The effectiveness of the paclitaxel-coated Luminor® balloon catheter versus an uncoated balloon catheter in superficial femoral and popliteal arteries in preventing vessel restenosis or reocclusion: study protocol for a randomized controlled trial.

BACKGROUND: The aim of this investigator-initiated trial is to evaluate the safety and efficacy of the novel Luminor® paclitaxel-coated drug-eluting balloon (DEB) catheter (iVascular, S.L.U., Barcelona, Spain) in inhibiting restenosis and in ensuring long-term vascular patency. METHODS/DESIGN: This is a multicenter randomized controlled trial to evaluate the Luminor® paclitaxel-coated DEB catheter for stenotic or occlusive lesions (length ≤15 cm) in the superficial femoral artery (SFA) and the popliteal artery (PA) up to the P1 segment compared to the noncoated, plain old balloon angioplasty (POBA) catheter. In total 172 subjects will be treated with either the DEB catheter or the POBA catheter in 11 German study centers in a 1:1 randomization study design. The primary endpoint is late lumen loss (LLL) at 6 months. Secondary endpoints are patency rate, target lesion/vessel revascularization, quality of life (assessed with the Walking Impairment Questionnaire (WIQ) and the EQ-5D), change of Rutherford stage and ankle-brachial index, major and minor amputation rate at the index limb, number of dropouts and all-cause mortality. DISCUSSION: EffPac represents a randomized controlled trial that will provide evidence on the effectiveness of the Luminor® paclitaxel-coated DEB catheter for the reduction of restenosis compared to the POBA catheter for the SFA and the PA. The results of EffPac will allow direct comparison to other already-completed RCTs applying paclitaxel-coated DEBs from different manufacturers with different coating technologies in the same target vessel. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02540018 , registered on 17 August 2015. Protocol version: CIP Version Final04, 11 February 2016. EUDAMED No: CIV-15-03-013204.

[Management of complications after revascularization due to peripheral arterial occlusive disease : Prophylaxis and consistent adequate therapy after timely diagnostics]. / Management von Komplikationen nach Revaskularisation wegen peripherer arterieller Verschlusskrankheit : Prophylaxe und konsequente adäquate Therapie nach zeitgerechter Diagnostik.

BACKGROUND: Complications are a threat to successful revascularization for treatment of perpheral arterial occlusive disease (PAOD) and must, therefore, be either primarily prevented or effectively treated after having occurred. OBJECTIVES: The aim of this article is to give a survey of possible complications after revascularization for treatment of PAOD and their management. MATERIAL AND METHODS: A systematic literature review was performed in PubMed and Medline. The analysis mainly considered recent publications with a higher level of evidence. RESULTS: Revascularization for treatment of PAOD can basically be performed by an open surgical approach, an endovascular approach or as a combination of both methods (hybrid operation). The spectrum of possible complications varies accordingly. A differentiation can be made between bleeding, ischemic and systemic complications as well as between vascular and non-vascular complications. Optimal management of complications begins with primary prophylaxis and further includes a timely diagnosis and treatment of established complications. The best prophylaxis consists of a high quality of indications and performance of revascularization. CONCLUSION: Optimal management of complications is essential and of utmost importance for successful revascularization to treat PAOD.

Endovascular aneurysm repair of abdominal aortic aneurysms: standards, technical options and advanced indications.

UNLABELLED: Since the introduction of endovascular aneurysm repair (EVAR) in 1991, the endovascular therapy with newest stent grafts has assumed a prominent role in the clinical management of abdominal aortic aneurysms (AAA) with a superior perioperative mortality of EVAR and an equivalent mid-term outcome, compared to open surgery. Newest techniques using chimney or periscope grafts and customized fenestrated and branched stent grafts allow the endovascular treatment of complex pararenal AAA. This article reviews EVAR in the treatment of AAA, evidence based results and advanced indication by newest interventional techniques and technical developments. KEY POINTS: • EVAR has become standard treatment of abdominal aortic aneurysm with equivalent results to open surgery.• Technical advancements and the introduction of newest stent grafts continually expand the indication of EVAR.• Chimney- and periscope grafts as well as custom-made prothesis systems allow endovascular treatment of complex para- and suprarenal aneurysms.

