Fibroblast Activation Protein Inhibitor-Positron Emission Tomography in Aortitis: Fibroblast pathology in active inflammation and remission.

OBJECTIVES: Epigenetically modified fibroblasts contribute to chronicity in inflammatory diseases. Reasons for the relapsing character of large vessel vasculitis (LVV) remain obscure, including the role of fibroblasts, in part due to limited access to biopsies of involved tissue.68Ga FAPI-46 (FAPI)-PET/CT detects activated fibroblasts in vivo. In this exploratory pilot study, we tested the detection of fibroblast activation in vessel walls using FAPI-PET/CT in LVV with aortitis. METHODS: 8 LVV patients with aortitis and 8 age- and gender-matched controls were included. Distribution of FAPI uptake was evaluated in the aorta and large vessels. FAPI-uptake was compared with MRI inflammatory activity scores. Imaging results were compared with clinical parameters such as serum inflammatory markers, time of remission and medication. RESULTS: Three aortitis patients were clinically active, five in remission. Irrespective of activity, FAPI uptake was significantly enhanced in aortitis compared with controls. Patients in remission had a mean duration of remission of 2.8 years (range 1-4 years), yet significant FAPI uptake in the vessel wall was found.In remitted aortitis, MRI inflammatory scores were close to be negative, while in 4/5 patients visually identifiable FAPI uptake was observed. CONCLUSIONS: This pilot feasibility study shows significant tracer uptake in the aortic walls in LVV. FAPI positivity indicates ongoing fibroblast pathology in clinically remitted LVV.

[Further development of regional early care-Many roads lead to Rome : Developmental stages of four established rheumatological early care concepts in different regions of Germany]. / Regionale Frühversorgung weiterentwickeln ­ Viele Wege führen nach Rom : Entwicklungsetappen von 4 etablierten rheumatologischen Frühversorgungskonzepten in verschiedenen Regionen Deutschlands.

In order to shorten the prognostically relevant waiting time until diagnosis and initiation of appropriate treatment in inflammatory rheumatic diseases, rheumatological centers in many regions across Germany have established and continuously developed specific early care concepts. Evaluated models from Altötting·Burghausen, Berlin Buch, Düsseldorf and Heidelberg and their developmental stages as a response to internal and external challenges are presented in this overview. The transparent publication of the developmental steps and the exchange of experiences aim at promoting new early care concepts in other regions and continuing the joint dialogue for improvement of the early detection and quality of care of inflammatory rheumatic diseases in Germany.

Titanium wear from magnetically controlled growing rods (MCGRs) for the treatment of spinal deformities in children.

Magnetically controlled growing rods (MCGRs) are an effective treatment method for early-onset scoliosis (EOS). In recent years, increasing titanium wear was observed in tissue adjacent to implants and in blood samples of these patients. This study aims to investigate the potential correlation between amount of metal loss and titanium levels in blood during MCGR treatment as well as influencing factors for metal wear. In total, 44 MCGRs (n = 23 patients) were retrieved after an average of 2.6 years of implantation and analyzed using a tactile measurement instrument and subsequent metal loss calculation. Titanium plasma levels (n = 23) were obtained using inductively coupled plasma-mass spectrometry (ICP-MS). The correlation of both parameters as well as influencing factors were analyzed. Titanium abrasion on MCGRs was observed in the majority of implants. There was no correlation of metal implant wear or titanium plasma values to the duration of MCGR implantation time, number of external lengthening procedures, patient's ambulatory status, gender, weight or height. Material loss on the MCGRs showed a positive correlation to titanium blood plasma values. The present study is one of the first studies to analyze retrieved MCGRs using high-precision metrological techniques and compare these results with ICP-MS analyses determining blood titanium values.

Reduced bone mineral density in adolescents with Duchenne Muscular Dystrophy (DMD) and scoliosis.

