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Purpose. To evaluate a 12-year follow-up of myopic patients after iris-fixated phakic intraocular lenses (IF pIOLs) implantation. Setting. Ophthalmology Department, Military University Hospital in Prague (Czech Republic). Design. Single-center retrospective cohort study. Methods. We describe the results of a cohort study that included 85 eyes of 46 myopic patients who underwent implantation of Verisyse myopia, Veriflex, and Verisyse myopia toric (all Abbott Medical Optics, Inc.) intraocular lenses. Refractive functions and adverse events were assessed preoperatively, at 6 months, and 1, 2, 5, and 12 years after IF pIOL implantation. Results. Mean spherical equivalent was measured as −9.37 ± 2.87 D, 0.14 ± 0.61 D, and −0.42 ± 1.08 D, preoperatively, at 6 months and 12 years postoperatively, respectively. There was a significant reduction in the cylinder after surgery. At 12 years postoperatively, 90% of eyes had uncorrected distance visual acuity (UDVA) of 20/40 and 64% of 20/20. The safety index was 1.10 for the whole postoperative follow-up period. We found cataract formation in 3 eyes (3.5%). The endothelial cells loss (EC loss) directly caused by IF pIOL implantation was 6.0%, 8.10%, 12.8%, and 11.9%, at 1, 2, 5, and 12 years, respectively. In our cohort, 95% of eyes lost a higher percentage of EC than would be expected from a physiological loss at 12 years postoperatively. We found a significant negative interaction between preoperative pachymetry and EC loss, indicating that the lower pachymetry leads to a faster decline in endothelial cells density (ECD). IF pIOL re-enclavation was found in 28% of eyes. 7% of subluxations were caused by trauma. The mean time of nontraumatic re-enclavation was 6 years postoperatively. Conclusions. The study confirmed the advantages of IF pIOL implantation due to rapid visual recovery and stable visual function over the 12-year follow-up and also showed the influence of lower corneal pachymetry regarding EC loss.

Aim: Heat shock protein 90 (Hsp90) is a molecular chaperone regulating immune response. We aimed to assess systemic Hsp90 as a biomarker for spondyloarthritis (SpA). Materials & methods: Total of 80 axial SpA (axSpA) and 22 psoriatic arthritis patients and a corresponding number of age- and sex-matched healthy controls (HC) were included. Plasma Hsp90 levels were measured by ELISA. Results: Hsp90 was significantly increased in axSpA patients compared with HC (median interquartile range: 15.7 [10.5–19.8] vs 8.3 [6.6–11.8] ng/ml, p

The somatic parameters and body composition are important indicators of physical fitness and general health not only non-athletes, but of athletes. The aim of this study was to determine the somatic characteristics and body composition in 15 Czech sub-elite female handball players (age 21.5 ± 1.8 years, body height 170.5 ± 6.6 cm, body weight 64.7 ± 10.2 kg, BMI 22.2 ± 2.9 kg m−2). Body composition was measured by a multifrequency bioimpedance method Tanita MC-980 (Tanita Europe BV). The monitored parameters were the following: fat mass (FM), fat free mass (FFM), muscle mass (MM), bone mass (BM), total body water (TBW), intracellular water (ICW), extracellular water (ECW) and segmental analysis of muscle distribution. In our female group, we recorded the mean value of FM = 21.5 ± 5.4% (14.3 ± 5.7 kg), FFM = 50.4 ± 5.9 kg, muscle mass = 47.9 ± 5.6 kg, bone mass = 2.6 ± 0.3 kg, TBW = 56.2 ± 3.2% (36.2 ± 4.8 kg), ICW = 22.6 ± 3.5 kg, ECW = 13.6 ± 1.3 kg. Monitoring of muscle distribution in the extremities showed a significant difference in upper extremities (p < 0.05, ES < 0.2) and in lower extremities (p < 0.05, ES < 0.2). Our results confirm on previous data about the presence of anthropometric differences and body composition differences between individual players in handball team.

Aims: Preoperative chemical vestibular ablation can reduce vestibular symptoms in patients who have gone through vestibular schwannoma resection. The goal of this study was to determine whether chemical vestibular prehabituation influences the patients' post-operative perception of visual stimulation, mental status and quality of life. We also tried to find out whether increases of optokinetic nystagmus, measured by routine electronystagmography, correlate with subjective symptoms. Methods: We preoperatively administered (2 months prior to surgery) 0.5 - 1.0 mL of 40 mg/mL nonbuffered gentamicin in three intratympanic instillations in 11 patients. Head impulse and caloric tests confirmed reduction of vestibular function in all patients. The control group consisted of 21 patients. Quality of life in both groups was evaluated using the Glasgow Benefit Inventory, the Glasgow Health Status Inventory and the Dizziness Handicap Inventory questionnaires. Visual symptoms and optokinetic sensation were evaluated using a specific questionnaire developed by our team and by measuring gains preoperatively and postoperatively in both groups using routine electronystagmography. The psychological profile was evaluated using the Zung Self-Rating Depression Scale and the Generalised Anxiety Disorder Assessment questionnaires. Results: There were no statistically significant differences between both groups with regards to the results of the questionnaires. Patients who received preoperative gentamicin were less sensitive to visual stimulation (P

Purpose:Hormone-secreting adenomas are treated in many neurosurgical centers within Europe. The goal of the survey is to shed light on different endocrinological aspects of hormone-secreting adenomas surgery.Methods: A list of departments performing pituitary surgery was created. The survey consisted of 58 questions. This study focuses on neurosurgical care of hormone-secreting adenomas. For analysis, the departments were divided into four subgroups: academic/non-academic, high-volume/low-volume, “mainly endoscopic/mainly microscopic practice” and geographical regions. Results: Data from 254 departments from 34 countries were obtained. Most centers surgically treat 1-5 hormone-secreting adenomas per year. In prolactinomas this is the case in 194 centers, (76.4%), in GH-secreting adenomas: 133 centers, (52.4%), ACTH-secreting adenomas: 172 centers, (69.8%). Surgery as a primary treatment of prolactinomas is considered in 64 centers (25.2%). In 47 centers (18.8%), GH-secreting microadenomas are often treated pharmacologically first. Debulking surgery for an invasive GH-secreting adenoma in which hormonal remission is not a realistic goal of the surgery and the patient has no visual deficit surgery is always or mostly indicated in 156 centers (62.9%). Routine postoperative hydrocortisone replacement therapy is administered in 147 centers (58.6%). Conclusions:Our survey shows that in most centers, few hormone-secreting adenomas are treated per year. In about 25% of the centers, prolactinoma surgery may be regarded as first-line treatment; in about 20% of the centers, medical treatment is the first-line treatment for GH-secreting adenomas. Pretreatment for ACTH-secreting adenomas is routinely used in 21% of centers. This survey may serve as plea for neurosurgical care centralization of hormone-secreting adenomas.

Investigate whether 123I-ioflupane SPECT (DaT SPECT) has the potential as a marker of basal ganglia damage in acute methanol poisoning. Prospective, single-centre, cohort study of patients with con...

Contains fulltext : 248317.pdf (Publisher’s version ) (Closed access) Pituitary adenoma surgery has evolved rapidly in recent decades, changing clinical practice markedly and raising new challenges. There is no current consensus or guidelines for perioperative care that includes possible complication management. This study aims to determine current practice across European neurosurgical centres. We created a list of eligible departments performing pituitary adenoma surgery based on cooperation with EANS, national neurosurgical societies, and personal communication with local neurosurgeons. We contacted the chairpersons from each department and asked them (or another responsible neurosurgeon) to fill out the survey. The survey consisted of 58 questions. For further analysis, departments were divided into subgroups: "academic"/ "non-academic centre", "high-volume"/"low-volume", "mainly endoscopic"/ "mainly microscopic"/ "mixed practise", and by geographical regions. Data from 254 departments from 34 countries were obtained. The average time to complete the survey was 18 min. Notably, the endoscopic approach is the predominant surgical approach in Europe, used in 56.8% of the centres. In routine cases without intraoperative cerebrospinal fluid leak, high-volume centres are less pedantic with sellar closure when compared with low-volume centres (p

BackgroundInterleukin 40 (IL-40) is a newly identified B cell-associated cytokine implicated in humoral immune responses and B cell homeostasis. As B cells play a pivotal role in autoimmunity, we investigated the function of IL-40 in rheumatoid arthritis (RA).MethodsIL-40 expression was determined in the synovial tissue from RA and osteoarthritis (OA) patients. IL-40 was analysed in the serum/synovial fluid of patients with RA (n=50), systemic lupus erythematosus (SLE, n=69), OA (n=44), and healthy controls (HC, n=50). We assessed the changes of IL-40 levels in RA patients following the B cell depletion by rituximab (n=29) or after the TNF inhibition by adalimumab (n=25). We examined the relationship between IL-40, disease activity, autoantibodies, cytokines, and NETosis markers. Effect of IL-40 on synovial fibroblasts was determined.ResultsIL-40 was overexpressed in RA synovial tissue, particularly by synovial lining and infiltrating immune cells. The levels of IL-40 were up-regulated in the synovial fluid of RA versus OA patients (pConclusionsWe show the up-regulation of IL-40 in RA and its decrease following B cell depleting therapy. The association of IL-40 with autoantibodies, chemokines, and markers of NETosis may imply its potential involvement in RA development. Moreover, IL-40 up-regulates the secretion of chemokines and MMP-13 in synovial fibroblasts, indicating its role in the regulation of inflammation and tissue destruction in RA.

