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.

[Pregnancy with lupus erythematosus-an update]. / Schwangerschaft bei Lupus erythematodes ­ ein Update.

Current research in the field of systemic lupus erythematosus (SLE) and pregnancy focuses on predictors of adverse pregnancy outcomes, the safety and efficacy of hydroxychloroquine (HCQ) in pregnancy and the importance of preconception counselling. In particular, the prospective predictors of pregnancy outcome: biomarkers in antiphospholipid antibody syndrome and SLE (PROMISSE) study adds to the understanding of risk factors for adverse outcomes. There is increasing evidence of the numerous benefits associated with continuing HCQ treatment in pregnancy and for the use of low-dose acetylsalicylic acid in the prevention of preeclampsia. The European League Against Rheumatism (EULAR) has published evidence-based recommendations for the treatment of women with SLE and/or antiphospholipid syndrome before, during and after pregnancy. Rheumatologists caring for women with SLE should be familiar with the current state of knowledge in order to help optimize the management and thus the outcome of pregnancy in their patients.

[Sexuality in adolescents with rheumatic diseases : Contraception, HPV vaccination and pregnancy]. / Sexualität bei Jugendlichen mit rheumatischen Erkrankungen : Verhütung, HPV-Impfung und Schwangerschaft.

Young patients and adolescents with chronic rheumatic diseases have the same desires, fears and needs in terms of sexuality and pregnancy as their healthy peers. In most cases adolescents are already sexually active before transition from pediatric to adult rheumatological care takes place. Pregnancies in women with rheumatic diseases are associated with increased maternal and fetal risks, especially when they occur unplanned in the course of active disease or under teratogenic drugs. Safe contraception is therefore crucial in preventing unwanted pregnancies. The choice of contraception should anticipate the safety of the method of contraception as well as age-dependent practicability. A strategy of "double protection" through the use of condoms for contraception and prevention of sexually transmitted diseases combined with another safe contraception method should be recommended. Women with rheumatic diseases are more susceptible to acquire persisting human papilloma virus (HPV) infections and the subsequent progression to cervical cancer. In women with rheumatic diseases HPV vaccination induces high seroconversion rates, is safe and does not seem to induce disease activity. The care of adolescent women with rheumatic diseases before, during and after medical transition needs to encompass an open, early and continuous counselling regarding these topics in order to retain the individual health-related quality of life and to adapt this care to age-specific needs.

A role for Rac1 activity in malignant progression of sebaceous skin tumors.

The small GTPase Rac1 is crucial for maintaining stem cells (SCs) in mammalian epidermis, and Rac1 activation leads to SC expansion. Loss or inhibition of Rac1 correlates with decreased frequency of skin cancer formation in a chemical carcinogenesis model. Here, we have addressed whether Rac1 activation would enhance carcinogenesis and result in tumor progression. We used K14ΔNLef1 mice, a model for differentiated sebaceous adenomas (SAs), and activated Rac1 in an epidermis-specific manner (K14L61Rac1). Surprisingly, Rac1 activation did not change the incidence and frequency of sebaceous tumors. However, tumors, which occurred exclusively in K14ΔNLef1/K14L61Rac1 double-transgenic mice, were poorly differentiated resembling malignant sebaceous tumors and were termed sebaceous carcinoma-like tumors (SCLTs). Compared with SAs, SCLTs showed an aberrant pattern of cell proliferation, invasive growth and less abundant expression of sebocyte differentiation markers, including stearoyl-CoA desaturase-1 and adipophilin. Interestingly, the adnexal SC marker Lrig1 was upregulated in SCLTs, showing that active Rac1 leads to the accumulation of sebocyte precursors in the context of K14ΔNLef1-induced skin tumors. In a search for targets of Rac1, we found cancer progression-related proteins, Dhcr24/Seladin1 and Nuclear protein 1/P8, to be strongly regulated in SCLTs. At last, Rac1 and Dhcr24/Seladin1 were detected in human sebaceous tumors demonstrating a potential high impact of our findings for human skin disease. This is the first study showing that Rac1 activity can lead to malignant progression of skin tumors.

[Whole body hyperthermia in pain therapy. A controlled trial on patients with fibromyalgia]. / Ganzkörperhyperthermie in der Schmerztherapie. Eine kontrollierte Studie an Patienten mit Fibromyalgiesyndrom.

