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Background and importance Patient adherence is a key determinant of treatment success in rheumatological immunomediated diseases. Available data about adherence to biological treatments and factors associated with non-adherence are limited in Spain. Moreover, no studies have compared adherence between subcutaneous and oral drugs. Aim and objectives To evaluate non-adherence to prescribed subcutaneous biologicals and oral drugs in patients with rheumatological immunomediated diseases and to assess possible predictor factors associated with treatment non-adherence. Material and methods A retrospective observational study was conducted in all patients receiving oral and subcutaneous treatment for rheumatological immune mediated diseases from 2017 to 2019 in the outpatient pharmaceutical care area of a tertiary university hospital. Non-adherence was evaluated by reviewing all scheduled drug dispensing visits in the computerised application. We considered non-adherent every time that a patient missed at least one drug administration. Data collected were demographic, total patients and patient treatments, total dispensing visits and route of administration for the drug dispensed in every visit. We classified patients as adherent and non-adherent considering the number of dispensing visits. In the non-adherent group, we recorded the number of dispensing visits, reasons for non-adherence, number of missed administrations per patient, and drug and predictor factors for non-adherence. Results 783 patients were included, aged 52.4 (13.7) years, 427 (54.5%) were women, 164 (20.9%) were smokers and 697 (89%) were Caucasian. 79 (10.1%) of 783 patients received more than one treatment. There were 869 patient treatments: 294 adalimumab (33.8%), 236 etanercept (27.2%), 78 golimumab (8.9%), 47 apremilast (5.4%), 39 certolizumab (4.5%), 34 secukinumab (3.9%) and 30 tocilizumab (3.5%). There were 9197 dispensing visits. Route of administration was 6406 subcutaneous (93.2%) and 374 oral (6.8%). Non-adherence analysis 2417 (26.3%) dispensing visits, reasons for non-adherence/dispensing visits: 92 unjustified (97.5%), 33 infection (1.4%), 18 surgery (0.7%), 3 pregnancy (0.1%), 6 other (0.3%). Number of missed administrations/patient treatments: 675 patients missed at least one administration (77.7%), mean 2.5 (±12.9) missed administrations. Number of missed administrations/drug: 9.9 baricitinib (±20.8), 15.8 tofacitinib (±31.2) and 25.4 apremilast (±53.2). Predictor factors for non-adherence: ethnicity (p=0.015), treatment with golimumab (p=0.006) and tocilizumab (p=0.036) and age (p=0.072). Conclusion and relevance Non-adherence to the prescribed drug occurred in 77.7% of patients with rheumatological immune mediated diseases. Demographic factors such as ethnicity as well as golimumab and tocilizumab treatment, despite their different frequency of administration, were predictors for non-adherence. Route of administration did not influence non-adherence. References and/or acknowledgements Conflict of interest No conflict of interest

RESUMEN El dolor de los pacientes con artrosis es un problema sociosanitario de primera magnitud y es el responsable de la importante limitación funcional y pérdida de calidad de vida en esta enfermedad. A pesar de haberse producido avances importantes en el conocimiento de los mecanismos fisiopatológicos del dolor, son muchos los interrogantes del dolor artrósico que todavía quedan por contestar. Uno de los aspectos menos estudiados del dolor crónico en la artrosis es el fenómeno de sensibilización central. La resonancia magnética nuclear funcional se ha mostrado como una técnica útil para el abordaje de este fenómeno. Diferentes estudios realizados a pacientes afectos de artrosis con distintos grados de sensibilización ponen de manifiesto que la incidencia de este fenómeno es elevada, que los pacientes sensibilizados y no sensibilizados muestran patrones diferentes en cuanto a la magnitud de la repuesta cerebral al dolor y que los patrones de conectividad difieren de una enfermedad a otra. Finalmente, en los pacientes candidatos a artroplastia de rodilla es importante evaluar el grado de sensibilización previo a la cirugía, puesto que son los pacientes con mayor grado de sensibilización los que presentarán evoluciones más tórpidas y mayores niveles de dolor posquirúrgico.

