S.G. Werner

Analysis of distribution and severity of inflammation in patients with osteoarthitis compared to rheumatoid arthritis by ICG-enhanced fluorescence optical imaging and musculoskeletal ultrasound: a pilot study

Background In rheumatoid arthritis (RA), hand synovitis appears especially in wrist, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. In hand osteoarthritis (OA), potential inflammatory changes are mainly present in PIP and distal interphalangeal (DIP) joints. Joint inflammation can be visualised by fluorescence optical imaging (FOI) and musculoskeletal ultrasound (US). Objective Comparison of the amount and distribution of inflammatory signs in wrist and finger joints of the clinically dominant hand in patients with OA and RA by FOI and gray-scale (GSUS) and power Doppler US (PDUS). Methods FOI and GSUS/PDUS were performed in 1.170 joints (wrists, MCP, PIP, DIP) in 90 patients (67 RA, 23 OA). Joint inflammation was graded by a semiquantitative score (0–3) for each imaging method. Results GSUS/PDUS showed wrist and MCP joints mostly affected in RA. DIP joints were graded higher in OA. In FOI, RA and OA featured inflammatory changes in the respective joint groups depending on the phase of fluorescence dye flooding. Conclusions US and FOI detected inflammation in both RA and OA highlighting the inflammatory component in the course of OA. The different inflammatory patterns and various shapes of fluorescence enhancement in FOI may offer opportunities to distinguish and determine the inflammatory status in both diseases.

Near-infrared Fluorescence Optical Imaging in Early Rheumatoid Arthritis: A Comparison to Magnetic Resonance Imaging and Ultrasonography

Objective. Near-infrared fluorescence optical imaging (FOI) is a novel imaging technology in the detection and evaluation of different arthritides. FOI was validated in comparison to magnetic resonance imaging (MRI), greyscale ultrasonography (GSUS), and power Doppler ultrasonography (PDUS) in patients with early rheumatoid arthritis (RA). Methods. Hands of 31 patients with early RA were examined by FOI, MRI, and US. In each modality, synovitis of the wrist, metacarpophalangeal joints (MCP) 2–5, and proximal interphalangeal joints (PIP) 2–5 were scored on a 4-point scale (0–3). Sensitivity and specificity of FOI were analyzed in comparison to MRI and US as reference methods, differentiating between 3 phases of FOI enhancement (P1–3). Intraclass correlation coefficients (ICC) were calculated to evaluate the agreement of FOI with MRI and US. Results. A total of 279 joints (31 wrists, 124 MCP and 124 PIP joints) were evaluated. With MRI as the reference method, overall sensitivity/specificity of FOI was 0.81/0.00, 0.49/0.84, and 0.86/0.38 for wrist, MCP, and PIP joints, respectively. Under application of PDUS as reference, sensitivity was even higher, while specificity turned out to be low, except for MCP joints (0.88/0.15, 0.81/0.76, and 1.00/0.27, respectively). P2 appears to be the most sensitive FOI phase, while P1 showed the highest specificity. The best agreement of FOI was shown for PDUS, especially with regard to MCP and PIP joints (ICC of 0.57 and 0.53, respectively), while correlation with MRI was slightly lower. Conclusion. FOI remains an interesting diagnostic tool for patients with early RA, although this study revealed limitations concerning the detection of synovitis. Further research is needed to evaluate its full diagnostic potential in rheumatic diseases.

Musculoskeletal ultrasound and other imaging modalities in rheumatoid arthritis.

Purpose of reviewThis review refers to the use of musculoskeletal ultrasound in patients with rheumatoid arthritis (RA) both in clinical practice and research. Furthermore, other novel sensitive imaging modalities (high resolution peripheral quantitative computed tomography and fluorescence optical imaging) are introduced in this article. Recent findingsRecently published ultrasound studies presented power Doppler activity by ultrasound highly predictive for later radiographic erosions in patients with RA. Another study presented synovitis detected by ultrasound being predictive of subsequent structural radiographic destruction irrespective of the ultrasound modality (grayscale ultrasound/power Doppler ultrasound). Further studies are currently under way which prove ultrasound findings as imaging biomarkers in the destructive process of RA. Other introduced novel imaging modalities are in the validation process to prove their impact and significance in inflammatory joint diseases. SummaryThe introduced imaging modalities show different sensitivities and specificities as well as strength and weakness belonging to the assessment of inflammation, differentiation of the involved structures and radiological progression. The review tries to give an answer regarding how to best integrate them into daily clinical practice with the aim to improve the diagnostic algorithms, the daily patient care and, furthermore, the diseases outcome.

