[The subanalysis of Rheuma-VOR demonstrates a considerable need for rheumatological care]. / Die Subanalyse von Rheuma-VOR zeigt den erheblichen Bedarf der rheumatologischen Versorgung auf.

BACKGROUND: Early diagnosis and treatment of inflammatory rheumatic diseases can prevent consequential damage such as permanently limited mobility and joint or organ damage. Simultaneously, there is an increasing deficit in medical care owing to the lack of rheumatological capacity. Rural regions are particularly affected. OBJECTIVES: The available unconfirmed diagnoses of the study Rheuma-VOR were analysed regarding another definitive inflammatory rheumatic disease. MATERIALS AND METHODS: The returned questionnaires of the rheumatologists participating in Rheuma-VOR were screened for definitive inflammatory rheumatic diseases other than the required diagnosis of rheumatoid arthritis, psoriatic arthritis or spondyloarthritis. RESULTS: Of 910 unconfirmed diagnoses, in 245 patients another definitive diagnosis could be confirmed. A total of 29.8% of the diagnoses corresponded to degenerative joint changes or chronic pain syndrome, whereas 26.1% involved different forms of inflammatory arthritis. The majority of diagnoses (40.5%) were collagenosis or vasculitis, DISCUSSION: The available data show that a rheumatological presentation was indicated for the majority of patients. Owing to the increasing deficits in medical care a prior selection of the patients is crucial to make optimal use of restricted rheumatological capacities.

Optically excited structural transition in atomic wires on surfaces at the quantum limit.

Transient control over the atomic potential-energy landscapes of solids could lead to new states of matter and to quantum control of nuclear motion on the timescale of lattice vibrations. Recently developed ultrafast time-resolved diffraction techniques combine ultrafast temporal manipulation with atomic-scale spatial resolution and femtosecond temporal resolution. These advances have enabled investigations of photo-induced structural changes in bulk solids that often occur on timescales as short as a few hundred femtoseconds. In contrast, experiments at surfaces and on single atomic layers such as graphene report timescales of structural changes that are orders of magnitude longer. This raises the question of whether the structural response of low-dimensional materials to femtosecond laser excitation is, in general, limited. Here we show that a photo-induced transition from the low- to high-symmetry state of a charge density wave in atomic indium (In) wires supported by a silicon (Si) surface takes place within 350 femtoseconds. The optical excitation breaks and creates In-In bonds, leading to the non-thermal excitation of soft phonon modes, and drives the structural transition in the limit of critically damped nuclear motion through coupling of these soft phonon modes to a manifold of surface and interface phonons that arise from the symmetry breaking at the silicon surface. This finding demonstrates that carefully tuned electronic excitations can create non-equilibrium potential energy surfaces that drive structural dynamics at interfaces in the quantum limit (that is, in a regime in which the nuclear motion is directed and deterministic). This technique could potentially be used to tune the dynamic response of a solid to optical excitation, and has widespread potential application, for example in ultrafast detectors.

Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials.

The heterogeneity of myelodysplastic syndromes (MDSs) has made evaluating patient response to treatment challenging. In 2006, the International Working Group (IWG) proposed a revision to previously published standardized response criteria (IWG 2000) for uniformly evaluating clinical responses in MDSs. These IWG 2006 criteria have been used prospectively in many clinical trials in MDSs, but proved challenging in several of them, especially for the evaluation of erythroid response. In this report, we provide rationale for modifications (IWG 2018) of these recommendations, mainly for "hematological improvement" criteria used for lower-risk MDSs, based on recent practical and reported experience in clinical trials. Most suggestions relate to erythroid response assessment, which are refined in an overall more stringent manner. Two major proposed changes are the differentiation between "procedures" and "criteria" for hematologic improvement-erythroid assessment and a new categorization of transfusion-burden subgroups.