BACKGROUND: The aim of this study was to evaluate whether mild water-filtered near infrared whole body hyperthermia in patients with fibromyalgia produces a benefit when applied as an addition to a standard multimodal rehabilitation. PATIENTS AND METHODS: In this study 67 patients at a German rehabilitation clinic were included and allocated to 3 study groups: the 2 intervention groups received additional mild water-filtered near infrared whole body hyperthermia once or twice a week over 3 weeks and the control group received only standard multimodal rehabilitation. Main outcome measure was pain intensity measured at baseline, discharge from the rehabilitation clinic and 6 months after discharge. RESULTS: Additional mild water-filtered near infrared whole body hyperthermia once a week proved to be significantly better than the second hyperthermia group and the control group with respect to pain reduction and affective sense of pain. Furthermore, hyperthermia once a week tended to result in better outcome regarding fibromyalgia-related quality of life and depression. CONCLUSION: There is evidence that mild water-filtered near infrared whole body hyperthermia is a reasonable complement to multimodal rehabilitation in the treatment of fibromyalgia.

[Importance of education level for effectiveness of multimodal pain therapy]. / Bedeutung des Bildungsniveaus für die Wirksamkeit der multimodalen Schmerztherapie.

BACKGROUND: The recommended treatment for chronic pain is multidisciplinary with a cognitive approach. The aim of this study was to investigate whether the education level of patients was predictive of main outcome dimensions (pain intensity, disability, depression, physical functioning and return to work). PATIENTS AND METHODS: This was a secondary analysis of 413 patients who participated in an in-patient multidisciplinary pain treatment program. All patients were studied at baseline and after 6 months. The aim was to find predictors for the changes in scores of outcome measures (from admission to follow-up). Possible predictors were educational level and other available variables that are considered prognostic of treatment outcome, including age, gender, body mass index, endurance of pain, pain intensity, depressive symptoms and work status. Classification trees were used to predict outcome variables. RESULTS: The outcome was markedly improved in the sampling collective at follow-up compared with baseline. Education was the best predictor of treatment outcome and affected 4 out of the 5 outcome dimensions analyzed. CONCLUSION: If education level proves to be an intervening variable in further research, education adjusted treatment programs should be developed and evaluated.

Enhanced contact allergen- and UVB-induced keratinocyte apoptosis in the absence of CD95/Fas/Apo-1.

FAS/CD95/Apo-1 is a ubiquitously expressed cell-surface receptor involved in the initiation of programmed cell death. Its function in epidermal keratinocytes has been incompletely defined. Available evidence from in vitro studies points to important roles of Fas in the pathogenesis of contact dermatitis and in keratinocyte apoptosis induced by ultraviolet light. To define functions of Fas in the epidermis in vivo, we have generated mice with epidermis-specific deletion of the fas gene and tested its requirement for 2,4-dinitrofluorobenzene-induced contact dermatitis and for ultraviolet light B (UVB)-induced keratinocyte apoptosis. We report here our unexpected finding that keratinocyte apoptosis induced by both a contact allergen and UVB irradiation was significantly enhanced in Fas-negative epidermis. Expression of Fas by epidermal keratinocytes was neither necessary for the normal development of contact hypersensitivity of the skin, nor required for keratinocyte apoptosis following UVB irradiation. Our study results thus show that in the epidermis in vivo Fas exerts antiapoptotic effects that outweigh its proapoptotic role in contact hypersensitivity responses of the skin and in the tissue response of the epidermis to UVB irradiation.

Resolving lesions in human cutaneous leishmaniasis predominantly harbour chemokine receptor CXCR3-positive T helper 1/T cytotoxic type 1 cells.

