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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.

Objective Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc) patients. We aimed to investigate the impact of sex on SSc-ILD. Methods EUSTAR SSc patients with radiologically confirmed ILD and available percentage predicted forced vital capacity (%pFVC) were included. Demographics and disease features were recorded. A change in %pFVC over 12 months (s.d. 6) (cohort 1) was classified into stable (≤4%), mild (5–9%) and large progression (≥10%). In those with 2-year longitudinal %pFVC (cohort 2), the %pFVC change at each 12-month (s.d. 6) interval was calculated. Logistic regression analyses [odds ratio (OR) and 95% CI] and Cox proportional hazards models adjusted for age and %pFVC were applied. Results A total of 1136 male and 5253 female SSc-ILD patients were identified. Males were significantly younger, had a shorter disease duration, had a higher prevalence of CRP elevation and frequently had diffuse cutaneous involvement. In cohort 1 (1655 females and 390 males), a higher percentage of males had stable ILD (74.4% vs 69.4%, P = 0.056). In multivariable analysis, disease duration and %pFVC [OR 0.99 (95% CI 0.98, 0.99) and OR 0.97 (95% CI 0.95, 0.99), respectively] in males and age, %pFVC and anti-centromere [OR 1.02 (95% CI 1.00, 1.04), OR 0.97 (95% CI 0.96, 0.98) and OR 0.39 (95% CI 0.245, 0.63), respectively] in females were associated with large progression. The 1-year mortality rate was higher in males (5.1% vs 2.5%, P = 0.013). In cohort 2 (849 females and 209 males), a higher percentage of females showed periods of large progression (11.7% vs 7.7%, P = 0.023), the percentage of patients with none, one or two periods of worsening was not different. The overall death rate was 30.9% for males and 20.4% in females (P Conclusions Male SSc-ILD patients have a poorer prognosis and sex-specific predictors exist in SSc-ILD.

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 …

Pulmonary involvement is a severe manifestation of systemic sclerosis (SSc). The study was designed to determine the serum level of surfactant protein D (SP-D) in patients with SSc in relation to clinical and laboratory parameters as well as to analyze dynamics of changes of these indices within one year of observation. SP-D was assayed in 41 patients with SSc and 15 healthy controls. Additionally, pulmonary function tests, chest high-resolution computed tomography (HRCT), and inflammatory markers were assessed. All tests were performed twice: at entry and repeated after one year of observation. The serum level of SP-D was significantly higher in patients with SSc than in healthy controls. Serum concentration of SP-D was significantly higher in patients with systemic sclerosis-related interstitial lung disease (SSc-ILD) than in those without SSc-ILD. SP-D was found to correlate with lung involvement evaluated with the Medsger score (diffusing capacity of the lung for carbon monoxide (DLCO), forced vital capacity, radiological changes, and estimated pressure in the pulmonary artery in echocardiography). SP-D correlated with the honeycombing and/or reticular pattern in HRCT and ground glass opacification pattern. Serum concentration of SP-D was elevated in patients with a decreased DLCO. Furthermore, SP-D was higher in patients with diffuse cutaneous type (dcSSc) of the disease than in those with SSc limited type (lcSSc). Because of the small size of the group, it was not possible to perform a statistical analysis for patients who had different results in HRCT, VC, and Medsger score between the first and the second evaluation. SP-D seems to be an index for assessing lung involvement. It reflects the state of pulmonary fibrosis but not the dynamics of the pulmonary fibrosis progression. Further studies are needed to evaluate clinical application of the index, and currently, there is no evidence for the recommendation of the application of SP-D in routine evaluation of patients with SSc.

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.

