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Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. Methods We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. Results Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. Conclusion The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

Background: The current subclassification of systemic sclerosis into cutaneous subtypes does not fully capture the heterogeneity of the disease. We aimed to compare the performances of stratification into LeRoy's cutaneous subtypes versus stratification by autoantibody status in systemic sclerosis. Methods: For this cohort study, we assessed people with systemic sclerosis in the multicentre international European Scleroderma Trials and Research (EUSTAR) database. Individuals positive for systemic-sclerosis autoantibodies of two specificities were excluded, and remaining individuals were classified by cutaneous subtype, according to their systemic sclerosis-specific autoantibodies, or both. We assessed the performance of each model to predict overall survival, progression-free survival, disease progression, and different organ involvement. The three models were compared by use of the area under the curve (AUC) of the receiver operating characteristic and the net reclassification improvement (NRI). Missing data were imputed. Findings: We assessed the database on July 26, 2019. Of 16 939 patients assessed for eligibility, 10 711 patients were included: 1647 (15·4%) of 10 709 were male, 9062 (84·6%) were female, mean age was 54·4 (SD 13·8) years, and mean disease duration was 7·9 (SD 8·2) years. Information regarding cutaneous subtype was available for 10 176 participants and antibody data were available for 9643 participants. In the prognostic analysis, there was no difference in AUC for overall survival (0·82, 95% CI 0·81–0·84 for cutaneous only vs 0·84, 0·82–0·85 for antibody only vs 0·84, 0·83–0·86 for combined) or for progression-free survival (0·70, 0·69–0·71 vs 0·71, 0·70–0·72 vs 0·71, 0·70–0·72). However, at 4 years the NRI showed substantial improvement for the antibody-only model compared with the cutaneous-only model in prediction of overall survival (0·57, 0·46–0·71 for antibody only vs 0·29, 0·19–0·39 for cutaneous only) and disease progression (0·36, 0·29–0·46 vs 0·21, 0·14–0·28). The antibody-only model did better than the cutaneous-only model in predicting renal crisis (AUC 0·72, 0·70–0·74 for antibody only vs 0·66, 0·64–0·69 for cutaneous only) and lung fibrosis leading to restrictive lung function (AUC 0·76, 0·75–0·77 vs 0·71, 0·70–0·72). The combined model improved the prediction of digital ulcers and elevated systolic pulmonary artery pressure, but did poorly for cardiac involvement. Interpretation: The autoantibody-only model outperforms cutaneous-only subsetting for risk stratifying people with systemic sclerosis in the EUSTAR cohort. Physicians should be aware of these findings at the time of decision making for patient management. Funding: World Scleroderma Foundation.

International audience; Objectives: Relapsing polychondritis is a rare, multi-systemic and inflammatory condition of unknown origin. We currently lack a core set of measures to assess and follow damage in patients suffering from this condition. Our primary aim was to derive a disease-specific damage measuring tool for relapsing polychondritis, the Relapsing Polychondritis Damage Index (RPDAM).Methods: We performed an international 4-round multicenter Delphi study during which experts were asked to rate the relevance of potential damage items for relapsing polychondritis (141 items were obtained from a literature review and 12 from expert suggestion), using a Likert Scale. The selection of items for each subsequent round was based on the median rating of each item.Results: Twenty-four experts from 11 nationalities participated in round 1 and 22 in rounds 2, 3 and 4. From the initial 153 potential damage items, 44 items were selected during round 1, 30 items during round 2 and 16 during round 3. During round 4, we refined the index to a total of 17 items referring to ear nose and throat, eye, respiratory, cardiovascular and hematological systems as well as to treatment-related specific damage items.Conclusion: We have developed by international consensus a scoring system to assess damage in patients with relapsing polychondritis. Following its validation, the RPDAM may contribute to improve the care of patients suffering from this rare condition as well as to standardize data collection for future clinical trials.