BACKGROUND: Cutaneous leishmaniasis (CL) is an epidemic disease affecting millions of individuals worldwide. Treatment options have several side-effects and a vaccine does not exist at present. OBJECTIVES: To translate information about protection against CL from mice to man, we studied the local immune response in CL skin biopsies and correlated these findings with clinical information. METHODS: The frequency of inflammatory cells was determined in skin biopsies of 20 patients diagnosed with CL using immunohistochemistry. In addition, the nature of the resulting adaptive immune response was assessed by (double) immunostaining against CD4 and chemokine receptors CXCR3 (T helper 1, Th1)/CCR4 (Th2). RESULTS: All lesions contained CD4+ and CD8+ T cells, B cells and CD68+ macrophages. CD1a+ epidermal Langerhans cells were absent above the centre of the lesions, but normally distributed in the surrounding tissue. Mast cell and CD56+ natural killer cell numbers were not affected. Interestingly, CCR4+ Th2 cells were not detected in any of the 20 samples. In contrast, the number of infiltrating CXCR3+ cells was high and the majority of these were CD4+ or CD8+ indicating that they represent interferon-gamma-producing Th1/T cytotoxic type 1 (Tc1) cells. Finally, these findings did not correlate with clinical information about the country where the infection was acquired, or age or sex of the patients. However, lesions that had already persisted for more than 6 months contained fewer CXCR3+ CD4 and CD8 T cells than those that had persisted for less than 6 months. CONCLUSIONS: Our data on the inflammatory infiltrate of human CL lesions underline the relevance of findings obtained in experimental models. Both Th1 and Tc1 cells appear to be critical for healing in CL in mouse and man.

Use of geographic and genotyping tools to characterise tuberculosis transmission in Montreal.

SETTING: In Canada, tuberculosis (TB) is increasingly an urban health problem. Montreal is Canada's second-largest city and the second most frequent destination for new immigrants and refugees. OBJECTIVES: To detect spatial aggregation of cases, areas of excess incidence and local 'hot spots' of transmission in Montreal. DESIGN: We used residential addresses to geocode active TB cases reported on the Island of Montreal in 1996-2000. After a hot spot analysis suggested two areas of overconcentration, we conducted a spatial scan, with census tracts (population 2500-8000) as the primary unit of analysis and stratification by birthplace. We linked these analyses with genotyping of all available Mycobacterium tuberculosis isolates, using IS6110-RFLP and spoligotyping. RESULTS: We identified four areas of excess incidence among the foreign-born (incidence rate ratios 1.3-4.1, relative to the entire Island) and one such area among the Canadian-born (incidence rate ratio 2.3). There was partial overlap with the two hot spots. Genotyping indicated ongoing transmission among the foreign-born within the largest high-incidence zone. While this zone overlapped the area of high incidence among Canadian-born, genotyping largely excluded transmission between the two groups. CONCLUSIONS: In a city with low overall incidence, spatial and molecular analyses highlighted ongoing local transmission.

Cytoskeletal polymer networks: the molecular structure of cross-linkers determines macroscopic properties.

In living cells the mechanical properties of the actin cytoskeleton are defined by the local activation of different actin cross-linking proteins. These proteins consist of actin-binding domains that are separated and geometrically organized by different numbers of rod domains. The detailed molecular structure of the cross-linking molecules determines the structural and mechanical properties of actin networks in vivo. In this study, we systematically investigate the impact of the length of the spacing unit between two actin-binding domains on in vitro actin networks. Such synthetic cross-linkers reveal that the shorter the constructs are, the greater the elastic modulus changes in the linear response regime. Because the same binding domains are used in all constructs, only the differences in the number of rod domains determine their mechanical effectiveness. Structural rearrangements of the networks show that bundling propensity is highest for the shortest construct. The nonlinear mechanical response is affected by the molecular structure of the cross-linker molecules, and the observed critical strains and fracture stress increase proportional to the length of the spacing unit.

[High-dose rate brachytherapy for high-risk prostate cancer]. / High-dose-rate-Brachytherapie beim Risikoprostatakarzinom.

To estimate disease-free survival it is necessary to allocate patients into tumor risk groups: locally advanced prostate carcinoma with extracapsular spread or localized prostate carcinoma of tumor stage T2c or one of the risk factors PSA >20 or Gleason > or =8 apply for the high-risk group. Intermediate-risk carcinomas are those belonging to tumor stage T2b or with PSA >10-20 or Gleason 7. Particularly for patients with intermediate and high-risk disease early PSA relapse is of major interest. This phenomenon could be a consequence of current inadequate imaging of lymph node or bone metastasis or as a consequence subclinical metastatic spread remains undetectable during radical treatment. However, tumor biology itself could lead to the progression of the disease in the high-risk group. As a consequence, risk-adapted therapy is very important in these cases. The applied radiation dose plays an important role in radiotherapy. Several publications have shown that the biochemical relapse correlates with the generally accepted risk factors and the radiation dose. Regarding this, high-quality treatment planning and HDR brachytherapy combined with EBRT (external beam radiation therapy) leads to good treatment results in selected groups. So far in our own experience, HDR brachytherapy in combination with EBRT is a successful form of treatment with few acute and late side effects in the first 42 patients examined. First results concerning to PSA relapse-free time, quality of life, miction, and erectile function are promising.