Background The structural and functional changes of the skeletal muscles in idiopathic inflammatory myopathies (IIM) caused by inflammation and immune changes can be severely disabling. The objective of this study was to assess the effect of a 24-week program combining a supervised training of activities of daily living (ADL), resistance, and stability with home exercise for improving muscle function, compared to a daily home-based exercise representing the regular outpatient care. Methods Fifty-seven patients with IIM were consecutively and non-selectively enrolled in an intervention (IG, n = 30) or control (CG, n = 27) group. Both groups were provided a standard-of-care pharmacological treatment and follow-up. Only the IG underwent the supervised intervention twice a week for 1 h per session. At baseline, 12, 24, and 48 weeks, all patients were assessed by an assessor blinded to the intervention for primary outcomes: muscle strength (Manual Muscle Testing of eight muscle groups [MMT-8]) and endurance (Functional Index-2 [FI-2]), and secondary outcomes: stability and body composition. Secondary outcomes also included questionnaires evaluating disability (Health Assessment Questionnaire [HAQ]), quality of life (Short Form 36 [SF-36]), depression (Beck’s Depression Inventory-II [BDI-II]), and fatigue (Fatigue Impact Scale [FIS]), and analysis of the systemic and local inflammatory response and perceived exertion to assess the safety of the intervention. Results Twenty-seven patients in the IG and 23 in the CG completed the entire program and follow-up. At week 24, compared to deterioration in the CG, we found a significant improvement in the IG in muscle strength (mean % improvement compared to baseline by 26%), endurance (135%), disability (39%), depression (26%), stability (11%), and basal metabolism (2%) and a stabilization of fitness for physical exercise. The improvement was clinically meaningful (a 24-week change by >20%) in most outcomes in a substantial proportion of patients. Although the improvement was still present at 48 weeks, the effect was not sustained during follow-up. No significant increase in the systemic or local expression of inflammatory markers was found throughout the intervention. Conclusions This 24-week supervised intervention focused on ADL training proved to be safe and effective. It not only prevented the progressive deterioration, but also resulted in a significant improvement in muscle strength, endurance, stability, and disability, which was clinically meaningful in a substantial proportion of patients. Trial registration ISRCTN35925199 (retrospectively registered on 22 May 2020).

Hearing loss is the most frequent sensory disorder and is genetically extremely heterogeneous. By far the most frequent cause of nonsyndromic autosomal recessive hearing loss (AR-NSHL) are biallelic pathogenic mutations in the GJB2 gene causing DFNB1. The worldwide search for the second most common type of AR-NSHL took almost two decades. Recently reported alterations (mostly deletions) of the STRC gene, also named DFNB16, seem to be the second most frequent cause of AR-NSHL. Genetic testing of STRC is very challenging due to the highly homologous pseudogene. Anecdotal evidence from single patients shows that STRC mutations have their typical audiological findings and patients usually have moderate hearing loss. The aim of this study is to discover if audiological findings in patients with biallelic pathogenic mutations affecting STRC have the characteristic features and shape of audiological curves and if there are genotype/phenotype correlations in relation to various types of STRC mutations. Eleven hearing loss patients with pathogenic mutations on both alleles of the STRC gene were detected during routine genetic examination of AR-NSHL patients. Audiological examination consisted of pure tone audiometry, stapedial reflexes, tympanometry and otoacoustic emission tests. The threshold of pure tone average (PTA) was 46 dB and otoacoustic emissions were not detectable in these DFNB16 patients. All patients were without vestibular irritation or asymmetry. Moderate sensorineural hearing loss is typical for DFNB16-associated hearing loss and there are no significant differences in audiological phenotypes among different types of mutations affecting STRC.

Objectives: To determine the prevalence and distribution of US-detected qualitative cartilage damage at metacarpal heads of patients with RA and hand OA. Methods: Fifty-two RA patients and 34 patients with hand OA were enrolled. US examination of the metacarpal head cartilage from the II to V finger of both hands was performed. A total of 414 MCP joints in RA and 266 MCP joints in OA patients were scanned with a linear probe up to 22 MHz. Qualitative assessments using a previously described scoring system for cartilage damage were performed. The prevalence and distribution of cartilage damage were analysed. Multivariate regression analysis was used to determine the predictive value of age, gender, BMI, disease duration and the presence of RF and anti-CCP antibodies for US-detected cartilage damage. Results: The metacarpal head cartilage was positive for cartilage damage in 35.7% (148/414) of MCP joints in RA and in 43.6% (116/266) of MCP joints in OA patients. In RA, the hyaline cartilage of the II and III metacarpal heads (bilaterally) was the most frequently affected. In OA, cartilage damage was more homogeneously distributed in all MCP joints. Multivariate regression analysis showed that age and disease duration, but not gender, BMI or autoantibody status, were independent predictors of US-detected cartilage damage in RA. Conclusion: Cartilage damage was found in more than one-third of the MCP joints in both RA and OA patients, and in RA patients, the II and III MCP joints were the most damaged.

Fattori predittivi di compensazione vestibolare centrale dopo chirurgia per lo schwannoma vestibolare.La rimozione chirurgica dello schwannoma vestibolare è causa di sintomi vestibolari acuti, inclusa la vertigine postoperatoria che rappresenta il fattore che influenza più negativamente la qualità della vita dei pazienti dopo questo tipo di chirurgia. Scopo principale di questo studio è stato quello di determinare se i risultati dell’ elettronistagmografia con risposte provocate patologiche possano prevedere una scarsa compensazione postoperatoria. Abbiamo inoltre ricercato se la compensazione postoperatoria possa essere correlata con parametri oggettivi come l’età, le dimensioni del tumore, la durata della chirurgia e la persistenza del nistagmo. Sulla base dei risultati dell’ elettronistagmografia preoperatoria, i pazienti sono stati divisi in tre gruppi: con sindrome vestibolare periferica, centrale o combinata. I segni di compensazione centrale sono stati valutati dalla presenza di nistagmo postoperatorio, vertigine, deviazione della verticale soggettiva ed “head impulse” test. Non vi sono state differenze statisticamente significative fra i due gruppi nei segni di compensazione osservati. Questi risultati suggeriscono che i parametri oculomotori centrali patologici non sono un fattore predittivo negativo per la compensazione vestibolare centrale.Surgical removal of vestibular schwannoma causes acute vestibular symptoms, including postoperative vertigo which is the most negative factor affecting quality of life in patients after vestibular schwannoma surgery. The main aim of this study is to determine whether the results from routine electronystagmography with pathological visually-provoked responses can predict poor postoperative compensation. We also investigate whether postoperative central compensation is related to objective parameters such age, tumour size, length of surgery and persistent nystagmus. According to the results from preoperative electronystagmography, patients were divided into three groups: peripheral, central and combined vestibular syndrome. Signs of central compensation were evaluated by the presence of postoperative nystagmus, vertigo, deviation of subjective visual vertical and head impulse test. There were no statistically significant differences between groups in observed signs of compensation. These results suggest that pathological central oculomotor parameters are not a negative predictive factor for central vestibular compensation.

Salivary gland carcinomas (SGCs) are extremely morphologically heterogeneous, and treatment options for this disease are limited. Immunotherapy with immune checkpoint inhibitors (ICIs) represents a revolutionary treatment approach. However, SGCs remain largely resistant to this therapy. An increasing body of evidence suggests that resistance to ICI therapy is modulated by the Fas (CD95)–Fas ligand (FasL, CD178) interplay between tumor cells and immune cells. In this study, we examined the Fas–FasL interplay between tumor cells and tumor-infiltrating immune cells (TIICs) in the center and periphery of SGCs from 62 patients. We found that the Fas-expressing tumor cells accumulated in the center of SGC tumors with increasing tumor stage. Furthermore, this accumulation occurred regardless of the presence of TIICs expressing high levels of FasL. On the contrary, a loss of Fas-expressing TIICs with increasing tumor stage was found in the tumor periphery, whereas FasL expression in tumor cells in the tumor periphery correlated with tumor stage. These data suggest that SGC cells are resistant to FasL-induced apoptosis by TIICs but could utilize FasL to eliminate these cells in high-stage tumors to provide resistance to immunotherapy.

Circulating miRNAs appear promising therapeutic and prognostic biomarkers. We aimed to investigate the predictive value of circulating miRNAs on the disease outcome following anti-TNF therapy in patients with ankylosing spondylitis (AS). Our study included 19 AS patients assessed at baseline (M0), after three (M3) and twelve months (M12) of therapy. Total RNA was isolated from plasma. A comprehensive analysis of 380 miRNAs using TaqMan Low Density Array (TLDA) was followed by a single assay validation of selected miRNAs. All AS patients had high baseline disease activity and an excellent response to anti-TNF therapy at M3 and M12. TLDA analysis revealed the dysregulation of 17 circulating miRNAs, including miR-145. Single assay validation confirmed that miR-145 is significantly downregulated at M3 compared to baseline. The decrease in the levels of miR-145 from M0 to M3 negatively correlated with the change in BASDAI from M0 to M3; and positively correlated with disease activity improvement from M3 to M12 as per BASDAI and ASDAS. The predictive value of the early change in miR-145 and levels of miR-145 at M3 were further validated by Receiver operating curves analysis. We show that the early change in circulating miR-145 may be a predictor for the future outcome of AS patients treated with TNF inhibitors. Patients with a more significant decrease in miR-145 levels may show further significant improvement of disease activity after 12 months. Monitoring the expression of miR-145 in plasma in AS patients may, therefore, influence our therapeutic decision-making.

Our previous study demonstrated increased expression of Heat shock protein (Hsp) 90 in the skin of patients with systemic sclerosis (SSc). We aimed to evaluate plasma Hsp90 in SSc and characterize its association with SSc-related features. Ninety-two SSc patients and 92 age-/sex-matched healthy controls were recruited for the cross-sectional analysis. The longitudinal analysis comprised 30 patients with SSc associated interstitial lung disease (ILD) routinely treated with cyclophosphamide. Hsp90 was increased in SSc compared to healthy controls. Hsp90 correlated positively with C-reactive protein and negatively with pulmonary function tests: forced vital capacity and diffusing capacity for carbon monoxide (DLCO). In patients with diffuse cutaneous (dc) SSc, Hsp90 positively correlated with the modified Rodnan skin score. In SSc-ILD patients treated with cyclophosphamide, no differences in Hsp90 were found between baseline and after 1, 6, or 12 months of therapy. However, baseline Hsp90 predicts the 12-month change in DLCO. This study shows that Hsp90 plasma levels are increased in SSc patients compared to age-/sex-matched healthy controls. Elevated Hsp90 in SSc is associated with increased inflammatory activity, worse lung functions, and in dcSSc, with the extent of skin involvement. Baseline plasma Hsp90 predicts the 12-month change in DLCO in SSc-ILD patients treated with cyclophosphamide.