Background and objective Statins, 3-hydroxyl-3-methyl-glutharyl Coenzyme A reductase inhibitors showed their therapeutic potential in the treatment of atherosclerosis-related diseases. Recently, the properties of statins, separate from their lipid lowering activity have attracted much attention. These properties that cover a wide area of physiopathological activities including cell maturation, immune response regulation, tissue fibrosis, endothelial activity and are called pleiotropic activity. Many in vitro studies demonstrated significant, statins-dependent regulation of immune system reactivity, reduction of pro-inflammatory and pro-fibrotic cytokines as well as suppression of endothelial activity and damage. Methods The present study reviewed the potential utility of statins as a concomitant regimen in the treatment of various connective tissue diseases. To address this we performed a methodical search though Pubmed database searching for term statins and pleiotropic effects and connective tissue disease or rheumatology. Results One hundred and thirty one prominent research and review papers were identified and analyzed. Majority of research papers focused on laboratory models of statins activity, only a few of them analyzed data from human studies. Conclusion Statins may have a therapeutic potential as a concomitant treatment for connective tissue diseases, that has been elegantly proven in many animal and laboratory studies. They deep interfere with immunological mechanism of autoantigen presentation, expressions of adhesion molecules. These phenomena may be recognized as the most important mode of action. Less is known about the potential of statins in clinical practice. Many small trials examined therapeutic potentials in various autoimmune diseases with contradictory results, disabling making the final conclusions. The future human studies should answer what patients population may benefit with concomitant statins' treatment.

OBJECTIVES: In agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with a strong sex bias. However, unlike lupus, the effects of sex on disease phenotype and prognosis are poorly known. Therefore, we aimed to determine sex effects on outcomes. METHOD: We performed a prospective observational study using the latest 2013 data extract from the EULAR scleroderma trials and research (EUSTAR) cohort. We looked at (i) sex influence on disease characteristics at baseline and (ii) then focused on patients with at least 2 years of follow-up to estimate the effects of sex on disease progression and survival. RESULTS: 9182 patients with SSc were available (1321 men) for the baseline analyses. In multivariate analysis, male sex was independently associated with a higher risk of diffuse cutaneous subtype (OR: 1.68, (1.45 to 1.94); p

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.

Objective: Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. Methods: Data collected between June 2004 and April 2013 were examined with focus on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile. Results: 30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy. Juvenile-onset SSc showed scleroderma pattern more frequently than adult-onset SSc (93.3% and 88%). The OR was 2.44 and 95% Cl 0.57-10.41. An active scleroderma pattern was present in 58% of juvenile- and 61% of adult-onset SSc. The OR was 0.91 and 95% Cl 0.28-2.93. The late scleroderma pattern was present in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% Cl 0.34-3.56. Conclusion: This is the first exploratory study on the comparison of capillaroscopy between juvenile- and adult-onset SSc in adulthood. Juvenile-onset SSc had an increase prevalence of sderoderma pattern, but a similar distribution of the three patterns was suggested. Further studies are needed to define this issue. (C) 2015 Elsevier Inc. All rights reserved.

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.

1 . The generalist versus the specialist During the last decades, new terminology has struggled to describe the changing trends in the practice of internal The 'hot debate' in internal medicine since its inception medicine. It has been suggested that the role of the has been the relationship between the general internist and traditional 'internist' can best be described by the term the sub-specialist. Since the early years of internal medi- 'generalist'. Lee (3) suggested that generalists and special- cine, internists have been medical scientists involved at ists take different attitudes towards the same medical every level of clinical and basic science research. As early problems and that they adopt different positions within any as 1895, Sir William Osler (1849-1919), the great Cana- health care system. The specialist tends to know more and dian internist, stated that the education of specialists in more about less and less, while the generalist knows a lot internal medicine should be based on pathology, bacteriol- about a lot. According to Lee (3), apart from the use of ogy, and chemistry and that they should pass through the different methods and equipment, there are other categori- laboratories to the wards, applying laboratory sciences cal differences between generalists and specialists. These directly to clinical medicine (1). This intimate connection include different boundaries and horizons to their clinical between science and bedside internal medicine produced care, as well as different clinical worries and attitudes enormous progress in understanding the pathophysiology towards risk. The generalist's view of a clinical problem of disease. This led to the development of numerous new and its relation to the external world includes the patient's diagnostic and therapeutic techniques, which, in turn, gave social and psychological predicament. It is more open and rise to new areas of interest based on their use (2). broader than the sub-specialist's, whose view is more Unfortunately, over the last 30 years, specialists have focused, narrower, and more limited. Moreover, since concentrated more and more on these areas of interest so generalists use less technical equipment, they can function that their practice has become more or less completely independently and without the need for expensive re- confined to their sub-specialty interest. At the present time, sources and support staff. in many countries, the general public now considers the Sub-specialists provide sophisticated forms of diagnosis terms 'sub-specialist' and 'specialist' to be synonymous. and therapy (4) and can solve many difficult medical Both are thought to be medical experts focusing on one problems, often providing dramatic cures. system or organ. According to this popular, but wrong, It is not surprising that the lay public, encouraged by the opinion, internists are not considered to be specialists. In media, find sub-specialty medicine fascinating and awe- Poland, for example, insurance companies' contracts no inspiring. Generalist medicine, on the other hand, is less longer pay internists as specialists. However, despite the spectacular and appears dull and uninteresting. Hence, oxymoron of being 'a general specialty', internal medicine their achievements appeal less to the mass media. General- was the original scientifically based medical specialty, the ists, however, have been responsible for a number of mastery of which requires more skill and experience than significant research achievements. These include scoring any of its sub-specialties.

