Patient-reported outcomes in large vessel vasculitis: insights from a retrospective analysis of disease activity and associated factors.

BACKGROUND: Patient-reported outcomes (PROs) play a crucial role in assessing rheumatic diseases, offering insights into disease evaluation and treatment efficacy. This study focuses on PRO assessment in large vessel vasculitides, including Takayasu Arteritis and Giant Cell Arteritis (GCA). METHODS: We retrospectively analyzed routine data from patients treated at our rheumatology clinic over a 10-year span. Patient and physician-rated global disease activity scale (G-DAS) scores, measured on a numeric rating scale (0-10 points), were collected at each visit. Clinical variables like age, sex, body mass index (BMI), disease duration, lab values, pain perception, and questionnaire responses were recorded. Linear regression and generalized additive linear regression (GAM analysis) examined associations between PROs and these factors. RESULTS: The study included 138 patients, primarily diagnosed with GCA (94.4%). Mean follow-up was 2.5 years (0-7.7). Patient and physician G-DAS exhibited a moderate correlation (Pearson R 0.19, CI 0.14-0.24, p < 0.001). Higher patient G-DAS correlated with younger age (CI -3.4 - -1.5, p < 0.001), increased pain (CI 3.5-4, p < 0.001), functional limitations (HAQ, CI 0.5-0.6, p < 0.001), reduced physical (CI 2.3-2.7, p ≤ 0.001) and psychological well-being (CI 2.1-2.5, p < 0.001), and higher BMI (CI 1.3-2.4, p < 0.001). Physician G-DAS correlated with Birmingham Vasculitis Activity Score (V3.0; R 0.42, p 0.046) and were significantly linked to serum CRP elevations (ß = 0.04, CI 0.0-0.08, p 0.028). CONCLUSIONS: These findings underscore the need to integrate PRO measures into vasculitis disease management strategies, enhancing the understanding of disease activity from the patient's perspective.

[Social media-Chances and risks for rheumatology]. / Social Media ­ Chancen und Risiken für die Rheumatologie.

The use of social media and social networks has increased significantly in recent years. They are becoming progressively more important as information channels in private and professional contexts. Also, in medicine, social media are already being used in a variety of ways. For example, professional societies and patient interest groups are being increasingly represented in social networks. The broad use and wide audience of these networks offer new opportunities for the field of rheumatology. This review article provides an overview of the characteristics of some major social media platforms and systematically analyses the existing publications in the context of rheumatology. Furthermore, advantages, but also potential risks that may arise due to social media use are being addressed.

MRI-based contrast clearance analysis shows high differentiation accuracy between radiation-induced reactions and progressive disease after cranial radiotherapy.

BACKGROUND: Pseudoprogression (PsP) or radiation necrosis (RN) may frequently occur after cranial radiotherapy and show a similar imaging pattern compared with progressive disease (PD). We aimed to evaluate the diagnostic accuracy of magnetic resonance imaging-based contrast clearance analysis (CCA) in this clinical setting. PATIENTS AND METHODS: Patients with equivocal imaging findings after cranial radiotherapy were consecutively included into this monocentric prospective study. CCA was carried out by software-based automated subtraction of imaging features in late versus early T1-weighted sequences after contrast agent application. Two experienced neuroradiologists evaluated CCA with respect to PsP/RN and PD being blinded for histological findings. The radiological assessment was compared with the histopathological results, and its accuracy was calculated statistically. RESULTS: A total of 33 patients were included; 16 (48.5%) were treated because of a primary brain tumor (BT), and 17 (51.1%) because of a secondary BT. In one patient, CCA was technically infeasible. The accuracy of CCA in predicting the histological result was 0.84 [95% confidence interval (CI) 0.67-0.95; one-sided P = 0.051; n = 32]. Sensitivity and specificity of CCA were 0.93 (95% CI 0.66-1.00) and 0.78 (95% CI 0.52-0.94), respectively. The accuracy in patients with secondary BTs was 0.94 (95% CI 0.71-1.00) and nonsignificantly higher compared with patients with primary BT with an accuracy of 0.73 (95% CI 0.45-0.92), P = 0.16. CONCLUSIONS: In this study, CCA was a highly accurate, easy, and helpful method for distinguishing PsP or RN from PD after cranial radiotherapy, especially in patients with secondary tumors after radiosurgical treatment.