The treatment options for patients with advanced salivary gland cancers (SGCs) are limited. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, the response to ICI immunotherapy is largely driven by the immune cell signatures within the tumor tissue and the para-tumoral tissue compartments. To date, there are no data on the expression of programed cell death protein-1/programed cell death protein-ligand 1 (PD-1/PD-L1) in SGC, which may enable the implementation of ICI immunotherapy for this disease. Thus, we performed an immunohistochemical analysis of PD-1 and PD-L1 expression in tumor cells and tumor-infiltrating immune cells (TIICs) in the tumor center and periphery of 62 SGC patients. The tumor periphery showed significantly higher expression of PD-L1 in tumor cells than in TIICs. Moreover, peripheral TIICs had significantly higher PD-1 expression than peripheral tumor cells. PD-1-positive tumor cells were detected exclusively in the tumor center of high-grade tumors, and most importantly, the presence of lymph node (LN) metastases and primary tumor stage significantly correlated with the presence of PD-L1-positive tumor cells in the tumor periphery. The PD-1/PD-L1 molecular signatures in SGC are clustered predominantly in the tumor periphery, reflect disease severity, and may predict the response to ICI immunotherapy in SGC patients.

Objectives Individuals carrying antibodies against citrullinated proteins (ACPA) are at high risk of developing RA. EULAR provided a clinical definition of individuals with arthralgia suspicious for progression to RA (clinically suspect arthralgia, CSA). The alteration of monocyte subpopulations in patients with established RA has been previously described. We analysed peripheral blood monocyte subpopulations in individuals with arthralgia at risk of RA. Methods We included 70 at-risk individuals, defined as having arthralgia without arthritis and being either ACPA+ or meeting the clinical CSA definition, 23 patients with early RA (ERA) and 19 healthy controls (HCs). Monocytes classified as classical (CD14++CD16−), intermediate (CD14++CD16+/++) and nonclassical (CD14−/+CD16++) were analysed by flow cytometry. Results Of the 70 at-risk individuals, 46 were ACPA+ and 45 met the CSA definition. The at-risk individuals and, especially, ERA patients had a lower percentage of classical monocytes and a higher percentage of nonclassical monocytes than the HCs. ACPA positivity had no effect on the difference in the distribution of the monocyte subsets between at-risk individuals and ERA patients, but a difference was determined in those reaching the ERA phase. However, when compared with HCs, the shift of monocyte subsets was more significant in ACPA+ than in ACPA− individuals with arthralgia. This trend was observed in individuals who did not meet the CSA definition. This finding was, however, determined by a selection bias, as these individuals were solely ACPA+. Conclusion The shift from classical to nonclassical monocyte subpopulations was observed already in individuals at risk of developing RA.

To study the dynamics and clinical determinants of chronic retinal nerve fiber layer thickness (RNFL) loss after methanol-induced optic neuropathy.Prospective cohort study.All patients underwent complete ophthalmic evaluation including spectral-domain optical coherence tomography 3 times during 4 years of observation: 4.9 (±0.6), 25.0 (±0.6), and 49.9 (±0.5) months after discharge.Eighty-four eyes of 42 survivors of methanol poisoning, mean age (standard deviation) of 45.7 (±4.4) years; and 82 eyes of 41 controls, mean age 44.0 (±4.2) years.Global and temporal RNFL loss.Abnormal RNFL thickness was registered in 13 of 42 (31%) survivors of methanol poisoning and chronic axonal loss in 10 of 42 (24%) patients. Significant decrease of global/temporal RNFL thickness during the observation period was found in the study population compared to the controls (P.001). The risk estimate of chronic global RNFL loss for arterial blood pH7.3 at admission was 11.65 (95% confidence interval 1.91-71.12) after adjusting for age and sex. The patients with chronic axonal degeneration demonstrated progressive visual loss in 7 of 10 cases. The patients with abnormal RNFL thickness had magnetic resonance signs of brain damage in 10 of 13 vs 8 of 29 cases with normal RNFL thickness (P = .003). Signs of brain hemorrhages were present in 7 of 13 patients with abnormal RNFL thickness vs 5 of 29 cases with normal RNFL thickness (P = .015).Methanol-induced optic neuropathy may lead to chronic retinal axonal loss during the following years. Arterial blood pH on admission is the strongest predictor of chronic RNFL thickness decrease. Chronic retinal neurodegeneration is associated with the progressive loss of visual functions and necrotic brain lesions.

Hereditary thrombophilia may play an important role in the rate of postoperative venous thromboembolism (VTE). We focused on the impact of hereditary thrombophilia on VTE incidence in colorectal cancer surgery patients within a 1-year postoperative period. Preoperatively, identifying of colorectal cancer patients with thrombotic mutations (PTM+) and without thrombotic mutations (PTM−) was performed by screening of factor V Leiden (FVL) and prothrombin G20210A mutation. Within prophylactic period (0–28 days postoperatively), coagulation markers (platelets, fibrinogen, D‑dimer) were measured and symptomatic VTE was observed. Within post-prophylactic period (2–12 months after surgery), symptomatic VTE was observed. In all, 202 patients were assessed and hereditary thrombophilia was detected in 9.9% (FVL 8.4%; prothrombin G20210A mutation 1.5%). In the prophylactic period, VTE incidence in PTM+ and PTM− was 0.0% and 1.6%, respectively (p = 0.730). Levels of coagulation markers were comparable in both patient cohorts within 28 days postoperatively. In the post-prophylactic period, VTE incidence in PTM+ and PTM− was 15.0% and 5.5%, respectively (p = 0.125), and detailed incidence of deep vein thrombosis (DVT) in PTM+ and PTM− was 15.0% and 3.3%, respectively (p = 0.048). We observed significantly increased incidence of lower extremity DVT in such patients with FVL (17.6%). The standard regimen of extended-duration VTE prophylaxis is adequate for colorectal cancer patients with thrombotic mutations and more intensified VTE prophylaxis within the 28-day postoperative period is not justified. However, the ongoing postoperative pharmacologic prophylaxis (>28 days) should be considered in patients with hereditary thrombophilia, especially with FVL.

The aim of this study was to analyse the dietary habits of subjects with spinal cord injury (SCI), especially to evaluate differences in the presence and distribution of various food groups among a group of males and females. Subjects (n = 50, n1 = 36 males, n2 = 14 females) completed a frequency questionnaire, which included questions focused on the detection of size of consumed foods and frequency of consumption of various food groups (cereals, potatoes, vegetables, fruits, dairy products, meat, meat products, fats, sweets). We noted significant differences in the composition of breakfast (meat intake), lunch (vegetable intake, dairy intake), dinner (dairy intake, sweet intake), snacks (fats intake) in males and females. Differences in dietary habits of males and females with SCI especially concerned sizes of consumed servings of food, but also the representation of individual food groups in the diet throughout the day. In this context, the adapted food pyramid can be used as a visual tool to facilitate understanding and the maintenance of a healthy diet.

Background:Our previous study demonstrated that Hsp90 is overexpressed in the skin of patients with systemic sclerosis (SSc), in cultured SSc fibroblasts and preclinical models of SSc in a TGF-β dependent manner. We showed that Hsp90 is a new regulator of canonical TGF-β signaling and its inhibition prevents the stimulatory effects of TGF-β on collagen synthesis and dermal fibrosis1.Objectives:The aim of this study was to evaluate plasma Hsp90 of SSc patients and characterize its potential association with skin changes and SSc-related features.Methods:A total of 92 patients (79 females; mean age 52.7; disease duration 6.0 years; diffuse cutaneous (dc)SSc / limited cutaneous (lc)SSc = 38/54) and 92 age- and sex- matched healthy individuals were included. Plasma Hsp90 levels were measured by ELISA (eBioscience, Vienna, Austria). Data are presented as median (IQR).Results:Plasma Hsp90 levels were increased in SSc patients compared to healthy controls [12.5 (9.6–17.9) vs. 9.8 (7.7–12.4) ng/mL, p=0.0001]. Hsp90 levels in all patients positively correlated with CRP (r=0.271, p=0.015). Furthermore, Hsp90 concentrations were negatively associated with functional parameters of ILD: FVC (r=-0.291, p=0.013), FEV1 (r=-0.248, p=0.036), DLCO (r=-0.290, p=0.012) and SpO2(r=-0.317, p=0.038). When adjusted for CRP, these correlations still remained significant in multivariate analysis. Higher Hsp90 concentrations were associated with presence of synovitis [17.6 (15.4 – 24.0) vs. 12.2 (9.3 – 17.3), p=0.039]. In addition, only in patients with dcSSc, Hsp90 levels positively correlated with the mRSS (r=0.437, p=0.006). In a prospective analysis of patients with progressive SSc-ILD treated with 6 (n=21 patients) or 12 (n=14 patients) monthly i.v. pulses of cyclophosphamide (CPA, 10 mg/kg) we did not observe any significant differences between the baseline sample (month 0) and blood drawn after 1, 6 and 12 months. However, baseline Hsp90 was able to predict long-term response after one year of CPA treatment (DLCOm12-m0; r=-0.494, p=0.037). Moreover, change in Hsp90 after one month of CPA treatment (Hsp90m1-m0) was able to predict the short-term inflammatory response (CRPm3-m0, r=-0.495, p=0.019; ESRm3-m0, r=-0.496, p=0.031). Concentrations of extracellular Hsp90 were not significantly affected by other main clinical parameters of SSc.Conclusion:We demonstrated higher plasma levels of Hsp90 in SSc patients compared to healthy controls. Concentrations of extracellular Hsp90 increase with higher inflammatory activity, with deteriorated lung functions in ILD and also with the extent and severity of the skin involvement in patients with diffuse cutaneous SSc. These data further highlight the role of Hsp90 as a significant regulator of fibroblast activation and tissue fibrosis in SSc. In addition, Hsp90 could become a predictor of treatment response.References:[1]Tomcik M et al., Ann Rheum Dis.2014;73(6):1215-22.Acknowledgments:Supported by AZV-16-33542A, MHCR 023728 and SVV – 260373.Disclosure of Interests:Hana Štorkánová: None declared, Sabina Oreska: None declared, Maja Špiritović: None declared, Barbora Heřmánková: None declared, Kristyna Bubova: None declared, Martin Komarc: None declared, Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Jiří Vencovský: None declared, Jörg Distler Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Paid instructor for: Boehringer Ingelheim, Speakers bureau: Boehringer Ingelheim, Ladislav Šenolt: None declared, Radim Bečvář Consultant of: Actelion, Roche, Michal Tomcik: None declared

SUMMARY: The measurement of body composition has become an important component in the diagnosis of health, physical conditioning and nutritional status. The aim of this study was to compare two methods of detecting body composition, bioelectrical impedance and air displacement plethysmography for athletes and non-athletes. Specifically, we compared the parameters as fat mass, fat free mass and the value of basal metabolic rate. A sample size of 52 men (age 26.2 ± 5.4 years) that included a group of mixed martial arts (MMA) fighters (n = 31, age 27.2 ± 5.5 years) and a group of the non-athletes (n =21, age 24.6 ± 5.1 years). Both groups were measured by bioelectrical impedance and air displacement plethysmography. Significant differences in % body fat (p

Context: The influence of co-morbid conditions on the outcome of acute methanol poisoning in mass poisoning outbreaks is not known.Objective: The objective of this is to study the impact of burden ...