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.

Human cartilage glycoprotein-39 (HC gp-30) is a secretory protein of several types of cells including chondrocytes. It has been suggested to be a laboratory index of joint damage. Thirty-two patients with systemic sclerosis (SSc) and 22 age-matched controls were investigated. An increased serum HC gp-39 level was shown in SSc patients and was found to correlate with inflammatory indices. There was no correlation with modified Rodnan score, joint involvement, or duration of symptoms of SSc. The obtained results indicate for possible relationship of HCgp-39 to inflammation but do not suggest determination of HC gp-39 as clinically applicable index of articular involvement in SSc patients.

Background: Interleukin-6 (IL-6) is a key cytokine in the initiation of the acute-phase reaction that accompanies myocardial infarction. The study was designed to evaluate changes in serum IL-6 in patients with myocardial infarction and to compare IL-6 alterations with serum creatine kinase (CK) activity. Methods: Serum IL-6 level and CK activity were measured in 19 males with acute myocardial infarction. Blood was taken on the 1st, 3rd, 5th, 7th and 21st days of the disease. Control values were obtained from 30 age-matched healthy males. IL-6 was determined according to the ELISA method and CK was measured with a routine procedure. Results: Serum IL-6 was found to increase on the 1st and 3rd days of the disease, followed by some decline on days 5–21. However, the last values measured were still higher than those in the controls. Patients with transmural myocardial infarction had higher IL-6 levels than those with non-Q myocardial infarction. There was no difference in serum IL-6 in patients with myocardial infarction of the inferior cardiac wall and of the anterior cardiac wall. A correlation was found between IL-6 level and CK activity in the patients, especially on the 1st and 3rd days of the disease. Conclusion: Serum IL-6 increases in patients with myocardial infarction, and this elevation seems to be related to the mass of the affected myocardium. The highest increase is found during the first days of the disease, although the enhanced IL-6 level lasts for at least 3 weeks, probably reflecting the healing process of the myocardium. The clinical value of IL-6 determination does not seem to exceed that of the indices commonly used.

The First and Second Solemn Meetings of Polish Internists were organized to celebrate the Centenary of the Polish Society of Internal Medicine. The aim of these educational conferences was to integrate the Polish national societies of various subspecialties related to internal medicine. More than one thousand participants took part in the First Solemn Meeting of the Polish Internists (Pierwsza Gala Interny Polskiej) held in Katowice on March 10–11, 2006. The conference was preceded by a solemn meeting of the Executive Board of the Polish Society of Internal Medicine with participation of the presidents of the Polish societies for several subspecialties and the Gala Dinner in the hotel Qubus (Fig. 1). During the dinner, the Centenary Medals were presented to a number of Polish internists. During the first day of the First Solemn Meeting of the Polish Internists the following lectures were presented: “Strategy of diagnostics and management of pulmonary embolism” (Adam Torbicki), “Treatment of cardiac arrhythmias” (Mary Trusz-Gluza), “The brain–heart–peripheral tissues” (Christopher Ziaja), “New strategies for management of patients with rheumatoid arthritis and osteoarthritis” (Witold Tlustochowicz), “Targeted therapy of proliferative hemopoietic disorders” (Andrew Hellmann), “Control tests after oncological treatment” (Marion Reinfuss), “New antithrombotic agents” (Cristina Zawilska), “Postprandial glycemia: clinical significance” (Hyacinth Sieradzki), “Thyroid diseases: modern view” (Barbara Jarząb), “Gastric and duodenal ulcer: what we currently know about” (Leszek Paradowski), “Management of acute and chronic infections

