[Interdisciplinary neurovascular networks: state of the art]. / Interdisziplinäre neurovaskuläre Netzwerke: eine Standortbestimmung.

BACKGROUND: In order to treat the complete spectrum of neurovascular diseases at a high level of quality, which goes beyond the purely acute treatment of stroke, the German Stroke Society (DSG) together with the German Societies for Neurosurgery and Neuroradiology developed a certification procedure for neurovascular networks (NVN). Structurally, a NVN consists of a coordinating center with at least three neurovascular network partners with a certified stroke unit. From 2018 to 2020 a total of 15 NVN have so far been audited and certified according to this new standard. OBJECTIVE: How efficient are the NVN? Are high standards maintained? MATERIAL AND METHODS: The reports of the audits were analyzed. The data were taken from the period 2017-2019. RESULTS: The 15 NVN treated a total of 86,510 stroke patients in the years examined and were networked with a total of 107 partner clinics, which were situated an average of 25 km from the coordinating center and transferred a total of 2726 patients. The coordinating centers performed 2463 thrombectomies and treated 2383 patients with nontraumatic intracerebral bleeding. In 712 patients with acute aneurysmatic subarachnoid hemorrhages endovascular treatment was carried out and clipping in 401. The audit was successful in the majority of the NVN. CONCLUSION: The certification process of NVN has been successfully established and the audits proved to be a useful instrument for quality control and improvement. The 15 NVN are highly efficient and treat more than one quarter of stroke patients in German stroke units.

[The development of real-time multispectral imaging for the diagnostics of bladder cancer]. / Entwicklung der Echtzeitmultispektralbildgebung für die Diagnostik des Harnblasenkarzinoms.

The performance of white light (WL) cystoscopy in the diagnostics of bladder cancer can be optimized by the use of modern imaging modalities, such as photodynamic diagnostics (PDD) and narrow band imaging (NBI). Real-time multispectral imaging (rMSI) enables simultaneous imaging of reflectance and fluorescence modalities in multiple spectral bands. We created a multiparametric cystoscopy image by digital overlapping of several modalities, e.g. WL, enhanced vascular contrast (EVC), raw fluorescence mode, protoporphyrin IX and autofluorescence (AF). The technical development and the subsequent clinical implementation of rMSI required a structured preclinical evaluation process, including both ex vivo and in vivo trials before the technology can be applied in patients. This review article presents the phases of testing, validation and the first clinical application of rMSI in urological endoscopy.

The application of STEP-technology® for particle and protein dispersion detection studies in biopharmaceutical research.

Particle detection and analysis techniques are essential in biopharmaceutical industries to evaluate the quality of various parenteral formulations regarding product safety, product quality and to meet the regulations set by the authority agencies. Several particle analysis systems are available on the market, but for the operator, it is quite challenging to identify the suitable method to analyze the sample. At the same time these techniques are the basis to gain a better understanding in biophysical processes, e.g. protein interaction and aggregation processes. The STEP-Technology® (Space and Time resolved Extinction Profiles), as used in the analytical photocentrifuge LUMiSizer®, has been shown to be an effective and promising technique to investigate particle suspensions and emulsions in various fields. In this study, we evaluated the potentials and limitations of this technique for biopharmaceutical model samples. For a first experimental approach, we measured silica and polystyrene (PS) particle standard suspensions with given particle density and refractive index (RI). The concluding evaluation was performed using a variety of relevant data sets to demonstrate the significant influences of the particle density for the final particle size distribution (PSD). The most challenging property required for successful detection, turbidity, was stated and limits have been set based on the depicted absorbance value at 320 nm (A320 values). Furthermore, we produced chemically cross-linked protein particle suspensions to model physically "stable" protein aggregates. These results of LUMiSizer® analysis have been compared to the orthogonal methods of nanoparticle tracking analysis (NTA), dynamic light scattering (DLS) and micro-flow imaging (MFI). Sedimentation velocity distributions showed similar tendencies, but the PSDs and absolute size values could not be obtained. In conclusion, we could demonstrate some applications as well as limitations of this technique for biopharmaceutical samples. In comparison to orthogonal methods this technique is a great complementary approach if particle data e.g. density or refractive index can be determined.

CT-derived left ventricular global strain in aortic valve stenosis patients: A comparative analysis pre and post transcatheter aortic valve implantation.

