Patient-activated three-dimensional multifrequency magnetic resonance elastography for high-resolution mechanical imaging of the liver and spleen.

PURPOSE: To introduce a novel in-vivo three-dimensional multifrequency magnetic resonance elastography (3D-MMRE) method for high-resolution mechanical characterization of the liver and spleen. MATERIALS AND METHODS: Ten healthy volunteers were examined by abdominal single-shot 3D-MMRE using a novel patient-activated trigger system with respiratory control. 10 contiguous slices with 2.5  mm cubic voxel resolution, 3 wave components, 8 time steps, and 2 averages were acquired at 7 mechanical excitation frequencies from 30 to 60  Hz. The total imaging time was approximately 15  min. For postprocessing, multifrequency dual elasto-visco (MDEV) inversion was used to calculate high-resolution mechanical parameter maps of the abdomen including the liver and spleen. RESULTS: Two parameters maps were generated from each image slice to capture the magnitude and the phase angle of the complex shear modulus. Both parameters depicted the mechanical structures of the abdomen with unprecedented high spatial resolution. Spatially averaged group mean values of the liver and spleen are 1.27 ±â€Š0.17 kPa and 2.01 ±â€Š0.69 kPa, indicating a significantly higher asymptomatic stiffness of the spleen compared to the liver. CONCLUSION: Patient-activated respiratory-gated 3D-MMRE combined with MDEV inversion provides highly resolved mechanical maps of the liver and spleen that are superior to previous elastograms measured by abdominal MRE.

[Quality management in intensive care medicine]. / Qualitätsmanagement in der Intensivmedizin.

Treatment of critical ill patients in the intensive care unit is tantamount to well-designed risk or quality management. Several tools of quality management and quality assurance have been developed in intensive care medicine. In addition to extern quality assurance by benchmarking with regard to the intensive care medicine, peer review procedures have been established for external quality assurance in recent years. In the process of peer review of an intensive care unit (ICU), external physicians and nurses visit the ICU, evaluate on-site proceedings, and discuss with the managing team of the ICU possibilities for optimization. Furthermore, internal quality management in the ICU is possible based on the 10 quality indicators of the German Interdisciplinary Society for Intensive Care Medicine (DIVI, "Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin"). Thereby every ICU has numerous possibilities to improve their quality management system.

[Quality management in intensive care medicine. Indispensable for daily routine]. / Qualitätsmanagement in der Intensivmedizin : Unverzichtbar in der täglichen Routine.

In areas requiring maximum safety like intensive care units or operating room departments, modern quality management and risk management are essential. Treatment of critically ill patients is associated with high risk and, therefore, demands risk management and quality management. External quality assessment in intensive care medicine has been developed based on a core data set and quality indicators. A peer review procedure has been established. In addition, regional networks of intensive care physicians result in improved local networking. In intensive care medicine, this innovative modular system of quality management and risk management is pursued more consequently than in any other specialty.

[Further education: a core responsibility of the German Society for Rheumatology and the Rheuma Academy]. / Weiterbildung - eine zentrale Aufgabe für DGRh und Rheumaakademie.

The first further education training program of the German Society of Rheumatology (DGRh) was an important milestone in further training in rheumatology. The workshop presented approaches on how to interest and gain students and young physicians for rheumatology and presented the possibilities planned by the DGRh in cooperation with partner organizations and the Rheuma Academy for improvement of further training in rheumatology and the potential to benefit inpatient further training. Many of the projects are dependent on financial support especially by industry. In this article the most important theses and arguments from the individual lectures will be presented.

[Amendment of the structural quality for inpatient rheumatology. A forward-looking concept]. / Neufassung der Strukturqualität der akut-stationären Rheumatologie. Ein zukunftsweisendes Projekt.

In 2010 a total of 9 guidelines on structural quality were endorsed by the Association of Rheumatology Clinics in Germany (VRA). These 9 structural criteria replace the regulations published in 2002 and were elaborated with the support of the German Rheumatology League. With guideline number 9 even the structural requirements for university hospitals are defined for the first time.Along with taking part in the quality project "Kobra" (continuous outcome benchmarking in rheumatology inpatient treatment) compliance with the new structural criteria constitutes a prerequisite for acquiring a quality certificate, which is awarded by an external institution.By this means the VRA sets the stage for its members to be prepared for future challenges and quality competition among hospitals. Furthermore, the provision of a high quality treatment for chronically diseased patients in rheumatology clinics will be effectively supported.