In vitro stent lumen visualisation of various common and newly developed femoral artery stents using MR angiography at 1.5 and 3 tesla.

OBJECTIVES: To evaluate stent lumen assessment of various commonly used and newly developed stents for the superficial femoral artery (SFA) using MR angiography (MRA) at 1.5 and 3 T. METHODS: Eleven nitinol stents and one cobalt-chromium stent were compared regarding stent lumen visualisation using a common three-dimensional MRA sequence. Maximum visible stent lumen width and contrast ratio were analysed in three representative slices for each stent type. A scoring system for lumen visualisation was applied. RESULTS: Nitinol stents showed significantly better performance than the cobalt chromium stent (P < 0.05) at 1.5 and 3 T. Maximum visible stent lumen ranged between 43.4 and 95.5 %, contrast ratio between 7.2 and 110.6 %. Regarding both field strengths, seven of the nitinol stents were classified as "suitable". Three nitinol stents were "limited", and one nitinol stent and the cobalt chromium stent were "not suitable". CONCLUSIONS: Intraluminal loss of signal and artefacts of most of the SFA stents do not markedly limit assessment of stent lumen by MRA at 1.5 and 3 T. MRA can thus be considered a valid technique for detection of relevant in-stent restenosis. Applied field strength does not strongly influence stent lumen assessment in general, but proper choice of field strength might be helpful.

A technical approach for transfemoral managing of hostile angulated pelvic vessel access in abdominal endovascular aneurysm repair: a new technique for establishing a buddy wire.

PURPOSE: Endovascular aneurysm repair (EVAR) can be challenging in angulated access vessels. The aim of this study was to evaluate a new wire technique for installing a buddy wire in the event of failure of simple advancing of a super stiff guide. MATERIALS AND METHOD: We investigated 8 patients eligible for EVAR. All patients presented with heavily kinked pelvic access and failure of primary advancing of a stiff guide wire through a placed catheter. A double wire technique with a combination of soft and stiff wires was applied to place a super stiff buddy wire. Cumulative angulation quantified by the sum of angles of the tortuous pelvic access vessels was measured in pre- and post-interventional CT as well as in angiographic studies of the EVAR procedure. Patients were followed up on by CT in the first 6 months. RESULTS: A buddy wire could be installed in all patients (100%) with significant straightening of the access vessel from a median cumulative angulation of 252.4±38.1° before intervention to 159.4±44.6° after placement of the buddy wire (p<0.001). There was no technical failure of device passage and all stent-grafts could be deployed safely. Three cases of stenosis caused by torsion distal to the aortic stent-graft were seen after stent-graft delivery. One case of stenosis was hemodynamically relevant and was successfully stented. No major adverse events occurred within the first 6 months of follow-up.  CONCLUSION: The new step-by-step wire technique is feasible and safe in the case of hostile pelvic vessel access, and facilitates the advancement of aortic stent-grafts in off-label patients.

[Advanced interventional techniques and therapies in the treatment of peripheral artery disease below the knee]. / Fortgeschrittene interventionelle Techniken und Therapien bei der Behandlung der peripheren arteriellen Verschlusskrankheit vom Unterschenkeltyp.

In patients with peripheral artery disease, the options for interventional therapy of critical limb ischemia have increased within the last few years. Different antegrade and retrograde techniques for vascular recanalization are used to pass even complex and long stenoses or occlusions below the knee (BTK). A variety of diverse wires, catheters and stent types allows arterial recanalization of the lower leg and increases the impact of therapeutic efforts. This review article describes indications, advanced techniques as well as materials in BTK interventions and summarizes current evidence-based study results.

[Endovascular therapy options in femoro-popliteal PAD]. / Endovaskuläre Therapieoptionen bei femoropoplitealer pAVK.

