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Background: Rheumatoid arthritis (RA) is a debilitating chronic disease with an unmet need for additional therapeutic approaches. Activating neuro-immune reflex pathways by stimulation of the vagus nerve (VNS) could represent a novel means of treating RA [1] and other immune-mediated inflammatory diseases. Last year we reported a 12-week proof-of-concept study using a VNS device, approved for drug-resistant epilepsy, showing reduction in the DAS28-CRP clinical disease activity score, with concomitant reductions in TNF and IL-6 levels [2]. Objectives: To understand the long term safety and efficacy of this novel treatment approach, we followed the patients in a 24 months long-term extension study and report on the safety and clinical efficacy data. Methods: VNS devices were implanted into 17 RA patients, mostly with insufficient response to multiple conventional and biologic disease-modifying antirheumatic drugs (DMARDs), on stable background of methotrexate (£25 mg weekly) therapy. The devices electrically stimulated the vagus nerve, 1–4 min/day, over a 12 week open label period. On completion, subjects were offered to enroll into a follow-up study, where the study physicians were given flexibility to alter VNS dosing parameters and/or to add a biologic DMARD to the treatment regimen. DAS28-CRP and Health Assessment Questionnaire-Disability Index (HAQ-DI) were collected over 2 years. Results: All subjects electively continued on VNS treatment through 24 months of the long term follow-up study. Biologic DMARDs were started in 1 and restarted in 8 of 17 subjects ; of these, 4 were non-responders to VNS, and 5 had stable improvement but had not yet achieved disease remission on VNS alone (table 1). At the start of the follow-up study, the mean DAS28–28 and HAQ-DI were significantly reduced compared to the pre-implant baseline (mean difference±SE in DAS28-CRP=-1.60±0.37, p

The data presented here demonstrate that VNS in subjects with RA is associated with a substantial reduction in disease activity that is sustained for 24 months without untoward safety signals. Further, the data suggest that biological DMARDs may be initiated safely in combination with VNS treatment, though this requires validation in larger cohorts. These results support additional development of VNS devices as an alternative therapeutic approach for RA treatment, which potentially can safely be combined with biologic DMARDs.

Background/Purpose: RA is a debilitating chronic disease with an unmet need for additional therapeutic approaches. Modulating innate neuro-immune re ex pathways by stimulation of the vagus nerve (VNS) could represent a novel means of treating RA (van Maanen MA et al. Nat Rev Rheumatol. 2009 ; 5:229-32). We recently reported a 12-week proof of concept study using a VNS device, approved for drugresistant epilepsy, showing reductions in the DAS28-CRP and in TNF-α and IL-6 levels (Koopman FA et al. PNAS 2016 ; 113:8284). To understand the long term safety and e cacy of this novel treatment approach, we followed the patients in a 24 months long-term extension study and report on the safety and clinical e cacy data. Methods: In the primary study, VNS devices were implanted into 17 RA patients, mostly with insu cient response to multiple conventional and biologic DMARDs, on stable background of methotrexate (≤25 mg weekly) therapy. The devices electrically stimulated the vagus nerve, 1-4 min/day, over a 12 week open label period. On completion, subjects were o ered to enroll into a follow-up study, where the study physicians were given exibility to alter VNS dosing parameters and/or to add a biologic DMARD to the treatment regimen. DAS28-CRP and Health Assessment Questionnaire-Disability Index (HAQ-DI) were collected over 2 years. Results: All subjects electively continued on VNS treatment through 24 months of the long term follow-up study. Biologic DMARDs were started in 1 and restarted in 8 of 17 subjects ; of these, 4 were nonresponders to VNS in the primary study, and 5 had stable improvement but had not yet achieved disease remission on VNS alone (Table 1). At the start of the follow-up study, the mean DAS28-28 and HAQ-DI were signi cantly reduced compared to the pre-implant baseline (mean di erence± SE in DAS28-CRP = -1.60± 0.37, p

Objective. In rheumatoid arthritis (RA) inflammation and damage lead to functional impairment. The hand is a typical site of the involvement, and therefore lower grip strength is often found in these patients. Better detailing of evaluation parameters such as the velocity and stability of hand grip in relation to present static measurements of grip force might be helpful for rehabilitation evaluation of the hand. The aim of this paper was to produce an analysis and interpretation method for measured data using a specially designed electrodynamometer that gives an objective and a more detailed evaluation of the functional state of the hand. Design and Method. An expert electronic measuring system for obtaining dynamic time series of the hand grip force was developed. We tested it in the sample of 24 participants, 12 patients with RA and 12 age- and sex-matched healthy controls. The main dynamometric parameters obtained were: maximal grip force, fatigue, grip velocity, functional potential. These were measured at the baseline and at 60, 120 and 180 days. Results. Compared to the control group, the patients with RA had significantly lower maximal grip force (68.2 vs. 97.3), sooner occurrence of fatigue (22.4 vs. 24.9), lower grip velocity (14.8 vs. 22.2) and functional potential (808.2 vs. 1876.3) at the baseline. The significant improvement in all measured variables was observed during the follow-up period. Conclusions. In our pilot-study we tested a new-developed electrodynamometer measuring system and found that it can demonstrate hand condition objectively and in details. This system has a potential to be used as a relevant indicator of hand function in patients with RA and to help tailor their rehabilitation.