Fluorescence Optical Imaging of Juvenile Arthritis

In juvenile idiopathic arthritis (JIA), valid detection of involved joints is essential for correct classification, therapeutic decisions, and prognosis1. Clinical assessment is a particular challenge, and reliable results depend on the ages of the children and their ability to cooperate. Ultrasonography (US) and magnetic resonance imaging are used for imaging in JIA, but have practical limitations. Fluorescence optical imaging (FOI) enables visualization of inflammation in arthritis …

Fluorescence optical imaging and musculoskeletal ultrasonography in juvenile idiopathic polyarticular disease before and during antirheumatic treatment - a multicenter non-interventional diagnostic evaluation

BackgroundValid detection of inflamed joints is essential for correct classification, therapeutic decisions, prognosis and assessment of treatment efficacy in juvenile idiopathic arthritis (JIA). Fluorescence optical imaging (FOI) enables visualization of inflammation in arthritis of finger and hand joints and might be used for monitoring.MethodsA 24-week observational study in polyarticular JIA patients newly starting treatment with methotrexate or an approved biologic was performed in three centers. Patients were evaluated clinically, by gray-scale ultrasonography (GSUS), power-Doppler ultrasonography (PDUS) and FOI at baseline, week 12 and week 24.ResultsOf 37 patients enrolled, 24 patients started methotrexate and 13 patients a biologic for the first time (etanercept n = 11, adalimumab and tocilizumab n = 1 each). Mean JADAS 10 decreased significantly from 17.7 at baseline to 12.2 and 7.2 at week 12 and 24 respectively. PedACR 30/50/70/100 response rates at week 24 were 85%/73%/50%/27%. The total number of clinically active joints in hand and fingers at baseline/week 12/week 24 was 262 (23.6%)/162 (16.4%)/162 (9.0%). By GSUS, at baseline/week 12/week 24, 192 (19.4%)/135 (16.1%)/83 (11.5%) joints showed effusions and 186 (18.8%)/107 (12.7%)/69 (9.6%) showed synovial thickening, and by PDUS 68 (6.9%)/15 (1.8%)/36 (5%) joints showed hyperperfusion. Any sign of arthritis was detected by US in a total of 243 joints (24.5%) at baseline, 161 joints (19.2%) at week 12 and 123 joints (17%) at week 24. By FOI at baseline/week 12/week 24, 430 (38.7%)/280 (29.2%)/215 (27.6%) showed a signal enhancement in at least one phase.Summarizing all three points of time, the highest numbers of signals were detected by FOI with 32% of joints, especially in phase 2, while by US 20.7% and by clinical examination 17.5% of joints were active. A high number of joints (21.1%) had FOI signals but were inactive by clinical examination. A total 20.1% of joints with signals in FOI did not show effusion, synovial thickening or hyperperfusion by US.Because of the high number of negative results, specificity of FOI compared with clinical examination/US/PD was high (84–95%), and sensitivity was only moderate.ConclusionFOI and US could detect clinical but also subclinical inflammation. FOI detected subclinical inflammation to a higher extent than US. Improvement upon treatment with either methotrexate or a biologic can be visualized by FOI and US.Trial registrationDeutsches Register Klinischer Studien DRKS00011579. Registered 10 January 2017.

Comparison of Photo Optical Imaging with Musculoskeletal Ultrasound and Clinical Examination in the Assessment of Inflammatory Activity in Proximal Interphalangeal Joints in Rheumatoid Arthritis and Osteoarthritis.

