[Development of quality standards for patients with axial spondyloarthritis for use in Germany]. / Entwicklung von Qualitätsstandards für Patient*innen mit axialer Spondyloarthritis zum Einsatz in Deutschland.

Quality standards (QS) are measurable constructs designed to quantify gaps in care and subsequently to improve quality of care. The Assessment of SpondyloArthritis International Society (ASAS) recently generated and published international QS for the management of patients with axial spondyloarthritis (axSpA) for the first time. The German Society of Rheumatology (DGRh) then decided to translate, review and possibly adopt these standards by a group of experts from different care settings. Against this background, national QS for the management of patients with axSpA for Germany were developed for the first time. The main focus was on feasibility and practical relevance. Ultimately, nine QS were defined with which the quality of care in Germany can and should be measured and improved.

Rituximab in routine care of severe active rheumatoid arthritis : A prospective, non-interventional study in Germany.

OBJECTIVE: To assess safety, effectiveness and onset of effect of rituximab (RTX) in routine clinical treatment of severe, active rheumatoid arthritis (RA). METHODS: Prospective, multi-centre, non-interventional study in rheumatological outpatient clinics or private practices in Germany. RTX-naïve adult patients were to receive RTX according to marketing authorisation and at their physician's discretion. Also according to their physician's discretion, patients could receive a second cycle of RTX (re-treatment = treatment continuation). Major outcome was the change in Disease Activity Score based on 28-joints count and erythrocyte sedimentation rate (DAS28-ESR) over 24 weeks and during 6 months of re-treatment. RESULTS: Overall, 1653 patients received at least one cycle RTX; 99.2% of these had received disease-modifying antirheumatic drugs (DMARD) pre-treatment and 75.5% anti-tumor necrosis factor(TNF)­α pre-treatment. After a mean interval of 8.0 months, 820 patients received RTX re-treatment. Mean DAS28-ESR decreased from 5.3 at baseline to 3.8 after 24 weeks (-1.5 [95% confidence interval, CI: -1.6; -1.4]), and from 4.1 at start of cycle 2 to 3.5 at study end (change from baseline: -1.8 [95% CI: -2.0; -1.7]). Improvements in DAS28-ESR and Health Assessment Questionnaire (HAQ) score occurred mainly during the first 12 weeks of RTX treatment, with further DAS28-ESR improvement until week 24 or month 6 of re-treatment. Improvements in DAS28-ESR and EULAR responses were more pronounced in seropositive patients. RF was a predictor of DAS28-ESR change to study end. Safety analysis showed the established profile of RTX. CONCLUSION: RTX was safe and effective in a real-life setting with rapid and sustained improvement in RA signs and symptoms.

[S2e guideline: treatment of rheumatoid arthritis with disease-modifying drugs]. / S2e-Leitlinie: Therapie der rheumatoiden Arthritis mit krankheitsmodifizierenden Medikamenten.

BACKGROUND: Medication-based strategies to treat rheumatoid arthritis are crucial in terms of outcome. They aim at preventing joint destruction, loss of function and disability by early and consistent inhibition of inflammatory processes. OBJECTIVE: Achieving consensus about evidence-based recommendations for the treatment of rheumatoid arthritis with disease-modifying anti-rheumatic drugs in Germany. METHODS: Following a systematic literature research, a structured process among expert rheumatologists was used to reach consensus. RESULTS: The results of the consensus process can be summed up in 6 overarching principles and 10 recommendations. There are several new issues compared to the version of 2012, such as differentiated adjustments to the therapeutic regime according to time point and extent of treatment response, the therapeutic goal of achieving remission as assessed by means of the simplified disease activity index (SDAI) as well as the potential use of targeted synthetic DMARDs (JAK inhibitors) and suggestions for a deescalating in case of achieving a sustained remission. Methotrexate still plays the central role at the beginning of the treatment and as a combination partner in the further treatment course. When treatment response to methotrexate is inadequate, either switching to or combining with another conventional synthetic DMARD is an option in the absence of unfavourable prognostic factors. Otherwise biologic or targeted synthetic DMARDs are recommended according to the algorithm. Rules for deescalating treatment with glucocorticoids and-where applicable-DMARDs give support for the management of patients who have reached a sustained remission. DISCUSSION: The new guidelines set up recommendations for RA treatment in accordance with the treat-to-target principle. Modern disease-modifying drugs, now including also JAK inhibitors, are available in an algorithm.