Resume Objectifs La polychondrite atrophiante (PCA) est une maladie inflammatoire, multi-systemique rare dont les causes sont encore inconnues. Nous ne disposons actuellement d’aucun score de mesure permettant d’evaluer et de surveiller les lesions chez les patients porteurs de cette pathologie. Notre objectif principal etait d’elaborer un outil de mesure concernant le damage au cours de la polychondrite atrophiante, le Relapsing Polychondritis Damage Index (RPDAM). Methodes Nous avons realise une etude internationale multicentrique par methode Delphi en 4 tours durant laquelle des experts ont ete invites a evaluer la pertinence des items lies au damage dans la PCA (141 items ont ete obtenus a partir d’une revue de la litterature et 12 ont ete proposes par les experts), en utilisant l’echelle de Likert. La selection des items pour chacun des tours suivants etait basee sur la cotation mediane attribuee a chaque item. Resultats Vingt-quatre experts de 11 nationalites differentes ont participe au premier tour et 22 aux 3 tours suivants. Parmi les 153 items initiaux lies au damage, 44 ont ete selectionnes durant le tour 1, 30 durant le tour 2 et 16 durant le tour 3. Au cours de la 4e etape, nous avons affine le score a un total de 17 items concernant les atteintes cartilagineuses auriculaires, nasales, laryngo-tracheo-bronchiques et les manifestations ophtalmologiques, respiratoires, cardiovasculaires et hematologiques ainsi que les effets secondaires lies au traitement. Conclusion Nous avons developpe, par consensus international, un score lesionnel d’evaluer chez les patients souffrant de PCA. Apres validation, le score RPDAM contribuera a ameliorer la prise en charge des patients souffrant de cette pathologie rare mais egalement a standardiser le recueil de donnees pour de prochains essais cliniques.

Gastrointestinal (GI) involvement is almost universal in patients with systemic sclerosis (SSc) and is associated with significant disease-related morbidity and mortality.1 The entire GI tract can be involved and other disease features (eg, low mood, terminal organ failure and functional hand impairment) can result in significant nutritional impairment. Severe GI involvement has been reported to occur in ~10% of patients with SSc and often occurs early in the course of the disease.2 However, identification of patients at high risk of clinically significant weight loss is extremely challenging, including from the high prevalence of GI symptoms in patients with SSc. Therefore, there is a need to understand high-risk patients including potentially modifiable risk factors, with a view to early intervention strategies. Against this background, the aim of this study was to examine potential clinical risk factors of significant weight loss in patients with SSc. We performed an analysis of patients with SSc enrolled in the multinational, longitudinal European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) database. In our study, we defined significant weight loss as 4.5 kg and/or least 5% of their body weight at 5 months onwards.3 Patients with a recorded second visit after 3 months and before 12 months were included in the analysis. We adopted a pragmatic approach (relevant to clinical practice) in …

The Central European Congress of Rheumatology (CECR) has been organized by seven Central European countries: Austria, Croatia, Czech Republic, Hungary, Poland, Slovakia, and Slovenia. These countries have lots of similarities, but also differences, with respect to rheumatology research. In this paper, based on questionnaires, we wish to demonstrate achievements and difficulties in rheumatology research performed in our region.

Osteoarthritis (OA) is characterized by deterioration of the joints and associated with considerable pain and disability. OA is a chronic disease that requires intervention with both non-pharmacological and pharmacological treatment modalities and, inevitably, disease progression may necessitate successive treatments throughout the course of the disease. There is increasing data on the shortfalls of current pharmacological treatment of OA, and safety concerns associated with analgesic therapy use in OA arising from increasing evidence of gastrointestinal, cardiovascular, hepatic and renal adverse events with paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs). Consequently, symptomatic slow-acting drugs for OA (SYSADOAs) may now be considered as a first-line treatment for knee OA, with a particular emphasis placed on the outstanding benefit: risk ratio of pharmaceutical-grade glucosamine and chondroitin sulfate formulations. In this short communication we review recent publications concerned with the safety of paracetamol, NSAIDs and SYSADOAs. Greater understanding of the benefits and limitations of current medications will lead to better disease management in OA. Furthermore, adherence to guideline recommendations across Europe and internationally, such as those from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), will promote evidence-based medicine and patient-centric care, ultimately leading to greater physician and patient satisfaction.