Objective. Lightscan is a novel, rapid, low-cost, easily operated and noninvasive imaging technology used to assess inflammatory activity in proximal interphalangeal (PIP) joints. The results are calculated automatically. To our knowledge, this is the first comparative study of photo optical imaging (POI), with clinical examination (CE), disease activity score at 28 joints (DAS28)-erythrocyte sedimentation rate (ESR), and musculoskeletal ultrasonography (US) in healthy subjects and patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Methods. There were 688 PIP joints of both hands examined in 87 subjects (38 RA, 21 OA, 28 healthy) by Lightscan and compared with CE for clinically swollen and tender joints, DAS28-ESR (only RA), and US. Results. With US as reference, POI had a sensitivity of 74% and a specificity of 93%. In the receiver-operating curve (ROC) analysis, the Lightscan showed a higher sensitivity and specificity [area under the curve (AUC) 0.879] for the distinction of healthy subjects versus patients (OA, RA) than US in greyscale (GSUS; AUC 0.797) and power Doppler (PDUS; AUC 0.67). POI correlated significantly with GSUS (r 0.473, p < 0.01) and PDUS (r 0.486, p < 0.01). The agreement rates between POI and GSUS were up to 79%, between POI and PDUS up to 92%, and between POI and CE up to 66%. POI did not correlate with DAS28-ESR. Conclusion. The Lightscan is a new technology offering sensitive imaging detection of inflammatory changes in subjects with RA and OA with PIP arthritis. POI was more sensitive than CE and correlated significantly to GSUS and PDUS, while presenting a higher sensitivity and specificity for the detection of healthy subjects versus patients (RA, OA) based on the ROC analysis.

Bildgebende Verfahren bei Psoriasisarthritis

This review presents an overview of the range of imaging modalities used in the diagnostic evaluation of patients with psoriatic arthritis (PsA). Conventional radiography is used to detect structural changes of the joints and tendon attachments. These changes occur late in the course of PsA hence conventional radiography contributes little to the early detection of PsA; however, the detection of periosteal proliferations on radiographs allows a relatively specific diagnosis of PsA. Skeletal scintigraphy and computed tomography are rarely used in PsA. Arthrosonography (ultrasound of the joints) is gaining increasing importance in the early identification of inflammatory soft tissue signs of PsA in the peripheral joints. Sonography enables early detection of synovitis and tenosynovitis as well as superficial erosions and also inflammatory processes of the tendon attachments. Magnetic resonance imaging (MRI) is indispensable for identifying possible involvement of the axial skeleton. Moreover, it allows good visualization of periostitis and arthritis. High resolution microcomputed tomography is an interesting novel diagnostic tool which allows highly sensitive evaluation of the bone structure and can detect very tiny bone lesions where typical signs of PsA are omega-shaped erosions and small corona-like spikes. Another interesting new diagnostic technique is fluorescence optical imaging (FOI) with the Xiralite system which is highly sensitive for detecting inflammatory processes of the hands.ZusammenfassungIn dem Beitrag werden die verschiedenen bildgebenden Verfahren in der Diagnostik der Psoriasisarthritis (PsA) dargelegt. Das konventionelle Röntgen wird zur Erfassung der strukturellen Veränderungen an den Gelenken und Sehnenansätzen eingesetzt. Jedoch kommen diese Veränderungen erst sehr spät zur Darstellung, womit dieses Verfahren gerade in der Frühdiagnostik nicht die notwendigen Informationen liefern kann. Jedoch ist durch den Nachweis von Periostproliferationen eine relativ spezifische Diagnose mithilfe des Röntgenbilds möglich. Die Skeletszintigraphie und Comptertomographie werden insgesamt selten in der Diagnostik der PsA eingesetzt. Die Gelenksonographie (Ultraschall) gewinnt zunehmend einen größeren Stellenwert in der Frühdiagnostik der entzündlichen Weichteilzeichen an den pripheren Gelenken bei der PsA. So ist die Arthrosonographie in der Lage die Synovitis und Tenosynovitis sowie oberflächlich liegende Erosionen frühzeitg zu detektieren, aber auch die entzündlichen Veränderungen an den Enthesen sind sonographisch gut objektivierbar. Die Magnetresonanztomographie (MRT) hat ihren Stellenwert in der Abklärung einer möglichen axialen Beteiligung im Rahmen der PsA und ist hier unverzichtbar. Periphere Manifestationen wie Periostitis und Arthritis kommen ebenfalls gut zur Darstellung. Die hochauflösende Mikro-Computertomographie ist ein neues, interessantes diagnostisches Verfahren, das die Knochenstruktur sehr sensitiv darstellt und damit kleinste Knochenläsionen aufzeigen kann. Typisch für die PsA ist die omegaförmige Erosion und der Nachweis von kleinen coronaförmigen Spikes. Ein weiteres neues diagnostisches Verfahren ist das fluoreszenzoptische bildgebende Verfahren (FOI) mit dem Xiralite-System, das sehr sensitiv entzündliche Veränderungen an den Händen aufzeigt.AbstractThis review presents an overview of the range of imaging modalities used in the diagnostic evaluation of patients with psoriatic arthritis (PsA). Conventional radiography is used to detect structural changes of the joints and tendon attachments. These changes occur late in the course of PsA hence conventional radiography contributes little to the early detection of PsA; however, the detection of periosteal proliferations on radiographs allows a relatively specific diagnosis of PsA. Skeletal scintigraphy and computed tomography are rarely used in PsA. Arthrosonography (ultrasound of the joints) is gaining increasing importance in the early identification of inflammatory soft tissue signs of PsA in the peripheral joints. Sonography enables early detection of synovitis and tenosynovitis as well as superficial erosions and also inflammatory processes of the tendon attachments. Magnetic resonance imaging (MRI) is indispensable for identifying possible involvement of the axial skeleton. Moreover, it allows good visualization of periostitis and arthritis. High resolution microcomputed tomography is an interesting novel diagnostic tool which allows highly sensitive evaluation of the bone structure and can detect very tiny bone lesions where typical signs of PsA are omega-shaped erosions and small corona-like spikes. Another interesting new diagnostic technique is fluorescence optical imaging (FOI) with the Xiralite system which is highly sensitive for detecting inflammatory processes of the hands.