Background:In our previous study we demonstrated that S100A4 is overexpressed in scleroderma (SSc) skin, SSc fibroblasts and preclinical models of SSc in a TGF-β dependent manner. We showed that S100A4 is a new regulator of TGF-β signalling and its inhibition prevents the pro-fibrotic effects of TGF-β. Inactivation of S100A4 prevented dermal fibrosis induced by bleomycin and in Tsk-1 miceObjectives:The aim of this study was to evaluate S100A4 in the peripheral blood of SSc patients and characterize its potential association with SSc-related features.Methods:A total of 33 patients (29 females; mean age 52.8; disease duration 4.2 years; dcSSc/lcSSc = 8/25) who met the 2013 EULAR/ACR classification criteria for SSc and 20 healthy age- and sex-matched individuals were included in this study. Plasma levels of S100A4 were measured using ELISA (CUSABIO, Houston, USA). Data are presented as median (IQR).Results:S100A4 plasma levels were significantly increased in SSc patients compared to healthy controls (78.6(32.3-146.5) vs. 43.4(32.3-53.4)ng/mL,p=0.011). Patients with diffuse cutaneous (dc)SSc had significantly higher levels of S100A4 than patients with limited cutaneous (lc)SSc or healthy controls (168.5(81.5-347.5) vs. 63.4(30.9-130.6),p=0.017,p=0.001, respectively). Plasma levels of S100A4 positively correlated with mRSS (r=0.556,p=0.001). Furthermore, S100A4 negatively correlated with forced vital capacity (FVC) and peripheral oxygen saturation (SpO2) (r=- 0.362,p=0.038;r=-0.414,p=0.029, respectively). S100A4 levels positively correlated with ESSG activity score (r=0.750,p2), we observed a significant decrease in plasma S100A4 levels between the baseline samples (month 0) and blood drawn after 6 months of CPA treatment (76.3(52.9–98.6) vs. 73.2(44.4–98.6)ng/mL,p=0.013). Furthermore, baseline S100A4 levels predicted the change (m0-m6) in CRP and ESR levels after 6 months of CPA therapy (r=0.472,p=0.004;r=0.528,p=0.003, respectively).Conclusion:We demonstrate that plasma S100A4 levels are significantly increased in SSc patients compared with healthy controls. Increased S100A4 is associated with the dcSSc subset, skin involvement, deteriorated parameters of interstitial lung disease and higher disease activity. In patients with progressive SSc-ILD, S100A4 declines after 6 months of cyclophosphamide therapy and predicts the systemic inflammatory response. These data further support our previous findings on the role of S100A4 as a regulator of TGF-β induced fibrosis in SSc.Acknowledgements:Supported by MHCR023728, SVV–260373.Disclosure of Interests:None declared

Background:Idiopathic inflammatory myopathies (IIM) are rare diseases characterized by chronic muscle inflammation and multiple organ involvement. These serious clinical manifestations can be associated with significant impairment of quality of life, including sexual life.Objectives:This study aimed to compare sexual function in patients with IIM to age-/sex-matched healthy controls (HC) and determine the potential impact of clinical features on sexual function.Methods:In total, 62 women with IIM [mean age: 53.1, disease duration: 5.2 years, dermatomyositis (DM, 29)/ polymyositis (PM, 27)/ necrotizing myopathy (IMNM, 5)/ inclusion body myositis (IBM, 1)], who fulfilled the Bohan/Peter 1975 criteria for DM/PM, or ENMC criteria for IMNM or IBM, and 62 healthy controls (HC) (mean age: 53.1) without rheumatic diseases filled in 11 well-established and validated questionnaires assessing sexual function (FSFI, SFQ28, BISF-W, SQoL-F), pelvic floor function (PFIQ-7, PISQ-12), fatigue (FIS, Fatigue Impact Scale), physical activity (HAP, Human Activity Profile), disability (HAQ, Health Assessment Questionnaire), depression (BDI-II, Beck’s Depression Inventory-II), and quality of life (SF-36, Medical outcomes study Short Form 36 – PCS, Physical Component Summary; MCS, Mental Component Summary). A routine laboratory testing was performed. Data are presented as median (IQR).Results:Patients with IIM reported significantly greater prevalence and severity of sexual dysfunction (FSFI, BISF-W, SFQ28, SQoL-F) and pelvic floor dysfunction (PISQ-12, PFIQ-7) compared to HC (Table 1). The prevalence of sexual dysfunction in patients with IIM according to the FSFI cut-off score was 59%. Worse scores in IIM patients were associated with greater muscle weakness of m. gluteus maximus [MMT: FSFI (r=0.289, p=0.035), PFIQ-7 (r=-0.407, p=0.003)], m. gluteus medius [MMT: PFIQ-7 (r=-0.381, p=0.005)], more pronounced fatigue [FIF: SQoL-F (r=-0.412, p=0.003)], severer depression [BDI-II: SQoL-F (r=-0.459, p=0.0007)], worse functional disability [HAQ: FSFI (r=-0.436, p=0.005)], reduced physical activity [HAP: FSFI (r=0.403, p=0.001), SQoL-F (r=0.368, p=0.007)], and decreased quality of life [SF-36 PCS: FSFI-total (r=0.381,p=0.002), SF-36 MCS: SQoL-F (r=0.407, p=0.002)]. We did not observe any associations with disease duration, the current prednisone dose, or serum levels of muscle enzymes.Conclusion:Women with IIM reported significantly impaired sexual function and pelvic floor function compared to age-/sex-matched healthy controls. Worse scores in IIM were associated with disease-related features.Table 1.Sexual function and pelvic floor function in women with IIM and healthy controlsQuestionnaire: score range (meaning)IIM (n=62)HC (n=62)p-valueFSFI: Female Sexual Function Index: 2 (worst) - 36 (best)18.2 (3.2-28.5)28.4 (14.4-32.1)p=0.006BISF-W: Brief Index of Sexual Function forWomen: -16 (worst) - 75 (best)18.6 (2.7-32.3)34.0 (8.0-44.7)p=0.004SQoL-F: Sexual Quality of Life Questionnaire – Female: 0 (worst) - 100 (best)60.0 (41.4-83.6)86.7 (70.8-95.6)pPISQ–12: Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form: 0 (best) - 48 (worst)14.5 (9.0-18.0)8.0 (5.0-12.0)pPFIQ7: Pelvic Floor Impact Questionnaire – short form 7: 0 (best) - 300 (worst)4.8 (0.0-23.8)0.0 (0.0-4.8)p=0.052SFQ-28: Sexual Functioning Questionnaire-28 desire: 5 (worst) - 31 (best)18.0 (13.3-20.0)19.0 (17.0-22.0)p=0.042SFQ-28 arousal sensation: 4 (worst) - 20 (best)9.5 (7.0-11.0)12.0 (9.0-14.3)p=0.082SFQ-28 arousal lubrication: 2 (worst) - 10 (best)6.0 (4.0-8.0)7.0 (5.0-9.0)p=0.112SFQ-28 arousal cognitive: 2 (worst) - 10 (best)6.0 (4.3-7.0)6.0 (5.0-7.3)p=0.235SFQ-28 orgasm: 1 (worst) - 15 (best)11.0 (8.0-13.0)12.0 (9.8-13.0)p=0.279SFQ-28 pain: 2 (worst) - 15 (best)12.0 (10.0-15.0)15.0 (13.0-15.0)p=0.004SFQ-28 enjoyment: 6 (worst) - 30 (best)19.0 (14.3-24.3)23.0 (19.0-25.0)p=0.027SFQ-28 partner: 2 (worst) - 10 (best)9.0 (8.0-10.0)10.0 (9.0-10.0)p=0.012Acknowledgements:Supported by MHCR 023728, GA UK 1578119, and SVV 260373Disclosure of Interests:None declared

