[Data analysis in rheumatology practices : Possibilities, limitations, and results]. / Datenanalysen in Rheumapraxen : Möglichkeiten, Grenzen und Ergebnisse.

Data analyses in rheumatology practices can be used as a feedback system in quality management. Implementation of a representative patient survey enables evaluation of one's own work and can be used for external presentation of the practice. Patient education and the structured use of specialist rheumatology assistants were evaluated by means of a survey. Systematic screening for depressive symptoms was carried out and enables a better understanding of patients and their "unmet needs". An analysis of the diseases and the patients in terms of physical function, disease activity, medication, and concomitant diseases is possible using structured patient documentation in a specialized documentation system. Within the RHADAR network (RheumaDatenRhePort G.b.R.), the proportion of rheumatoid arthritis patients treated with Janus kinase inhibitors was compared between different centers. Patients suitable for clinical trials can be filtered out of a structured documentation system.

T cells, natural killer cells, and γδT cells in a large patient cohort with rheumatoid arthritis: influence of age and anti-rheumatic therapy.

Objective: The aim of this cohort study was to evaluate the distribution of natural killer (NK) cells and T-cell subsets, including γδT cells, in the peripheral blood of patients with rheumatoid arthritis (RA) in a large real-life patient cohort, taking into account the patients' demographics, disease characteristics, and anti-rheumatic therapy.Method: The study recruited 508 RA patients between November 2013 and August 2015. Lymphocyte differentiation using eight-colour flow cytometry (fluorescence-activated cell sorting) of the peripheral blood was performed for all patients. Clinical data, including age, gender, disease duration, serostatus, disease activity, antibody status, immunosuppressive therapy including use of different biological disease-modifying anti-rheumatic drugs (bDMARDs) and conventional synthetic DMARDs, were retrospectively assessed using electronic patient files. Multivariate regression analysis was performed to assess the effect of these variables on T-cell, NK-cell, and γδT-cell counts.Results: The median patient age was 61.0 years and 74.1% were female. The median disease duration of RA was 12.0 years. Median Disease Activity Score based on 28-joint count was 2.8 and 56.3% were treated with bDMARDs. There were no differences in immunosuppressive therapy between different age groups. While rituximab, abatacept, and tocilizumab had no influence on lymphocyte subdifferentiation, tumour necrosis factor (TNF) inhibitors and age significantly influenced the numbers of T cells, T-helper cells, T-NK cells, NK cells, and γδT cells.Conclusion: Age and TNF-inhibition therapy influence lymphocyte subdifferentiation in patients with RA. It may be prudent to use age- and therapy-adjusted standard values for lymphocyte subsets during clinical trials and treatment of RA.

Simple screening tools predict death and cardiovascular events in patients with rheumatic disease.

OBJECTIVES: Patients with rheumatic disease (RD) have an increased mortality risk compared with the general population, mainly due to cardiovascular disease (CVD). We aimed to identify patients at high risk of CVD and mortality by comparing three screening tools suitable for clinical practice. METHOD: In this prospective, single-centre study, consecutive patients with rheumatoid arthritis (RA), systemic autoimmune disease (SAI), or spondyloarthritides (SpA) including psoriatic arthritis underwent a comprehensive cardiovascular risk assessment. Patients were predefined as being at high risk for cardiovascular events or death if any of the following were present: European Systematic COronary Risk Evaluation (SCORE) ≥ 3%, N-terminal pro-brain natriuretic peptide (NT-proBNP) ≥ 200 pg/mL, or any pathological electrocardiogram pattern. RESULTS: The patient population (n = 764) comprised 352 patients with RA, 260 with SAI, and 152 with SpA. After a median follow-up of 5.2 years, 6.0% of RD patients had died (7.0%, 7.2%, and 1.4% of patients in the RA, SAI, and SpA subgroups), and 5.0% had experienced a cardiovascular event (5.0%, 6.4%, and 2.8%, respectively). For all RD patients and the RA and SAI subgroups, NT-proBNP ≥ 200 pg/mL and SCORE ≥ 3% identified patients with a 3.5-5-fold increased risk of all-cause death and cardiovascular events. Electrocardiogram pathology was associated with increased mortality risk, but not with cardiovascular events. CONCLUSION: NT-proBNP ≥ 200 pg/mL or SCORE ≥ 3% identifies RA and SAI patients with increased risk of cardiovascular events and death. Both tools are suitable as easy screening tools in daily practice to identify patients at risk for further diagnostics and closer long-term follow-up.