INTRODUCTION: We assessed the potential of CT strain to detect changes in myocardial function in patients referred for TAVI pre and post intervention. PATIENTS AND METHODS: 25 consecutive patients with symptomatic aortic valve stenosis in whom TAVI had been performed were included in this analysis. Functional CT data sets acquired before and 3 to 6 months after TAVI were available. Multiphase reconstructions in increments of 10% of the cardiac cycle were rendered and transferred to a dedicated workstation (Ziostation2, Ziosoft Inc., Tokyo, Japan). For quantification of left ventricular strain, multiplanar reconstructions of the left ventricle in standard 4 chamber, 2 chamber as well as apical 3 chamber views were rendered. The perimeter of the left ventricle was traced dynamically through the cardiac cycle. Peak strain was calculated for each patient pre and post intervention. Furthermore, for quantification of 3-dimensional maximum principal strain, 2 volumetric regions of interests (VOI) were placed per each basal, mid and apical segment of the previously mentioned MPRs and peak maximal principal strain was calculated. Maximum principal strain as well as perimeter-derived longitudinal strain values in the three standard windows were averaged to obtain global strain. RESULTS: 25 patients were included in this analysis (mean age 78 ±â€¯9 years, 13 males). Peak global maximum principal strain was significantly higher at follow-up compared to baseline (0.46 ±â€¯0.19 vs. 0.59 ±â€¯0.18, respectively, p = 0.001). Similarly global longitudinal strain derived by perimeter was significantly lower - implying better contraction - compared to baseline (-8.6% ±â€¯2.8% vs. -9.8% ±â€¯2.6%, respectively, p = 0.006). CONCLUSION: Using dedicated software, assessment of CT derived left ventricular strain is feasible. In patients treated with transcatheter aortic valve replacement, CT-derived parameters of global myocardial strain improve onshort-term follow-up.

[Juvenile stroke - what is important?] / Juveniler Schlaganfall ­ was gibt es zu beachten?

Stroke in young adults is a diagnostic and therapeutic challenge for all persons involved. Approximately 15% of ischemic strokes occur in young adults. Lack of awareness of the symptoms in emergency departments often results in delayed diagnosis and access to specific therapeutic options, such as revascularization. The causes are often heterogeneous and necessitate specific investigations. The etiology of juvenile stroke includes drug abuse, vasculitis and arteriopathies, such as reversible vasoconstriction syndrome and posterior reversible encephalopathy syndrome, although the prevalence of classical vascular risk factors is high. The most frequent causes of ischemic stroke in young adults are cardioembolism and microangiopathy; furthermore, dissection of vessels of the neck are more frequent compared to older patients. According to the results of currently available studies reperfusion strategies, such as intravenous fibrinolysis and mechanical thrombectomy are efficacious and safe in young patients.

[Cerebral amyloid angiopathy associated with inflammation]. / Zerebrale Amyloidangiopathie assoziiert mit Inflammation.

Cerebral amyloid angiopathy (CAA) associated with inflammation is a rare form of a potentially reversible encephalopathy in a subgroup of patients with CAA. The cerebral amyloid deposition can in isolated cases induce an inflammation predominantly of the cerebral blood vessels and a multifocal edema of the cerebral white matter. The courses can occur as monophasic, relapsing remitting and primarily progressive forms. We present seven cases with different courses of the disease and give an overview of the pathophysiology, clinical aspects and treatment of the disease with reference to the current literature. The cases presented show a very different and often difficult differential diagnostic clinical picture and all showed a significant improvement under steroid medication without signs of recurrence of the disease during the course. The recognition and early consistent treatment of inflammatory forms of CAA with and without direct inflammatory involvement of vessels can be decisive for successful treatment.