Duchenne muscular dystrophy is a progressive disease usually associated with loss of ambulation and progressive scoliosis. Immobilisation and glucocorticoid treatment are predisposing factors for reduced bone mineral density (BMD). Analysis of quantitative computed tomography revealed low BMD in thoracic and lumbar vertebrae in comparison to age- and sex-matched healthy controls. INTRODUCTION: Evaluation of vertebral bone mineral density (BMD) in Duchenne Muscular Dystrophy (DMD) adolescents with untreated advanced scoliosis and comparison with the BMD values of healthy age-matched controls, based on quantitative computer tomography. METHODS: Thirty-seven DMD adolescents (age 15.6 ± 2.5 years) with spinal deformity were evaluated clinically and radiologically prior to definite spinal fusion and compared to 31 male and age-matched healthy individuals (age 15.7 ± 2.3 years). Data related to previous medical treatment, physiotherapy and ambulatory status was also analysed. Scoliotic curves were measured on plain sitting radiographs of the spine. The BMD Z-scores of the thoracic and lumbar vertebrae were calculated with QCTpro® (Mindways Software Inc., USA), based on data sets of preoperative, phantom pre-calibrated spinal computed tomography scans. RESULTS: A statistically significant lower BMD could be found in DMD adolescents, when compared to healthy controls, showing an average value for the lumbar spine of 80.5 ± 30.5 mg/cm3. Z-scores deteriorated from the upper thoracic towards the lower lumbar vertebrae. All but the uppermost thoracic vertebrae had reduced BMD values, with the thoracolumbar and lumbar region demonstrating the lowest BMD. No significant correlation was observed between BMD and the severity of the scoliotic curve, previous glucocorticoid treatment, cardiovascular impairment, vitamin D supplementation, non-invasive ventilation or physiotherapy. CONCLUSION: DMD adolescents with scoliosis have strongly reduced BMD Z-scores, especially in the lumbar spine in comparison to healthy controls. These findings support the implementation of a standardised screening and treatment protocol. Level of evidence/clinical relevance: therapeutic level III.

[Development of quality standards for patients with rheumatoid arthritis for use in Germany]. / Entwicklung von Qualitätsstandards für die Versorgung von Patient*innen mit rheumatoider Arthritis zur Anwendung in Deutschland.

Despite a qualitatively and structurally good care of patients with rheumatoid arthritis (RA) in Germany, there are still potentially amendable deficits in the quality of care. For this reason, the German Society for Rheumatology (DGRh) has therefore decided to ask a group of experts including various stakeholders to develop quality standards (QS) for the care of patients with RA in order to improve the quality of care. The QS are used to determine and quantitatively measure the quality of care, subject to relevance and feasibility. The recently published NICE and ASAS standards and a systematic literature search were used as the basis for development. A total of 8 QS, now published for the first time, were approved with the intention to measure and further optimize the quality of care for patients with RA in Germany.

[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.

[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.

Mission statement from rheumatologists in the German Society of Rheumatology (DGRh e. V.) : We live rheumatology.

Systemic disease demands systemic thinkers. In this mission statement we define rheumatology, describe the role of the German Society of Rheumatology and the rheumatologist's spirit to their discipline. Rheumatologists are dedicated to improving the quality of life of their acute, chronic, and rehabilitative patients on the basis of up to date evidence and strong physician-patient relations. We think, act and interact systemically, scientifically, consistently, transparently, reliably, inclusively, innovatively and enthusiastically.

[Mission statement from rheumatologists in the German Society of Rheumatology (DGRh e. V.) : We live rheumatology. German version]. / Leitbild der Rheumatologinnen und Rheumatologen in der Deutschen Gesellschaft für Rheumatologie e. V. (DGRh e. V.) : Wir sind die Rheumatologie.

Systemic disease demands systemic thinkers. In this mission statement we define rheumatology, describe the role of the German Society of Rheumatology and the rheumatologist's spirit to their discipline. Rheumatologists are dedicated to improving the quality of life of their acute, chronic, and rehabilitative patients on the basis of up to date evidence and strong physician-patient relations. We think, act and interact systemically, scientifically, consistently, transparently, reliably, inclusively, innovatively and enthusiastically.