[Rheumatoid symptoms in patients with hematologic neoplasms]. / Rheumatische Krankheitserscheinungen bei hämatologischen Neoplasien.

Paraneoplastic syndromes in lymphatic or myeloid neoplasms can present with musculoskeletal symptoms, vasculitis-like or febrile symptoms. Hematologic diseases are also associated with rheumatic diseases whereas inflammatory rheumatic diseases are often associated with an increased risk for lymphoproliferative disease. Atypical disease characteristics, lack of disease-specific antibodies or therapeutic response are red flags for diagnosing paraneoplastic or coexistent malignant diseases. New onset of systemic symptoms, worsening of general condition, night sweats or weight loss need to be considered during follow-up and differential diagnostics. This article focuses on musculoskeletal, vasculitis-like and systemic signs of lymphatic or myeloid neoplasms either because of coexistency, tumor association or paraneoplastic disease.

[Medical treatment of rheumatoid arthritis in 2014 : Current data from the German Collaborative Arthritis Centers]. / Versorgung der rheumatoiden Arthritis 2014 : Aktuelle Daten aus der Kerndokumentation.

BACKGROUND: Since the introduction of biologic treatment in rheumatoid arthritis (RA), disease activity and treatment modalities have changed substantially. The current provision and developments in recent years are analyzed with annual data from the National Database of the Collaborative Arthritis Centers in Germany. METHODS: To analyze disease activity, diagnostics and treatment in RA patients in 2014 with regard to seropositivity and disease duration. Time trends from 2007-2014 are reported for disease activity (DAS28) distribution and biologic treatment. RESULTS: In 2014, a total of 8,084 RA patients were analyzed: 72 % were rheumatoid factor and/or ACPA positive, the mean age was 62 years and the mean disease duration 12 years. According to DAS28, 35.9 % were in remission, 19.2 % had low, 37.1 % moderate and 7.8 % high disease activity. An increase since 2007 was only observed in patients with a disease duration >2 years. Synthetic DMARDS were used for treatment in 78 %. Biologic treatment increased from 16 % (2007) to 27 % (2014). Especially those patients with a disease duration >5 years were treated more frequently with biologics. Seronegative patients had slightly less severe mean disease activity parameters. They were treated equally frequent with DMARDS but only half as often with biologics compared to seropositive patients. CONCLUSION: The use of biologics in RA patients has increased since 2007; however this was not observed in patients with short disease duration. Early intensive treatment adaption seems justified to improve disease activity in the large portion of patients who do not reach low disease activity under conventional DMARDs.

[Disease-modifying antirheumatic drugs in rheumatoid arthritis patients with a history of colorectal cancer]. / Basistherapie bei Patienten mit rheumatoider Arthritis und kolorektaler Tumoranamnese.

BACKGROUND: Cells of the adaptive immune system are relevant for the anti-tumor immune response; therefore, the basal therapy with disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis patients with a history of gastrointestinal cancer must be carefully considered. OBJECTIVE: This article presents the evidence regarding colorectal cancer (CRC) and rheumatoid arthritis. METHOD AND RESULTS: The article is based on a PubMed search as well as a search in congress abstracts of the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Current recommendations regarding screening and follow-up of CRC are summarized for clinically active rheumatologists. The current status of therapy and future therapeutic options are presented. The lower incidence of CRC in rheumatoid arthritis (RA) patients and the incidence under treatment with various DMARDs are described. The treatment options for RA patients in different tumor situations, e.g. during cytostatic therapy, palliative and curative situations are discussed, as well as the available evidence. In spite of the unsatisfactory level of evidence, conclusions and practical considerations for use by rheumatologists in clinical practice are discussed.

