) cells at the site of the infection. A functional role for these monocytic cells in local angiogenesis in leishmaniasis has not been described so far. Here, we show that CD11b(+) cells express high levels of the myeloid differentiation antigen carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). In experimental cutaneous leishmaniasis in C57BL/6 wild-type (B6.WT) and B6.Ceacam1(-/-) mice, we found that only B6.Ceacam1(-/-) mice develop edemas and exhibit impairment of both hemangiogenesis and lymphangiogenesis. Because CEACAM1 expression correlates with functional angiogenesis, we further analyzed the role of the CD11b(+) population. In B6.Ceacam1(-/-) mice, we found systemic reduction of Ly-6C(high)/CD11b(high) monocyte precursors. To investigate whether CEACAM1(+) myeloid cells are causally related to efficient angiogenesis, we used reverse bone marrow transplants (BMTs) to restore CEACAM1(+) or CEACAM1(-) bone marrow in B6.Ceacam1(-/-) or B6.WT recipients, respectively. We found that angiogenesis was restored by CEACAM1(+) BMT only. In addition, we observed reduced morphogenic potential of inflammatory cells in Matrigel implants in CEACAM1(-) backgrounds or after systemic depletion of CD11b(high) macrophages. Taken together, we show for the first time that CEACAM1(+) myeloid cells are crucial for angiogenesis in inflammation.

Vimentin expression influences flow dependent VASP phosphorylation and regulates cell migration and proliferation.

The cytoskeleton plays a central role for the integration of biochemical and biomechanical signals across the cell required for complex cellular functions. Recent studies indicate that the intermediate filament vimentin is necessary for endothelial cell morphogenesis e.g. in the context of leukocyte transmigration. Here, we present evidence, that the scaffold provided by vimentin is essential for VASP localization and PKG mediated VASP phosphorylation and thus controls endothelial cell migration and proliferation. Vimentin suppression using siRNA technique significantly decreased migration velocity by 50% (videomicroscopy), diminished transmigration activity by 42.5% (Boyden chamber) and reduced proliferation by 43% (BrdU-incorporation). In confocal microscopy Vimentin colocalized with VASP and PKG in endothelial cells. Vimentin suppression was accompanied with a translocation of VASP from focal contacts to the perinuclear region. VASP/Vimentin and PKG/Vimentin colocalization appeared to be essential for proper PKG mediated VASP phosphorylation because we detected a diminished expression of PKG and p(Ser239)-VASP in vimentin-suppressed cells, Furthermore, the induction of VASP phosphorylation in perfused arteries was markedly decreased in vimentin knockout mice compared to wildtypes. A link is proposed between vimentin, VASP phosphorylation and actin dynamics that delivers an explanation for the important role of vimentin in controlling endothelial cell morphogenesis.

Bifurcation of the main pancreatic duct in the body of the pancreas. Two case reports and literature study of a rare anatomical variant of the pancreatic duct.

INTRODUCTION: Bifurcation of the pancreatic duct is a very rare anomaly and clinical significance is not known. Literature on this topic is scarce. We present two similar case reports with bifurcation of the main pancreatic duct from the body to the tail of the pancreas. Both cases were symptomatic, one had acute pancreatitis and the other recurrent pancreatitis. In both cases the most ventral duct was aberrant as a consequence of pancreatitis. DISCUSSION: We performed a literature study and found 22 relevant articles containing 26 case reports, of these cases, 12 were considered asymptomatic and were found incidentally, the other 14 cases were symptomatic with signs of acute, chronic or recurrent pancreatitis. To our knowledge this is the first article with a summary of previous published data on the subject. CONCLUSION: Bifurcation of the pancreatic duct seems to be a possible cause of pancreatitis, but a large group remains asymptomatic. Since diagnosis is often difficult, the incidence is probably underestimated. More attention to this anomaly is recommended. Further reports are needed to draw conclusion.

Transjugular intrahepatic portosystemic shunt placement for symptomatic non- bleeding anorectal varices in nodular regenerative hyperplasia.