Objective:The aim of this study was to evaluate the effect of therapeutic exercise with or without electromagnetotherapy on functional ability in patients with hand osteoarthritis (OA). MATERIAL AND METHODS: The study included 30 consecutive patients with verified diagnosis of hand OA, according to ACR criteria, who visited the physiatric and rheumatological outpatient clinic of the University Hospital Centre Sestre milosrdnice in Zagreb (Croatia). All patients underwent therapeutic exercise for hands and received the active or „sham“ electromagnetotherapy in duration of 15 minutes. In the active group the frequency of the magnetic field was 900-1500 Hz and the power of the magnetic field was 0.5-52 Gauss. In the „sham“ group the device was not active. For evaluation of hand functional ability we used AUSCAN questionnaire. The intensity of pain in rest and in movement was tested on visual analog scale (VAS). Those variables were obtained before the therapy (T0), after 15 therapies cycle (T1), as well as one month upon completion of the therapy (T2). Significance was set up at the level of 0.05. Results: There was a statistically significant reduction of pain in rest in all patients in T1 time point and reduction of pain in movement in T1 and T2 time points. Also, in all patients in T1 and T2 time-points there was a statistically significant improvement in AUSCAN variables: „Pain in lifting“, „Total pain“, „Total physical functioning“ „Total“ and one month upon completion the therapy in variable „Lifting heavy objects“. There was neither statistically significant difference in variables pain in rest and pain in movement, nor in AUSCAN variables, between patients who underwent electromagnetotherapy and those who did not. with hand osteoarthritis the improvement was observed in all patients regardless the difference between active or sham group, regarding the decrease of pain and improvement of functional ability. In comparison to the control (sham) group the biomagnetotherapy of certain parameters has shown a positive effect in some parameters of AUSCAN, whereas this was not the case for the majority of other tested parameters. For making the firm conclusion about the effect of biomagnetotherapy on symptoms and sings of hand osteoarthritis a larger sample of subjects is necessary and that is why we continue the study. Graf 1: PAIN in rest (AUSCAN) Graf 2: BODY FUNCTION - peeling (AUSCAN) CONCLUSION:Hand exercises have positive effect on pain reduction and on improvement of AUSCAN parameters in patients with hand OA, while electromagnetotherapy did not show

Objective: To determine the contribution of vertebral fracture assessment (VFA) using DXA as well as the influence of degenerative changes in the lumbar spine in the interpretation of BMD among patients with psoriatic arthritis (PsA). Methods: The study included 105 patients (52women, 53men ; mean age 57.9±11.2 years) with PsA. BMD measurement and VFA from T4-L4 was performed using aDXAscanner. Diagnosis of vertebral fracture (VF) was based on the Genant semiquantitative classification system. After standard BMD L1-L4 analysis, selected lumbar vertebrae were excluded from the DXA scan according to the recommendations of the International Society of Clinical Densitometry (ISCD). Results: A total of 74 vertebral fractures were detected in 45 (42.8%) patients: 58 grade 1 vertebral fractures, and 16 vertebral fractures of grades 2-3. A total of 64 vertebrae in 42 patients (23 without and 19 with VF) were excluded from the L1-L4 BMD analysis according to the ISCD criteria ; 26 (40.6%) vertebrae at the L4 level. Osteoporosis according to the WHO classification (T-score ≤-2.5 SD) was observed in 11 (10.5%) patients. By the addition of grade 2-3 VFs and exclusion of selected lumbar vertebrae from DXA among patients without osteoporosis, the number of patients considered as osteoporotic increased to 23.8%. BMD values, T-scores, and Z-scores at all measured regions did not differ significantly between patients with (n=45) and without (n=60) VFs. There was neither a significant difference in disease duration nor in the usage of corticosteroids, methotrexate, and sulfasalazine among patients with and without VFs. The higher disability level assessed by the HAQ questionnaire in the group of patients with VFs was significantly associated with lower BMDin the femoral neck and total hip region (p 0.019 and 0.010, respectively). Conclusion: According to our results in patientswith PsA, BMDreportswith consideration of both the results of VFA and vertebral exclusions from L1-L4 DXA applying the ISCD criteria should be included into the evaluation of the disease and thereby give a better insight into the real osteoporosis status.