Imaging modalities in psoriatic arthritis

This review presents an overview of the range of imaging modalities used in the diagnostic evaluation of patients with psoriatic arthritis (PsA). Conventional radiography is used to detect structural changes of the joints and tendon attachments. These changes occur late in the course of PsA hence conventional radiography contributes little to the early detection of PsA; however, the detection of periosteal proliferations on radiographs allows a relatively specific diagnosis of PsA. Skeletal scintigraphy and computed tomography are rarely used in PsA. Arthrosonography (ultrasound of the joints) is gaining increasing importance in the early identification of inflammatory soft tissue signs of PsA in the peripheral joints. Sonography enables early detection of synovitis and tenosynovitis as well as superficial erosions and also inflammatory processes of the tendon attachments. Magnetic resonance imaging (MRI) is indispensable for identifying possible involvement of the axial skeleton. Moreover, it allows good visualization of periostitis and arthritis. High resolution microcomputed tomography is an interesting novel diagnostic tool which allows highly sensitive evaluation of the bone structure and can detect very tiny bone lesions where typical signs of PsA are omega-shaped erosions and small corona-like spikes. Another interesting new diagnostic technique is fluorescence optical imaging (FOI) with the Xiralite system which is highly sensitive for detecting inflammatory processes of the hands.ZusammenfassungIn dem Beitrag werden die verschiedenen bildgebenden Verfahren in der Diagnostik der Psoriasisarthritis (PsA) dargelegt. Das konventionelle Röntgen wird zur Erfassung der strukturellen Veränderungen an den Gelenken und Sehnenansätzen eingesetzt. Jedoch kommen diese Veränderungen erst sehr spät zur Darstellung, womit dieses Verfahren gerade in der Frühdiagnostik nicht die notwendigen Informationen liefern kann. Jedoch ist durch den Nachweis von Periostproliferationen eine relativ spezifische Diagnose mithilfe des Röntgenbilds möglich. Die Skeletszintigraphie und Comptertomographie werden insgesamt selten in der Diagnostik der PsA eingesetzt. Die Gelenksonographie (Ultraschall) gewinnt zunehmend einen größeren Stellenwert in der Frühdiagnostik der entzündlichen Weichteilzeichen an den pripheren Gelenken bei der PsA. So ist die Arthrosonographie in der Lage die Synovitis und Tenosynovitis sowie oberflächlich liegende Erosionen frühzeitg zu detektieren, aber auch die entzündlichen Veränderungen an den Enthesen sind sonographisch gut objektivierbar. Die Magnetresonanztomographie (MRT) hat ihren Stellenwert in der Abklärung einer möglichen axialen Beteiligung im Rahmen der PsA und ist hier unverzichtbar. Periphere Manifestationen wie Periostitis und Arthritis kommen ebenfalls gut zur Darstellung. Die hochauflösende Mikro-Computertomographie ist ein neues, interessantes diagnostisches Verfahren, das die Knochenstruktur sehr sensitiv darstellt und damit kleinste Knochenläsionen aufzeigen kann. Typisch für die PsA ist die omegaförmige Erosion und der Nachweis von kleinen coronaförmigen Spikes. Ein weiteres neues diagnostisches Verfahren ist das fluoreszenzoptische bildgebende Verfahren (FOI) mit dem Xiralite-System, das sehr sensitiv entzündliche Veränderungen an den Händen aufzeigt.AbstractThis review presents an overview of the range of imaging modalities used in the diagnostic evaluation of patients with psoriatic arthritis (PsA). Conventional radiography is used to detect structural changes of the joints and tendon attachments. These changes occur late in the course of PsA hence conventional radiography contributes little to the early detection of PsA; however, the detection of periosteal proliferations on radiographs allows a relatively specific diagnosis of PsA. Skeletal scintigraphy and computed tomography are rarely used in PsA. Arthrosonography (ultrasound of the joints) is gaining increasing importance in the early identification of inflammatory soft tissue signs of PsA in the peripheral joints. Sonography enables early detection of synovitis and tenosynovitis as well as superficial erosions and also inflammatory processes of the tendon attachments. Magnetic resonance imaging (MRI) is indispensable for identifying possible involvement of the axial skeleton. Moreover, it allows good visualization of periostitis and arthritis. High resolution microcomputed tomography is an interesting novel diagnostic tool which allows highly sensitive evaluation of the bone structure and can detect very tiny bone lesions where typical signs of PsA are omega-shaped erosions and small corona-like spikes. Another interesting new diagnostic technique is fluorescence optical imaging (FOI) with the Xiralite system which is highly sensitive for detecting inflammatory processes of the hands.