In this paper we present the case of a male 55-year old patient with known ulcerative colitis and nodular regenerative hyperplasia, a rare form of noncirrhotic portal hypertension. He presented four visits to the emergency department with rapidly progressive anal discomfort. After two weeks a transjugular intrahepatic portosystemic shunt was placed using the gun-sight technique with immediate relief of the unbearable anal pain and pressure. To our knowledge, this is the first case where transjugular intrahepatic portosystemic shunt placement is applied for non- bleeding, congestive anorectal varices.

Carcinoembryonic antigen-related cell adhesion molecule 1 modulates vascular remodeling in vitro and in vivo.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a cellular adhesion molecule of the Ig superfamily, is associated with early stages of angiogenesis. In vitro, CEACAM1 regulates proliferation, migration, and differentiation of murine endothelial cells. To prove that CEACAM1 is functionally involved in the regulation of vascular remodeling in vivo, we analyzed 2 different genetic models: in Ceacam1-/- mice, the Ceacam1 gene was deleted systemically, and in CEACAM1(endo+) mice, CEACAM1 was overexpressed under the control of the endothelial cell-specific promoter of the Tie2 receptor tyrosine kinase. In Matrigel plug assays, Ceacam1-/- mice failed to establish new capillaries whereas in CEACAM1(endo+) mice the implants were vascularized extensively. After induction of hind limb ischemia by femoral artery ligation, Ceacam1-/- mice showed significantly reduced growth of arterioles and collateral blood flow compared with their WT littermates. In agreement with a causal role of CEACAM1 in vascular remodeling, CEACAM1(endo+) mice exhibited an increase in revascularization and collateral blood flow after arterial occlusion. Our findings indicate that CEACAM1 expression is important for the establishment of newly formed vessels in vivo. Hence CEACAM1 could be a future target for therapeutic manipulation of angiogenesis in disease.

Effects of potential antimicrobial ingredients used to control Listeriamonocytogenes on quality of natural casing frankfurters.

Listeriosis concerns have led to increased antimicrobial use; reformulation may affect quality. The objective was to determine the effects of potential antimicrobials on quality of natural casing frankfurters. Eleven treatments were used: no antimicrobials (control); 3.0% sodium lactate and sodium diacetate blend (SL+SD); 1.0%, 2.5%, and 3.5% buffered sodium citrate (SC); 1.0%, 2.5%, and 3.5% buffered sodium citrate and sodium diacetate blend (SC+SD); and 1.0%, 2.5%, and 5.0% whey protein peptides (WP). Trained and consumer panelists analyzed sensory characteristics. Cooking yield was unaffected by treatment (P>0.05). Addition of SC and SC+SD decreased pH (P<0.05). Texture profile analysis was conducted. Hunter color values and growth of aerobic bacteria and lactic acid bacteria were monitored over 15 weeks of storage. No samples reached spoilage. SL+SD 3% caused few changes; WP caused changes perceived as negative; and SC and SC+SD caused changes often perceived as positive.

Mapping TES Temperature Sensitivity and Current Sensitivity as a Function of Temperature, Current, and Magnetic Field with IV curve and Complex Admittance Measurements.

We have specialized astronomical applications for X-ray microcalorimeters with superconducting transition edge sensors (TESs) that require exceptionally good TES performance, but which operate in the small-signal regime. We have therefore begun a program to carefully characterize the entire transition surface of TESs with and without the usual zebra stripes to see if there are reproducible local "sweet spots" where the performance is much better than average. These measurements require precise knowledge of the circuit parameters. Here, we show how the Shapiro effect can be used to precisely calibrate the value of the shunt-resistor. We are also investigating the effects of stress and external magnetic fields to better understand reproducibility problems.

Heparins increase endothelial nitric oxide bioavailability by liberating vessel-immobilized myeloperoxidase.