The Routine Assessment of Patient Index Data 3 (RAPID3) is a patient-reported disease activity measure used to assess physical function, pain, and global health in patients with rheumatoid arthritis (RA) without formal joint counts. Since hand involvement and its decreased function are hallmarks of RA, the aim of our study was to investigate the performance of RAPID3 scores with regard to hand function and to confirm previous findings that the RAPID3 score as a disease activity measure is strongly correlated with the DAS28 score. Sixty-eight consecutive patients with RA (85% female), aged 18–75 years, were included in the study and were recruited during their outpatient visit. Apart from demographic and clinical data, the obtained parameters of interest included RAPID3 scores and assessments of the function of the hand, namely, the signal of functional impairment (SOFI)-hand, grip strength, and pulp-to-palm distance, as well the Health Assessment Questionnaire- Disability Index (HAQ-DI) and DAS28 scores. Pearson’s correlation coefficient, Student’s t test and linear regression were used in the statistical analysis of the results. The significance was set to p < 0.05. A positive correlation was found between RAPID3 scores and HAQ-DI scores, SOFI-hand scores, and pulp-topalm distance, and negative correlation was observed between RAPID3 scores and grip strength. The order regarding the strength of correlations between RAPID3 scores and other variables (from the strongest to the weakest) was as follows: HAQ-DI, grip strength, SOFI-hand and pulp-to-palm distance. The hand assessment variables had stronger correlations with RAPID3 scores than with DAS28 scores. Our preliminary study showed that RAPID3 scores were strongly correlated with measurements of the functional ability of the hand, demonstrating that RAPID3 can be used as a measure of disease activity in clinical practice and to characterize hand function. Further studies are needed to confirm this result.

BACKGROUND: In the European Prospective Osteoporosis Study (EPOS), a past spine fracture increased risk of an incident fracture 3.6 - 12-fold even after adjusting for BMD. We examined the possibility that biochemical marker levels were associated with this unexplained BMD-independent element of fracture risk. METHODS: Each of 182 cases in EPOS of spine or non-spine fracture that occurred in 3.8 years of follow-up was matched by age, sex and study centre with two randomly assigned never-fractured controls and one case of past fracture. Analytes measured blind were: osteocalcin, bone-specific alkaline phosphatase, total alkaline phosphatase, serum creatinine, calcium, phosphate and albumin, together with the collagen cross-links degradation products serum CTS and urine CTX. Most subjects also had bone density measured by DXA. RESULTS: Cases who had recent fractures did not differ in marker levels from cases who had their last fracture more than 3 years previously. No statistically significant effect of recent fracture was found for any marker except osteocalcin, which was 17.6% lower in recent peripheral cases compared to unfractured controls (p

The study aimed to investigate the influence of some generally recognized risk factors for hormone receptor (HR)- and human epidermal growth factor receptor 2 (HER2)-defined breast cancer among Slovenian postmenopausal women.Eligible women diagnosed with breast cancer were compared with 709 controls of the same age and ethnicity. Immunohistochemistry and FISH analyses were used to classify cases into molecular subtypes: 454 HR(+), 106 HR(-), 81 HER2(+) and 603 HER2(-). Adjusted odds ratios and 95% confidence intervals were estimated using multivariate logistic regression analysis.Overweight and obese women were at increased risk of HR(+), HER2(-) and of HR(+), HR(-), HER2(-) tumors, respectively. Women who started menstruating at the age of 11 years or earlier were at decreased risk of ER(-)PR(-) tumors. Users of hormone replacement therapy (HRT) were negatively associated with HR(+) and HER2(-) tumors. The inverse effect was most pronounced with the use of estrogen-only HRT, and longer duration of HRT use did not result in a significant change in risk. In contrast, combined HRT decreased the risk of HER2(+) tumors. Having a first-degree relative with breast and/or ovarian cancer increased the risk of HR(+) and HER2(-) tumors.We conclude that certain breast cancer risk factors may vary by molecular subtypes. According to our results, HRT use may have a greater influence on HR (+) and HER2(-) breast cancers and the risk of HER2-defined breast cancer may differ with respect to the regimen of HRT.