The endovascular treatment of femoro-popliteal PAD is still challenging. The number of endovascular procedures in this vessel segment has increased over the past years. Despite new technologies, the outcome of endovascular therapy in terms of durability is still weak. In the meantime, the latest developments are progressing, such as the combination of mechanical angioplasty and drug delivery. Additionally, there are former techniques, such as debulking by atherectomy, which have been technically improved and now contribute to modern concepts of endovascular treatment. This article provides an overview on treatment indications and technical options including the latest technical developments.

Drug eluting stents versus PTA with GP IIb/IIIa blockade below the knee in patients with current ulcers--The BELOW Study.

The study was designed as a feasibility trial to evaluate the use of GP IIb/IIIa blockade in connection with drug eluting stents, bare stents and PTA only. Sixty patients with current ulcers were randomly assigned to receive abciximab plus a sirolimus coated stent (N.=14), abciximab plus a bare stent (N.=16), abciximab plus PTA (N.=14) and PTA alone (N.=19). Angiographic control was performed at two and six months. Recanalization was successful in all cases. Two month restenosis rate was 9%, 45.5%, 67% and 46%. At six month follow-up restenosis rate was 9%, 67%, 75% and 58%, respectively; 14% of all patients had major amputations within six months. Adjunctive administration of abciximab during peripheral arterial intervention below the knee was found to be safe. Sirolimus coated stent administration was followed by a higher patency rate.

Endovascular repair of infrarenal abdominal aortic aneurysm associated with a horseshoe kidney and graft thrombosis in early follow-up.

Endovascular aneurysm repair (EVAR) is a well-established alternative to open surgery. The presented case underwent endovascular therapy of an abdominal aortic aneurysm (AAA) with the anatomical prerequisite of a horseshoe kidney. We describe the technique used, including the embolization of aortic side branches, to avoid endoleaks, and the management of thrombotic complications during follow-up.

Value of contrast-enhanced multiphase CT in combined PET/CT protocols for oncological imaging.

To evaluate the additional value of contrast-enhanced multiphase CT in comparison with low-dose non-contrast CT in combined positron emission tomography (PET)/CT protocols for oncological imaging, we retrospectively analysed 100 patients with different malignant tumours. All patients underwent a PET/CT consisting of a multiphase CT protocol including a low-dose non-enhanced attenuation scan and an arterial and portal-venous contrast-enhanced scan followed by a whole-body PET. PET/CT studies were analysed by different categories to determine the added value of contrast-enhanced CT. The additional value was defined as new information provided by diagnostic CT and not available from the low-dose CT, resulting in change of PET/CT interpretation. The results were validated either by histopathology or by clinical-radiological follow up at > or =6 months. The clinical impact was evaluated with respect to changes in patient management. Diagnostic multiphase CT was of additional value in 52 out of 100 patients with 85 suspected lesions. In 40 out of 100 patients, no additional value could be detected. Eight patients were excluded due to inconclusive diagnosis in both methods including fusion. The analysis showed the greatest benefit of diagnostic CT in the categories localization of pathological fluorodeoxyglucose (FDG) uptake and precise tumour delineation, changing PET/CT interpretation in 42% and 31% of patients, respectively. The benefit of diagnostic CT was influenced by the tumour type demonstrating the highest impact in gastrointestinal, lung and neuroendocrine tumours. Diagnostic CT changed clinical management in 21 patients (21%). Diagnostic multiphase CT as part of the combined PET/CT protocol has the potential to provide considerable additional value in specific clinical conditions with resultant change of management in a substantial proportion of patients.

[Evaluation of different breathing and contrast-protocols concerning quality and alignment in 18F-FDG PET/CT]. / Vergleich verschiedener Atem- und Kontrastmittelprotokolle bezüglich Bild- und Koregistrierungsqualität bei 18F-FDG-PET/CT-Untersuchungen.