[Magnetic resonance angiography in rheumatology]. / Magnetresonanzangiographie in der Rheumatologie.

The potentials and pitfalls of magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) in the diagnosis of large vessel vasculitis are summarized in this review article. With the ability to visualize the lumen and vessel walls of large and medium sized arteries, MRI and MRA have great potential to play a unique role in the diagnosis of large vessel vasculitis. This is underlined by the fact that mural inflammatory changes typically involve uptake of contrast agent that can be visualized with MRI. The cranial, intracranial and extracranial involvement pattern can be studied in a combined approach including an MRI examination of the superficial cranial arteries and an MRA examination of the thoracic aorta with its major supra-aortic branches. Typical MRI sequence parameters are given including monophasic MRA and time-resolved MRA protocols at 3 T. The MRI and MRA techniques have the potential to determine the most suitable (inflamed) segment for temporal artery biopsy and to monitor treatment. Initial results of multicenter studies for the diagnostic accuracy of these relatively new methods are expected soon. The MRA technique is recognized as an interesting alternative to invasive catheter angiography for the evaluation of central nervous system (CNS) vasculitis.

[German 2012 guidelines for the sequential medical treatment of rheumatoid arthritis. Adapted EULAR recommendations and updated treatment algorithm]. / S1-Leitlinie der DGRh zur sequenziellen medikamentösen Therapie der rheumatoiden Arthritis 2012. Adaptierte EULAR-Empfehlungen und aktualisierter Therapiealgorithmus.

Following the EULAR recommendations published in 2010 German guidelines for the medical treatment of rheumatoid arthritis were developed based on an update of the systematic literature search and expert consensus. Methotrexate is the standard treatment option at the time of diagnosis, preferably in combination with low dose glucocorticoids. Combined disease-modifying antirheumatic drugs (DMARD) therapy should be considered in patients not responding within 12 weeks. Treatment with biologicals should be initiated in patients with persistent high activity no later than 6 months after conventional treatment and in exceptional situations (e.g. early destruction or unfavorable prognosis) even earlier. If treatment with biologicals remains ineffective, changing to another biological is recommended after 3-6 months. In cases of long-standing remission a controlled reduction of medical treatment can be considered.

Effectiveness and safety of the interleukin 6-receptor antagonist tocilizumab after 4 and 24 weeks in patients with active rheumatoid arthritis: the first phase IIIb real-life study (TAMARA).