Background:Heat shock proteins (Hsps) are chaperones playing important roles in skeletal muscle physiology, adaptation to exercise or stress, and activation of inflammatory cellsObjectives:The aim of our study was to assess Hsp90 expression in muscle biopsies and plasma of patients with idiopathic inflammatory myopathies (IIM) and to characterize its association with IIM-related features.Methods:Total of 277 patients with IIM (198 females, 79 males; mean age 54.8; disease duration 4.1 years; DM, 104/PM, 108/CADM, 31/IMNM, 25) and 157 healthy individuals (92 females, 65 males; mean age 47.0) were included in plasma analysis. Muscle biopsy samples (PM, DM, IMNM, myodystrophy, myasthenia gravis) were stained for Hsp90α (Thermo Fisher Scientific, USA) and Hsp90β (Abcam, UK). Plasma Hsp90 was measured by ELISA kit (eBioscience, Vienna, Austria). The cytokines/chemokines were analysed by using Bio-Plex ProTMhuman Cytokine 27-plex Assay (BIO-RAD, California, USA.Data are presented as median(IQR).Results:In muscle biopsies, Hsp90 expression of both subunits (alpha and beta) was higher in IIM than in controls. Increased Hsp90 was detected in perifascicular degenerating and regenerating fibers, inflammatory cells (DM, PM), and necrotic and regenerating fibers (IMNM). Plasma Hsp90 levels were increased in IIM patients compared to healthy controls (55.9 (46.9 – 62.5)vs 9.76(7.5 – 13.8), pTab 1Clinical parametersSpearman’s rp – valueLDH; AST; ALT0.554; 0.383; 0.181< 0.0001; < 0.0001; 0.003PtDGA; PhDGA; MITAX; MYOACT0.223; 0.217; 0.175; 0.159< 0.001; < 0.001; 0.004; 0.012Pulmonary disease activity0.2010.001Muscle disease activity0.1460.018MMT8, total score; m. biceps brachii; m. gluteus maximus; m. iliopsoas-0.126; -0.125; -0.159; -0.1430.042; 0.043; 0.011; 0.023MDI – Myositis damage index – severity0.1500.041Current Prednisone equivalent dose0.1830.006Cytokines:IL-1b; IL-2; IL-4; IL-6; IFN-γ0.188; 0.269; 0.190; 0.182; 0.2290.002; < 0.0001; 0.002; 0.003; < 0.0001Conclusion:We demonstrate increased Hsp90 expression in IIM muscle biopsy samples, specifically in inflammatory cells, degenerating, regenerating and/or necrotic fibers. Increased Hsp90 plasma levels in IIM patients are associated with disease activity and damage, and with the involvement of proximal skeletal muscles, heart and lungs.Acknowledgments:Supported by AZV-16-33542A, MHCR 023728 and SVV – 260373.Disclosure of Interests:Hana Štorkánová: None declared, Sabina Oreska: None declared, Maja Špiritović: None declared, Barbora Heřmánková: None declared, Olga Kryštůfková: None declared, Heřman Mann: None declared, Martin Komarc: None declared, Josef Zámečník: None declared, Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Jiří Vencovský: None declared, Ladislav Šenolt: None declared, Michal Tomcik: None declared

The application of nanomaterials has been rapidly increasing during recent years. Inhalation exposure to nanoparticles (NP) may result in negative toxic effects but there is a critical lack of human studies, especially those related to possible DNA alterations. We analyzed pre-shift and post-shift a group of nanocomposite researchers with a long-term working background (17.8 ± 10.0 years) and matched controls. The study group consisted of 73.2% males and 26.8% females. Aerosol exposure monitoring during a working shift (involving welding, smelting, machining) to assess the differences in exposure to particulate matter (PM) including nanosized fractions

Thousands of researchers and workers worldwide are employed in nanocomposites manufacturing, yet little is known about their respiratory health. Aerosol exposures were characterized using real time and integrated instruments. Aerosol mass concentration ranged from 0.120 mg/m3 to 1.840 mg/m3 during nanocomposite machining processes, median particle number concentration ranged from 4.8 &times, 104 to 5.4 &times, 105 particles/cm3. The proportion of nanoparticles varied by process from 40 to 95%. Twenty employees, working in nanocomposite materials research were examined pre-shift and post-shift using spirometry and fractional exhaled nitric oxide (FeNO) in parallel with 21 controls. Pro-inflammatory leukotrienes (LT) type B4, C4, D4, and E4, tumor necrosis factor (TNF), interleukins, and anti-inflammatory lipoxins (LXA4 and LXB4) were analyzed in their exhaled breath condensate (EBC). Chronic bronchitis was present in 20% of researchers, but not in controls. A significant decrease in forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) was found in researchers post-shift (p ˂ 0.05). Post-shift EBC samples were higher for TNF (p ˂ 0.001), LTB4 (p ˂ 0.001), and LTE4 (p ˂ 0.01) compared with controls. Nanocomposites production was associated with LTB4 (p ˂ 0.001), LTE4 (p ˂ 0.05), and TNF (p ˂ 0.001), in addition to pre-shift LTD4 and LXB4 (both p ˂ 0.05). Spirometry documented minor, but significant, post-shift lung impairment. TNF and LTB4 were the most robust markers of biological effects. Proper ventilation and respiratory protection are required during nanocomposites processing.

Background Accurate disease activity measurement is a key component of rheumatoid arthritis (RA) management. In 2012, multi-biomarker disease activity (MBDA) test using 12 serum proteins was presented 1 . Objectives To develop a novel test for measuring inflammatory activity in RA. Methods Serum samples were obtained from 82 patients with RA (60 females, median disease duration 4.2 years, median age 55.2 years, RF positivity 60.3%, ACPA positivity 69.7%). A detailed stepwise analysis of 20 candidate biomarkers selected from the literature search (IL1β, IL-6, IL-7, IL-8, IL-12p70, IL-17A, IL-22, IL-33, IL-34, IFNγ, VEGF, YKL-40, CXCL-13, MMP-3, resistin, visfatin, leptin, adiponectin, calprotectin and CRP) was performed. Methods of factor analysis (a statistical method used to describe variability among observed, correlated variables in terms of a potentially lower number of unobserved variables called factors) were used in order to develop a tool composed of different serum markers that would optimally reflect disease activity in RA. Spearman correlation index was used to explore associations between newly designed tool and clinical as well ultrasound parameters (German US7 score) of disease activity. Results We have developed a “Molecular Disease Activity” test covering underlying pathophysiological processes composed of 8 serum markers: calprotectin, CRP, IL-6, MMP-3, VEGF, resistin, IL-22 and IL-7 that optimally reflected inflammatory activity in RA. This model was significantly associated with clinical (DAS28-ESR, DAS29-CRP, CDAI, SDAI) and ultrasound variables (PD syn score, GS syn score) of disease activity in RA, as shown in table 1. Conclusions We believe that this newly designed test based on 8 serum markers may contribute to more accurate measurement of inflammatory activity in RA and improvement of patients‘ outcomes. Further evaluation of this tool in a larger cohort is needed. Reference [1] Centola M, Cavet G, Shen Y, et al. Development of a Multi-Biomarker Disease Activity Test for Rheumatoid Arthritis. Plos One2013Apr 9;8(4). Acknowledgements Supported by the project of Ministry of Health, Czech Rep. No. 0 23 728 and SVV No. 260 373. Disclosure of Interest None declared

Introduction The altered expression of miRNAs is involved in the pathophysiology of inflammatory conditions. Moreover, circulating miRNAs appear promising therapeutic and prognostic biomarkers. Objectives To investigate the effect of anti-TNF therapy on the levels of circulating miRNAs in patients with ankylosing spondylitis (AS). Methods Our study included 19 AS patients. Clinical and laboratory parameters of disease activity were assessed at baseline (M0) and after 3 (M3) and 12 months (M12) of therapy. Total RNA from plasma was isolated using miRNeasy Serum/Plasma Kit (Qiagen). First, a comprehensive analysis of miRNAs was performed using TaqMan Low Density Array (TLDA) in 3 patients. Next, single assays were used for validation of selected miRNAs. dCt method was used for relative quantification. Data were analysed using ANOVA with Bonferroni corrections and Spearman’s correlation coefficient. Results All AS patients had high disease activity at baseline and had a good therapeutic response to anti TNF therapy at M3 and M12 (BASDAI p Out of all 380 miRNAs analysed by TLDA, 125 miRNAs were detected in all samples, 148 miRNAs were detected at M0, 154 at M3 and 151 at M12. Validation of 17 selected miRNAs confirmed significant downregulation of miR-145 at M3 (TLDA 1.59-change; single assays 1.62-change, p=0.024), but the downregulation did not reach statistical significance at M12 (TLDA 1.46-change; single assays 1.11-change, p>0.05). The decrease in miR-145 expression from M0 to M3 significantly correlated with disease activity improvement over time from M3 to M12 as per BASDAI (r=0.672, p=0.002) and ASDAS scores (r=0.607, p=0.006) and VAS at M12 (r=0.515, p=0.024). Although the overall clinical efficacy of anti-TNF therapy sustained, 6 patients revealed some ASDAS worsening at M12. This may have resulted to correlation of higher miR-145 levels at M3 with disease activity worsening as per increase in ASDAS from M3 to M12 (r=0.593, p=0.007) and higher ASDAS (r=0.533, p=0.019) and VAS (r=0.564, p=0.012) at M12. Conclusions We propose that an early change in miR-145 levels may be a predictor for the future outcome of AS patients as it’s early decrease after anti-TNF initiation correlated with further disease activity improvement. These data suggest the potential to use circulating miRNAs as biomarkers of treatment response in AS. Acknowledgements Grants 17-33127A and SVV 260263. Disclosure of interest None declared

Approximately half of patients with rheumatoid arthritis (RA) have normal C-reactive protein (CRP) levels. Calprotectin is a promising and likely more specific biomarker of disease activity than conventionally used acute phase reactants. We aimed to analyse the levels of serum calprotectin in RA patients with clinically active disease and with normal/low CRP. A total of 160 RA patients underwent clinical examination (DAS28-ESR and CDAI). The levels of calprotectin were analysed in patients with moderate to high disease activity with normal/low CRP levels and in 32 healthy subjects. The discriminatory capacity of calprotectin to identify clinically active patients in spite of normal/low CRP was assessed using ROC curves. Out of all RA patients, 74/160 (46.3%) were in remission or had low disease activity according to DAS28 and had normal/low CRP levels. However, 51/160 (32%) had normal/low CRP levels despite having moderate to high disease activity. In these patients, calprotectin levels were significantly higher than those in patients who had normal/low CRP and were in remission or showed low disease activity (2.7 ± 1.5 vs. 2.1 ± 1.2 μg/mL, p = 0.043), which differed from those in healthy subjects (2.7 ± 1.5 vs. 1.9 ± 1.2 μg/mL, p = 0.011). The discriminatory capacity for calprotectin to distinguish clinically active vs. inactive disease despite normal/low CRP using AUC of the DAS28 was 0.607 (95% CI 0.503 to 0.711, p = 0.043). The present study demonstrates that calprotectin may reflect inflammatory activity in RA patients where CRP fails to do so.