BACKGROUND: Neutrophils and monocytes are centrally linked to vascular inflammatory disease, and leukocyte-derived myeloperoxidase (MPO) has emerged as an important mechanistic participant in impaired vasomotor function. MPO binds to and transcytoses endothelial cells in a glycosaminoglycan-dependent manner, and MPO binding to the vessel wall is a prerequisite for MPO-dependent oxidation of endothelium-derived nitric oxide (NO) and impairment of endothelial function in animal models. In the present study, we investigated whether heparin mobilizes MPO from vascular compartments in humans and defined whether this translates into increased vascular NO bioavailability and function. METHODS AND RESULTS: Plasma MPO levels before and after heparin administration were assessed by ELISA in 109 patients undergoing coronary angiography. Whereas baseline plasma MPO levels did not differ between patients with or without angiographically detectable coronary artery disease (CAD), the increase in MPO plasma content on bolus heparin administration was higher in patients with CAD (P=0.01). Heparin treatment also improved endothelial NO bioavailability, as evidenced by flow-mediated dilation (P<0.01) and by acetylcholine-induced changes in forearm blood flow (P<0.01). The extent of heparin-induced MPO release was correlated with improvement in endothelial function (r=0.69, P<0.01). Moreover, and consistent with this tenet, ex vivo heparin treatment of extracellular matrix proteins, cultured endothelial cells, and saphenous vein graft specimens from CAD patients decreased MPO burden. CONCLUSIONS: Mobilization of vessel-associated MPO may represent an important mechanism by which heparins exert antiinflammatory effects and increase vascular NO bioavailability. These data add to the growing body of evidence for a causal role of MPO in compromised vascular NO signaling in humans.

Rectal red blood loss in a healthy toddler is not always a juvenile polyp.

Aim Heterotopic gastric mucosa is a well-known congenital anomaly in Meckel's diverticula and duplication cysts. Solitary heterotopic gastric mucosa in the rectum is a rare and frequently overlooked abnormality. Starting from a patient history, the literature is searched and all cases reported over the past 20 years are reviewed and compared to a summary of the older cases. Differences between adult and childhood presentation are outlined and our patient is compared with prior reported cases. Case A 3-year-old girl presented with recurrent rectal blood loss caused by heterotopic gastric mucosa without duplication cyst. She was endoscopically treated with two-stage endoscopic surgical dissection (ESD). Up to now, rectal heterotopic gastric mucosa has been reported in 34 adults and 24 children, including this patient. There is an overall male dominance (69%). Presenting complaints in children were recurrent fresh blood loss per anum (96%), pain (46%), perineal ulcers (25%), diarrhoea (8%) and one patient had an ano-cutaneous fistula. Endoscopy revealed a mucosal elevation with a slightly different aspect (33%), a polyp (42%) and a solitary ulcer (25%). Endoscopy in adults reveals more frequently polyps compared to children. Treatment in childhood is mainly surgical where adults are more frequently treated with endoscopic techniques. Conclusion In a child with recurrent rectal bleeding in good general health, it is important to withhold heterotopic gastric mucosa in the differential diagnosis and take sufficient biopsies during endoscopy.

Tissue resident cells play a dominant role in arteriogenesis and concomitant macrophage accumulation.

Collateral growth is characterized by macrophage accumulation, suggesting an important role of circulating cells. To study origin and function of macrophages during arteriogenesis, we related the extent of macrophage accumulation to vascular proliferation and investigated the fate of fluorescently (CMFDA) labeled blood cells that were injected at the time of femoral artery occlusion. The effect of bone marrow depletion via cyclophosphamide before femoral artery occlusion on collateral proliferation and macrophage accumulation was studied, and we looked for the presence of bone marrow-derived stem cells in the vicinity of growing collateral vessels. Finally, we investigated the arteriogenic effect of macrophage activation via MCP-1 in bone marrow-depleted animals. Maximal macrophage accumulation occurred during the first 3 days after femoral artery occlusion and paralleled the extent of vascular proliferation. Fluorescently labeled leukocytes homed to spleen and wound but they were absent in proliferating collateral arteries during maximal macrophage accumulation. Depletion of circulating cells did neither affect macrophage accumulation nor collateral growth. Staining of monocyte-depleted animals for BrdUrd and ED2, alphaSMA, or VE-Cadherin demonstrated local proliferation of macrophages and vascular cells, whereas C-Kit, SSEA1, or Thy1-positive bone marrow-derived stem cells were not detectable. Enhancement of macrophage accumulation via MCP-1 was independent of circulating monocytes and promoted arteriogenesis in the absence of direct effects on vascular cells. We propose that the initial phase of vascular growth is characterized by local proliferation of tissue resident precursors rather than by migration of blood born cells. The full text of this article is available online at http://circres.ahajournals.org.