Clinical osteoporosis prescreening tools are intended to select individuals most likely to benefit from BMD testing. This study aims to develop and validate Osteoporosis Risk Score (ORS), a new prescreening tool intended to be used in women aged 45 years and older. Two cohorts of women aged 45–87 years without previous diagnosis of osteoporosis participated in the development (n= 200) and the validation (n =1000) of the ORS tool. Data on risk factors for osteoporosis were assessed by questionnaire and BMD by DXA (Hologic Delphi C, Bedford, USA). Risk factors that best predicted Tscore≤− 2.5 at the femoral neck region were selected for inclusion into the ORS. Logistic regression analysis was used to select significant predictors of BMD, whereas receiveroperating characteristic (ROC) analysis was used to assess the discriminatory performance of the ORS tool. Validation of the ORS tool and comparison with other validated osteoporosis tools were evaluated in terms of sensitivity and specificity using the original developer’s cutoffs and densitometric target outcomes. The ORS tool was developed based on four variables: age >65 years (3 points), years post-menopause of >14 years (3 points), height < 160 cm (2 points) and weight < 73 kg (1 point). Cut-off value of > 6 points (out of 9 possible) was associated with the 80.0 % sensitivity and 81.6 % specificity to identify women with low bone mass. Applying the ORS tool among the study population(validation cohort) showed lower sensitivity (58.9 %) and higher specificity (82.1 %) compared to ORAI, ABONE, OST tools (sensitivity of 86.3 %, 83.6 %, 80.8 % and specificity of 52.5 %, 55.9 %, 58.6 %), respectively.ORS tool showed better prediction of low BMD among women above 65 years compared to group of women. The Osteoporosis Risk Score tool is a simple scoring system based on four risk factors for osteoporosis. Due to its higher specificity and somewhat lower sensitivity ORS tool showed better performance in discrimination of women in whom BMD testing is unnecessary. Further investigation is needed to determine prescreening osteoporosis scoring system among women aged 45–64 years.

Background: Polymorphisms of the vitamin D receptor (VDR) gene have been implicated in the genetic regulation of bone mineral density (BMD). However, the clinical impact of these variants remains unclear. Objective: To evaluate the relation between VDR polymorphisms, BMD, and fractures. Design: Prospective multicenter large-scale association study. Setting: The Genetic Markers for Osteoporosis consortium, involving 9 European research teams. Participants: 26 242 participants (18 405 women). Measurements: Cdx2 promoter, FokI, BsmI, ApaI, and TaqI polymorphisms; BMD at the femoral neck and the lumbar spine by dual x-ray absorptiometry; and fractures. Results: Comparisons of BMD at the lumbar spine and femoral neck showed nonsignificant differences less than 0.011 g/cm2 for any genotype with or without adjustments. A total of 6067 participants reported a history of fracture, and 2088 had vertebral fractures. For all VDR alleles, odds ratios for fractures were very close to 1.00 (range, 0.98 to 1.02) and collectively the 95% CIs ranged from 0.94 (lowest) to 1.07 (highest). For vertebral fractures, we observed a 9% (95% CI, 0% to 18%; P = 0.039) risk reduction for the Cdx2 A-allele (13% risk reduction in a dominant model). Limitations: The authors analyzed only selected VDR polymorphisms. Heterogeneity was detected in some analyses and may reflect some differences in collection of fracture data across cohorts. Not all fractures were related to osteoporosis. Conclusions: The FokI, BsmI, ApaI, and TaqI VDR polymorphisms are not associated with BMD or with fractures, but the Cdx2 polymorphism may be associated with risk for vertebral fractures.

Background: Smoking is a big public health problem that represents a risk factor for the onset and progression of rheumatoid arthritis. The physician and the patient are partners in the treatment process in which mutual understanding and cooperation lead to betterment. Objectives: Assessing patient compliance investigating the efficiency of spoken medical advice in quitting smoking in patients smokers with rheumatoid arthritis. Type of Research: Observational, multicenter. Methods: The research included ninety-six patients (82 women, 14 men ; average age 60.2 + 11.99) with rheumatoid arthritis diagnosed based on modified criteria of the American College of Rheumatology from 1987. All the patients were from continental Croatia, recruited in cooperation between two rheumatology departments. Out of the total number of patients there were twenty smokers (20.8%) and 76 non-smokers (79.2%). DAS28CRP values of disease activity were analyzed, as well as the patient's assessment of disease activity on a visual analogue scale (on a 10cm visual analogue scale – VAS) in smokers and non-smokers. Smokers were given short, spoken advice about the harms of smoking, and advice to quit smoking. The results of efficiency of spoken advice to quit smoking in smokers with RA were analyzed after 1 month, and descriptively presented. Results: Average duration of rheumatoid arthritis was 11.8 + 9.90 years. DAS28CRP and VAS values were analyzed in smokers and non-smokers, and no statistically significant difference was noticed between study groups (p>0.05), although the medial VAS value of pain in non-smokers was 5, and in smokers 6. In 45% of non-smokers and in 30% of smokers the DAS28CRP value was between 3.2 and 5.1. 20% of non-smokers and 30% of smokers had the DAS28CRP value >5.1. After spoken medical advice to quit smoking, two patients (10%) quit smoking in the period of one month. Conclusions: Spoken medical advice to quit smoking in patients smokers with RA was efficient in a small number of patients, which raises the question about patient compliance in general.