Chikungunya fever (CF) is an acute illness caused by Chikungunya virus (CHIKV) belonging to the alphavirus genus of the Alphaviruses (Togaviridae) family. The virus is transmitted by Aedes mosquitoes. CF is primarily tropical disease occurring in Africa, Asia and Indian Ocean islands but in the last decade an outbreak of CHIKV autochthonous infections were reported in Italy and France. It is associated with viral genome mutations facilitating transmission of the disease by Aedes albopictus, a mosquito occurring in several European countries. The CF is highly symptomatic, characterized by fever, cutaneuos rash and severe athralgia and arthritis. In some patients severe neurological or hemorrhagic manifestations occur. The disease is self-limiting but a part of the patients suffers from a long-lasting arthritis akin to rheumatoid arthritis. Treatment is only symptomatic. Prevention includes reduction of mosquito bite (mosquito net, repellent) or application of measures against mosquito larvae. Vaccination is not currently available but investigations are in progress. CF presents a significant worldwide health problem affecting in the last decade millions of person, and currently dangerous also for European countries.

Incidence of cardiovascular disease in patients with chronic autoimmune disorder like rheumatoid arthritis is much higher than in general population. Cardiovascular events (e.g. myocardial infarction or stroke) are caused by premature accelerated development of atherosclerosis. Chronic inflammation-enhanced atherosclerosis syndrome is proposed as a separate syndrome occurring in patients suffering of chronic inflammation. It is suggested that atherosclerosis as an inflammatory disease and long-lasting extravascular inflammation have common mechanisms resulting in an increase in atherosclerosis and its sequellae, cardiovascular diseases.

The influence of thyroid hormones upon renin-angiotensin-aldosterone system is poorly understood. Under basal conditions, individuals belong to normal, low or high plasma renin activity (PRA) subjects. The study was designed to evaluate basal and poststimulatory PRA and serum aldosterone (Aldo) level in patients with hyperthyroidism or hypothyroidism during therapy.We examined 73 women with hyperthyroidism, 27 women with hypothyroidism and 36 healthy controls. The patients were investigated before initiation of therapy and after attainment of euthyroid state. All subjects were investigated under basal conditions (normal-sodium diet) and after application of a low-sodium diet for three days and upright position for 3 hr. PRA, serum Aldo level, blood pressure, serum sodium, potassium and thyroid hormone levels were determined in all subjects. The subjects were classified as low PRA (1.0 ng/ml/h), normal PRA (1.0-4.0 ng/ml/h) and high PRA (4.0 ng/ml/h) individuals according to results obtained under basal conditions.Relatively higher poststimulatory enhancement in PRA was found in patients with hyperthyroidism, especially those with low basal PRA, than in those with hypothyroidism. In women with thyroid dysfunctions poststimulatory increase in Aldo were relative lower than poststimulatory enhancement of PRA. After therapy these difference disappeared. The poststimulatory changes in PRA depended on the basal PRA.Poststimulatory PRA is higher in hyperthyroid women, especially those with low basal PRA. In women with hypothyroidism, basal and poststimulatory PRA is low. Blood pressure and severity of thyroid dysfunction was found to be similar in the patients with low, normal or high basic PRA. In women with thyroid dysfunctions, serum Aldo level and its relative poststimulatory increments are inadequate to changes of PRA; it is suggested that the dissociation in the renin-angiotensin-aldosterone system occurs in hyperthyroid and hypothyroid women.

Rats were intoxicated with sodium selenite (0.3 mg kg body wt.) for 10 weeks. An increase in total collagen content in skin and a decrease in the lungs, liver and kidneys were observed. Enhanced serum and urine levels of collagen metabolites were found. Elastin content was shown to be increased in the lung, liver, heart muscle and kidney of selenium-intoxicated rats.

Publisher Summary This chapter discusses the perspectives of the application of computer aided process engineering tools in clinical medicine. This chapter evaluates the possible and predictable perspectives of application of computers in clinical medicine. The assessment is based on specification of intrinsic features of clinical medicine. These characteristics may limit application or may indicate new areas or forms of further investigations on computer applications to clinical medicine. In this regard, the chapter lists a number of the typical characteristics of clinical medicine. They include: (a) unique nature of every patient, both in terms of unique human nature (psychological) and in terms of biological nature (inherited genetic material, features resulted from influence of the environment), (b) limitation of physician action because of respect of the human nature of the object of the activity and limitation in the methods used by a physician, (c) the lack of adequate data for majority of clinical situations, (d) the nonspecificity of the majority of data referring to clinical situations.