[Osteoporosis diagnosis and therapy according to the 2010 guidelines]. / Leitliniengerechte Diagnostik und Therapie der Osteoporose 2010.

Osteoporotic fractures are a frequent cause of disability and loss of quality of life in old age. Maintaining muscle function and balance, a daily calcium intake of 1000 mg, sufficient vitamin D and prudent use of drugs associated with falls and osteoporosis are key components to fracture prevention. The German guideline recommends that a specific long-term osteoporosis medication be initiated in individuals with a 30% 10-year risk for hip fractures and vertebral fractures.

A glimpse into the future: recombinant proteins and small molecules for targeted therapies in rheumatic diseases.

Whether the differences in the clinical picture and in the pathogenesis between rheumatoid arthritis (RA) and ankylosing spondylitis (AS) will lead to different therapeutic approaches is unclear at present. Since anti-TNF-alpha agents and other biologics are not efficacious in all patients new developments are clearly needed.

Biologics in the treatment of rheumatoid arthritis and ankylosing spondylitis.

There are clear differences in the clinical picture and in the pathogenesis between rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Biologic agents targeting TNF-alpha are efficacious in both diseases, with some tendency to work even better in spondyloarthritides (SpA) on a clinical basis. However, anti-TNF therapy was shown to inhibit radiographic progression in RA but not in AS. This is probably due to the outstanding difference in pathogenesis: while in RA osteodestructive lesions such as erosions predominate, AS patients will rather develop osteoproliferative changes such as syndesmophytes. There is some evidence that anti-TNF agents may show longterm efficacy and acceptable safety profiles over 5-10 years. There are some differences between the agents.Whether the recent developments of targeted therapies in RA with agents such as rituximab, abatacept and tocilizumab will also work for AS is unknown at present.

[Successful treatment of clinical manifestations of Muckle-Wells syndrome with anakinra]. / Erfolgreiche Behandlung der klinischen Manifestationen des Muckle-Wells-Syndroms mit Anakinra.

HISTORY: A 58-year-old woman and her 18-year-old daughter were first seen in our rheumatology centre after having experienced many years of periodic fever, arthralgia and urticaria. Some months ago a diagnosis of Muckle-Wells syndrome (MWS) had been made and confirmed by genetic testing. The mother had developed partial deafness and substantial loss of vision. Her daughter had been suffering mainly from urticaria and fever at least once daily. THERAPY: Because of the established role of interleukin (IL)-1 in this hereditary disease and some positive case reports, we decided to treat these patients with the IL-1 receptor antagonist anakinra. The patients reported a great success of this treatment with virtually complete absence of any acute MWS-associated symptoms. CONCLUSION: Therapy of MWS with anakinra seems to be highly efficacious for several clinical manifestations of this disease, including laboratory markers for inflammation. It is possible that organ destruction may be prevented by this medication.

[Structures of acute rheumatic care]. / Strukturen der akutstationären rheumatologischen Versorgung.

Severe rheumatological systemic diseases demand high levels of diagnostic and therapeutic measures and differentiated and complex methods of care. In Germany, specialised rheumatologists and, if hospitalisation is indicated, specialised rheumatology hospitals or departments are responsible for the treatment of these patients. Early rehabilitation procedures, provided by a multidisciplinary therapeutic team, are an important component of the treatment concept in these facilities. Early rehabilitation is integrated into the patients acute medical treatment plan, with careful consideration of the patients current health problems and functional capabilities (body functions and structures, activities and participation as outlined in the ICF), thereby providing a comprehensive, integrated therapy strategy which has long been acknowledged as necessary for the successful treatment of rheumatoid patients. This article presents an analysis concerning the development, organisation, facilities and processes of the acute medical in-patient care for patients with rheumatological disorders in Germany. In total there are 4188 beds in 88 acute hospitals exclusively available for rheumatological in-patients in Germany at present. There is at least one facility specialised in rheumatology in every German federal state. The density of care in the German federal states varies between 131.8 beds per 1 million inhabitants in Bremen and 9 beds per 1 million inhabitants in Saxony. In most regions of Germany the acute in-patient care for patients with rheumatological disorders is provided by hospitals specialised in rheumatology. Rheumatological patients are treated in a variety of hospital departments. In the year 2000 only 47% of the inpatients with rheumatoid arthritis, 56% of those with ankylosing spondylitis and 28% of those with systemic lupus erythematosus were treated in a ward specialising in rheumatology. Rheumatoid arthritis, with a total share of nearly 30%, was the most frequently treated rheumatic disease in wards specialising in rheumatology, followed by soft tissue disorders (e.g. fibromyalgia), diseases with systemic involvement of connective tissue and inflammatory spinal disorders such as ankylosing spondylitis.