Interferometry with Bose-Einstein condensates in microgravity.

Atom interferometers covering macroscopic domains of space-time are a spectacular manifestation of the wave nature of matter. Because of their unique coherence properties, Bose-Einstein condensates are ideal sources for an atom interferometer in extended free fall. In this Letter we report on the realization of an asymmetric Mach-Zehnder interferometer operated with a Bose-Einstein condensate in microgravity. The resulting interference pattern is similar to the one in the far field of a double slit and shows a linear scaling with the time the wave packets expand. We employ delta-kick cooling in order to enhance the signal and extend our atom interferometer. Our experiments demonstrate the high potential of interferometers operated with quantum gases for probing the fundamental concepts of quantum mechanics and general relativity.

Screening for latent tuberculosis infection: performance of tuberculin skin test and interferon-γ release assays under real-life conditions.

OBJECTIVES: To characterise optimal screening strategies for latent tuberculosis infection (LTBI) prior to the initiation of anti-tumour necrosis factor therapy. METHODS: Patients in 62 German rheumatology centres were evaluated for LTBI. Each patient was screened with a tuberculin skin test (TST) and one form of an interferon-γ release assay (IGRA), either TSPOT.TB (TSPOT) or Quantiferon TB Gold (QFT). RESULTS: A total of 1529 patients with rheumatological disease were tested with a TST, 844 with TSPOT and 685 with QFT. TST was positive in 11.3% (n=173). The prevalence of LTBI was 8.0% when defined as a positive TST and no previous Bacille Calmette-Guérin (BCG) vaccination and 7.9% when based on a positive IGRA. Combining both estimates increased the prevalence of LTBI to 11.1%. Clinical risk factors for LTBI were found in 122 patients (34 with a history of prior TB, 81 close contacts and 27 with suggestive chest x-ray lesions). A compound risk factor (CRF) was defined as the presence of at least one of these three risk factors. Statistical analyses were conducted to examine the association between CRF and LTBI test outcomes. In multivariate analysis, TST was influenced by CRF (OR 6.2; CI 4.08 to 9.44, p<0.001) and BCG vaccination status (OR 2.9; CI 2.00 to 4.35, p<0.001). QFT and TSPOT were only influenced by CRF (QFT: OR 2.6; CI 1.15 to 5.98, p=0.021; TSPOT: OR 8.7; CI 4.83 to 15.82, p<0.001). ORs and the agreement of TST and IGRA test results varied by rheumatological disease. CONCLUSION: LTBI test results in an individual patient need to be considered in the context of prior BCG vaccination and clinical risk factors. In patient populations with low rates of TB incidence and BCG vaccination, the use of both TST and IGRA may maximise sensitivity in detecting LTBI but may also reduce specificity.

RF positivity has substantial influence on the peripheral memory B-cell compartment and its modulation by TNF inhibition.

OBJECTIVES: The role of B cells in rheumatoid arthritis (RA) has been well established with the advent of B-cell targeted therapies. Alterations of peripheral B-cell subsets in RA and heterogeneous modulations of the B-cell compartment under tumour necrosis factor (TNF) inhibition have been described. In this study we examined the influence of rheumatoid factor (RF) positivity on the peripheral B-cell compartment and its modulation under TNF blockade. METHODS: Consecutive patients with RA and inadequate response to methotrexate (MTX) were stratified according to RF status and a subset of them was included in a prospective study of weekly etanercept treatment. RESULTS: At baseline, RF-negative patients had a significant higher percentage of overall CD27+ B cells compared to healthy controls (HC) and RF-positive patients. In detail, RF-negative patients had 46.6% (range 15.7-86.8%) CD27+ B cells compared to 31.3% (12.9-56.9%, p = 0.026) in HC and 29.8% (19-73.3%, p = 0.04) in RF-positive patients. Within the CD27+ compartment, CD27+/immunoglobulin (Ig)D+ memory B cells were significantly increased to 26.4% (range 5.9-54.7%) in RF-negative patients compared to 14.9% (4.1-27.3%, p = 0.006) in HC and 10.5% (3.4-41.1%, p = 0.003) in RF-positive patients. During anti-TNF therapy, memory B cells increased significantly in relative and absolute numbers only in RF-negative patients. CONCLUSIONS: In RF-negative patients, we observed an enhanced frequency of peripheral memory B cells and an accumulation of pre-switch memory B cells. During anti-TNF therapy, memory B cells increased significantly only in RF-negative patients, suggesting that the peripheral memory B-cell compartment is more amenable to TNF inhibition in these patients.