BACKGROUND Fibulin-3 (Fib-3) is a new potential biomarker of articular cartilage metabolism. OBJECTIVES The aim of the study was to evaluate the effect of anti-TNF therapy on serum fibulin-3, cartilage oligomeric matrix protein (COMP), procollagen II C-propeptide (PIICP), and urinary C-terminal telopeptide of type II collagen (CTX-II) levels in relation to calprotectin (MRP8/14) and disease activity in rheumatoid arthritis patients. MATERIAL AND METHODS In the study, 35 female patients with rheumatoid arthritis (RA) were investigated. The concentration of fibulin-3, COMP, PIICP, MRP8/14, and urinary CTX-II in serum was measured before and after anti-TNF therapy. Ten healthy women were investigated as the controls. RESULTS The concentration of fibulin-3 in RA patients before treatment did not differ significantly from the concentration of fibulin-3 in the control group. A significantly higher concentration of fibulin-3 was noted prior to treatment in the group of women with a worse response to the therapy (non-responders) compared to the concentration of fibulin-3 in the healthy women. During the anti-TNF therapy, the serum fibulin-3 level decreased in patients. The fibulin-3 level correlated with CRP and ESR after anti-TNF treatment. Significant lowering of MRP8/14 was noted in the patients after anti-TNF therapy. No correlation between fibulin-3 and MRP8/14 was observed in the study group or in the control group. CONCLUSIONS During the anti-TNF therapy, the serum fibulin-3 level decreased in RA patients. Serum MRP8/14 concentration also decreased. No correlation between fibulin-3 and MRP8/14 was observed in the study group before and after the treatment. We found a poor correlation between serum fibulin-3 and other cartilage metabolism biomarkers after anti-TNF therapy.

Granulomatosis with polyangiitis (GPA), previously known as Wegener’s granulomatosis, is a rare form of systemic vasculitis of unknown etiology, commonly associated with serum cANCA. Typical manifestations include necrotizing vasculitis and granulomatous inflammation which occur in the upper and lower respiratory tracts and kidneys, however the range of clinical manifestations of GPA can involve almost any organ. Epidemiological studies suggested that prevalence of GPA in Poland is 36/1,000,000 and is slightly lower than in other European countries. A statistically significant decrease in the GPA incidence was found within 2011–2015. Both sexes are affected equally, and a mean age at diagnosis is 40 yrs. Clinical manifestations are heterogeneous and the following presentation of the disease should be taken into consideration: cutaneous (leucocytoclastic vasculitis, purpura, digital infarcts and gangrene), oral (ulcers, granulomatous lesions, gingival hyperplasia with strawberry-like aspect), ocular (episcleritis, scleritis, conjunctivitis, keratitis, uveitis, retinal vasculitis or thrombosis, blindness, proptosis and orbital granulomatous masses), auricular (sensorineural hearing loss and conductive hearing loss), cardiovascular (small vessel vasculitis, occlusive vascular disease, pericarditis, cardiomyopathy, valvular heart disease, ischemic heart disease, heart failure), gastrointestinal (acute abdomen secondary to peritonitis or bowel ischemia), neurological (meningitis, seizures, cerebrovascular accidents, spinal cord lesions, cranial nerve palsies, sensory or motor peripheral neuropathy, mononeuritis multiplex, cerebral mass lesions) as well as musculoskeletal involvements. Therapy should be adjusted to individual patient. Various programs have been proposed for the induction of remission and its maintenance, and management of relapses. Glucocorticoids and cyclophosphamide are the most commonly used medication although rituximab is particularly useful in patients with refractory or relapsing disease, women of childbearing potential, and patients previously treated with cyclophosphamide as well as is more effective than cyclophosphamide for treating relapses. Azathioprine is also used for remission maintenance. Plasma exchange is indicated in patients with alveolar hemorrhage.

In the Original Publication, the e-mail address of the author Milan Petronijevic is incorrect. The correct e-mail address is milanpetronijevic@yahoo.com.