[Association of physical activity with fatigue and functional capacity in patients with rheumatoid arthritis]. / Zusammenhang von körperlicher Aktivität mit Fatigue und Funktionskapazität bei Patienten mit rheumatoider Arthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) tend to be less physically active. Physical activity has been shown to have a positive impact on disease activity and quality of life and is recommended by the European League Against Rheumatism (EULAR) as an integral component of standard treatment. OBJECTIVE: A cross-sectional analysis of RA patients was carried out assessing disease activity, functional capacity and fatigue associated with physical activity. MATERIAL AND METHODS: Physical activity, functional capacity and the global fatigue index (GFI) were examined using standardized questionnaires: the international physical activity questionnaire short form (IPAQ-SF), the functional questionnaire Hannover (FFbH) and the multidimensional assessment of fatigue (MAF). The data were evaluated using SPSS 26 (IBM, Armonk, NY, USA). The level of significance was tested with bivariate and partial correlations and nonparametric tests. RESULTS: In total 164 patients were included in the study. The majority of the patients were female (127/164; 77%) and the median age of the cohort was 58.3 years (range 21-86 years). The median duration of disease-related symptoms at inclusion was 169 months (range 0-713 months). Physical activity was low in 39%, moderate in 37% and high in 24%. Patients reporting higher levels of physical activity reported significantly lower GFI (p < 0.001), functional limitations (p < 0.001) and disease activity (p = 0.045) scores than those with less physical activity. CONCLUSION: Physical activity in RA patients was significantly correlated with functional capacity and levels of fatigue. In order to reduce the proportion of patients with low physical activity, the possibilities for functional training should be expanded and the patients should be encouraged to undertake sporting activities.

[Rheumatology in German MD curricula]. / Rheumatologie im Medizinstudium.

Transmitting a substantial amount of basic knowledge in Rheumatology to all medical students is essential for the future medical care of patients with rheumatic diseases for two reasons: on the one hand, future general practitioners will need to master the patterns of rheumatic diseases to recognize them fast enough in new-onset patients and to refer them in time and directly to rheumatologists. On the other hand, the shortage of rheumatologists can only then be relieved in the future when we are able to inspire enthusiasm for our specialty. Adequate rheumatological structures are established only in some of the German faculties of medicine. Structural improvements happen in small steps only but were achieved at several sites. The better the local structures, the higher the chances of committed university teachers in rheumatology to reach all medical students. Probably from 2026 onwards, the learning objectives relevant for examinations will be defined by the national competence-based catalogue of learning objectives in medicine (NKLM), which is currently in the final stages of completion together with the German Federal Institute for Medical and Pharmaceutical Examinations (IMPP). It now appears that systemic autoimmune diseases and inflammatory rheumatic diseases are adequately depicted in this catalogue. If this is achieved, students will know more about these diseases in the future and will diagnose them faster in patients. Work on the NKLM is therefore of highest importance. In addition to the work on the learning objectives, up to date learning materials are required, which have to be available throughout Germany. A Rheumatology script just finished by the committee for medical student education of the German Society of Rheumatology (DGRh) and now available on the DGRh homepage should close this gap.

Thermally Induced Crossover from 2D to 1D Behavior in an Array of Atomic Wires: Silicon Dangling-Bond Solitons in Si(553)-Au.

The self-assembly of submonolayer amounts of Au on the densely stepped Si(553) surface creates an array of closely spaced "atomic wires" separated by 1.5 nm. At low temperature, charge transfer between the terraces and the row of silicon dangling bonds at the step edges leads to a charge-ordered state within the row of dangling bonds with ×3 periodicity. Interactions between the dangling bonds lead to their ordering into a fully two-dimensional (2D) array with centered registry between adjacent steps. We show that as the temperature is raised, soliton defects are created within each step edge. The concentration of solitons rises with increasing temperature and eventually destroys the 2D order by decoupling the step edges, reducing the effective dimensionality of the system to 1D. This crossover from higher to lower dimensionality is unexpected and, indeed, opposite to the behavior in other systems.