Leaflet thrombosis following transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is increasingly being offered to high-risk patients with symptomatic aortic valve stenosis. Recent reports have suggested a high incidence of subclinical leaflet thrombosis following bioprosthestic aortic valve replacement. We report the frequency and clinical presentation of leaflet thrombosis identified by cardiac CT in patients referred for follow-up contrast enhanced CT angiography following TAVI. METHODS: 91 consecutive patients referred for follow-up contrast-enhanced CT angiography following TAVI were screened for inclusion in this analysis. Out of these, 13 patients were excluded. All CT examinations were performed using a 2nd or a 3rd generation dual-source system (Somatom Definition Flash/Force, Forchheim, Germany). In all patients, retrospectively ECG-gated spiral acquisition with tube modulation was performed to allow for assessment of leaflet motion. All prostheses were analyzed for presence of leaflet thrombosis defined as hypo-attenuated leaflet thickening with or without leaflet restriction. Post-procedural antithrombotic regimen as well as symptom status was documented in all patients. RESULTS: 78 consecutive patients (35 males, 81 ± 4 years) were analyzed. TAVI had been performed in all patients (76 transfemoral access, 2 transapical access) with either balloon-expandable prostheses (4 Sapien XT, 64 Sapien 3) or self-expandable prostheses (5 SJM Portico, 5 Symetis Acurate). Follow-up CT angiography was performed at a median of 4 months following index procedure (Interquartile range 1 month). Leaflet thrombosis was detected in 18 patients (23%, 14 Sapien 3, 1 Sapien XT, 2 SJM Portico, 1 Symetis Acurate). In patients with leaflet thickening on CT, only 11% were on either oral anticoagulation or new oral anticoagulants versus 50% for patients with no leaflet thickening (p 0.002). In patients with leaflet thrombosis, 3 leaflets were affected in 5 patients, 2 leaflets in 5 patients and in 8 patient only 1 leaflet was affected. Clinical symptoms (angina, dyspnea or both) were reported in 2/18 patients with leaflet thrombosis (11%) and in both patients a significant increase of the mean echocardiographic gradient over the prosthesis was documented. The peak and mean echocardiographic gradients obtained at the day of CT examination was significantly higher in symptomatic patients versus asymptomatic patients (peak 46 ± 7 vs. 23 ± 11 mmHg, mean 29 ± 7 vs. 12 ± 6 mmHg, p = 0.01 and 0.002, respectively). Follow-up CT was available for 4 patients with complete resolution of the hypo-attenuated leaflet thickening following treatment. CONCLUSION: Leaflet thrombosis following TAVI is a relatively frequent finding in patients referred for contrast enhanced CT angiography following TAVI. In the majority of patients it follows a subclinical course and is substantially more frequent in individuals who are not on oral anticoagulation. However, in patients with relevant increase in prosthetic gradients, symptomatic presentations are possible.

[Not Available]. / IQWiG Arbeitspapier GA15-02: "Stents zur Behandlung intrakranieller Stenosen: VISSIT Studie und Akutbehandlung in Deutschland". Kommentar des Berufsverbandes der Neuroradiologen (BDNR), der Deutschen Gesellschaft für Neuroradiologie (DGNR), der Deutschen Gesellschaft für Neurologie (DGN) und der Deutschen Schlaganfall-Gesellschaft (DSG).

There is an ongoing discussion about reimbursement of stent-angioplasty for the treatment of intracranial stenoses in Germany. The discussion was initiated by the statutory health insurance companies after publication of the SAMMPRIS study results, which were in favor for medical management compared to stent-angioplasty with the Wingspan® stent system. A report (Rapid report N14-01) mainly based on SAMMPRIS was written by the German Institute for Quality and Efficiency in Health Care (IQWiG) and serves as a basis for the decision-making process. This report was previously commented by the medical societies involved. Limitations of the SAMMPRIS trial and vital indications for intracranial stenting were outlined in this comment (acute vessel occlusion, hemodynamic impairment, recurrent symptoms under medical treatment). Currently also emergency stent procedures are a matter of debate. In this context a second IQWiG report was commissioned (GA 15 - 02) addressing the results of the VISSIT trial, the transferability of the results of the first report to emergency treatments and the practice of emergency intracranial stent treatment in Germany. Regarding transferability of results the main conclusion was that there was no evidence that the results of the studies analyzed for the first report (mainly SAMMPRIS) could not be transferred to emergency treatments. From a medical professional and scientific standpoint it is inacceptable to compare outcomes of a secondary prophylactic treatment with emergency procedures. The analysis of emergency treatments in Germany based on retrospective case series with a cumulative number of 31 patients. Since most emergency procedures are performed in a clinical context and are not necessarily subject to scientific evaluation, this does not reflect current practice in Germany. The first part of this statement briefly outlines the design of SAMMPRIS and VISSIT and the interpretation of the trial results from a professional perspective. The current state of discussion regarding reimbursement of intracranial stenting is summarized. The second section contains a detailed comment on the current IQWiG report GA15-02 "Stents for the treatment of intracranial artery stenosis: VISSIT study and acute treatment in Germany".

IQWiG Arbeitspapier GA15-02: "Stents zur Behandlung intrakranieller Stenosen: VISSIT Studie und Akutbehandlung in Deutschland" : Kommentar des Berufsverbandes der Neuroradiologen (BDNR), der Deutschen Gesellschaft für Neuroradiologie (DGNR), der Deutschen Gesellschaft für Neurologie (DGN) und der Deutschen Schlaganfall-Gesellschaft (DSG).