Background: Patients with ankylosing spondylitis (AS) who develop total spinal ankylosis (TSA) experience more functional impairment and are at higher risk for serious complications (e.g. spinal fractures). They also might have more signs and symptoms of active disease (1) Objectives: To evaluate the efficacy and safety of adalimumab in patients with AS and TSA. Primary endpoint. The ASsessment in AS International Working Group criteria for 20% improvement (ASAS20) at week 12 and 52. Type of research. Multicenter, prospective. Methods: Nineteen patients (17 men, 2 women ; mean age 49.1 ± 11.2 years) diagnosed with AS according to the 1987 modified NY criteria and TSA were recruited from the databases of eight rheumatology departments in Croatia. All patients had active disease (BASDAI ≥ 4) and treated with adalimumab (40mg/bi-weekly) (2). A structured questionnaire containing demographic and clinical data was used. Following variables were evaluated at week 12 and 52: function using BASFI, disease activity using BASDAI, patient's and physician's global assessment of disease activity, total back pain and fatigue, all of them measured on visual analogue scale (VAS). Both efficacy and safety results are summarised descriptively. Results: Mean disease duration was 20.2± 11.6 years. Compared to baseline measures, there was a significant improvement in BASFI and BASDAI at week 52: BASFI (6.9 ± 1.19 and 3.13 ± 1.54, respectively) and BASDAI (6.8 ± 1.03 and 2.28 ± 1.45, respectively). Significant improvement was also seen at baseline and week 52 in other observed variables: patient's and physician's global assessment, total back pain and fatigue. At month 3 ASAS20 was reached in 18/19 patients and at months 12 in 17/19 patients. Injection site erythema was reported in 2 patients only at first months of the treatment. No serious side effects were observed during 12-month treatment with adalimumab. Conclusions: In our 12-month study adalimumab treatment of patients with AS and TSA resulted in clinically significant improvement regarding function and disease activity. No serious adverse side effects were reported in our cohort.

Edukacija bolesnika jedan je od ključnih elemenata liječenja bolesnika s reumatskim bolestima. Nova brošura za bolesnike “Živjeti s reumatoidnim artritisom” pru- ža najbitnije informacije bolesnicima s tom najčešćom upalnom reumatskom bolesti, napose u svjetlu novih mogućnosti liječenja (biološki lijekovima), kojima se u većine bolesnika postiže niska aktivnost bolesti ili njezino potpuno povlačenje. U brošuri su vrlo pregledno prikazani podaci o tome koga i koliko pogađa reumatoidni artritis, kako se liječi i kome se zbog toga obratiti. Čitatelje/bolesnike se upućuje na to da budu iskreni prema sebi, te da sami postave ciljeve liječenja, a u čemu će uspjeti ako budu ustrajni. Liječenje treba započeti što ranije i pridržavati se uputa liječnika i drugih zdravstvenih djelatnika. Za bilježenje simptoma korisno je koristiti se jednostavnim bilješkama u kalendaru. Naglašava se da za uspješno liječenje bolesnik mora biti dio tima, pa je objašnjenja uloga svakog od članova tog tima. Ako smatraju potrebnim bolesnici se ne smiju ustručavati zamoliti za pomoć psihologa ili psihijatra. Uz odgovarajuće lijekove naglašena je važnost provođenja fi zikalne terapije, te napose medicinskih vježbi. Prije provođenja potonjih preporučljivo je konzultirati se s liječnikom ili fi zioterapeutom. Načelno, preporuča se svakodnevno lagano do umjereno vježbanje tridesetak minuta, a navedeni su savjeti kako procijeniti dostatnost intenziteta vježbanja, te što činiti kad se bolest pogorša. Posebna vrijednost priručnika je da su slikovno prikazani primjeri vježbi za pojedine djelove tijela. Na kraju, za daljnje informacije, tu su i adrese udruga te njihove web stranice. Ovu brošuru je izdala udruga bolesnika “Remisija”, u suradnji s udrugama “Kolagenoze” i “Hrvatska liga protiv reumatizma”. Predstavlja značajan doprinos u sveukupnom naporu liječenja bolesnika s reumatoidnim artritisom.

Izvanzglobni reumatizam uključuje upalne i degenerativne promjene mekih tkiva, najčešće tetiva, enteza i sluznih vreća. Iako prevalentan, ovaj oblik reumatizma nerijetko predstavlja dijagnostički problem. Postavljanje točne i pravodobne dijagnoze temelji se na anamnezi i kliničkom pregledu, pomoći mogu i dijagnostičke metode, osobito dijagnostički ultrazvuk. U ovom radu su prikazani najvažniji entiteti lokaliziranog izvanzglobnog reumatizma.