[Computed tomographic examination of muscle volume, cross-section and density in patients with dysgnathia]. / Computertomographische Untersuchung von Muskelvolumen, -querschnitt und -dichte bei Dysgnathiepatienten.

PURPOSE: The individual jaw position is determined by the masticatory muscle among other factors. Before surgical treatment of malocclusions, thorough evaluation of the muscles is required to estimate the relapse risk. MATERIALS AND METHODS: By means of computer tomography, lateral radiographs of the skull and denture models, the relationships between morphological parameters of the masticatory muscles and the jaw bone were analyzed. Furthermore, possible causes for the extent of the malocclusion are described. RESULTS: A patient group with deep overbite was found to have significantly higher muscle densities (measured in Hounsfield units [HU]) in the medial pterygoideus muscle (59.89 +/- 3.91 HU to 48.94 +/- 4.14 HU, p < 0.01), masseter muscle, and genioglossus muscle (p < 0.05) in comparison to open bite patients. Significant differences of the muscle cross-section were measured in the masseter muscle between patients with retroclined maxillary incisors and with an open bite (5.4 +/- 0.7 cm (2) to 3.8 +/- 0.4 cm (2), p < 0.05). CONCLUSION: The results show a correlation between different jaw positions and masticatory muscles. They also suggest that the function of each muscle may be different. Additional examinations of the muscle structures are required for verification of the influence of the masticatory muscles on facial morphology.

[Evaluation of specific stabilizing exercise in the treatment of low back pain and lumbar disk disease in outpatient rehabilitation]. / Wertigkeit der muskulären segmentalen Stabilisierung zur Behandlung von Rückenschmerz und Bandscheibenerkrankungen im Rahmen der ambulanten Rehabilitation.

AIM: The aim of the study was to evaluate the outcome of outpatient rehabilitation in patients with low back pain and lumbar disk disease with a specific stabilizing exercise of the M. multifidus and M. transversus abdominis. METHOD: 99 outpatients admitted to a rehabilitation unit were included in a prospective randomized controlled interventional trial. The interventional group consisted of 50 patients (34 male, 16 female; mean age 41.1 +/- 9.1, range; 21 - 54 years), 49 patients (31 male, 18 female; mean age 37.9 +/- 9.5, range; 19 - 55 years) were in the control group. Outcomes were assessed at the beginning and the end of the treatment and at a three month follow-up with the Oswestry Low Back Pain Disability Questionnaire, the Hannover Functional Ability Questionnaire FFbH-R, the pain scale SES and a numeric rating scale. RESULTS: In both groups there was a significant functional improvement as measured with the Oswestry Score and the FFbH-R. The interventional group showed better values at the end of the treatment. Pain as well could be reduced significantly by the treatment, but no differences were noted between the two groups. CONCLUSION: Outpatient rehabilitation improved functional capacity and pain in both groups. Advantages could be seen in the interventional group concerning functional status. The specific stabilizing exercise approach appears to be effective in conservative treatment programs of low back pain and lumbar disk disease.

[Outcome of inpatient rehabilitation following total knee replacement using the HSS-Score]. / Ergebnisevaluation der stationären Rehabilitation nach Knieendoprothetik mit dem HSS-Score.

AIMS: The aim of the study was to evaluate the outcome of inpatient rehabilitation following total knee arthroplasty using the HSS score (Hospital for Special Surgery). Factors influencing the result were analysed. METHOD: 182 patients admitted to a rehabilitation unit after total knee replacement were included. There were 146 female and 36 male patients, with mean age of 72 (+/- 6.1) years (range; 49 to 84 years). RESULTS: At admission, the HSS score was 47.4 (+/- 10.6) and was significantly improved to 69.8 (+/- 8.8) at discharge. The percentage of patients with a poor result was markedly decreased from 86.8 % to 10.4 %. The outcome was independent of sex, age, concomitant diseases or postoperative weight bearing. 34 patients could not be discharged after 3 weeks as usually and stayed for another 8.3 (+/- 2.6) days. These patients had significantly lower scores at admission (41.9 +/- 11.2) than patients who stayed for three weeks (48.6+/- 10.1). At discharge, scores were comparable with 67.7 (+/- 9.4) and 70.2 (+/- 8.6), respectively. CONCLUSION: Inpatient rehabilitation following knee arthroplasty significantly improved the HSS score independent of sex, age, concomitant diseases and weight bearing.