[Paths to academic rheumatology]. / Weg in die akademische Rheumatologie.

BACKGROUND: The development of rheumatology into one of the most progressive medical disciplines is mainly based on the enormous scientific knowledge gained in recent decades. Physician scientists have played a substantial role in this development. With respect to the ongoing challenges, physician scientists will be urgently needed in the future. Therefore, young physicians need to be attracted to scientific research in rheumatology. OBJECTIVE: This article describes possible paths into academic rheumatology, highlights facilitators and barriers to a scientific career and discusses ideas for the recruitment of young scientists for rheumatology based on the existing literature. RESULTS AND DISCUSSION: It is without doubt that young scientists are urgently needed in rheumatology; however, the number of young physician scientists seems to be declining. The paths to academic rheumatology are manifold and variable but setting the course early on during medical school by science-oriented teaching, research internships and doctoral theses, appears to be advantageous. Favorable factors for the decision to pursue an academic career in rheumatology are enjoyment in research, recognition of research rotations for rheumatology training and improved career opportunities. The greatest barriers are considered to be the exemption from clinical duties as well as lack of experience with scientific methods and acquisition of research funding. Therefore, it is important to make potential scientists enthusiastic about the research underlying modern rheumatology and to encourage research during medical school in order to attract young people to academic rheumatology.

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.

[Muscle weakness and CK elevation: is it myositis?] / Muskelschwäche und CK­Erhöhung: Ist es immer eine Myositis?

Rheumatologists are often confronted by patients with muscle weakness and elevated creatine kinase (CK) levels. Myositis cannot always be determined to be the cause of the complaints. This article presents two cases from our hospital where the diagnosis could only be determined by muscle biopsy. In the first case the patient presented with muscle weakness, pathological weight loss and a significant increase in CK levels. A muscle biopsy revealed an immune-mediated necrotizing myopathy (IMNM) caused by anti-3-hydroxy-3-methyl-gulatryl-CoA reductase (HMG-CoA reductase) autoantibodies due to the intake of statins. The second patient presented with cramp-like and burning muscle pain and weakness of the extremities without a relevant increase in CK level. Myoadenylate deaminase deficiency was also detected by muscle biopsy, and further confirmed by genetic testing.

[Treat to target in systemic lupus erythematosus]. / Treat-to-Target beim systemischen Lupus erythematodes.

BACKGROUND: For the first time, the European League Against Rheumatism (EULAR) recommendations for the management of systemic lupus erythematosus (SLE) include a treat to target (T2T) strategy, naming remission as the main target. The aim is to improve the long-term survival, prevent damage and optimize the health-related quality of life. Compared to rheumatoid arthritis (RA) for which the T2T approach is already widely used, establishing T2T in SLE remains challenging due to its heterogeneity and limited treatment options. OBJECTIVE: The aim of this article is to outline the current status of the T2T concept for SLE and to identify challenges and particularities. A special focus is placed on the use of activity scores and the importance of steroids in targeted treatment of SLE. RESULTS AND CONCLUSION: The use of T2T for SLE remains a challenge. With the definitions of the lupus low disease activity states (LLDAS) and the definitions of remission in SLE (DORIS) a big step forward has been taken on the road towards the ideal treatment target; however, many aspects of the "treat" remain unclear. As an example, due to a lack of data there are no explicit strategies for steroid reduction although it is often mandatory to achieve the targets. The T2T also includes much more than only immunosuppressive treatment and antimalarial agents, as disease damage which has already occurred and damage due to drugs, concomitant phenomena (such as depression) and comorbidities as well as measures for secondary prophylaxis must also be included.