Background: Free radicals have been said to contribute to vascular damage in patients with systemic sclerosis. The aim of the study was to determine the level of lipid peroxidation products and antioxidative enzyme activity in patients with systemic sclerosis and in healthy controls. Methods: 10 women with definite systemic sclerosis and 10 age-matched healthy women were studied. Results: A significant increase in serum lipid peroxidation product levels (i.e. diene conjugates and thiobarbituric acid-reactive substances) was found in patients with systemic sclerosis. These changes were accompanied by a decrease in superoxide dismutase, catalase, and glutathione peroxidase activity in erythrocyte lysate. Furthermore, there was diminished activity of glutathione reductase and a depressed total serum level of antioxidants compared to the controls. Blood thiol group concentration in patients with systemic sclerosis was also found to be decreased. Conclusions: The results obtained indicate increased oxidative stress in patients with systemic sclerosis.

Background : Systemic sclerosis (SSc) is a disease characterized by widespread fibrosis of the skin and multiple organs, including the lungs. This study was designed to evaluate pulmonary function in SSc patients without symptoms of lung involvement. Methods : Spirometric measurements were done in 26 female SSC patients without symptoms of pulmonary involvement. Results : Maximal voluntary ventilation was found to be decreased in half of the patients, and forced vital capacity was decreased in 23% of the patients. Forced expiratory flow rate was impaired in about half of the SSc patients, especially the flow at 50–75% of forced vital capacity. Peak expiratory flow rate was decreased in 77% of asymptomatic patients. Conclusions : A functional defect, mainly of the restrictive type, was observed in the majority of asymptomatic patients with SSc. Pulmonary function testing is recommended for all SSc patients.

Serum level of endostatin, a natural angiogenesis inhibitor, was measured in 12 patients with hyperthyroidism and 9 patients with hypothyroidism. Control values were obtained from 12 healthy individuals. Hyperthyroidism was shown to be associated with an increased level of endostatin and hypothyroidism with a decreased endostatin level. There was no correlation of serum endostatin with thyroid hormone levels. Endostatin is a fragment of type XVIII collagen, and it is possible that reported changes are related to the effect of thyroid hormones on connective tissue metabolism.

Sir—The role of exogenous estrogen in the induction of raloxifen. After a few days of hospitalization, the patient flare in patients with systemic lupus erythematosus (SLE) was discharged. Prednisone (10 mg/day) was given, and remains controversial, although it is generally accepted the dose was tapered slowly without symptoms or signs of that the hypoestrogenemic state is protective against flare. disease exacerbation [1]. Estrogens are believed to play a It is difficult to conclude that raloxifen was the cause of role in the etiology of SLE, presumably through the SLE exacerbation. The natural history of the disease activation of their cellular receptors. Estrogen receptors remains unclear. Yet, cessation of raloxifen was beneficial, have been found in activated T cells [2]. Estrogen has also which suggests that raloxifen was involved in a flare. The been found to evoke a direct increase in calcineurin presumed mechanism of action of raloxifen remains unexpression in T cells from female SLE patients [3] and to known, but may result from its estrogen-like influence on enhance B-cell activity and the production of anti-doubleautoimmune phenomena. Or it may be a non-specific effect stranded DNA antibody [4]. similar to those of several other drugs or chemicals known Raloxifen is a selective estrogen receptor modulator that to exacerbate SLE. From a clinical point of view, adminisshares with estrogens the ability to protect bone against tering raloxifen to SLE patients must be done with extra postmenopousal osteoporosis and to reduce plasma levels caution, and monitoring of the patients is strongly advised. of atherogenic lipoproteins. At the same time, raloxifen has been found to be a weak estrogenic antagonist in the reproductive organs [5]. The effect of the drug on auReferences toimmune phenomena that are believed to be estrogendependent remains unknown. In this letter, we report a [1] Mok CC, Lau CS, Wong RW. Use of exogenous estrogens in systemic lupus erythematosus. Semin Arthritis Rheum 2001;30:426– case of SLE exacerbation in a patient receiving raloxifen. 35. A 45-year-old woman suffering from SLE for 2 years [2] Kassi EN, Vlachoyiannopoulos PG, Moutsopoulos HM, Sekeris CE, was admitted to the hospital due to exacerbation of the Moutsatsou P. Molecular analysis of estrogen receptor alpha and disease (butterfly rash, arthralgia, signs of vasculitis). The beta in lupus patients. Eur J Clin Invest 2001;31:86–93. patient had been in remission for 3 months. The remission [3] Rider V, Jones SR, Evans M, Abdou N. Molecular mechanisms involved in the estrogen-dependent regulation of calcineurin in was induced by intravenous administration of a single dose systemic lupus erythematosus T cells. Clin Immunol 2000;95:124– of cyclophosplamide (1 g) and prednisolone 10 mg daily. 34. During the remission, raloxifen had been given in a dose of [4] Kanda N, Tsuchida T, Tamaki K. Estrogen enhancement of anti60 mg/day, and after 1 month of administration a flare had double-stranded DNA antibody and immunoglobulin G production occurred. After admission, raloxifen was discontinued and in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. Arthritis Rheum 1999;42:328–37. disease activity decreased. Careful evaluation of the patient [5] Mitlak BH, Cohen FJ. Selective estrogen receptor modulators. did not show any known reason for exacerbation but Drugs 1999;57:635–63.