OBJECTIVES: To confirm the effectiveness and safety of the interleukin 6-receptor antagonist tocilizumab in patients with rheumatoid arthritis (RA) in a setting close to real-life medical care in Germany. METHODS: A multicentre open-label phase IIIb study was undertaken. Patients with active RA with a 28-joint Disease Activity Score (DAS28) >3.2 despite previous disease-modifying antirheumatic drugs (DMARDs) were treated with tocilizumab 8 mg/kg every 4 weeks. The primary end point was the proportion of patients achieving LDAS ≤3.2 at week 24; secondary end points included American College of Rheumatology (ACR), European League Against Rheumatism (EULAR) or Clinical Disease Activity Index (CDAI) responses and decrease in acute phase. Analyses in subgroups such as rheumatoid factor (RF)-positive versus RF-negative patients and patients with an inadequate response to treatment with DMARDs (DMARD-IR) versus those with an inadequate response to tumour necrosis factor (TNF) antagonists (TNF antagonist-IR) were performed. Safety was assessed by adverse event documentation. RESULTS: 286 patients were treated and 83.6% completed the study. 41.6% had previously been treated with TNF antagonists. 57% of the intention-to-treat patients achieved the primary end point of LDAS, 47.6% achieved DAS remission <2.6 and a EULAR 'good response' was achieved by 54.9%; ACR50/70 response rates at week 24 were 50.7% and 33.9%, respectively. The mean±SD decrease in CDAI from baseline to week 24 was 71±29%. C reactive protein levels normalised rapidly within 1 week. Major improvements in fatigue, pain and morning stiffness were observed in the first 4 weeks and further improved until week 24. DAS28, EULAR and ACR responses at week 24 did not differ between RF-positive and RF-negative patients. TNF antagonist-naive patients responded better than patients who had previously failed on TNF antagonists. The safety profile of tocilizumab was comparable to that previously observed in the phase III trial programme. Serious infections were observed in 3.1% of patients. CONCLUSIONS: Tocilizumab is highly effective in a setting close to real-life medical care with a rapid and sustained improvement in signs and symptoms of RA. A manageable safety profile was seen over the 24-week study period.

[Magnetic resonance imaging in rheumatology]. / Magnetresonanztomographie in der Rheumatologie.

Imaging plays a major role in the diagnosis and meanwhile also in the therapy control of rheumatic diseases. Besides the commonly used X-ray technique and musculoskeletal ultrasound, magnetic resonance imaging (MRI) is able to provide a three-dimensional view of musculature, ligaments, tendons, capsules, synovial membranes, bones and cartilage with high resolution quality. Therefore, MRI is being employed more and more in the early diagnosis of inflammatory joint and spinal diseases. Contrast-enhanced MRI enables an assessment of disease activity and a differentiation between active and chronic joint manifestation. The technical examinations by MRI are these days standardized and invariably reproducible. This makes it possible to document the course of a disease and allows subsequent treatment decisions. In addition to midfield (>0.5<1.0 T) and high field MRI (>1.0 T), low field MRI (<0.5 T) is used in rheumatology as a patient-friendly office-based technique.

[Low-field magnetic resonance imaging for rheumatoid arthritis]. / Niederfeldmagnetresonanztomographie bei rheumatoider Arthritis.

Magnetic resonance imaging (MRI) as a cross-sectional imaging procedure allows a three-dimensional representation of musculature, ligaments, tendons, capsules, synovial membranes, bones and cartilage with high resolution quality. An activity assessment is further possible by application of a contrast medium (gadolinium-DTPA) to differentiate between active and chronic inflammatory processes. Evidence of a bone marrow edema detected by MRI in patients with rheumatoid arthritis (RA) can be interpreted as a prognostic and predictive factor for the development of bone erosions. On the basis of these advantages MRI is being employed more and more in the early diagnosis of inflammatory joint diseases. Semi-quantitative scores for analysis and grading of findings have already been developed and are in clinical use. Because MRI technical performances are invariably reproducible they can be practically retrieved in the course of examination which is particularly relevant in rheumatology. Therapy response or progression can thus be adequately displayed. Open, dedicated low-field MRI with a low signal strength of 0.2 Tesla (T) has been known since the 90s and now represents new MRI examination options in rheumatology. Smaller devices with lower acquisition and maintenance expenses as well as considerably more convenience due to the device itself result in a higher subjective acceptability by the patients as well as objectively more data records of low-field MRI scans of RA, which underline the significance of this new technical method. The German Society for Rheumatology (DGRh), represented by the Committee for "Diagnostic Imaging", meets this development with the release of recommendations and standards for the procedures of low-field MRI and their scoring and summarizes the most important technical data and information on clinical indications.

[Color Doppler sonography for investigation of peripheral joints and ligaments]. / Farbdopplersonographie bei der Untersuchung peripherer Gelenke und Sehnen.