[Specialist training quo vadis?] / Facharztweiterbildung quo vadis?

BACKGROUND: In May 2018 a revision of the training regulations for German doctors (MWBO) was passed which will significantly impact the medical training for German rheumatologists. The goal of this paper was to create an overview of the status quo in advanced medical training in this field. METHODS: A quantitative and qualitative analysis was conducted to identify the strengths and weaknesses of the current continuous education in the field of rheumatology in Germany. The number of newly trained specialists in rheumatology in the years 2015 to 2017 was determined from the regional medical associations. Furthermore, an online survey assessing the training conditions of assistant physicians was conducted. 71 physicians participated in the nationwide survey. RESULTS: In 2015 (53 specialists), in 2016 (43 specialists) and in 2017 (43 specialists) completed their training in the field of rheumatology. The online survey of assistant physicians found that the medical training was graded 3.1 on a scale of 1 to 6 (SD ± 1.1). 19.4% of respondents reported that they had regular mentoring, and 41.7% had on-the-job evaluations. Deficits were evident concerning practical diagnostic skills: 22.8% of the physicians were not practicing joint ultrasonography and another 20% performed it only once a month. As points of criticism 46.6% mentioned a missing structure in training programme and 33.3% noted a lack of supervision. The majority of respondents wanted more training options, supervision and better practical training in ultrasound diagnostics. CONCLUSION: The nationwide number of newly acquired specialist qualifications (between 2015 and 2017) showed a decreasing trend. It is to be feared that the numbers will continue to stagnate, which increases the importance to invest further in medical education. The online survey also showed that the current medical training in Germany has deficits. Here, the new MWBO could create better guidelines for a structured training, which should be guided by the principle of "Teach to Target".

[State of the art: systemic lupus erythematosus]. / State of the Art: systemischer Lupus erythematodes.

As long as we cannot cure diseases such as systemic lupus erythematosus (SLE), it must be our goal that people with SLE can live a largely normal life. It should not be dominated by the disease. The main goal is secondary prevention, i. e. the prevention of harm. In 2020 we want to make a better contribution to this aim. For this article on SLE, being fit for 2020 therefore means applying the basic concepts of care for patients with SLE on a regular basis. The focus is on the new concepts resulting from the new classification criteria, the optimized basic care (BASIC), the complex communication with those affected, the new EULAR recommendations for monitoring SLE, the integration of biologics into the treatment regimen, the targeted therapy (T-2-T) and thus the criteria low disease activity and remission, the question of new care structures for rare and complex systemic diseases and finally the outlook on future treatment concepts, the basis of which we will all create in the coming years. If we consistently apply the current options, we will be able to further improve the life situation and quality of life of those affected even without newly approved drugs.

Isthmocervical labelling and SPECT/CT for optimized sentinel detection in endometrial cancer: technique, experience and results.

OBJECTIVE: We evaluated the clinical feasibility of a new injection technique for sentinel detection in endometrial carcinoma (EC), transcervical subepithelial injection into the isthmocervical region of the myometrium. We compared detection of sentinel lymph nodes (SLN) by single photon emission computed tomography with CT (SPECT/CT) with planar lymphoscintigraphy. METHODS: This is a unicentric prospective study. In all patients, transcervical injection of 10 MBq Technetium-99m-nanocolloid was performed into the isthmocervical myometrium without anaesthesia. After 40 (30-60) min, lymphoscintigraphy and SPECT/CT were performed. Patent blue was administered before surgery. The number and localisation of SLN detected in SPECT/CT and lymphoscintigraphy were recorded and compared to the SLN and non-SLN dissected intra-operatively. RESULTS: Between August 2008 and March 2012, 31 patients with EC were enrolled. The new transcervical injection of labelling substances led to high intra-operative (90.3%) detection rates, pelvic bilateral (57%), para-aortic (25%). SPECT/CT significantly identified more SLN than lymphoscintigraphy (mean 2.2 (1-8) to 1.3 (1-7)) in more patients (29/31 (93.5%) to 21/31 (68%), p<0.01). If SLN were identified in one hemi-pelvis, the histological evaluation of the SLN correctly predicted lymph node (LN) metastases for this basin which led to sensitivity 100%, negative predictive value (NPV) 100%, and false negative results 0%. CONCLUSION: Transcervical SLN marking in combination with SPECT/CT is easily applicable and leads to high physiologic detection rates in pelvic and para-aortic lymphatic drainage areas. Non-affected SLN truly predicted a non-affected LN basin. Combining both methods SLN dissection may be a safe and feasible staging technique for clinical routine in EC.

Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome.

Cardio-facio-cutaneous (CFC) and Costello syndrome (CS) are congenital disorders with a significant clinical overlap. The recent discovery of heterozygous mutations in genes encoding components of the RAS-RAF-MAPK pathway in both CFC and CS suggested a similar underlying pathogenesis of these two disorders. While CFC is heterogeneous with mutations in BRAF, MAP2K1, MAP2K2 and KRAS, HRAS alterations are almost exclusively associated with CS. We carried out a comprehensive mutation analysis in 51 CFC-affected patients and 31 individuals with CS. Twelve different BRAF alterations were found in twenty-four patients with CFC (47.0%), two MAP2K1 mutations in five (9.8%) and two MAP2K2 sequence variations in three CFC-affected individuals (5.9%), whereas three patients had a KRAS alteration (5.9%). We identified four different missense mutations of HRAS in twenty-eight cases with CS (90.3%), while KRAS mutations were detected in two infants with a phenotype meeting criteria for CS (6.5%). In 14 informative families, we traced the parental origin of HRAS alterations and demonstrated inheritance of the mutated allele exclusively from the father, further confirming a paternal bias in the parental origin of HRAS mutations in CS. Careful clinical evaluation of patients with BRAF and MAP2K1/2 alterations revealed the presence of slight phenotypic differences regarding craniofacial features in MAP2K1- and MAP2K2-mutation positive individuals, suggesting possible genotype-phenotype correlations.

In-vivo tissue optical properties derived by linear perturbation theory for edge-corrected time-domain mammograms.

A valuable method is described to analyze time-domain optical mammograms measured in the slab-like geometry of the slightly compressed female breast with a method based on linear perturbation theory including edge correction. Perturbations in scattering and absorption coefficients were mapped applying a computationally efficient point model.

Unusual mutations in high functioning fragile X males: apparent instability of expanded unmethylated CGG repeats.

We report on further cases of high functioning fragile X males showing decreased expression of FMR1 protein, absence of detectable methylation at the EagI site in the FMR1 gene promoter, and highly unusual patterns of fragile X mutations defined as smear of expansions extending from premutation to full mutation range. Very diffuse and therefore not easily detectable patterns of full mutations were also observed on prenatal testing using DNA from chorionic villi sampled at a time of development when full mutations were still unmethylated in this particular tissue. In the search for possible determinants of such unusual patterns, repeat expansions in the premutation and in the lower full mutation range were identified on genomic PstI blots previously prepared for fragile X DNA testing. Cases with 130 or more triplets, and a number of shorter repeats, were reinvestigated on EcoRI plus EagI digests. Among the 119 expansions, there were 22 in our sample showing either blurred bands or smears on PstI blots. This particular characteristic was strongly associated with the coincidence of a repeat size of more than 130 triplets and absence of EagI site methylation. Our data set also includes cases of mosaic patterns consisting of smears of unmethylated expansions to more than 130 CGGs and of clear bands of methylated expansions. We therefore suggest that in fragile X syndrome unusual smeared patterns of mutations result from somatic instability of larger repeats under circumstantial absence of repeat methylation.