Therapy of ankylosing spondylitis. Part II: biological therapies in the spondyloarthritides.

Therapeutic options for patients with active and severe spondylarthritis (SpA) have been fairly limited in the past decades. There is now accumulating evidence that biological therapy with agents directed against tumour necrosis factor-alpha (TNF-alpha) is highly efficacious in the spondyloarthritides, especially in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). The TNF blocking agents currently available, infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira), are approved for the treatment of rheumatoid arthritis (RA) in Europe and the USA. In contrast to rheumatoid arthritis (RA) disease-modifying anti-rheumatic drugs (DMARDs) have limited efficacy in SpA. No DMARDs are available for AS patients with active spinal disease. Thus, for AS patients whose condition is not sufficiently controlled with non-steroidal anti-inflammatory drugs (NSAIDs), therapy with TNF blockers may be considered as a first-line treatment. For infliximab, a dose of 3-5 mg/kg seems to be required, and intervals between 6 and 12 weeks are necessary to suppress disease activity continually. The standard dosage of etanercept is 2 x 25 mg subcutaneously (s.c.) per week. There are very few studies with adalimumab (standard dose in RA 20-40 mg s.c. every 1-2 weeks) in SpA. Infliximab and etanercept are now both approved for AS in Europe. There is some evidence that both agents also work in other SpA, especially in PsA. Withdrawal of long-term therapy in AS patients led to relapses of disease after several months. Less radiographic progression after 2 years of continuous treatment with infliximab compared to conventional therapy has been suggested in a small study. Serious adverse events on anti-TNF therapy have remained rare. However, severe infections, including tuberculosis, have been reported. These can be largely prevented by appropriate screening. The benefits of anti-TNF therapy in AS seem to outweigh these shortcomings.

Adverse haematological effects of vinblastine, prednisolone and cimetidine treatment: a retrospective study in fourteen dogs with mast cell tumours.

Vinblastine toxicity is poorly documented in dogs. The aim of this study was to investigate the haematological alterations in dogs treated with vinblastine and prednisolone. Fourteen dogs with mast cell tumours (MCT) were selected on at least one of the following criteria: lymph node infiltration, surgical margin infiltration, grade II MCTs with Ki-67 >10%, and grade III MCTs. Starting 15 days after surgery, the dogs were given vinblastine (2 mg/m2 i.v. four times weekly, then twice monthly for 2 months) and prednisolone (2 mg/kg/day p.o.). An EDTA blood sample was collected weekly for complete blood count (CBC). A total of 98 doses of vinblastine were given to the 14 dogs and 114 CBC were performed. Abnormal haematological findings were observed in 12 CBCs from five dogs, which represent a prevalence of 20% of the total CBCs performed in these animals. The most prevalent abnormal finding was thrombopenia (9/12) most often with grade I toxicity (6/9). In conclusion, the risk of occurrence of adverse haematological effects resulting from vinblastine-prednisolone treatment seems limited in dogs with MCT and it should not be overestimated.

Therapeutic use, efficiency and safety of the proteolytic pineapple enzyme Bromelain-POS in children with acute sinusitis in Germany.

The therapeutic efficiency and safety of the proteolytic enzyme bromelaine obtained from pineapple (Bromelain-POS, Ursapharm GmbH, Saarbrücken, Germany) was evaluated in children under the age of 11 years diagnosed with acute sinusitis. Data from 116 patients from 19 centres located across Germany were analysed in a pharmacoepidemiological cohort study. Patient cohorts were either treated with Bromelain-POS (N = 62), in combination with Bromelain-POS and standard therapies (N = 34), or with standard therapies (N = 20). The primary parameter measuring effectiveness of the different treatment groups was the duration of symptoms. The shortest mean period of symptoms was observed in patients treated with Bromelain-POS alone (6.66 days), followed by the standard therapy (7.95 days) and those treated with a combination of Bromelain-POS and the standard therapy (9.06 days). Patients of the Bromelain-POS monotherapy group showed a statistically significant faster recovery from symptoms (p = 0.005) compared to the other treatment groups. One 10-year-old male patient, with a known pineapple allergy, showed a self-limiting mild allergic reaction. No other unwanted side-effects were reported. This trial documents that the proteolytic pineapple enzyme Bromelain-POS is widely used in the treatment of young children diagnosed with acute sinusitis in Germany and that the use of proteolytic enzymes can benefit such patients.