[Severe polyneuropathy in primary Sjögren's syndrome : Sjögren's syndrome should be considered in patients with motor neuropathy]. / Schwere Polyneuropathie bei primärem Sjögren-Syndrom : Bei Patienten mit motorischen Neuropathien auch an Sjögren-Syndrom denken!

A 64-year-old male patient developed over a period of 20 years a peripheral neuropathy symmetrically affecting the upper and lower limbs. The histological examination of a sural nerve biopsy revealed a severe axonal neuropathy. Despite extensive laboratory investigations including immunological and metabolic tests the origin could not be identified. Finally, a Schirmer test revealed xerophthalmia. A subsequent salivary gland biopsy from the lower lip revealed a grade III lymphocytic inflammation according to Chisholm and Mason and confirmed the diagnosis of Sjögren's syndrome.

[Treatment of systemic sclerosis-associated interstitial lung disease]. / Therapie der systemischen Sklerose-assoziierten interstitiellen Lungenerkrankung.

BACKGROUND: Systemic sclerosis (SSc) is a fibrosing autoimmune disease of the connective tissue. In addition to skin fibrosis, pulmonary involvement and interstitial lung disease (ILD) in particular are the most common and severe manifestations of SSc. The disease is associated with a substantial risk of morbidity and mortality, especially in progressive ILD. In the last 5 years new treatment concepts for SSc-ILD have been investigated in numerous clinical studies. MATERIAL AND METHODS: This review is based on a literature search in PubMed, focusing on the most relevant papers published up to the end of 2018 with the keywords "SSc" and "treatment". RESULTS: The treatment of SSc-ILD has changed over the last few years due to the results of many clinical studies. The updated guidelines of the European League Against Rheumatism (EULAR) recommend the use of cyclophosphamide or hematopoietic stem cell transplantation. Data for a positive influence on SSc-ILD are also available for mycophenolate, tocilizumab and anabasum. Because of the pathophysiological similarities to idiopathic pulmonary fibrosis, the use of the antifibrotic agents nintedanib and pirfenidone is currently being investigated in randomized, multicenter clinical trials and could be a novel and promising therapeutic strategy. CONCLUSION: Current drug studies may provide innovative therapeutic perspectives for SSc-ILD and could significantly improve the prognosis of affected patients in the future.

[Experiences and results from Rheuma-VOR]. / Erfahrungen und Ergebnisse aus Rheuma-VOR.

Rheumatoid arthritis, psoriatic arthritis and axial spondylarthritis are the most common chronic autoimmune rheumatic diseases. For all three diseases an early diagnosis and initiation of treatment is crucial. The proof of concept network study "Rheuma-VOR" is a further developed version of the predecessor project ADAPTHERA and was extended to several federal states. The aim of this prospective study is to improve the early diagnosis of rheumatoid arthritis, psoriatic arthritis and axial spondylarthritis and thus positively impact the quality of care for patients with the help of multidisciplinary coordinating centers. To date 3710 disease-specific questionnaires from patients with the suspected diagnosis of rheumatoid arthritis, psoriatic arthritis or axial spondylarthritis from 1298 different primary care providers were registered in the multidisciplinary coordination centers. A total of 1958 appointments were made with 1 of the 53 participating rheumatology specialists. In 876 patients, 1 of the 3 rheumatic diseases was diagnosed in an early stage. The waiting period was on average 42.5 days depending on the federal state, which is well below the nationwide average. It should also be noted that the coordinated cooperation and risk stratification of the Rheuma-VOR coordination centers relieved the capacity of rheumatology specialists by 1281 appointments (34.5%). In addition, the 2­week Rheuma Bus Tour and the accompanying initiatives in Rhineland-Palatinate (Rheuma-VOR screening app and the triage consultation) are showing first promising positive results.

[Early recognition and screening consultation: a necessary way to improve early detection and treatment in rheumatology? : Overview of the early recognition and screening consultation models for rheumatic and musculoskeletal diseases in Germany]. / Früh- und Screeningsprechstunden: Ein notwendiger Weg zur besseren Frühversorgung in der internistischen Rheumatologie? : Rheumatologische Früh- und Screeningsprechstundenmodelle in Deutschland.