Free radical-mediated oxidative stress has been implicated in the etiopathogenesis of several autoimmune disorders. We investigated the prooxidant-antioxidant status in order to evaluate the possible deleterious role of oxidative phenomena in patients with Graves' disease. Thirty patients with hyperthyroidism due to Graves' disease were investigated. Thirty age-matched healthy subjects were studied as a control group. Free radical activity indices, antioxidant defense systems, and thyroid and pituitary hormone levels were measured in fasting blood samples. Blood samples were taken before initiation of therapy and after attainment of euthyroid state. A significant increase in lipid peroxidation activity indices, i.e., conjugated dienes and thiobarbituric acid-reacting substances, was found in blood serum of the patients with untreated Graves' disease. These changes were accompanied by a decrease in plasma thiol and erythrocyte lysate thiol groups concentrations. Hyperthyroidism resulted in a marked increase in intracellular antioxidant enzymes, i.e., superoxide dismutase, catalase and glutathione peroxidase activities as compared to the controls. Extracellular anti-free radical scavenging systems potential, measured by glutathione reductase activity and total antioxidant status level, was found to be significantly decreased in untreated Graves' patients. Treatment with thiamazole resulted in normalization of the free radical and antioxidant activity indices. The obtained results indicate an enhanced generation of reactive oxygen species and impairment of cellular and extracellular antioxidant systems potential in patients with Graves' disease. The attainment of euthyroid state led to an improvement in oxidative stress indices and antioxidant potential parameters.

This study reports the effect of salmon calcitonin on airway function and peripheral blood parameters in asthmatic subjects. The premise for the study is that calcitonin is given to asthmatics that require systemic corticosteroids as a way to counter problems with calcium balance and osteoporosis, and that it has an immunosuppressive effect. Salmon calcitonin (100 IU) was administered to 18 patients with atopic bronchial asthma, and the following spirometric parameters were evaluated: forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak respiratory flow rate (PEFR) and forced expiratory flow rates at 25%, 50% and 75% of the forced vital capacity (FEF25%, FEF50% and FEF75%). Calcitonin significantly decreased the levels of FVC and FEV1 by 20 min after starting the infusion. The effect of 500 mg aminophylline, used as a reference drug in this study, was much more profound, with a significant increase in all investigated parameters. Also, the effect of salmon calcitonin on some immune parameters (white blood cell count, number of eosinophils, serum levels of immunoglobulins IgG, IgM and IgA, and serum levels of lymphocytes subpopulations CD3, CD4, CD8 and CD19) was determined in another group of 30 patients suffering from atopic bronchial asthma. Calcitonin at a dose of 100 IU/day subcutaneously for 3 days did not alter the immune parameters studied, thus rendering it safe for such and similar treatment schedules in a variety of medical conditions.