There is an ongoing discussion about reimbursement of stent-angioplasty for the treatment of intracranial stenoses in Germany. The discussion was initiated by the statutory health insurance companies after publication of the SAMMPRIS study results, which were in favor for medical management compared to stent-angioplasty with the Wingspan® stent system. A report (Rapid report N14-01) mainly based on SAMMPRIS was written by the German Institute for Quality and Efficiency in Health Care (IQWiG) and serves as a basis for the decision-making process. This report was previously commented by the medical societies involved. Limitations of the SAMMPRIS trial and vital indications for intracranial stenting were outlined in this comment (acute vessel occlusion, hemodynamic impairment, recurrent symptoms under medical treatment).Currently also emergency stent procedures are a matter of debate. In this context a second IQWiG report was commissioned (GA 15 - 02) addressing the results of the VISSIT trial, the transferability of the results of the first report to emergency treatments and the practice of emergency intracranial stent treatment in Germany6. Regarding transferability of results the main conclusion was that there was no evidence that the results of the studies analyzed for the first report (mainly SAMMPRIS) could not be transferred to emergency treatments. From a medical professional and scientific standpoint it is inacceptable to compare outcomes of a secondary prophylactic treatment with emergency procedures. The analysis of emergency treatments in Germany based on retrospective case series with a cumulative number of 31 patients. Since most emergency procedures are performed in a clinical context and are not necessarily subject to scientific evaluation, this does not reflect current practice in Germany.The first part of this statement briefly outlines the design of SAMMPRIS and VISSIT and the interpretation of the trial results from a professional perspective. The current state of discussion regarding reimbursement of intracranial stenting is summarized. The second section contains a detailed comment on the current IQWiG report GA15-02 "Stents for the treatment of intracranial artery stenosis: VISSIT study and acute treatment in Germany".

Treatment and outcome of coronary artery perforations using a dual guiding catheter technique.

OBJECTIVES: To evaluate the success rate and outcome of coronary artery perforation treatment using a dual guiding catheter technique. BACKGROUND: Coronary artery perforation is a rare but severe complication during percutaneous coronary intervention (PCI) with high mortality. The use of a second guiding catheter is a helpful technique to minimize hemorrhage through the perforation during interventional repair. METHODS: We screened all patients between March 2004 and December 2014 who underwent PCI in our department for the occurrence of peri-interventional coronary perforation that was treated using a dual catheter technique. Patient and lesion characteristics as well as outcome were determined. RESULTS: We identified 8 patients who experienced coronary artery perforations (Ellis grade III) during coronary intervention and were treated using a dual guiding catheter approach. The procedure was technically successful (placement of covered stent and sealing of perforation) in 6 patients. Pericardiocentesis was required in 3 patients (38%). Total mortality was 12% (n=1). No coronary or peripheral vascular access complication occurred due to the use of a second guiding catheter. CONCLUSIONS: We suggest that the dual guiding catheter technique is a useful and alternative approach to treat severe Ellis grade III coronary artery perforations that occur in the context of percutaneous coronary interventions.

Clopidogrel Resistance in Neurovascular Stenting: Correlations between Light Transmission Aggregometry, VerifyNow, and the Multiplate.

BACKGROUND AND PURPOSE: Clopidogrel resistance is blamed for thromboembolic complications in neurovascular stent placement. Platelet-function assays are weakly standardized. The aim of this study was to correlate the results of 3 different platelet-inhibition measurements (from light transmission aggregometry, the VerifyNow P2Y12 test, and the Multiplate analyzer) and their relation to periprocedural thromboembolic complications in elective neurovascular stent placement. MATERIALS AND METHODS: Clopidogrel resistance was determined on the day of the intervention according to predefined platelet reactivity cutoff values. All 3 tests were performed in 103 consecutive neurovascular stent-placement procedures in 97 patients (extracranial, n = 77; intracranial, n = 26). RESULTS: The clopidogrel resistance rates were 47.6% (light transmission aggregometry), 50.5% (VerifyNow), and 35.9% (Multiplate). In 67% of the patients, clopidogrel resistance was present according to at least one method. The correlations of qualitative results that classified a patient as responsive or resistant to clopidogrel were 67.9% for light transmission aggregometry with VerifyNow, 77.7% for light transmission aggregometry with the Multiplate, and 66% for VerifyNow with the Multiplate. Periprocedural thromboembolic complications (n = 9) occurred more frequently in patients who were determined by all 3 methods to be clopidogrel resistant. The difference was most pronounced with light transmission aggregometry (complication rates, 14.4% [clopidogrel-resistant patients] vs 3.7% [clopidogrel-responsive patients]). Sensitivity and specificity rates of clopidogrel resistance in relation to embolic complications were, respectively, 78% and 55% for light transmission aggregometry, 67% and 51% for VerifyNow, and 44% and 67% for the Multiplate. CONCLUSIONS: Clopidogrel resistance is a frequent finding in patients who undergo neurovascular stent placement. The correlations among the different testing methods are only modest and differ considerably. Light transmission aggregometry results seem to correlate with thromboembolic complications more accurately than with VerifyNow and Multiplate point-of-care methods.