In order to reduce the prognostically relevant time interval between the initial manifestation of a rheumatic and musculoskeletal disease and diagnosis as well as the consecutive initiation of an appropriate treatment, several rheumatological centers in Germany have improved the access to initial rheumatologic evaluation by establishing early recognition/screening clinics at their respective sites. Corresponding models located at Altoetting·Burghausen, Bad Pyrmont, Berlin Buch, Duesseldorf, Heidelberg, Herne, Mannheim as well as supraregional/multicenter initiatives Rheuma Rapid, RhePort and Rheuma-VOR are presented in this overview along with the respective characteristics, potential advantages and disadvantages, but also first evaluation results of several models. The aim of this publication is to promote early detection of rheumatic and musculoskeletal diseases as one of the most important challenges in current rheumatology by encouraging further rheumatologic centers and practices to launch their own early recognition/screening consultation model on the basis of aspects presented herein.

Erythropoiesis-stimulating agents significantly delay the onset of a regular transfusion need in nontransfused patients with lower-risk myelodysplastic syndrome.

BACKGROUND: The EUMDS registry is an unique prospective, longitudinal observational registry enrolling newly diagnosed patients with lower-risk myelodysplastic syndrome (MDS) from 17 European countries from both university hospitals and smaller regional hospitals. OBJECTIVE: The aim of this study was to describe the usage and clinical impact of erythropoiesis-stimulating agents (ESAs) in 1696 patients enrolled between 2008 and 2014. METHODS: The effects of ESAs on outcomes were assessed using proportional hazards models weighting observations by propensity to receive ESA treatment within a subset of anaemic patients with or without a regular transfusion need. RESULTS: ESA treatment (median duration of 27.5 months, range 0-77 months) was administered to 773 patients (45.6%). Outcomes were assessed in 897 patients (484 ESA treated and 413 untreated). ESA treatment was associated with a nonsignificant survival benefit (HR 0.82, 95% CI: 0.65-1.04, P = 0.09); this benefit was larger amongst patients without prior transfusions (P = 0.07). Amongst 539 patients for whom response to ESA treatment could be defined, median time to first post-ESA treatment transfusion was 6.1 months (IQR: 4.3-15.9 months) in those transfused before ESA treatment compared to 23.3 months (IQR: 7.0-47.8 months) in patients without prior transfusions (HR 2.4, 95% CI: 1.7-3.3, P < 0.0001). Responding patients had a better prognosis in terms of a lower risk of death (HR 0.65, 95% CI: 0.45-0.893, P = 0.018), whereas there was no significant effect on the risk of progression to acute myeloid leukaemia (HR 0.71, 95% CI: 0.39-1.29, P = 0.27). CONCLUSION: Appropriate use of ESAs can significantly delay the onset of a regular transfusion need in patients with lower-risk MDS.

Breast cancer in systemic lupus.

Objective There is a decreased breast cancer risk in systemic lupus erythematosus (SLE) versus the general population. We assessed a large sample of SLE patients, evaluating demographic and clinical characteristics and breast cancer risk. Methods We performed case-cohort analyses within a multi-center international SLE sample. We calculated the breast cancer hazard ratio (HR) in female SLE patients, relative to demographics, reproductive history, family history of breast cancer, and time-dependent measures of anti-dsDNA positivity, cumulative disease activity, and drugs, adjusted for SLE duration. Results There were 86 SLE breast cancers and 4498 female SLE cancer-free controls. Patients were followed on average for 7.6 years. Versus controls, SLE breast cancer cases tended to be white and older. Breast cancer cases were similar to controls regarding anti-dsDNA positivity, disease activity, and most drug exposures over time. In univariate and multivariate models, the principal factor associated with breast cancers was older age at cohort entry. Conclusions There was little evidence that breast cancer risk in this SLE sample was strongly driven by any of the clinical factors that we studied. Further search for factors that determine the lower risk of breast cancer in SLE may be warranted.