Using proteomic approach in this study, we sought to identify proteins with heparin affinity associated with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and non-inflammatory arthritis (NIA). Plasma samples from adult RA, PsA and NIA patients, 20 of each, were collected. After enrichment of proteins with heparin affinity, SDS-PAGE and in-gel digestion with trypsin were performed. Peptides were concentrated, micro-purified, separated and measured by nano-scale HPLC system coupled to a mass spectrometer. Peak lists were generated from raw spectra and searched against human complete proteome set by MaxQuant software. Statistical analysis of protein relative expression levels was done in IPython interactive Python shell using NumPy and Matplotlib libraries. Individual protein impact on the whole dataset correlation was done by excluding one protein at a time and calculating the correlation coefficient of remaining data points. Three hundred and eighty-four different proteins were identified keeping false discovery rate to 1%, from which 163 were identified in all three conditions. The plasma proteome showed a good correlation between rheumatoid (RA) and psoriatic arthritis (PsA). Out of 10 proteins whose impact on the correlation coefficient fell outside of two standard deviations from the mean, four were up-regulated (complement factor I, complement component C8 beta, glyceraldehyde-3-phosphate dehydrogenase and inter-alpha-trypsin inhibitor heavy chain H1), and two were down-regulated (immunoglobulin heavy chain V-III region BRO, and immunoglobulin J chain), both in PsA and RA by a similar ratio when compared to NIA. The remaining four proteins (Serpin A11, complement factor H-related protein 5, cartilage acidic protein 1 and coagulation factor IX) were down-regulated in PsA and up-regulated in RA when compared to NIA. We found differently expressed proteins in patients with inflammatory and non-inflammatory rheumatic conditions. Out of 384 proteins with heparin affinity four proteins should be further validated as potential diagnostic biomarkers in patients with RA and PsA.

Među lijekovima koji mijenjaju tijek bolesti (eng. skr. DMARDs) metotreksat (MTX) je, “zlatni standard” u liječenju bolesnika s reumatoidnim artritisom (RA). Ako se liječenje metotreksatom te još jednim DMARD-om pokaže nedovoljno učinkovitim u terapiju se uključuju i biološki lijekovi. Međutim, svjetski registri biološke terapije pokazuju da 30% bolesnika uzima biološki lijek kao jedini lijek, odnosno bez kombinacije s DMARD-om. Razlozi tome su kontraindikacije za uzimanje MTX/drugog DMARD-a ili nuspojave. U cilju postizanja što boljeg rezultata a sa što manje štetnosti za bolesnika preporuča se iscrpiti sve mogućnosti, pa se tako u tih bolesnika u slu- čaju pojave nuspojava (uključivo jetrenih, bubrežnih ili hematoloških poremećaja) može smanjiti doza lijeka, lijek se može primijeniti u obliku injekcije, dati dodatnu terapiju za ublažavanje nuspojava ili primijeniti drugi DMARD. Ipak, ako se time ne postigne zadovoljavajuća kontrola aktivnosti bolesti, što je nerijetko slučaj, prelazi se na liječenje biološkim lijekom i to kao jedinim lijekom koji usporava/sprječava upalu i napredovanje bolesti. Prilikom odabira optimalnog liječenja reumatolog će uzeti u obzir pridružene bolesti i istodobnu primjenu drugih lijekova, postojeće dokaze o učinkovitost lijekova, o ne- željenim nuspojavama, kao i o troškovima liječenja. Biološka monoterapija pokazala se kao učinkovit i siguran način liječenja u skupini bolesnika s RA-om u kojih je kontraindicirana primjena MTX-a (ili drugog DMARDa) ili liječenje tim lijek/-ovima nije primjereno. Informacije koje bolesnik ima o mogućnostima liječenja su vrlo važne u odabiru lijeka, jer se odluka o tome donosi u partnerskom odnosu i dogovoru bolesnika i reumatologa.