[Risk of atherosclerosis mediated by inflammation in rheumatoid arthritis]. / Atheroskleroserisiko durch Inflammation bei rheumatoider Arthritis.

Systemic inflammation is one of the pivotal pathogenetic principles in atherogenesis and progression of atherosclerosis. Patients with rheumatoid arthritis (RA) exhibit an increased cardiovascular risk that is not explained by traditional cardiovascular risk factors but rather by a chronic systemic inflammatory reaction. Reduction of inflammatory activity in RA patients was shown to reduce cardiovascular morbidity and mortality. Besides this specific approach traditional cardiovascular risk factors need to be carefully controlled in order to improve mortality in RA patients; however, this task is difficult to implement in everyday practice as RA patients usually have decisively different medical needs that need to be addressed irrespective of the well-acknowledged limitations of medical resources, such as time and costs.

[Rheumatic diseases with initial manifestations in middle age: gout, rheumatoid arthritis and ANCA-associated vasculitides]. / Rheumatische Erkrankungen mit Erstmanifestation im mittleren Lebensalter: Gichtarthritis, rheumatoide Arthritis und ANCA-assoziierte Vaskulitiden.

Rheumatic diseases are manifested in all ages. First manifestations of gout are frequent between the ages of 40-60 years. Furthermore, the incidence of rheumatoid arthritis increases as well as anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides. Recently new treatment options for gout were established but colchicine, which has been used to treat gout for a long time was also further optimized in its use. Remarkable advantages in the treatment of rheumatoid arthritis towards remission have been made by the introduction of biological agents 10 years ago. In granulomatosis with polyangiitis (formerly Wegener's disease) therapeutic optimization has led to a reduction in toxicity and rituximab has proven to be an effective treatment option.

[Cardiovascular comorbidity and its risk factors in rheumatoid arthritis]. / Kardiovaskuläre Komorbidität und ihre Risikofaktoren bei rheumatoider Arthritis.

Rheumatoid arthritis (RA) is still associated with an increased mortality mainly due to an increase in cardiovascular risk. This increase is not solely explained by traditional cardiovascular risk factors but also by disease characteristics, e.g. inflammation, positive rheumatoid factor and anti-citrullinated peptide antibodies (ACPA). Control of disease activity with disease-modifying drugs (DMARDs) was shown to reduce cardiovascular risk in RA patients. Use of non-steroidal antirheumatic drugs (NSAIDs) and glucocorticoids might be associated with an increased risk. The EULAR recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis have been established. These recommendations are based on national guidelines regarding control of traditional cardiovascular risk factors.

[Systemic lupus erythematosus. A problem based approach]. / Systemischer Lupus erythematodes. Eine problemorientierte Annäherung.

Systemic lupus erythematosus (SLE) is a chronic autoinflammatory disease of unknown etiology with predominance of the female sex. Clinical criteria as well as immunological characteristics, e. g. autoantibodies, are necessary for diagnosis. The clinical course of SLE is variable and may be characterized by periods of remissions and chronic or acute relapses. New symptoms are often challenging regarding differential diagnosis. This review will discuss symptoms with a problem based approach. Parameters of activity are helpful to differentiate between disease activity and associated problems, e. g. infections. Lupus patients have a 5 times increased mortality compared to the normal population. The main reasons for mortality are infections and cardiovascular events, rather than disease manifestations. Therefore, besides the fast and precise use of immunosuppressants the consequent therapy of co-morbidities is a major issue in dealing with these patients. Cardiovascular risk factors need to be controlled, life style modifications should be started early, and diagnosis and therapy of osteoporosis should not be neglected.