Mass or cluster methanol poisonings are frequently reported from around the world. The comparative effectiveness of ethanol and fomepizole as antidotes for methanol poisoning is unknown due to the difficulty of performing a randomized controlled trial.During an outbreak of mass poisonings in the Czech Republic in 2012-2014, we compared the effects of antidotes on the frequency of health sequelae and mortality.The study was designed as a cross-sectional case series and quasi-case-control study. Patients with a diagnosis of methanol poisoning on admission to hospitals were identified for the study. Diagnosis was established when (i) a history of recent ingestion of illicit spirits was available and serum methanol was higher than 6.2 mmol/L (20 mg/dL), or (ii) there was a history/clinical suspicion of methanol poisoning, and serum methanol was above the limit of detection with at least two of the following: pH7.3, serum bicarbonate20 mmol/L, and anion gap or AG ≥ 20 mmol/L. Fomepizole was given as a bolus dose of 15 mg/kg i.v. diluted in isotonic saline, followed by 10 mg/kg every 12 h (every 4 h during hemodialysis); ethanol was administered both intravenously as a 10% solution in 5% glucose, and per os in boluses of 20% solution. Multivariate regression was applied to determine the effect of antidote on outcome. Additionally, for a retrospective quasi-case-control study, a control group of patients treated with ethanol, matched carefully on severity of poisoning and other key parameters, was selected.Data were obtained from 100 hospitalized patients with confirmed poisoning: 25 patients treated with fomepizole were compared with 68 patients receiving ethanol (seven patients did not receive any antidote). More severely acidotic (p0.001) and late-presenting (12 h; p = 0.028) patients received fomepizole more often than ethanol, as reflected in the higher number of fomepizole-treated patients being intubated (p = 0.009). No association was found between the type of antidote and the survival in either the case series (p = 0.205) or the quasi-control groups (p = 0.705) in which patients were very closely matched to minimize confounding by allocation. In the multivariate analysis, positive serum ethanol (odds ratio [OR], 10.8; 95% confidence interval [CI], 2.9-39.9) and arterial blood pH (OR, 3.7; 95% CI, 1.3-10.5) on admission were the only independent variables for the survival. The median intensive care unit length of stay was 6 (range, 2-22) days in the fomepizole group and 4 (range, 1-33) days in the ethanol group (p = 0.131). There were no differences in the use of elimination techniques between the two groups (neither in the full material (n = 100), nor the case-control groups (n = 50)).This study on antidotes for methanol poisoning did not show any evidence of different clinical effectiveness. Although ethanol is generally associated with a higher incidence of complications, this study suggests that both antidotes are similarly effective and that ethanol should not be avoided on grounds of effectiveness.

Summary Introduction We found midline epithelial adhesions in the glandar urethral plate in patients with hypospadias. After dissolution, a blind epithelized channel becomes visualized inside of the plate pointing to immature embryonic luminization. In addition it reveals that the epithelized surface of the distal urethral plate is larger than previously considered. Objective To determine the incidence and extent of these new anatomical details of urethral plate in hypospadias patients. Methods We prospectively assessed the detailed anatomy of the urethral plate in 72 consecutive patients with hypospadias. We recorded the presence of adhesions in the middle of the glandar urethral groove that can be easily dissoluted (dissolution line – D-line). We recorded the plate width before and after D-line dissolution, the presence of the hidden blind channel at continuation of D-line (channel type-A) and of the visible blind channel between D-line and urethral hypospadiac meatus (type-B) ( Figure ). In 62 patients, where the urethral plate tubularization was considered (Duplay, TIP), septs between channels were opened in the midline and a final width of the plate was measured by rolling the plate around a tube. Results Midline adhesions (D-line) were found in all 72 patients. Mean length of D-line was 5.13 ± O.17 mm. Mean plate width before dissolution was 5.9 ± 0.15 mm, and after dissolution 7.8 ± 0.16 mm. A blind channel of type A was detected in 22 patients (31%), type B in 24 (33%), type A and B in 16 (22%), and none in 10 patients (14%). Mean final plate width after D-line dissolution and opening of septs between channels in 62 patients with urethral plate tubularization was 8.7 ± 0.15 mm. Discussion The main contribution of our study is a new perspective of distal urethral plate anatomy that enables enlargement of the epithelized surface of the distal urethral plate by dissolution of the preexisting epithelized groove and opening of epithelized channels within the plate. To the best of our knowledge, this anatomical anomaly has not been described previously. Conclusions The distal urethral plate of all hypospadias patients is partially “folded” in the midline by epithelial adhesions of different depth and extent that may be easily dissoluted. In half of the patients (53%) the “folded” part of the plate continues proximally as a blind channel inside the urethral plate (type A channel). Opening of these structures together with the well-known urethral plate pits (type B channel) helps augment the width and the overall epithelized surface of the distal urethral plate. Download high-res image (97KB) Download full-size image Figure . Position of epithelized groove and channels in distal urethral plate: (U) urethra; (B) channel type-B; (A) hidden channel type-A; (D) groove under D-line.

Background Intermittent hemodialysis (IHD) is the modality of choice in the extracorporeal treatment (ECTR) of acute methanol poisoning. However, the comparative clinical effectiveness of intermittent versus continuous modalities (CRRT) is unknown. During an outbreak of mass methanol poisoning, we therefore studied the effect of IHD versus CRRT on mortality and the prevalence of visual/central nervous system (CNS) sequelae in survivors. Methods The study was designed as prospective observational cohort study. Patients hospitalized with a diagnosis of acute methanol poisoning were identified for the study. Exploratory factor analysis and multivariate logistic regression were applied to determine the effect of ECTR modality on the outcome. Results Data were obtained from 41 patients treated with IHD and 40 patients with CRRT. The follow-up time in survivors was two years. Both groups of patients were comparable by age, time to presentation, laboratory data, clinical features, and other treatment applied. The CRRT group was more acidemic (arterial blood pH 6.96 ± 0.08 vs. 7.17 ± 0.07; p 0.05). Conclusions In spite of the faster correction of the acidosis and the quicker removal of the toxic metabolite in intermittent dialysis, we did not find significant differences in the treatment outcomes between the two groups after adjusting for the degree of acidemia and the severity of poisoning on admission. These findings support the strategy of “use what you have” in situations with large outbreaks and limited dialysis capacity.

Background About a half of patients with rheumatoid arthritis (RA) have normal or low C-reactive protein (CRP) levels 1–3 . Calprotectin is a promising and probably more specific biomarker of disease activity than conventionally used acute phase reactants. Objectives The aim of this study was to analyse levels of serum calprotectin in RA patients with clinically active disease and with low CRP ( Methods A total of 160 RA patients and 32 healthy subjects were enrolled in this study. All patients underwent clinical examination (DAS28). The levels of calprotectin were analyzed in patients with moderate to high disease activity with low CRP levels and in healthy subjects. The discriminatory capacity of calprotectin to identify clinically active patients in spite of normal CRP was assessed using ROC curves. Results Out of all RA patients, 74/160 (46.3%) had low CRP and were in remission or had low activity at the same time. However, 51/160 (32%) had low CRP levels despite moderate to high disease activity according to DAS28. In these patients, calprotectin levels were significantly higher than in patients with low CRP in remission or with low disease activity at the same time (mean 2.7±1.5 vs. 2.1±1.2 μg/mL, p=0.043) and differed from that in healthy subjects (mean 2.7±1.5 vs. ± 1.9±1.2 μg/mL, p=0.011) (Figure 1). The discriminatory capacity for calprotectin to distinguish clinically active vs. inactive patients in spite of low CRP using AUC of the DAS28 was 0.607 (95% CI 0.503 to 0.711, p=0.043) with an optimal cut-off 2.5 μg/mL. Conclusions The present study demonstrates that calprotectin may reflect inflammatory activity in RA patients where CRP fails to do so. References Pincus T, Sokka T. Laboratory tests to assess patients with rheumatoid arthritis: advantages and limitations. Rheum Dis Clin North Am 2009;35(4):731–4. Sokka T, Pincus T. Erythrocyte sedimentation rate, C-reactive protein, or rheumatoid factor are normal at presentation in 35%>45% of patients with rheumatoid arthritis seen between 1980 and 2004: analyses from Finland and the United States. J Rheumatol 2009;36(7):1387–90. Pincus T, Gibson KA, Shmerling RH. An evidence-based approach to laboratory tests in usual care of patients with rheumatoid arthritis. Clin Exp Rheumatol 2014;32(5 Suppl 85):S-23–8. Acknowledgements This work was supported by a project of the Ministry of Health of the Czech Republic for conceptual research development by organization [023728], Charles University Grant Agency (GAUK grant), Czech Republic [880217] and Specific Academy Research Projects (SVV) [260 031]. Disclosure of Interest None declared

The aim of this article was to study the role of serum formate (S-formate) in diagnosing methanol poisoning. A prospective study was undertaken of 38 patients from the Czech methanol mass poisoning in 2012 - median age 51 [interquartile range (IQR) 37-62] years with confirmed methanol poisoning. S-formate was measured enzymatically. The receiver operating characteristics (ROC) curve was used to examine the predictive ability of S-formate. Asymptomatic patients had median S-formate of 1.9 (IQR 1.5-2.4) mmol/L. The median S-formate was 15.2 (IQR 13.9-17.6) mmol/L in symptomatic subjects with visual disturbances, 15.4 (12.1-18.0) mmol/L in subjects with dyspnoea and 15.7 (IQR 12.8-18.5) mmol/L in comatose patients. The differences in serum formate concentrations in symptomatic patients depending on clinical features were not significant (all p > 0.05). Patients with long-term visual sequelae of poisoning had median S-formate of 16.1 (IQR 14.3-19.9) mmol/L; with central nervous system (CNS) sequelae, patients had 15.9 (IQR 14.2-19.5) mmol/L. In lethal cases, the median S-formate was 15.2 (IQR 13.8-15.9) mmol/L. The probability of a poor outcome (death or survival with sequelae) was higher than 90% in patients with S-formate ≥17.5 mmol/L, S-lactate ≥7.0 mmol/L and/or pH

Methanol poisonings occur frequently globally, but reports of larger outbreaks where complete clinical and laboratory data are reported remain scarce. The objective of the present study was to report the data from the mass methanol poisoning in the Czech Republic in 2012 addressing the general epidemiology, treatment, and outcomes, and to present a protocol for the use of fomepizole ensuring that the antidote was provided to the most severely poisoned patients in the critical phase.A combined prospective and retrospective case series study of 121 patients with confirmed methanol poisoning.From a total of 121 intoxicated subjects, 20 died outside the hospital and 101 were hospitalized. Among them, 60 survived without, and 20 with visual/CNS sequelae, whereas 21 patients died. The total and hospital mortality rates were 34% and 21%, respectively. Multivariate regression analysis found pH7.0 (OR 0.04 (0.01-0.16), p0.001), negative serum ethanol (OR 0.08 (0.02-0.37), p0.001), and coma on admission (OR 29.4 (10.2-84.6), p0.001) to be the only independent parameters predicting death. Continuous hemodialysis was used more often than intermittent hemodialysis, but there was no significant difference in mortality rate between the two [29% (n = 45) vs 17% (n = 30), p = 0.23]. Due to limited stockpiles of fomepizole, ethanol was administered more often; no difference in mortality rate was found between the two [16% (n = 70) vs. 24% (n = 21), p = 0.39]. The effect of folate administration both on the mortality rate and on the probability of visual sequelae was not significant (both p0.05).Severity of metabolic acidosis, state of consciousness, and serum ethanol on admission were the only significant parameters associated with mortality. The type of dialysis or antidote did not appear to affect mortality. Recommendations that were issued for hospital triage of fomepizole administration allowed conservation of valuable antidote in this massive poisoning outbreak for those patients most in need.