Doppler ultrasound is able to visualize blood flow by the change in frequency (Doppler shift) of sound waves which are reflected by moving blood cells inside the vessels (Doppler effect). As hyperemia caused by vasodilatation and angiogenesis is the earliest detectable pathologic change in the beginning of synovitis, Doppler ultrasonography can be used to assess inflammatory activity. Several studies could show a strong correlation between magnetic resonance imaging (MRI) as well as histological findings (blood vessel density) and Doppler sonographic determination of synovial perfusion. Equipment settings must be adapted to slow blood flow in very small blood vessels to reach an appropriate imaging quality. Color and power Doppler ultrasound can depict different grades of intra-articular and peritendinous blood flow, which allows an estimation of inflammatory activity and facilitates the differentiation and monitoring of rheumatic diseases during follow up.

Eradication of Helicobacter pylori with pantoprazole and two antibiotics: a comparison of two short-term regimens.

BACKGROUND: High rates of Helicobacter pylori eradication can be achieved by combining proton pump inhibitors with two antibiotics. However, in the search for an optimal therapy a direct comparison of different regimens is necessary. METHODS: For this open study, 331 patients with duodenal ulcer were screened and randomly allocated to either pantoprazole 40 mg b.d., clarithromycin 500 mg b.d., and metronidazole 500 mg b.d. (PCM) or pantoprazole 40 mg b.d., amoxycillin 1000 mg b.d., and clarithromycin 500 mg b.d. (PAC) for 7 days. Both combinations were followed by a 7-day therapy with pantoprazole 40 mg o.d. alone. Eradication of H. pylori was assessed by use of a 13C-urea breath test 4 weeks after the intake of the last medication. RESULTS: Eradication rates were 90% in intention-to-treat patients from the PCM (132 out of 147; 95% CI: 84-94%) and the PAC group (135 out of 150; 95% CI: 84-94%). H. pylori was eradicated in 112 out of 117 per protocol patients of the PCM group (96%; 95% CI: 90-99%) and in 119 out of 126 patients of the PAC group (94%; 95% CI: 89-98%). Rapid relief from ulcer pain and a decrease in the mean intensity of other gastrointestinal symptoms was observed. Sixty-nine patients reported adverse events, none of which were related to the intake of pantoprazole. Four serious adverse events, none related to the trial medication, were observed. CONCLUSIONS: Both pantoprazole-based short-term triple therapies are highly effective and well-tolerated treatment regimens in the eradication of H. pylori.

Immunogenetics of spondyloarthropathies.

The association of HLA-B27 with ankylosing spondylitis and related spondyloarthropathies has been known for two decades and has provided a great impetus to the epidemiologic studies and also helped broaden the clinical spectrum of these diseases. The etiology of these diseases is likely to be multifactorial and include genetic, immunologic, and environmental mechanisms. The detailed three-dimensional x-ray crystallographic structure of B27 has now been reported. It has revealed electron density compatible with oligopeptides that are nine amino acid-long (nonamers) bound in the antigen-binding cleft of the molecule. Microsequence analysis of 11 peptides eluted from the antigen-binding cleft has confirmed that all are nonamers. The most restricted position in the bound peptide is the second position, where all the 11 peptides contain arginine. The side chain of arginine extends into the B pocket ("45 pocket"), which seems to act as a specificity side pocket in the antigen-binding cleft of the B27 molecule. It is very likely that an understanding of the detailed structure of B27, including the peptide-binding motif and the structural domains recognized by cytotoxic T cells, along with the recent development of the B27 transgenic rat model for spondyloarthropathies, will further enhance our understanding of the immunogenetics of these diseases. It is hoped that this will lead to the source of the arthritogenic triggers and possibly disease prevention by antigen-specific immunomodulation. Because T-cell activation is initiated by the formation of antigen-MHC complexes that are the ligands that are recognized by the antigen-specific T-cell receptor (TCR), it might be possible to inhibit this activation by blocking the antigen-binding cleft of MHC molecules by using high-affinity MHC-binding peptides (MHC blockade) or by a novel, new, and more efficient method of TCR antagonism.