[Acute monarthritis]. / Differenzialdiagnostik der akuten Monarthritis.

Common causes of acute monarthritis are osteoarthritis, an acute attack of gout or other crystal arthropathies in older patients or a reactive arthritis or gonococcal arthritis in younger patients. The differential diagnosis should primarily rule out septic arthritis. An arthrocentesis with a microbiological work up and a fresh specimen should be prepared for the diagnosis of crystal arthropathies and if an infectious origin is suspected or if nothing remarkable was found during the primary examination. Further diagnosis und therapy should be performed by a specialist.

Echocardiographic morphometry and geometry of the left ventricular outflow tract in fixed subaortic stenosis.

OBJECTIVES: This study was designed to identify, by echocardiography, morphometric abnormalities of the left ventricular outflow tract in children with fixed subaortic stenosis and to determine whether these abnormalities precede the development of subaortic obstruction. BACKGROUND: Fixed subaortic stenosis typically develops and progresses after the 1st year of life and is therefore often regarded as an acquired lesion. Although it has been speculated that there may be an underlying anatomic substrate, there are no data to support this hypothesis. METHODS: The size of the aortic annulus, mitral-aortic valve separation, aorto-left ventricular septal angle and degree of aortic override were determined in two groups of children. Group 1 comprised 35 patients with isolated subaortic stenosis noted on initial echocardiogram who were compared with an age- and weight-matched normal control group (Group 1A). Group 2 comprised 23 patients with ventricular septal defect or coarctation of the aorta, or both, who had no subaortic stenosis on initial echocardiogram but who developed it subsequently. This group was compared with an age-, weight- and lesion-matched control group (Group 2A). RESULTS: Compared with control subjects, patients with isolated subaortic stenosis had a significantly wider mitral-aortic separation ([mean +/- SD] 5.1 +/- 1.3 vs. 3.4 +/- 0.9 mm, p < 0.001), a steeper aortoseptal angle (131 +/- 6 degrees vs. 144 +/- 5 degrees, p < 0.001) and an exaggerated aortic override (p < 0.05). Similar differences were found on initial echocardiogram in Group 2 patients before development of subaortic stenosis: wider mitral-aortic separation (4.2 +/- 1.2 vs. 2.5 +/- 0.7 mm, p < 0.001), a steeper aortoseptal angle (132 +/- 7 degrees vs. 145 +/- 7 degrees, p < 0.001) and an exaggerated aortic override (p < 0.05). CONCLUSIONS: A left ventricular outflow tract malformation characterized by a wider mitral-aortic separation, an exaggerated aortic override and a steeper aortoseptal angle are present in children with ventricular septal defect or coarctation of the aorta, or both, who subsequently develop subaortic stenosis. These morphometric features can be used to identify by echocardiography patients who are at risk for developing fixed subaortic stenosis.

Myocarditis in children with dilated cardiomyopathy: incidence and outcome after dual therapy immunosuppression.