Background: NanoTiO 2 is used in many applications as a high volume commercially important engineered nanomaterial. Experimental studies documented oxidative stress, inflammation, and lung injury. Human health data are extremely limited (1, 2). Methods: In exhaled breath condensate (EBC) of 36 workers occupationally exposed to TiO 2 we studied post-shift a panel of biomarkers of lipid oxidation: malondialdehyde (MDA), 4-hydroxy-trans-hexenale (HHE), 4-hydroxy-trans-nonenale (HNE), 8-isoProstaglandin F2α (8-isoprostane) and aldehydes C 6 -C 12 in 2012 and 2013. Identical examination was done in 45 controls. Results: Median particle number concentration in the production area ranged from 1.98x10 4 to 2.32x10 4 particles/cm 3 with 80-85% of the particles 3 . All 11 markers of lipid oxidation were elevated in workers comparing to controls (p 2 and markers of lipid oxidation in the EBC. No association was found with age or lifestyle factors. Conclusion: Lipid oxidation in EBC of workers following nanoTiO 2 exposures is consistent with the oxidative stress hypothesis and suggests, at the molecular level, sustained lung injury. Markers of oxidation of lipids in EBC, in addition to oxidative products of nucleic acids and proteins (1) appear a useful and sensitive technique for non-invasive monitoring of workers exposed to engineered nanoparticles of nanoTiO 2 similarly as to Fe oxides (2). Acknowledgement: P25/1LF/2, P28/1LF/6. References: 1. Pelclova D et al. Occup Environ Med. 2016;73:110-8. 2. Pelclova D, et al. J Breath Res. 2016 1;10(1):016004.

Background: NanoTiO 2 is widely used as a high volume engineered nanomaterial, however human health data for exposed workers are scarce. Experimental and in vitro studies found lung inflammation and injury. Methods: In 30 workers occupationally exposed to TiO 2 in 2012/2013, post-shift spirometry, fractional exhaled nitric oxide (FeNO) and leukotrienes (LTs) as markers of inflammation in exhaled breath condensate (EBC) were examined: LT B4 and cysteinyl-LTs C4,D4 and E4. Identical examination was done in 22 office employees from the same factory; and in 45 unexposed controls. Results: The aerosol TiO 2 exposure mildly lowered from 2012 to 2013; respirable mass concentration was 0.4 and 0.65 mg/m 3 and the median particle number concentration in the production area 1.98x10 4 and 2.32x10 4 particles/cm 3 in 2012 and 2013, respectively. In both years, 80-85% of the particles had Conclusion: These findings are consistent with the inflammation in the respiratory tract and suggest a lung injury. LTs in EBC appear a useful and sensitive technique for non-invasive monitoring of workers exposed to engineered nanoTiO 2 , similarly as oxidation products of nucleic acids and proteins(1). FeNO and lung functions are not sensitive enough. Acknowledgement: P25/1LF/2, P28/1LF/6. Reference: 1. Pelclova D et al. Occup Environ Med 2016;73:110-8.

Human health data regarding exposure to nanoparticles are extremely scarce and biomonitoring of exposure is lacking in spite of rodent pathological experimental data. Potential markers of the health-effects of engineered nanoparticles were examined in 30 workers exposed to TiO2 aerosol, 22 office employees of the same plant, and 45 unexposed controls. Leukotrienes (LT) B4, C4, E4, and D4 were analysed in the exhaled breath condensate (EBC) and urine via liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Fractional exhaled nitric oxide (FeNO) and spirometry was also measured. The median particle number concentration of the aerosol in the production ranged from 1.98 × 10(4) to 2.32 × 10(4) particles cm(-3); about 80% of the particles were

Surgery for benign disease is associated with a low-risk of developing venous thromboembolism (VTE). Despite a relatively low incidence of postoperative VTE in patients after elective cholecystectomy and abdominal hernia repair there are data proving hypercoagulability in the early postoperative period. We focused on assessment of the systemic inflammatory response and coagulation status in these surgical patients after hospital discharge. Prospectively, patients who underwent surgery for benign disease were included. Two hundred sixteen patients were enrolled - 90 patients in laparoscopic cholecystectomy (LC) group and 126 patients in hernia surgery (HS) group. Risk assessment of VTE according to the Caprini risk assessment model was performed in all patients. Prevalence of VTE in postoperative period was observed. Markers of systemic inflammatory response (IL-6, CRP, α-1-acid glycoprotein, transferrin) and coagulation markers (PLT, fibrinogen, prothrombin fragment F1 + 2 and D-dimer) were measured before surgery, on 7–10th postoperative day and on 28–30th postoperative day. Clinically apparent deep vein thrombosis was diagnosed in only one patient - 0.46 %. Statistically significant elevation of inflammatory markers IL-6, CRP and α-1-acid glycoprotein (p

Surgical removal of vestibular schwannoma causes acute vestibular symptoms, including postoperative vertigo and oscillopsia due to nystagmus. In general, the dominant symptom postoperatively is vertigo. Preoperative chemical vestibular ablation can reduce vestibular symptoms postoperatively. We used 1.0 mL of 40 mg/mL nonbuffered gentamicin in three intratympanic installations over 2 days, 2 months preoperatively in 10 patients. Reduction of vestibular function was measured by the head impulse test and the caloric test. Reduction of vestibular function was found in all gentamicin patient groups. After gentamicin vestibular ablation, patients underwent home vestibular exercising for two months. The control group consisted of 10 patients who underwent only home vestibular training two months preoperatively. Postoperative rates of recovery and vertigo in both groups were evaluated with the Glasgow Benefit Inventory (GBI), the Glasgow Health Status Inventory (GHSI), and the Dizziness Handicap Inventory questionnaires, as well as survey of visual symptoms by specific questionnaire developed by us. There were no statistically significant differences between both groups with regard to the results of questionnaires. Patients who received preoperative gentamicin were more resilient to optokinetic and optic flow stimulation (p<0.05). This trial is registered with clinical study registration number NCT02963896.

Visual disturbances due to the toxic effect of formic acid in acute methanol poisonings are generally transient. The subjective symptoms of visual toxicity may resolve within few weeks and fundoscopic signs of acute optic neuropathy subside within 1-2 months; therefore, the prevalence of long-term visual sequelae in the population of survivors of poisonings may be underestimated.To study the prevalence and character of long-term visual sequelae of acute methanol poisonings based on the data from the Czech mass methanol outbreak in 2012.A total of 50 patients with confirmed methanol poisoning were included in this longitudinal cross-sectional study, median age: 48 (range, 23-73) years. The following tests were performed: optical coherence tomography or OCT with evaluation of the retinal nerve fibers layer (RNFL), visual evoked potentials (VEP), magnetic resonance imaging (MRI) of brain, complete ocular examination (visual acuity/field, color vision, contrast sensitivity, and fundus), neurological examinations, and biochemical tests.Of 50 patients, 7/50 (14%) were discharged with diagnosed visual sequelae and 6/50 (12%) were discharged with both visual and central nervous system sequelae of poisoning. On the follow-up examination, 20/50 (40%) of the patients had long-term visual sequelae, with 8% of blindness. A total of 38% of the patients had abnormal (28% borderline) findings on RNFL, and 40% had abnormal (18% borderline) VEP. Among the patients discharged without detected visual sequelae, 8/37 (22%) had abnormal RNFL and VEP. Patients with visual sequelae had brain lesions more often (70% vs. 27%, p0.01). MRI identified optic nerve lesions in 2/20 cases with abnormal VEP only. The groups with and without visual sequelae differed in serum methanol, ethanol, HCO3-, formate, pH, anion gap, and base deficit (all p0.01). Visual disturbances on admission and coma were more prevalent in the patients with visual sequelae (p0.05). Patients with positive serum ethanol on admission were 93% less likely to have optical axonal damage (OR: 0.07 (95% CI: 0.01-0.8); p0.05). No association was found between visual sequelae and type of antidote administered, mode of hemodialysis, or folate substitution. Pre-hospital administration of ethanol seemed beneficial: these patients were 90% less likely to have abnormal RNFL findings (OR: 0.10 (95% CI: 0.02-0.52); p0.01).The long-term visual sequelae were clearly underestimated on discharge, suggesting a significantly higher amount of patients with long-term sequelae than earlier reported. Thorough examinations before discharge and during follow-up will likely uncover a higher morbidity also after methanol poisonings in general.