Long-term comparison of a calcium-free phosphate binder and calcium carbonate--phosphorus metabolism and cardiovascular calcification.

BACKGROUND: Calcium carbonate used as a phosphate binder may contribute to cardiovascular calcification. Long-term comparisons of sevelamer, a non-calcium polymeric phosphate binder, and calcium carbonate (CC) are lacking. METHODS: 114 adult hemodialysis patients were randomly assigned to open label sevelamer or CC for 52 weeks. Study efficacy endpoints included changes in serum phosphorus, calcium, calcium-phosphorus product, and lipids. In addition, initial and sequential electron beam computerized tomography scans were performed to assess cardiovascular calcification status and change during follow-up. Safety endpoints were serum biochemistry, blood cell counts and adverse events. RESULTS: Patients receiving sevelamer had a similar reduction in serum phosphorus as patients receiving CC (sevelamer -0.58 +/- 0.68 mmol/l, CC -0.52 +/- 0.50 mmol/l; p = 0.62). Reductions in calcium-phosphorus product were not significantly different (sevelamer -1.4 +/- 1.7 mmol2/l2, CC -0.9 +/- 1.2 mmol2/l2; p = 0.12). CC produced significantly more hypercalcemia (> 2.8 mmol/l in 0% sevelamer and 19% CC patients, p < 0.01) and suppressed intact parathyroid hormone below 150 pg/ml in the majority of patients. Sevelamer patients experienced significant (p < 0.01) reductions in total (-1.2 +/- 0.9 mmol/l, -24%) and LDL cholesterol (-1.2 +/- 0.9 mmol/l, -30%). CC patients had significant increases in coronary artery (median +34%, p < 0.01) and aortic calcification (median +32%, p < 0.01) that were not observed in sevelamer-treated patients. Patients on sevelamer required more grams of binder (sevelamer 5.9 g vs. CC 3.9 g) and experienced more dyspepsia than patients on calcium carbonate. CONCLUSIONS: Sevelamer is an effective phosphate binder that unlike calcium carbonate is not associated with progressive cardiovascular calcification in hemodialysis patients.

[Fecal incontinence]. / Stuhlinkontinenz: Therapieoptionen.

Diagnosis and management of fecal incontinence requires exact understanding of the anatomic and pathophysiologic principles involved and demands a methodical, stepwise approach. Despite the potential appeal of surgical intervention, a considerable number of patients can be helped by comparatively simple, noninvasive measures. Initial treatment should be medical, including biofeedback in combination with a bowel management program. In the presence of a severely denervated pelvic floor, physiotherapeutic techniques rarely give rise to a satisfactory and long-lasting response. Obvious external sphincter defects and patients who failed medical management are treated surgically. Many injuries of the external sphincter can be treated by direct sphincter repair. If patients with intact external sphincters are unresponsive to medical measures, descending perineum and resultant idiopathic fecal incontinence will improve by radio-frequency delivery, sacral nerve stimulation, or postanal plication. Patients with complex neurologic disorders or extensive sphincter defects or who have undergone previous unsuccessful attempts at repair of the puborectalis itself should be considered for dynamic gracilis plastic or an artificial sphincter.

Biological therapies in the spondyloarthritides--the current state.