SAT0416 Interreader-reliability of standardized evaluation of ICG-enhanced fluorescence-optical imaging

Background Interpretation of medical images needs to be standardized and trained. This applies also to fluorescence-optical imaging (FOI), a novel tool for assessment of inflammation in patients with arthritis (1). In this study we refined and evaluated the inter-reader reliability of the previously described algorithm of image interpretation of FOI. Objectives To determine the inter-reader reliability of the fluorescence optical imaging activity score (FOIAS) 7 readers from 4 centres each evaluated 34 randomly selected cases (5 RA, 5 PsA, 5 remissions, and 19 EA). FOIAS was analyzed in PrimaVistaMode (PVM) and 3 phases (P1, P2, P3). All participants were blinded for diagnosis and clinical findings. Overall, 28560 data sets were evaluated. Methods All participants were initially trained in software use and basic image interpretation by the supplier of the system. 5 of the 7 readers had no knowledge in the standardized image evaluation. Before starting the study a 2.5h training session was carried out and repeated once. All participants obtained a guideline and picture samples. For image interpretation, the automatically generated gain had to be checked by the readers and corrected as appropriate. The readers had to determine the 3 phases, and evaluate all 4 datasets of each case according to the guideline. Spearman correlations, agreement rates (2) and Cohen’s kappa coefficients were calculated. Results Correlations and agreement rates are presented in table 1. Two readers (2,4) showed relevant difference to the other readers. Cohen’s Kappa was between moderate and substantial. Highest Kappa was found for PVM (κ=0.68). FOIAS Spearman correlations, Spearman correlations Agreement rates, Agreement rates All readers without 2 and 4 All readers without 2 and 4 PVM 0.5 ≤r≤0.9 0.7 ≤r≤0.9 69%≤AR≤91% 82%≤AR≤91% P1 0.4 ≤r≤0.8 0.5 ≤r≤0.8 85%≤AR≤94% 88%≤AR≤94% P2 0.5 ≤r≤0.9 0.6 ≤r≤0.9 53%≤AR≤83% 72%≤AR≤83% P3 0.5 ≤r≤0.8 0.5 ≤r≤0.8 79%≤AR≤95% 87%≤AR≤93% Conclusions There was overall a good to nearly perfect correlation between readers. Thus standardized FOI evaluation gives high agreement in assessment of disease activity using FOIAS. There was high agreement for the decision if a joint is affected or not. Cohens Kappa showed that the standardized protocol is reliable after training. Highest Kappa was found for PVM. This is explicable with the fact, that PVM is a static image, while the image stack is dynamic. Reader 2 and 4 had problems in image interpretation depending on a dyschromatopsia and wrong image adjusting. Further training will be helpful. In conclusion, the used standardized protocol for assessment of inflammatory activity in FOI seems to be reliable and useful in daily practice. Redetermination of interreader-reliability after further refining of the protocol and training is planned. References Werner SG, Langer HE, Ohrndorf et al. Inflammation assessment in patients with arthritis using novel in vivo fluorescence optical imaging technology. Ann Rheum Dis 2011, Epub ahead of print. Schwenke C and Busse R. Analysis of differences in proportions from clustered data with multiple measurements in diagnostic studies. Meth Inform Med 2007 (46), 548-552 Disclosure of Interest S. Werner Grant/Research support from: Pfizer, U. Käßer: None Declared, C. Amberger: None Declared, M. Piesga: None Declared, F. Spiecker: None Declared, C. Volberg: None Declared, C. Schwenke: None Declared, H.-E. Langer Grant/Research support from: Pfizer, M. Backhaus Grant/Research support from: Pfizer