The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm for knee osteoarthritis (OA) recommends symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) first line for the medium to long term management of OA, due to their ability to control pain, improve function, and delay joint structural changes. Among SYSADOAs, glucosamine is probably the most widely used intervention. In the present review of glucosamine for knee OA, we have investigated whether the evidence is greater for the patented crystalline glucosamine sulfate (pCGS) preparation (Rottapharm/Meda) than for other glucosamine formulations. Glucosamine is actually widely available in many forms, as the prescription-grade pCGS preparation, generic and over-the-counter formulations of glucosamine sulfate (GS) and food supplements containing glucosamine hydrochloride (GH), which vary substantially in molecular form, pharmaceutical formulation and dose regimens. Only pCGS is given as a highly bioavailable once daily dose (1500 mg) with a proven pharmacological effect. pCGS consistently reaches the plasma levels of around 10 μM required to inhibit interleukin-1 induced expression of genes involved in the pathophysiology of joint inflammation and tissue destruction, compared with sub-therapeutic levels achieved with GH. It is evident, from careful consideration of the evidence base, that only the pCGS formulation of glucosamine reliably provides an effect size on pain that is higher than that of paracetamol and equivalent to that provided by non-steroidal anti-inflammatory drugs. In comparison, the effect size on pain of non-crystalline GS preparations and GH from randomized controlled trials is repeatedly demonstrated to be zero. In addition, there is evidence that chronic administration of pCGS has disease-modifying effects, with a reduction in the need for total joint replacement surgery lasting for at least 5 years after treatment cessation. Consequently, the pCGS preparation (Rottapharm/Meda) is the logical choice, with demonstrated medium-term control of pain and lasting impact on disease progression.

TNF-α is one of the key proinflammatory cytokines in pathogenesis of rheumatoid arthritis (RA). TNF-α was also found to enhance synthesis of leptin. Leptin is mainly adipocyte-derived hormone controlling appetite and energy expenditure. It acts through inhibition of neuropeptide Y secretion. It is possible that TNF-α-induced leptin secretion contributes to body mass reduction in patients with RA. The study was designed to determine the influence of inactivation of the TNF-α with infliximab on plasma leptin and neuropeptide Y concentrations in patients with RA. Sixteen female patients with RA treated with infliximab and 16 healthy women were investigated. Plasma leptin and neuropeptide Y concentrations were determined before, during and after 1 year management of the patients with infliximab and were compared with body mass index and body fatty and lean mass. There was no difference in plasma leptin concentration between the rheumatoid patients before therapy and the controls (15.6 ± 1.85 and 14.5 ± 2.15 ng/ml, respectively). Neuropeptide Y concentration was higher in the patients than in the controls (54.5 ± 3.96 and 24.8 ± 2.80 pmol/l, respectively). Treatment with infliximab resulted in enhancement in leptin concentration (18.5 ± 2.34 ng/ml) and a slight increase in neuropeptide Y concentration (58.7 ± 4.66 pmol/l). Physiological relationship between leptin and body mass was shown in the patients and was not altered during the treatment. There was no significant correlation between the disease activity and plasma leptin or neuropeptide Y concentrations.

Kashubians known also as Kassubians (in Kashubian language: Kaszëbi) are the Slavonic ethnic group inhabiting the Eastern Pomerania in Poland. They speak the Kashubian language that is classified as the West Slavonic language belonging to the Lekhitic group of languages. Kashubians are the direct descendants of Pomeranians [1]. The Pomeranians came into the northern part of Poland about the 5th century AC. The region they lived is now known as Pomerania. The oldest mention of the region’s name is a seal of prince Barnin the First of Pomerania from the 13th century.

Targeted anti-tumor necrosis factor-alpha (TNFα) therapy in patients with rheumatoid arthritis (RA) has resulted in dramatic improvement in the disease course and prognosis. One of the features of RA is hyperplasia of synovial cells, particularly RA synovial fibroblasts (RA-SF), caused partially by impaired apoptosis of RA-SF cells. It has been shown that TNFα may inhibit apoptosis in RA-SF cells and this process may be reversed by the use of TNFα antagonists.To determine the influence of etanercept, an anti-TNFα agent, on sFas (CD 95) receptor.We analyzed serum levels of sFaS and TNFα in a group of 26 patients with high RA disease activity who were selected to start treatment with etanercept. Assessment of sFas receptor and TNFα levels was performed before and 6 months after treatment with etanercept.Treatment with etanercept resulted in increased TNFα levels (log TNFα 0.602 vs. 1.17, P0.05) but no change in sFas levels (log sFas 3.17 vs. 3.11, P = 0.37). As expected, treatment resulted in significant reduction in both disease activity and levels of inflammatory markers.Etanercept may increase TNFα levels in patients with RA. We also speculate that the Fas pathway is not the main apoptotic pathway in patients with RA treated with etenercept, since sFas, a marker of apoptotic activity, remained unchanged and was not influenced by disease activity and concomitant treatment.