Bolesnici koji razviju totalnu spinalnu ankilozu (TSA) podložniji su funkcionalnoj onesposobljenosti, ali i većem riziku ozbiljnijih komplikacija bolesti (npr. osteoporotski prijelomi, deformacije kralježnice). Osim toga, mogu imati znakove i simptome aktivnog ankilozantnog spondilitisa. Cilj rada bio je ocijeniti učinkovitost i sigurnost primjene svih TNF-α blokatora kod bolesnika sa AS i TSA. Primarni ishod: dostizanje ASAS 20 (the Assessment in AS International Working Group criteria for 20% improvement) u 12. i 52. tjednu primjene lijeka. Vrsta istraživanja: opservacijsko, multicentrično. Trideset bolesnika (26 muškaraca, 4 žene, prosječne životne dobi 49, 2 ± 11, 6 godina) s ankilozantnim spondilitisom dijagnosticiranim na temelju modifi ciranih NY kriterija iz 1987. godine i aktivnom bolesti (BASDAI ≥ 4) uključeno je u ovo istraživanje. Svi bolesnici s dijagnozom AS i TSA su regrutirani iz kliničkih baza podataka sedam različitih reumatoloških odjela u Hrvatskoj. Lije- čenje TNF-α inhibitorima indicirano je na temelju smjernica Hrvatskog reumatološkog društva iz 2007. godine i odobreno je od strane Povjerenstva za lijekove nadlež- nih zdravstvenih ustanova. Devetnaest je ispitanika bilo Sažetak Abstract2013. 60(2) Reumatizam 115 na terapiji adalimumabom, devet ispitanika etanerceptom, a po jedan ispitanik na terapiji golimumabom odnosno infl iximabom. U istraživanju je korišten strukturirani upitnik koji sadržava demografske i kliničke podatke. Srednje vrijednosti slijedećih varijabli su evaluirane u na početku liječenja, u 12. i 52. tjednu praćenja: funkcija (BASFI), aktivnost bolesti (BASDAI), bolesnikova i liječnikova globalna procjena aktivnosti bolesti na vizualnoj analognoj skali, te ukupni intenzitet križobolje i umora na (na 10 cm vizualnoj analognoj skali - VAS). Rezultati učinkovitosti i sigurnosti primjene lijekova deskriptivno su prikazani. Prosječna dužina trajanja bolesti je 18, 7± 12, 4 godine. Dvadeset osam bolesnika je HLA-B27 pozitivno. Nakon 3 mjeseca liječenja, ASAS20 je postiglo 29/30 bolesnika, a nakon 12 mjeseci liječenja 23/30 bolesnika. Prosječne vrijednosti pojedinačnih analiziranih varijabli na početku liječenja su bile slijedeće: BASFI 6, 79±1, 18, BASDAI 6, 42±1, 15, ukupni intenzitet boli 7, 23±1, 36, bolesnikova globalna procjena aktivnosti bolesti 7, 33±1, 63, liječnikova globalna procjena aktivnosti bolesti 7, 45±1, 26, intenzitet umora 6, 67±1, 65. U usporedbi sa inicijalnim vrijednostima, uočeno je statistički je značajno poboljšanje u domeni funkcije (BASFI) i aktivnosti bolesti (BASDAI) nakon 12, odnosno 52 tjedna primjene TNF-α antagonista: BASFI (3, 4±1, 53 odnosno 2, 85±1, 57) i BASDAI (2, 96±1, 67 odnosno 2, 01±1, 41). Statistički značajno poboljšanje uočeno je na nakon 12. odnosno 52. tjedna liječenja i u ostalim promatranim domenama: ukupna bol (3, 53±1, 91 odnosno 1, 78±1, 11), bolesnikova globalna procjena aktivnosti bolesti (3, 27±1, 78 odnosno 2, 50±1, 84), liječ- nikova globalna procjena aktivnosti bolesti (3, 5±1, 87 odnosno 2, 31±1, 72) i intenzitet umora (2, 97±2, 1 odnosno 1, 71±1, 19). Eritem na mjestu injiciranja lijeka imalo je 4 bolesnika, i to na početku liječenja. Ozbiljnih sistemskih neželjenih nuspojava nije bilo tijekom prvih 12 mjeseci primjene lijekova. Inhibitori TNF-α su se u bolesnika s AS i TSA pokazali djelotvornim: značajno poboljšanje funkcije i smanjenje aktivnosti bolesti. U kohorti naših ispitanika nisu registrirane ozbiljnije sistemske nuspojave.

Croatian Society for Rheumatology of Croatian Medical Association updated the proposal for the application of TNF-alpha inhibitors in adult patients with spondyloartritides (SpA) in accordance with the new classification of SpA and european recommendations for the treatment of SpA with biologic agents. In this way a standardized method of diagnosis, targeted treatment, monitoring and evaluating outcomes are proposed.

Cilj rada je validiranje praktične primjene ASAS klasifi kacijskih kriterija za aksijalni spondiloartritis (axSpA) u bolesnika oboljelih od spondiloartritisa. Istraživanje je bilo retrospektivno, opservacijsko. Retrogradno su analizirani podaci 194 bolesnika (45 muškaraca, 149 žena) hospitaliziranih u Klinici za reumatologiju, fi zikalnu medicinu i rehabilitaciju KBC Sestre Milosrdnice u Zagrebu u kojih je utvrđena dijagnoza sakroileitisa ili spondiloartritisa u razdoblju 2010.-2012. godine U istraživanju je korištena njihova medicinska dokumentacija (povijesti bolesti, otpusna pisma). Analizirani su slijedeći parametri: ASAS kriteriji za upalnu križobolju (početak