SAT0392 ICG-enhanced fluorescence optical imaging in clinical remission: Longitudinal data in RA and PSA patients with pre/post comparisons

Background ICG (Indocyanine-Green) fluorescence optical imaging (FOI) is a novel imaging technology in rheumatology (1) and may be a suitable tool for monitoring of disease activity and treatment response (2). Objectives This is the first study with longitudinal data of FOI in RA and PsA patients in clinical remission. The objective was to compare clinical activity and FOI findings before, at and after achievement of clinical remission. Methods A total of 113 subjects were included in a prospective study of FOI in RA and PsA patients with low disease activity (inception cohort: disease activity ≤1 at global assessment by patient or physician, NRS 0-10). All patients received a clinical examination by an independent investigator, and blood samples were taken for measurement of systemic inflammation (ESR, CRP). Inflammatory activity in FOI was assessed by an experienced reader using the semiquantitative fluorescence optical imaging activity score (FOIAS) (1), which comprises of the measurement of joint-related fluorescence signals in an automatically generated composite image (Prima Vista Mode, PVM) and in three predefined phases of FOI (P1, P2, P3).In 38 subjects with DAS28 remission (DAS28 <2,6) at least one FOI study had been performed either prior to remission (≥3 months, n=34) or at follow-up (≥3 months, n=31). 11 subjects had sequential FOI examinations prior to and after remission. The sample with a total of 103 FOI studies was selected for further analysis. Results In most patients clinical and FOI activity were following a uniform trend (table). Cross-sectional analysis revealed a moderate correlation of (r=0.4) of DAS28 and FOIAS. FOI evidence of subclinical disease activity was more pronounced in the various phases of a FOI sequence than in PVM. 11 subjects had treatment changes (reduction of DMARDs, tapering of steroid dose) due to clinical remission. In individual patients FOIAS increased with ongoing clinical remission. In joint-to-joint comparisons, those patients showed at first decreasing FOI activity in originally symptomatic joints with the achievement of remission. When treatment was reduced at this stage, then even clinically still asymptomatic patients demonstrated an increase in FOI activity in those same joints. DAS28 TJC SJC FOIASPVM FOIASP1 FOIAS P2 FOIAS P3 FOAIS P1-3 Prior to remission (n=34) 3,87 5 3 11 9 23 7 38 At remission (n=38) 1,7 1 0 5 3 11 2 16 Follow-up (n=31) 1,98 1 0 5 1 7 1 10 Conclusions FOI is a useful tool for monitoring disease activity and treatment response in RA and PsA patients. Most subjects with clinical remission showed residual activity in FOI. Pre/post-comparisons in individual patients suggest that subclinical disease activity in FOI may announce an initiating relapse in patients with premature withdrawal of treatment. References Werner SG, Langer HE, Ohrndorf et al. Inflammation assessment in patients with arthritis using novel in vivo fluorescence optical imaging technology. Ann Rheum Dis Oct 2011, Epub ahead of print. Werner S et al. 2011 ACR/ARHP Annual Scientific Meeting, Chicago, IL, Nov. 4 -9, 2011, Poster 199 Disclosure of Interest S. Werner Grant/Research support from: Pfizer, F. Spiecker: None Declared, C. Hermsen: None Declared, M. Bahner Shareholder of: mivenion GmbH, M. Backhaus Grant/Research support from: Pfizer, H.-E. Langer Grant/Research support from: Pfizer