[Magnetic resonance imaging (MRI) diagnostics in axial spondyloarthritis]. / Magnetresonanztomographie-Diagnostik bei axialer Spondyloarthritis.

BACKGROUND: Axial spondyloarthritis (axSpA) is a frequent disorder, which is difficult to diagnose in the early phase. Currently, magnetic resonance imaging (MRI) of the sacroiliac joints and the spine is frequently applied in this phase, when conventional X rays still provide inconclusive results. OBJECTIVE: To explain the typical pathological results and the role of MRI in diagnosing axSpA. RESULTS: The use of MRI of the sacroiliac joints plays a central role in the assessment of the Spondyloarthritis International Association Society (ASAS) classification criteria of axSpA. Bone marrow edema is central to the definition of a positive MRI of the sacroiliac joints. In addition, chronic changes in the sacroiliac joints, such as fat depositions and erosion are taken into account in making the diagnosis of axSpA. When the results are not clear, an additional MRI of the area of the spine in which the patient reports the most pronounced complaints can be performed. A bone marrow edema in at least three vertebral edges can be associated with axSpA. CONCLUSION: The MRI investigation of the sacroiliac joints has evolved into one of the most important methods in diagnosing axSpA.

[Musculoskeletal-related chest pain]. / Muskuloskeletal bedingter Thoraxschmerz.

BACKGROUND: Approximately 10-50% of chest pains are caused by musculoskeletal disorders. The association is twice as frequent in primary care as in emergency admissions. AIM: This article provides an overview of the most important musculoskeletal causes of chest pain and on the diagnostics and therapy. METHODS: A selective search and analysis of the literature related to the topic of musculoskeletal causes of chest pain were carried out. RESULTS AND CONCLUSION: Non-inflammatory diseases, such as costochondritis and fibromyalgia are frequent causes of chest pain. Inflammatory diseases, such as rheumatoid arthritis, spondyloarthritis and systemic lupus erythematosus are much less common but are more severe conditions and therefore have to be diagnosed and treated. The diagnostics and treatment often necessitate interdisciplinary approaches. Chest pain caused by musculoskeletal diseases always represents a diagnosis by exclusion of other severe diseases of the heart, lungs and stomach. Physiotherapeutic and physical treatment measures are particularly important, including manual therapy, transcutaneous electrical stimulation and stabilization exercises, especially for functional myofascial disorders.

[Intestinal microbiota in individualized therapies]. / Die intestinale Mikrobiota als Ansatz für individuelle Therapien.

During recent years, the analysis of the human microbiota has been receiving more and more scientific focus. Deep sequencing analysis enables characterization of microbial communities in different environments without the need of culture-based methods. Hereby, information about microbial communities is increasing enormously. Numerous studies in humans and animal models revealed the important role of the microbiome in emergence and natural course of diseases such as autoimmune diseases and metabolic disorders, e. g., the metabolic syndrome. The identification of causalities between the intestinal microbiota composition and function, and diseases in humans and animal models can help to develop individualized therapies targeting the microbiome and its modification. Nowadays, it is established that several factors influence the composition of the microbiota. Diet it is one of the major factors shaping the microbiota and the use of pro- and prebiotica may induce changes in the microbial community. Fecal microbiome transfer is the first approach targeting the intestinal microbiota which is implemented in the clinical routine for patients with therapy-refractory infections with Clostridium difficile. Herewith, the recipient's microbiota can be changed permanently and the patient can be cured from the infection.

Prognostic pre-transplant factors in myelodysplastic syndromes primarily treated by high dose allogeneic hematopoietic stem cell transplantation: a retrospective study of the MDS subcommittee of the CMWP of the EBMT.