[Biosimilars: opportunities and risks]. / Biosimilars ­ Chancen und Risiken.

BACKGROUND: Biologic therapies are a key component of modern medicine, especially in the treatment of chronic conditions and in particular immune-mediated diseases. Biosimilars are molecularly highly similar variants of biologic therapies approved after patent expiration of the original product. OBJECTIVES: To provide an overview of the emerging role of biosimilars and present data with respect to efficacy and safety. CURRENT DATA: Since the approval of human insulin as the first biologic therapy, over 150 biologic therapeutics have been approved in the European Union (EU). Due to the high cost of development and production, biologic therapies place a heavy burden on healthcare systems and, at costs totaling 13.8 billion Euros annually, comprise one third of the annual drug expenditure in Germany. Biosimilars are highly similar versions of already approved biologic therapies that do not have clinically relevant differences with respect to efficacy, safety and immunogenicity, as far as can currently be ascertained. Through competition with the original product, biosimilars have been able to drive down prices and relieve the healthcare system without changing overall efficacy. The potential savings through biosimilars are estimated to be 500 million Euros in Germany alone. Currently, over 50 biosimilars of 16 different biologic therapies are approved in the EU. CONCLUSIONS: Biosimilars are safe and economical alternatives to biooriginal drugs that can boost access to modern, high-cost therapies and relieve healthcare systems.

[Current guidance of the German Society of Rheumatology for the care of patients with rheumatic diseases during the SARS-CoV-2/Covid 19 pandemic]. / Aktuelle Handlungsempfehlungen der Deutschen Gesellschaft für Rheumatologie für die Betreuung von Patienten mit rheumatischen Erkrankungen während der SARS-CoV­2/Covid 19-Pandemie.

In the current SARS-CoV-2 pandemic there are many questions regarding the safe treatment of patients with inflammatory rheumatic diseases. Many of these questions cannot yet be answered on an evidence-based basis and this does not make patient care easy. The German Society for Rheumatology (DGRh) hopes that these initial recommendations will provide support for specific issues in the care of patients with inflammatory rheumatic diseases in view of the current threat posed by SARS-CoV-2. In order to take advantage of the dynamic worldwide gain in knowledge for our patients, the recommendations will be updated regularly. The updated versions of the recommendations are deposited on the homepage of the DGRh.

[Fever in systemic lupus erythematosus: disease exacerbation or infection?] / Fieber bei systemischem Lupus erythematodes: Krankheitsschub oder Infektion?

The differential diagnosis of fever, especially in the context of autoimmune diseases is broad. Accordingly, the spectrum of diagnostic procedures is extensive and the therapeutic consequences are partly contradictory. Fever is basically the manifestation of an increased cell proliferation, such as classically seen in tumors, infections or autoimmune inflammation. Systemic lupus erythematosus (SLE) is one of the most multifaceted rheumatological diseases. Fever is one component of the new classification criteria which help to classify and possibly diagnose SLE. The differential work-up of fever is a special challenge for clinicians particularly in the context of the initial diagnosis of SLE or another autoimmune disease and also in the course of the disease in patients with autoimmune diseases. Based on a case report this article discusses differential diagnostic considerations and proposes a concrete differential diagnostic procedure. The patient's history is highlighted as an extremely important source of relevant information. Without claiming completeness various factors are listed, which help to differentiate fever as a consequence of SLE activity versus fever as a consequence of an infection.

[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.

[Surgical "no-touch" distraction technique to correct pediatric scoliosis]. / Operative "No-touch"-Techniken zur Korrektur kindlicher Skoliosen.