Therapeutic options for patients suffering from the more severe spondyloarthritides (SpA) have been rather limited in the last decades. Evidence is now accumulating that anti-tumour necrosis factor (TNF) therapy is highly effective in SpA, especially in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Based on the data recently published concerning more than 1000 patients with AS and PsA, this treatment seems to be even more effective than in rheumatoid arthritis (RA). The anti-TNFalpha agents currently available, infliximab (Remicade), etanercept (Enbrel) and adalimumab (Humira), are approved for the treatment of RA in the USA and Europe. The situation for SpA is different from RA because there is an unmet medical need, especially in AS, since no therapies with disease-modifying anti-rheumatic drugs (DMARDs) are available for severely affected patients, especially those with spinal disease. Thus, TNF blockers may even be considered a first-line treatment in a patient with active AS and PsA whose condition is not sufficiently controlled with non-steroidal anti-inflammatory drugs (NSAIDs) in the case of axial disease, and sulphasalazine or methotrexate in the case of peripheral arthritis. For infliximab, a dose of 5 mg/kg is required, and intervals of between 6 and 12 weeks are necessary to constantly suppress disease activity-also a major aim for long-term treatment. The standard dosage of etanercept is 2 x 25 mg subcutaneously per week. There are almost no studies yet on adalimumab (standard dose in RA, 20-40 mg subcutaneously every 1-2 weeks) in SpA. Infliximab and etanercept are now both approved for AS in Europe. The efficacy of etanercept was first demonstrated in PsA, and it is now approved for this indication in the USA and Europe. There is preliminary evidence that both agents also work in other SpA, such as undifferentiated SpA (uSpA). Studies should be performed to document the long-term efficacy of this treatment. There is hope that ankylosis may be preventable, but it remains to be shown whether patients benefit from long-term anti-TNF therapy and whether radiological progression and ankylosis can be stopped. Severe adverse events have remained rare. Complicated infections including tuberculosis have been reported. These can largely be prevented by appropriate screening. As it stands now, the benefits of anti-TNF therapy in AS seem to outweigh these shortcomings.

Cytokine release of whole blood from adult female donors challenged with mistletoe lectin-1 standardised mistletoe extract and E. coli endotoxin or phytohaemagglutinin (PHA).

Cytokine (TNF, alpha, interleukin-6) release of whole blood from healthy donors was challenged with mistletoe extract standardised for mistletoe lectin-1 (sML) and control substances (E. coli endotoxin; phytohaemagglutinin). The rationale of this investigation was non-proven warnings that pro-inflammatory cytokines induce by the application of standardised mistletoe lectins may induce tumor cell proliferation. These investigations provided evidence that non-cytotoxic concentrations of sML did not induced enhanced TNFa or interleukin-6 secretion compared to non-challenged control cells. Cytotoxic concentrations of sML, however, induced significantly higher cytokine levels than the control, obviously due to non-physiological stimuli. Immunomodulation with clinically relevant, low-dose sML incubation did not induce proinflammatory cytokine secretion in vitro.

Therapy for ankylosing spondylitis: new treatment modalities.

The therapeutic options for patients suffering from the more severe forms of spondyloarthritis (SpA) have been rather limited in recent decades. There is now accumulating evidence that anti-tumour necrosis factor (anti-TNF) therapy is highly effective in SpA, especially in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Based on the data recently published on more than 200 AS patients, and more than 100 PsA patients, this treatment seems to be even more effective than it is in rheumatoid arthritis (RA). The two major anti-TNF-alpha agents currently available, infliximab (Remicade) and etanercept (Enbrel), are approved for the treatment of RA in Europe and in the USA. The situation in SpA is different from RA because there is an unmet medical need, especially in AS, because disease-modifying anti-rheumatic therapy is not available for severely affected patients. Thus, TNF blockers might even be considered first-line immunosuppressive treatment in patients with active AS who are not sufficiently treated with non-steroidal anti-inflammatory drugs (NSAIDs). For infliximab, a dose of 5mg/kg was required, and intervals between 6 and 12 weeks were necessary for constant suppression of disease activity - a major aim also for long-term treatment. However, it remains to be shown whether patients benefit from long-term therapy and whether radiological progression and ankylosis can be stopped. The optimal doses of infliximab might well be determined individually. Allergic reactions and increased susceptibility to tuberculosis are rare side-effects which need to be recognized early. As it stands now, the benefits of anti-TNF therapy in AS seem to outweigh these shortcomings. The efficacy of etanercept was first demonstrated in PsA. A double-blind study has now been performed in AS - with similar results. There is preliminary evidence that both agents also work in other SpA such as undifferentiated SpA. Hopefully, both agents will be approved soon for the short-term treatment of severe SpA. In parallel, studies should be performed to document the long-term efficacy and safety of this treatment.