Study objective Methanol poisoning outbreaks are a global public health issue, with delayed treatment causing poor outcomes. Out-of-hospital ethanol administration may improve outcome, but the difficulty of conducting research in outbreaks has meant that its effects have never been assessed. We study the effect of out-of-hospital ethanol in patients treated during a methanol outbreak in the Czech Republic between 2012 and 2014. Methods This was an observational case-series study of 100 hospitalized patients with confirmed methanol poisoning. Out-of-hospital ethanol as a "first aid antidote" was administered by paramedic or medical staff before the confirmation of diagnosis to 30 patients; 70 patients did not receive out-of-hospital ethanol from the staff (12 patients self-administered ethanol shortly before presentation). Results The state of consciousness at first contact with paramedic or medical staff, delay to admission, and serum methanol concentration were similar among groups. The median serum ethanol level on admission in the patients with out-of-hospital administration by paramedic or medical staff was 84.3 mg/dL (interquartile range 32.7 to 129.5 mg/dL). No patients with positive serum ethanol level on admission died compared with 21 with negative serum ethanol level (0% versus 36.2%). Patients receiving out-of-hospital ethanol survived without visual and central nervous system sequelae more often than those not receiving it (90.5% versus 19.0%). A positive association was present between out-of-hospital ethanol administration by paramedic or medical staff, serum ethanol concentration on admission, and both total survival and survival without sequelae of poisoning. Conclusion We found a positive association between out-of-hospital ethanol administration and improved clinical outcome. During mass methanol outbreaks, conscious adults with suspected poisoning should be considered for administration of out-of-hospital ethanol to reduce morbidity and mortality.

Background Calprotectin may be a sensitive biomarker of rheumatoid arthritis (RA) disease activity. Objectives In the current study, we investigated whether calprotectin is a better biomarker than CRP for predicting clinical activity and ultrasound parameters in patients with RA. Methods A total of 160 patients with RA underwent clinical (swollen joint count—SJC, tender joint count—TJC, Disease Activity Score—DAS28, Clinical Disease Activity Index—CDAI, and simplified Disease Activity Index—SDAI) and ultrasound (German US7) examination. Clinical and laboratory measures were correlated with ultrasound findings using Spearman´s correlation coefficient. Differences in serum calprotectin levels in patients with variable disease activity according to the DAS28-ESR and CDAI scores were assessed using ANOVA. Multivariate regression analysis was used to determine the predictive values of calprotectin, CRP and SJC for CDAI and PD US synovitis scores. Results Serum calprotectin was significantly associated with DAS28-ESR (r = 0.321, p

Objective Clinical remission in some patients with rheumatoid arthritis (RA) may be associated with ongoing synovial inflammation that is not always detectable on clinical examination or reflected by laboratory tests but can be visualized by musculoskeletal ultrasound. The goal of our study was to determine the levels of serum calprotectin, a major leukocyte protein, in patients with RA in clinical remission and to investigate the ability of serum calprotectin levels to distinguish patients in ultrasound-defined remission from those with residual ultrasound subclinical inflammation. Methods Seventy RA patients in clinical remission underwent clinical and ultrasound examination. Ultrasound examination was performed according to the German US7 score. Ultrasound remission was defined as grey scale (GS) range 0–1 and power Doppler (PD) range 0. The levels of serum calprotectin and C-reactive protein (CRP) were determined. The discriminatory capacity of calprotectin and CRP in detecting residual ultrasound inflammation was assessed using ROC curves. Results The total number of patients fulfilling the DAS28-ESR, DAS28-CRP, SDAI and CDAI remission criteria was 58, 67, 32 and 31, respectively. Residual synovial inflammation was found in 58–67% of the patients who fulfilled at least one set of clinical remission criteria. Calprotectin levels were significantly higher in patients with residual synovial inflammation than in those with ultrasound-defined remission (mean 2.5±1.3 vs. 1.7±0.8 μg/mL, p

Objectives To estimate the time to reach reliable results in a larger group of rheumatologists at onset of their musculoskeletal ultrasound (MSUS) training in modified 7-joints scoring system (US7). Methods US7 has been shown a useful tool to estimate activity of rheumatoid arthritis (RA) in daily clinical practice. The system has been extensively described including an atlas. Targets of the US7 include synovitis (in B-mode and Power Doppler (BM+PD)), tenosynovitis (BM+PD) and erosive changes of 7 joints (wrist, MCP II+III, PIP II+III, MTP II+V) on the dominant site. We used a modification of the original US7 published, assessing both palmar and dorsal view of MCP and PIP joints. 9 rheumatologists with basic/intermed. level of MSUS underwent a training in general MSUS+US7. At month 1, reliability testing in scoring of static pictures was performed. At months 3 and 12, two reliability-testing sessions were organized. 4 patients with various stages of activity and disease progression of RA were repeatedly scanned, in 2 rounds per session. Sonographers were blind to all patients9 data. 2 US machines were used for each session and the setting was fixed before the start. Smoking or drinking alcohol was not allowed. Each patient was investigated by the same US machine in the same daytime in each round of a testing session. Inter-/intra-observer agreement was calculated for each modality of US7 (synovitis score in BM+PD, tenosynovitis score in BM+PD, erosion score) by using non-weighted Cohen kappa (intra-observer agreement) and Light9s kappa (inter-observer agreement). Results At month 1, mean intra- and inter-observer agreement in scoring of static images was reached; κ=0,61 and 0,60 respectively (good). At month 3, mean inter-observer reliability was low (κ Conclusions Ultrasound is an operator dependent technique. The level of experience necessary to obtain reliable results in modified US7 (as an example of easy and well determined US method) was achieved after 12 months of low intensity training with direct supervision of a specialist on demand. Low intensity training is in the authors9 experience the most frequently used method among beginners in MSUS. Scoring of static images was reliable already after 1 month. Although the probe positions in US7 are well defined, the inter-/intra-observer reliability in scoring of self-obtained images was none in month 3 and the difference leading to good results in month 12 must have been achieved in this later period of training. The difference between higher intra-observer and none inter-observer agreement in month 3 suggests that direct supervision of a specialist in MSUS in this stage of education would lead to quicker progress and better results in achieving reliability among the group members. Acknowledgement Supported by the project for conceptual development of research organization 023728 and by project no. NT12437. Disclosure of Interest None declared

Background Adipocytokines are soluble mediators secreted by adipose tissue and immune cells with potent immune regulatory functions. Some adipocytokines have been previously associated with disease activity and radiographic progression in patients with rheumatoid arthritis (RA) 1 . Objectives To investigate associations between adipocytokines, clinical and traditional laboratory markers as well as with ultrasound synovitis in patients with RA. Methods A total of 82 patients with RA (62 females, median disease duration 4.2 years) were enrolled into this study. All patients underwent clinical examination (swollen joint count - SJC, tender joint count – TJC, Disease activity score - DAS28-ESR and DAS28-CRP, Clinical disease activity index - CDAI, Simplified disease activity index - SDAI). Moreover, ultrasound examination of 7 selected joints mostly affected in RA (wrist, second and third metacarpophalangeal and proximal interphalangeal, and second and fifth metatarsophalangeal joints) was performed to measure synovial hypertrophy in Grey Scale (GS) and pathological neovascularization in Power Doppler (PD) using semi-quantitative grading 0–3 3 . Blood samples were taken at the same day as clinical and ultrasound assessments. Serum concentrations of adiponectin, resistin, visfatin, leptin and CRP were measured. Clinical and laboratory measures were correlated with ultrasound findings using Spearman9s correlation coefficient. Results Serum visfatin and resistin levels were associated with the disease activity (Figure 1) and correlated significantly with DAS28-ESR (r=0.473, p Conclusions Our study supports circulating visfatin and resistin as promising serum pro-inflammatory biomarkers reflecting clinical, laboratory as well as ultrasound parameters of synovial inflammation in RA. References Senolt L, Krystufkova O, Hulejova H, Kuklova M, Filkova M, Cerezo LA, Belacek J, Haluzik M, Forejtova S, Gay S, Pavelka K, Vencovsky J: The level of serum visfatin (PBEF) is associated with total number of B cells in patients with rheumatoid arthritis and decreases following B cell depletion therapy. Cytokine 2011, 55: 116–121 Acknowledgement This work was supported by the project (Ministry of Health, Czech Republic) for consensual development of research organization 023728, IGA grant No. NT12437 and GAUK grant No. 1010213. Disclosure of Interest None declared

Background Calprotectin (S100A8/9, MRP8/14) is a promising circulating biomarker reflecting disease activity in patients with rheumatoid arthritis (RA). In two small previous studies in RA patients 1,2 , serum calprotectin correlated with ultrasound synovial inflammation. Objectives To investigate associations between serum calprotectin, clinical and ultrasound-determined disease activity in a larger cohort of RA patients in a cross-sectional study. Methods A total of 167 patients with RA (134 females) were enrolled in this study. All patients underwent clinical assessment (SJC, TJC, DAS28-ESR) and ultrasound examination according to the US-7 score 3 to assess synovitis by gray-scale (GS) and power Doppler (PD) using semiquantitative grading (0-3). Serum calprotecin was measured by ELISA. Associations between serum calprotectin, C-reactive protein (CRP) and clinical as well as ultrasound findings were explored using Spearman9s correlation coefficient. A multiple regression analysis was used to determine the predictive value of calprotectin (mg/l), CRP (mg/l) and DAS28 for GS and PD synovitis score. Results Serum calprotectin significantly correlated with DAS28 (r=0.357, p Using a multivariate linear regression model with calprotectin, CRP and DAS28-FW as explanatory variables, calprotectin and DAS28, but not CRP, were significant predictors for GS (β=0.371, p Conclusions This study confirms in a large cohort of RA patients that serum levels of calprotectin are significantly associated with clinical, laboratory and ultrasound assessments of disease activity. Calprotectin is more closely associated with local joint inflammation than CRP and thus may represent a more specific circulating biomarker for monitoring synovial inflammation in RA patients. References Hammer HB, Fagerhol MK, Wien TN, Kvien TK. The soluble biomarker calprotectin (an S100 protein) is associated to ultrasonographic synovitis scores and is sensitive to change in patients with rheumatoid arthritis treated with adalimumab. Arthritis Res Ther. 2011;13(5):R178. Hurnakova J, Hanova P, Hulejova H, et al. Serum calprotectin (S100A8/9) correlates with clinical and ultrasound outcomes in patients with early rheumatoid arthritis. In Ann Rheum Dis. 2014; Suppl (2):658–658. Backhaus M, Ohrndorf S, Kellner H, Strunk J, Backhaus TM, Hartung W, et al. Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project. Arthritis Rheum. 2009 Sep 15; 61(9):1194-1201. Acknowledgements This work was supported by the project (Ministry of Health, Czech Republic) for consensual development of research organization 023728, IGA grant No. NT12437 and GAUK grant No. 1010213. Disclosure of Interest None declared