PURPOSE: The purpose of this study was to establish a reliable and simple parameter for alignment evaluation and the evaluation and optimization of state-of-the-art contrast-enhanced examination protocols for (18)F FDG-PET/CT. MATERIALS AND METHODS: 44 consecutive patients were referred to 4 examination protocols. Group A and B underwent single-phase, contrast-enhanced CT (90 s delay) performed either during free shallow breathing (FA; group A) or normal expiration (NormExp; group B). Groups C and D underwent arterial and portal venous multiphase examinations performed during FA (group C) or during NormExp (group D) followed by a low-dose CT scan for attenuation correction. Organ displacement in the cranio-caudal direction was correlated with a 3D-vectorial shift. For alignment evaluation discrepancies with respect to size and liver location, the spleen and kidneys were calculated. Additionally, the groups were compared with regard to the presence of CT artifacts. RESULTS: Cranio-caudal organ shift and 3D-vectorial shift showed a high correlation (r > 0.8). Single-phase CT scans performed during NormExp yielded better image quality (p < 0.001) and alignment (p < 0.01 for liver, spleen and right kidney) than those performed during FA. Differences in organ size did not differ during FA and NormExp. Depending on the evaluated organ, breathing and contrast protocol misalignment was in the cranio-caudal direction 0-27 mm (mean: 6.8; standard deviation: +/- 4.9) in multiphase CT compared to 0 - 11 mm (mean: 4.5 +/- 2.3) in single-phase examinations. CONCLUSION: 1. Organ shift in the cranio-caudal direction is a good and simple parameter for alignment evaluation. 2. Alignment and CT quality are best in expiration protocols. 3. Despite comparatively low alignment quality, integrated multiphase CT examinations show acceptable quality and alignment.

Intrinsic locomotor outcome in dorsal transection of rat spinal cord: predictive value of minimal incision depth.

STUDY DESIGN: Experimental, prospective, blinded, animal study. OBJECTIVES: Subtotal transection models in rodents are widely used in spinal cord injury (SCI) research. In this model, we investigate the effect of the dorso-ventral incision depth (ID) of the spinal cord on functional locomotor outcome using the Basso, Beattie, Bresnahan (BBB) scale. We introduce the minimal incision depth (ID(min)) and the average lesion depth (ID(mean)) as reliable, fast and easily available predictive parameters for intrinsic locomotor function. SETTING: Tuebingen, Germany. METHODS: Dorsal over-hemisection at the level of T8 was performed in male Lewis rats. Functional outcome 4 weeks after SCI and histological analysis of the lesion were studied and correlated in 36 animals. Animals reaching weight support (BBB> or =9) were considered as having reached functional recovery. Data analysis was performed in linear (ordinary least squares; OLS) and nonlinear (logistic) regression models for correlation of histological parameters and functional outcome. RESULTS: BBB scores revealed a strong correlation with ID(mean) and ID(min), showing a higher value in predicting functional outcome for the latter parameter. Based on logistic regression analysis, animals with an ID(min) of 69% would have a 95% probability of reaching weight support. CONCLUSION: These results demonstrate that histological analysis is crucial when functional outcome parameters are used in the dorsal over-hemisection SCI model. A simple and feasible histological evaluation can reliably predict spontaneous functional locomotor recovery in dorsal transection models and could provide a simple tool to identify treatment effects of new experimental therapeutic approaches.

[Large vessel vasculitis as cause of fever of unknown origin (FUO) or systemic inflammation. Diagnosis using 18-F-fluor-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET)]. / Vaskulitiden der grossen Gefässe als Ursache eines Fiebers unklarer Genese (FUO) oder unklarer Entzündungskonstellationen Diagnostik mittels 18-F-Fluor-2-deoxy-D-Glukose Positronen-Emissionstomographie (18F-FDG-PET).

BACKGROUND: Diagnosis and treatment of FUO or systemic inflammation with unknown reason are still a great challenge for the treating physician. We used (18)F-FDG-PET for further diagnostic work in patients in whom a diagnosis could not be established despite intensive diagnostic efforts. METHODS/RESULTS: We studied nine patients with (18)F-FDG-PET. Two female patients with known Takayasu's arteritis but undefined disease activity, and seven patients with the clinical suspicion of an underlying large vessel vasculitis. The diagnosis of active vasculitis could be confirmed by the PET-results in eight patients. Active vasculitis could be nearly ruled out in one. The diagnoses could be confirmed by follow-up visits. CONCLUSION: (18)F-FDG-PET is a useful diagnostic tool in patients with unclear systemic inflammation and FUO. Especially when large vessel vasculitis is suspected, further diagnostic work by PET seems to be of benefit. Furthermore, it offers the opportunity to evaluate disease activity and to check which vessels are involved.