Many pre-transplant factors are known to influence the outcome of allogeneic stem cell transplantation (SCT) treatment in myelodysplastic syndromes (MDS). However, patient cohorts are often heterogeneous by disease stage and treatment modalities, which complicates interpretation of the results. This study aimed to obtain a homogeneous patient cohort by including only de novo MDS patients who received upfront allogeneic SCT after standard high dose myelo-ablative conditioning. The effect of pre-transplant factors such as age, disease stage, transfusions, iron parameters and comorbidity on overall survival (OS), non-relapse mortality (NRM), and relapse incidence (RI) was evaluated in 201 patients. In this cohort, characterized by low comorbidity and a short interval between diagnosis and transplantation, NRM was the most determinant factor for survival after SCT (47 % after 2-year follow-up). WHO classification and transfusion burden were the only modalities with a significant impact on overall survival after SCT. Estimated hazard ratios (HR) showed a strongly increased risk of death, NRM and RI, in patients with a high transfusion-burden (HR 1.99; P = 0.006, HR of 1.89; P = 0.03 and HR 2.67; P = 0.03). The HR's for ferritin level and comorbidity were not significantly increased.

[Immunological principles of IgG4 related diseases]. / Immunologische Grundlagen der IgG4-RD.

In contrast to the other IgG subclasses, IgG4 does not bind to low affinity Fc receptors or activate the classical complement pathway. In addition, it is unstable and can dissociate into two hemimolecules; therefore, IgG4 most likely has an immunosuppressive role. On the other hand, there a few examples of an immunostimulatory role of IgG4 antibodies; therefore, the function of IgG4 in IgG4 related diseases is not yet entirely clear. The trigger factors of IgG4 related diseases (allergic or autoimmune) are still under debate. The activation of T helper (Th) 2 and regulatory T cells has been shown to be important in the pathophysiology of IgG4 related diseases as they produce cytokines which contribute to the formation of IgG4 and to fibrosis of various tissues.

[Immunological principles of IgG4 related diseases]. / Immunologische Grundlagen der IgG4-RD.

In contrast to the other IgG subclasses, IgG4 does not bind to low affinity Fc receptors or activate the classical complement pathway. In addition, it is unstable and can dissociate into two hemimolecules; therefore, IgG4 most likely has an immunosuppressive role. On the other hand, there a few examples of an immunostimulatory role of IgG4 antibodies; therefore, the function of IgG4 in IgG4 related diseases is not yet entirely clear. The trigger factors of IgG4 related diseases (allergic or autoimmune) are still under debate. The activation of T helper (Th) 2 and regulatory T cells has been shown to be important in the pathophysiology of IgG4 related diseases as they produce cytokines which contribute to the formation of IgG4 and to fibrosis of various tissues.

[Therapeutic administration of immunoglobulins]. / Einsatz von Immunglobulinen.

BACKGROUND: Intravenously administered immunoglobulins have multiple modes of action that are anti-inflammatory. They can therefore be beneficial in a number of autoimmune disorders. OBJECTIVE: The aim of this article is to analyze and summarize studies on the administration of intravenous immunoglobulins in rheumatological diseases. METHODS: A selective search and analysis of the literature was carried out related to the mode of action and efficacy of intravenous immunoglobulins in rheumatological diseases. RESULTS AND CONCLUSION: Intravenous immunoglobulins have a broad mode of action and can therefore be beneficial in almost all autoimmune diseases. Conditions in which they are of special benefit include immunothrombopenia (ITP), Kawasaki disease and idiopathic inflammatory myopathies. In rare situations, they may also be indicated in systemic lupus erythematosus (SLE), Sjögren's syndrome and neuropathies, catastrophic antiphospholipid syndrome (APS), scleroderma, antineutrophil cytoplasmic antibody (ANCA) associated vasculitis, pyoderma gangrenosum and scleromyxedema. Severe adverse events are rare. In view of the high costs of the therapy, intravenous immunoglobulins are mostly applied in emergency situations, as salvage therapy when other standard therapies have failed or when severe infections are a contraindication to the administration of immunosuppressants.