BACKGROUND: The true incidence and prognosis of myocarditis in children with acute dilated cardiomyopathy (DCM) at presentation remains uncertain. This study examines the incidence of lymphocytic myocarditis in a consecutive cohort of children with acute DCM at presentation and outcome after dual therapy immunosuppression with cyclosporine and steroids. METHODS: Twenty-nine consecutive children with acute DCM underwent early endomyocardial biopsy. Children with "definite" myocarditis comprised group I (n = 9) and were treated with cyclosporine and prednisolone. Group II (n = 2) had "borderline" myocarditis, and group III (n = 18) nonspecific histologic findings. Outcome was assessed by echocardiographic measurement of left ventricular end-diastolic dimension and fractional shortening, with follow-up endomyocardial biopsy in group I subjects. RESULTS: Myocardial inflammation with or without myocardial necrosis (groups I and II) was present in 38% of all cases. There were no initial clinical, electrocardiographic, or echocardiographic features to distinguish patients in group I from patients in group III. At presentation, the mean +/- SEM left ventricular end-diastolic dimension and fractional score-Z scores of group I patients were 4.6 +/- 1.7 and -5.1 +/- 0.8, respectively, compared with 0.8 +/- 0.3 and -0.9 +/- 0.4, respectively, at withdrawal of immunosuppression (p < 0.001 for both). Both of these parameters did not differ significantly from normal controls at least follow up. Two group I patients had a biopsy-proven relapse after withdrawal of therapy that responded to reinstitution of immunosuppression. At latest follow-up, all nine group I patients had regained normal left ventricular function compared with four of 18 group III patients (p < 0.001). CONCLUSION: Lymphocytic myocarditis is frequent in children with dilated cardiomyopathy and cannot be predicted from noninvasive investigations. The use of cyclosporine and steroids is associated with a favorable outcome, and a controlled trial of dual therapy immunosuppression in children is therefore warranted.

Clinical, electrocardiographic, and histologic correlations in children with dilated cardiomyopathy.

OBJECTIVE: To determine whether presenting electrocardiography is related to histologic findings and clinical outcomes in children with dilated cardiomyopathy. BACKGROUND: Lymphocytic myocarditis is an important cause of childhood dilated cardiomyopathy, the outcome of which is unclear. The results of non-invasive investigations are often used to infer the presence or absence of lymphocytic myocarditis. METHODS: Thirty-four children, presenting acutely with dilated cardiomyopathy, underwent both early electrocardiography and endomyocardial biopsy. The parameters examined included heart rate, PR, QRS, and corrected QT intervals, R-wave voltages in Leads V(1) and V(6), S-wave voltages in Leads V(1) and V(6), and sum of SV(1) and RV(6). We expressed measurements as Z scores, based on published normal values for age and gender. RESULTS: A total of 15 patients had lymphocytic myocarditis on endomyocardial biopsy (Group I), and 19 had non-specific histologic findings (Group II). We did not distinguish the 2 groups by age, time to endomyocardial biopsy, or duration of follow-up. Group I patients had significantly smaller R-wave Z scores in Leads V(1) and V(6), and combined S in V(1) and R in V(6) Z scores (p < 0.02 for each). The positive and negative predictive values of an R-wave amplitude in V(6) < 5th percentile were 75% and 65%, respectively, for the diagnosis of lymphocytic myocarditis. An R-wave amplitude in V(6) > 95th percentile had a positive and negative predictive value of 80% and 63%, respectively, for the diagnosis of idiopathic dilated cardiomyopathy. Survival and freedom from late cardiac dysfunction were more common among Group I patients compared with Group II (p

Pulmonary vascular resistance and reactivity in children with end-stage cardiomyopathy.

Pulmonary vascular resistance (PVR) and reactivity were compared in 63 children with end-stage cardiomyopathy (CM) referred for cardiac transplantation. Diagnostic category of CM was the sole determinant of PVR. Compared with other patients, children with restrictive CM were younger at diagnosis and had a significantly higher pulmonary vascular resistance index (PVRI). Children with a baseline PVRI of up to 11.8 units per meter squared (U.m(2)) who showed reactivity underwent successful orthotopic cardiac transplantation.

[Systemic sclerosis]. / Systemische Sklerose.

Systemic sclerosis (SSc; syn. systemic scleroderma) is a rare autoimmune disorder with characteristic cutaneous manifestations. Prevalence in women is fivefold higher than in men. The course of the disease is slowly progressive with a variable degree of internal organ involvement due to fibrosis and obliteration of small vessels. The diffuse form shows more frequent and severe organ manifestations compared to the limited form. Increased mortality is particularly related to a cardiopulmonary involvement leading to a 5-year survival of around 75%. Treatment indications are dependent on the severity of the disease. In the acute state, immunosuppressive agents are needed in case of significant organ involvement. Vasodilative drugs are often used for the symptomatic treatment of Raynaud's phenomenon.