Urični artritis je jedan od najčešćih oblika artritisa u razvijenim zemljama. Unatoč tome čini se da je njegovo liječenje loše prvenstveno zbog ograničenja u medikamentoznom liječenju, nedostatku široko prihvaćenih strategija liječenja i podcjenjivanju važnosti same bolesti. Značajna proporcija napose starijih bolesnika s uričnim artritisom nemaju dobar odgovor ili ne podnose primjenu dostupnih lijekova. Svjedoci smo porasta prevalencije uričnog artritisa i napretka u razumijevanju njegove patofiziologije što je oboje doprinijelo povećanju zanimanja znanstvenika i kliničara. U radu su prikazani novi lijekovi za urični artritis, koji djeluju putem različitih mehanizama: antagonisti interleukina (IL)-1 (anakinra, canakinumab, rilonacept) prekidaju simptome akutnog uričnog artritis, febuksostat je novi selektivni inhibitor ksantin-oksidaze, poli(etilen) glikol-urikaza je nedavno razvijeni urikolitik, kao i nekoliko novih urikozurika. Skupa s konceptom “liječenje prema cilju” s jasnim ciljnim vrijednostima serumskih urata, navedeni novi lijekovi će pomoći u skrbi za bolesnike s uričnim artritisom.

For multiligamentary knee injury essential is multidisciplinary team approach: early surgical treatment - reconstruction of the joint capsule and ligament construction, appropriate immobilization, early rehabilitation and thromboprophylaxis.

Program MAXIMA (Management of Axial SpA) je međunarodni, multicentrični program koji za cilj ima poboljšanje općeg znanja o aksijalnom spondiloartritisu (Axial SpA), ranom prepoznavanju, klasifi ciranju i odgovarajućem liječenju. Kao svojevrsna početna točka programa provedena je međunarodna anketa kako bi se dobio trenutni i činjenični uvid u regionalni i lokalni pristup dijagnostici i liječenju aksijalnog spondiloartritisa. Upitnik se sastojao od 35 pitanja podijeljenih u 7 kategorija, a evaluirani su dijagnostika, značajke bolesti i terapijska praksa. U Hrvatskoj je upitnik ispunilo 8 reumatologa, od kojih je dvoje bilo “čistih” praktičara, dok su ostali istovremeno angažirani na fakultetu. Prema rezultatima bolesnika s kroničnom križoboljom koja traje tri mjeseca, dobi

Mišićnokoštane bolesti i stanja su česta u cijelom svijetu i imaju vrlo veliki negativni učinak na pojedinca i na društvo. Integrativni model, koji se temelji na bio-psiho-socijalnom principu, Međunarodna klasifikacija funkcioniranja, nesposobnosti i zdravlja (ICF) je vrlo korisna za strukturirano identificiranje nesposobnosti u tim stanjima. ICF obuhvaća domene zdravlja i domene koje se odnose na zdravlje: tjelesne funkcije i strukture, aktivnost i sudjelovanje i okolinske čimbenike. U kliničkoj praksi ICF se primjenjuje za ocjenu funkcionalnog stanja, utvrđivanja ciljeva, planiranja i praćenja liječenja, kao i mjerenja ishoda. Njegova uporaba je olakšana ako se koriste aplikacije temeljene na ICF-u, kao što su ICF listovi i ICF sržni setovi. U ovom članku se iznose spoznaje sa stanovišta ICF-a o mišićnokoštanim bolestima i stanjima najvažnijima za reumatološku praksu, a komplementaran je članku istog autora objavljenom u prošlom broju ovog časopisa.

Unatoč napretku farmakoterapije nefarmakološke metode i poglavito terapijske vježbe su osnov liječenja spondiloartropatija. U ovom pregledu obrađeni su različiti programi fizikalne terapije u ankilozantnom spondiitisu i u drugim spondiloartropatijama s naglaskom na njihovu dobrobit i potencijalne indikacije, kao i na ograničenja kako u kliničkoj praksi tako i u istraživanjima. Dokazano je da formalna fizikalna terapija pod nadzorom fizioterapeuta rezultira smanjenjem boli i zakočenosti, te da poboljšava držanje, pokretljivost, funkciju i kvalitetu života. Osim terapijskih vježbi na suhom, korisne mogu bit i vježbe u vodi (uključivo balneoterapiju), a u najtežim slučajevima može biti indicirana i hospitalna rehabilitacija. Liječnici moraju primijeniti nefarmakološku terapiju kao dio sveobuhvatne terapijske strategije. Iako su podaci nedostatni da bi se utvrdilo koji se specifični programi fizikalne terapije preporučuju ovaj pregled pokazuje da je fizikalna terapija učinkovit oblik intervencije i ostaje bitni dio liječenja s naglaskom na kontinuirano i redovito provođenje terapijskih vježbi.