OBJECTIVE: Reduction and retention of the scoliotic curve in children with progressive spinal deformities. INDICATIONS: Progressive neuromyopathic scoliosis which cannot be controlled conservatively (especially by walking disability), and/or development of a thorax insufficiency syndrome (TIS). CONTRAINDICATIONS: Insufficient soft tissue coverage; body weight < 11.4 kg; body mass index (BMI) > 25 or >50 kg; missing osseous anchoring structures (ribs); adult skeleton (usually age < 12 years at surgery); severe spasticity. SURGICAL TECHNIQUE: Indirect correction and distraction of the spinal deformity by two extendable, paravertebral telescopic implants, anchored to the cranial ribs and the iliac crest; the spine is not compromised surgically. POSTOPERATIVE MANAGEMENT: Early functional therapy, no brace; multiple surgical (VEPTR®-system) or externally (magnetically controlled rods) controlled extensions per year. RESULTS: The surgical paravertebral "no-touch" technique for spine correction is particularly suitable for children with neuromyopathic scoliosis with a body weight > 11.4 kg. Our prospective group of children (n = 45), was treated with a combination of the classic vertical expandable prosthetic titanium rib (VEPTR®) anchored to the ribs and iliac crest combined with a magnetically controlled telescopic implant (MAGEC®). The primary correction of >50% was achieved, while progression was effectively prevented over years. In 495 outpatient lengthening procedures, the rate of implant-associated complications requiring surgery was 3.7%. Of the 45 children, 13 (29%) underwent surgical revision. With the proposed surgical "no-touch" technique for scoliosis correction of pediatric neuromyopathic deformities, an effective reduction of the scoliotic curve can be achieved and maintained. Advantages of the method are a partial retention of spinal flexibility and a reduction of spinal ossifications, which facilitates dorsal spondylodesis as the final treatment.

[Improvement of prognosis by timely treatment : Requirement: initial presentation within 6 weeks]. / Verbesserung der Prognose durch frühzeitige Therapie : Forderung: Erstvorstellung in 6 Wochen.

Rheumatoid arthritis (RA) is one of the most frequent chronic inflammatory rheumatic diseases and when untreated leads to chronic tissue destruction and increased mortality. Due to innovative systemic treatment strategies established over the last 20-25 years, the prognosis has considerably improved in terms of disease and socioeconomic burdens, symptoms, long-term prognosis, ability to work and mortality; however, as a rule a prerequisite is long-term and continuous treatment. A medicinal cure of RA is still not in view. For many patients this means the long-term use of very expensive medications. In addition to hemato-oncology, rheumatology has become the second most expensive discipline in Germany in terms of cost per patient. Convincing data from many studies imply that an early start of treatment within the first few weeks after clinical onset of symptoms improves the prognosis, reduces the necessity for expensive drugs and thereby considerably decreases medical costs. This results in the requirement that every patient with symptoms of arthritis must be seen by a rheumatologist within the first 6 weeks following initial manifestation of the disease. Such an improvement in treatment can only be achieved in Germany if the numbers of rheumatologists and trained healthcare professionals in practices such as clinics are considerably increased. This is not only in the interests of patients but also in the interests of the health insurance companies because the investment in the healthcare infrastructure with internistic rheumatologists will result in substantial economic benefits for the cost bearer. It must be the common task of all players in healthcare policy, cost bearers and internistic rheumatologists to provide optimal conditions in medical as well as economical terms.

[Infections]. / Infektionen.

The individual risk assessment concerning infections in patients with rheumatic diseases is based on the detailed personalized documentation of relevant risk factors, such as the underlying disease itself, the intensity of immunosuppressive therapy and the severity of any comorbidities. From the perspective of infectiology, the history of repeated and severe infections as well as previous illnesses, such as (latent) tuberculosis and chronic hepatitis B or C need to be considered. In some instances prophylactic antibiotic therapy might be required, which should otherwise be avoided in order to prevent selection of resistant pathogens. Furthermore, vaccinations are particularly suitable to specifically minimize the risk for frequent infectious diseases.

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.