[Inpatient rehabilitation of patients following total hip replacement--a study using the Harris hip score]. / Stationäre Rehabilitation nach Hüftendoprothetik - eine Verlaufsbeobachtung mit dem Harris-Hip-Score.

AIMS: The aim of the study was to evaluate the outcome of inpatient rehabilitation following total hip arthroplasty using the Harris hip score. Factors influencing the result were analysed. METHOD: 338 patients admitted to a rehabilitation unit after total hip replacement were included in a prospective study. There were 252 female and 86 male patients, with a mean age of 69 (+/- 9.7) years (range, 34 to 88 years). RESULTS: At admission the Harris hip score was 63.1 (+/- 10.4) and was improved by almost 25 % to 79.1 (+/- 7.1) at discharge. The percentage of patients with a poor score was decreased from 71.9 % to 8 % after rehabilitation. The result of rehabilitation was independent of sex, age, concomitant diagnoses or weight bearing. 61 patients could not be discharged after three weeks as usual and stayed for another 8.0 (+/- 4.5) days. At admission these patients had significantly lower scores (58.5 +/- 10.8) than the patients who stayed for three weeks (64.1 +/- 10.0). At discharge scores were comparable with 77.0 (+/- 7.2) and 79.6 (+/- 7.0), respectively. CONCLUSION: An inpatient rehabilitation after hip arthroplasty significantly improves the Harris hip score independent of sex, age, concomitant diseases and weight bearing.

A role for mitogen-activated protein kinase activation by integrins in the pathogenesis of psoriasis.

In normal epidermis, beta1 integrin expression is confined to the basal layer, whereas in hyperproliferative epidermis, integrins are also expressed in the suprabasal layers. Transgenic mice in which integrins are expressed suprabasally via the involucrin promoter have a sporadic psoriatic phenotype; however, the mechanism by which integrins contribute to the pathogenesis of psoriasis is unknown. We observed activation of mitogen-activated protein kinase (MAPK) in basal and suprabasal keratinocytes of human and transgenic mouse psoriatic lesions and healing mouse skin wounds, correlating in each case with suprabasal integrin expression. Phenotypically normal human and transgenic mouse epidermis did not contain activated MAPK. Transgene-positive keratinocytes produced more IL-1alpha than controls did, and keratinocyte MAPK could be activated by ligation of suprabasal integrins or treatment with IL-1alpha. Constitutive activation of MAPK increased the growth rate of human keratinocytes and delayed the onset of terminal differentiation, recreating many of the histological features of psoriatic epidermis. We propose that activation of MAPK by integrins, either directly or through increased IL-1alpha production, is responsible for epidermal hyperproliferation in psoriasis and wound healing, and that the sporadic phenotype of the transgenic mice may reflect the complex mechanisms by which IL-1 release and responsiveness are controlled in skin.

Fibroblasts in mechanically stressed collagen lattices assume a "synthetic" phenotype.

Fibroblasts are subjected to changes of the mechanical force balance during physiological as well as pathological situations, such as wound healing, development of hypertrophic scars, and fibrogenesis. However, the molecular response and the changes in fibroblast gene expression upon mechanical stimulation remain poorly understood. As an in vitro model, human dermal fibroblasts were cultured within a three-dimensional network of fibrillar collagen either under high (stressed) or low tension (relaxed). cDNA microarray technology in combination with Northern blot analysis led to identification of mechano-responsive genes coding for extracellular matrix proteins, fibrogenic growth factors, protease inhibitors, components of focal adhesions, and the cytoskeleton. Application of biaxial strain to fibroblasts cultured on flexible silicone membranes revealed that the type of strain as well as the properties of the substrate induced different patterns of gene regulation. The transcriptional profile of mechanically induced genes in collagen lattices suggests that mechanical stimuli lead to a "synthetic" fibroblast phenotype characterized by induction of connective tissue synthesis while simultaneously inhibiting matrix degradation.