Rapidly progressive seronegative spondylarthropathy with atlantodental subluxation in a patient with moderately advanced HIV infection.

It has been suggested that the immunosuppressed state associated with HIV infection may influence the clinical course of rheumatic diseases. We describe the case of a patient with moderately advanced HIV infection who developed a psoriatic rash and a rapidly progressive spondylarthropathy of the cervical spine with atlantodental subluxation requiring spondylodesis. This case supports the hypothesis that HIV infection may be associated with uncommon manifestations and a rapidly progressive course refractory to medical therapy in patients with spondylarthropathy.

Joint forces in the human pelvis-leg skeleton during walking.

For the calculation of the forces in the hip, knee and ankle joints during walking the knowledge of the three-dimensional movements of the human body and of the forces between foot and ground is a prerequisite. It is shown how this information may be obtained and what accuracy is obtainable. For the calculation of the statically indeterminate system of the lower limbs, consisting of muscles, bones and joints an optimization method is applied. The optimization criterion is the minimization of the muscle forces. Measurements were taken with seventeen male and five female persons. The maximum joint forces are plotted against gait speed, body weight and body size. In addition some statistical distributions are presented.

Aortic valve debridement by ultrasonic surgical aspirator in degenerative, aortic valve stenosis: follow-up with Doppler echocardiography.

OBJECTIVE: Recently there has been an emphasis on reconstructing diseases native valves as an alternative to prosthetic valve replacement. Whereas; the surgical repair of aortic valve stenosis has been always problematic. This study was performed to estimate the clinical results after aortic valve debridement using ultrasonic energy. METHODS: Between 1990-1994 26 patients underwent ultrasonic aortic valve decalcification. There were 15 females and 11 males, the age was in average 74 years. As a concomitant diagnosis 88% patients (23) had mostly mild, aortic valve insufficiency, 16 (61%) had coronary artery disease and 11 (42%) had mild mitral valve incompetence. All of the patients were operated with cardiopulmonary bypass using moderate hypothermia, cardioplegical arrest and topical cooling for myocardial protection. The calcifications were removed tangentially using Cavitron Ultrasonic Surgical Aspirator. (CUSA), CAVITRON, USA. Leaflet perforation and/or unsatisfactory valve closure have been indications for aortic valve replacement. RESULTS: Two operative death (8%) have occurred and six patients have died in the further course (follow-up mean 17 months ranging from 4 to 61 months). Postoperative Doppler-Echocardiography results taken directly after surgery and then again 17 months later (n = 18) showed a decrease of peak and mean gradients across the aortic valve three and two times respectively (p < 0.001). 17 months after debridement we observed a mild rise in both gradients (by peak gradient p < 0.05). Directly postoperative, the aortic valve area increased doubly and decreased 17 months later slight, but it was still statistically significant in comparison with our preoperative data (p < 0.001). Follow-up echocardiography demonstrated late onset of moderate aortic valve insufficiency in 6 patients. The classification of New York Heart Association was improved in 13 (72%) survivors after 17 months. CONCLUSIONS: Ultrasonic debridement of aortic valve stenosis allows precise and energy-controlled removal of calcium, increased doubly the valve area and decreased of peak and mean gradients statistically significant. The advantages of preserving the native aortic valve in elderly patients are relative good arguments; although a longer follow-up is necessary to establish this procedure.

[Determination of skull volume (author's transl)]. / Untersuchungen zur Schädelvolumenbestimmung

Various means for indirect skull volume determination were investigated. For this purpose--the procedure of direct measurement of skull volume was improved first, using a latex method. The examinations were carried out on 20 macerated skulls, which were x-rayed in the usual manner and stereoscopically also. Various distances and planes were then determined from the radiographs and varied calculations carried out. From these calculations it appears that skull volume can be simply determined most accurately from the product of transverse diameter (greatest width) and the area of median plane.