The LPS receptor (CD14) links innate immunity with Alzheimer's disease.

To rapidly respond to invading microorganisms, humans call on their innate immune system. This occurs by microbe-detecting receptors, such as CD14, that activate immune cells to eliminate the pathogens. Here, we link the lipopolysaccharide receptor CD14 with Alzheimer's disease, a severe neurodegenerative disease resulting in dementia. We demonstrate that this key innate immunity receptor interacts with fibrils of Alzheimer amyloid peptide. Neutralization with antibodies against CD14 and genetic deficiency for this receptor significantly reduced amyloid peptide induced microglial activation and microglial toxicity. The observation of strongly enhanced microglial expression of the LPS receptor in brains of animal models of Alzheimer's disease indicates a clinical relevance of these findings. These data suggest that CD14 may significantly contribute to the overall neuroinflammatory response to amyloid peptide, highlighting the possibility that the enormous progress currently being made in the field of innate immunity could be extended to research on Alzheimer's disease.

Effects of statins on human cerebral cholesterol metabolism and secretion of Alzheimer amyloid peptide.

Cerebral cholesterol metabolism has been linked with production of amyloid peptide (Abeta) crucial in AD. The association between use of cholesterol-lowering drugs (statins) and AD disease is currently being intensely discussed. In this case-control study on elderly nondemented subjects, the authors provide the first evidence that statins in clinically relevant dosages indeed affect cerebral cholesterol metabolism. However, these changes were not associated with altered intrathecal secretion of Alzheimer Abeta.

[2D-phase contrast flow evaluation and contrast-enhanced MR angiography for perioperative assessment of internal mammary artery grafts]. / 2D-Phasenkontrast-Flussquantifizierung und kontrastangehobene 3D-MR-Angiographie zur perioperativen Untersuchung des Arteria-mammaria-interna-Bypasses.

PURPOSE: To evaluate LV functional parameters, graft flow and patency in patients with IMA grafts using a combined MR protocol with phase-contrast technique and contrast enhanced MR angiography. MATERIAL AND METHODS: Using a 1.5 T MR system 27 patients with 27 left internal mammary artery (LIMA) and 41 venous grafts were examined before and 6 months after CABG surgery. A T(1)w-TSE sequence (slice thickness 5 mm) was applied for morphological imaging. LV function (EF, CO) was evaluated on cine images (segmented FLASH 2D, TR(eff) 11 ms, TE 4.8 ms, flip angle 25 degrees ). A phase-contrast FLASH 2D (TR 24 ms, TE 5 ms, flip angle 20 degrees ) sequence was applied for aortic and IMA flow measurements. Postoperatively, a contrast enhanced FLASH 3D MR angiography (TR 3.8 ms, TE 1.4 ms, flip angle 30 degrees ) with 25 ml Gd-DTPA was performed to assess bypass patency. RESULTS: In patients with reduced LV function (ejection fraction < 50 %) an improvement of the ejection fraction from 38.4 +/- 10.3 % to 49.8 +/- 15.3 % (p < 0.05) was found postoperatively. LIMA grafts were occluded in 1/27 patients, while 6/41 venous grafts were occluded. Distal LIMA anastomoses were demonstrated in 33 % by MRA. Flow of LIMA decreased from 21.2 +/- 11 ml/min/m(2) preoperatively to 14.4 +/- 9.6 ml/min/m(2) postoperatively (p < 0.01). CONCLUSION: MR imaging allows accurate combined assessment of LV function, bypass patency and flow. The protocol of this study may be applicable for perioperative follow-up studies in patients after CABG surgery.