Ghrelin is a gastric hormone that posses multiple functions, including induction of growth hormone release, regulation of proinflammatory cytokines and control of food intake and energy homeostasis. A few reports on serum ghrelin level in chronic inflammatory states revealed contradictory results. The study was undertaken to determine ghrelin in patients with rheumatoid arthritis receiving infliximab, a TNF-α blocking agent. Serum ghrelin was determined in 18 female rheumatoid patients before the treatment with infliximab, 1 week after the first infusion and after 53 weeks of medication and compared with 15 age-matched healthy women. Serum ghrelin level was shown to be increased in the patients. A decrease in serum ghrelin level was found after the first infusion of infliximab and similarly decreased ghrelin level but still higher than in the control was shown in the 53rd week of medication. The obtained results suggest that ghrelin level is related to inflammation, and its serum level in patients with severe rheumatoid arthritis behaves similarly to acute-phase reactants.

Hyperthyroidism or hypothyroidism are commonly associated with altered blood pressure (BP). Restriction of sodium in the diet produces a decrease in BP in some individuals. It is also well known that hormones other than thyroid affect BP. The present study was designed to evaluate the influence of a low sodium diet on BP in patients with hyperthyroidism or hypothyroidism during therapy. The occurrence of salt-sensitive or salt-nonsensitive BP was compared with hormonal levels (plasma renin activity, aldosterone, atrial natriuretic peptide, and arginine vasopressin). Patients with hyperthyroidism (75 subjects) were investigated before the initiation of treatment, 2 weeks after the treatment, and after the attainment of euthyroid state. Patients with hypothyroidism (31 subjects) were studied before the treatment and in the euthyroid state. Control values were obtained from 37 healthy individuals. Blood pressure, changes of plasma volume, serum aldosterone, atrial natriuretic peptide, vasopressin levels, and plasma renin activity were measured in all investigated subjects after application of a normal sodium diet and after 3 days on a low sodium diet. Elevated systolic BP was found in patients with hyperthyroidism and hypothyroidism. Mean arterial BP was higher only in the untreated hypothyroid patients. The high incidence of salt-sensitive BP was found only in untreated hypothyroid patients. Also in hypothyroid patients the application of a low sodium diet led to a lower increase in plasma renin activity in subjects with salt-sensitive BP than in individuals with salt-resistant BP. Therefore, different mechanisms are responsible for BP elevation in patients with hyperthyroidism or hypothyroidism.

Msciwoj Maria Thaddaeus Semerau-Siemianowski was born on May 19, 1885, in Ruschuk (now Ruse) in northeastern Bulgaria. He graduated with a degree in medicine in 1910 and received the M.D. degree in 1911 from the University of Strassburg, Germany (now in France). He was an assistant in the department of internal medicine at the university until World War I. In 1918, Semerau-Siemianowski became a lecturer at the University of Warsaw in Poland, and in 1924, he was appointed head of the department of internal medicine at St. Lazarus Hospital in Warsaw. In 1929, he became a professor at the University of Warsaw. During World War II, the German army occupied Poland, and the Nazi regime removed Semerau-Siemianowski from all his positions. He then became involved in the underground teaching of medicine, inasmuch as all forms of education were prohibited to Poles. After the Warsaw insurrection during the German occupation, he was imprisoned, but he escaped. After the war, he taught at the universities of Lodz and Gdansk in Poland. In 1948, he began teaching at the Warsaw School of Medicine; subsequently, he became head of the second department of internal medicine there. Semerau-Siemianowski was coauthor and editor of a twovolume handbook on internal medicine. He also contributed to many organizations that were associated with the teaching of medicine, and he was a member of the Polish Academy of Sciences and several other scientific associations. Semerau-Siemianowski died in Warsaw on June 20, 1953. Most of his research had been focused on cardiology, and he had been one of the founders of the Polish Society of Cardiology. He was honored on a postcard issued by Poland on the 20th anniversary of the founding of that society.

We studied 54 patients with ankylosing spondylitis with questionnaire in order to determine their view on threat to quality of their life related to the disease. We have show that pain and significant disability are the main threats associated with the disease in view of the patients. Social aspects (losing of job or decreasing of income) are also important for the patients, while management of the disease is not considered as arduous. The results of patients' opinion may be helpful in designing of educational programs for them.