BackgroundOsteoarthritis (OA) is the most common degenerative joint disease, but its pathogenesis is still poorly understood. OA is characterized by articular cartilage loss due to an imbalance in anabolic and catabolic gene expression of the chondrocyte, together with aberrant expression of transcription factors and inflammatory mediators.ObjectivesWe aim to evaluate de genes implicated in the chondrocyte failure regarding the four issues assessed to evaluate cartilage integrity using Mankin score (MkS): surface integrity, cellularity, cell cloning and staining.MethodsKnee OA (KOA) patients aged 60-75 undergoing a total knee replacement, were recruited. At surgery, tibial plateau and femur condyles were deposited in DMEM medium and sent to the laboratory within 4 hours of the extraction. Punches from areas located at low, medium and high load (1) were excised from each sample (approximately 11 areas per patient). For RNA analysis, punches were kept in RNAlater at -20ºC until analyzed. RNA extraction, cDNA synthesis and cDNA amplification of the selected genes were performed previous to gene expression quantifycation by OpenArray Assay with custom plates. ΔCt was analyzed by ExpressionSuite V1.3 using 6 housekeeping genes. For histology study, punchs were fixated in formalin and embedded in parafin. Sections of 4 µm were stained with hematoxilin eosin and Safranin O-Fast Green. Slices were scored using the modified MkS (2) by 3 independent observers. R (v3.3.2) analysis was used to explored the results with principal components analysis (PCA) and linear regression (LR).ResultsSurgical samples were obtained from a total of 27 patients and 219 different areas were analyzed. ΔCt of the 51 genes analyzed by PCA showed that 9 components were enough to represent >80% of variance of the model. The genes associated with each component are summarized in Table 1. LR shows that second and first component were significantly associated to all or most of the fields included in the MkS, respectively. In contrast, component 4, 5 and 9 were not associated with any field. Lower expression of genes represented in component 1 (mainly related with extracellular matrix content) are associated with higher MkS values. On the other hand, component 2 summarizes data of genes mainly related with factors regulating cell metabolism. In this case, higher expression of TNFαIP6, NGF, IGFBP1, CRLF1, TNFα, and lower expression of ACAN, COL11A2, COL2A1, COL10A1, SOX9 and TGFβ1, among others, are associated with increased MkS values.Table 1.Genes that most contribute (by order) to component 1 & 2 (due to space limitation). Data of LR analysis for each component and MkS item. Significant association marked in bold.ComponentGenesMankin score item (β coefficient; p-value)Surface integrityCellularityCell cloningStaining1SERPINE2, COL8A2, OGN, COL5A, TIMP3, BMP6, CRLF1, TIMP2, WISP1, ST3GAL1, SERPINE1, TNFSF10, ASPN, NGF, CD44, TNFRSF11B, TGFA, ADAMTS5, COL15A1, LUM, TNFAIP6, PTGS2, BMP2-0.092; 0.006-0.025; 0.047-0.028; 0.078-0.043; 0.0152ACAN, GPC5, CFH, FGFR3, COL11A2, TGFB1, GREM1, TNFAIP6, NGF, SOX9, IGFBP1, MMP3, FGF2, CRLF1, TNFa, COL2A1, COL10A10.261; 2.54 10-70.050; 0.0100.066; 0.0050.072; 0.0073-0.174; 0.003-0.029; 0.191-0.076; 0.0060.004; 0.89840.068; 0.410-0.019; 0.543-0.055; 0.161-0.021; 0.6275-0.082; 0.3640.051; 0.1460.020; 0.644-0.052; 0.28360.050; 0.6050.023; 0.5480.111; 0.0170.062; 0.2287-0.120; 0.266-0.090; 0.0320.010; 0.839-0.113; 0.0528-0.134; 0.2740.006; 0.892-0.198; 0.001-0.131; 0.0479-0.220; 0.096-0.041; 0.425-0.101; 0.1100.020; 0.780ConclusionThere is a correlation between the expression level of the studied genes and the MkS values, although the role played by each gene might be different according to the MkS issue evaluated. These results could be useful to describe biomarkers that identify burden of disease in KOA.References[1]Adouni M, Shirazi-Adl A. J Orthop Res. 2014 Jan;32(1):69-78.[2]Moody HR, Heard BJ, et al. J Anat. 2012 Jul;221(1):47-54.AcknowledgementsWe acknowledge Berend Bremmen for his help in Mankin Score bibliography revision and image scoring.Disclosure of InterestsNone declared

BackgroundJoint involvement in SLE is the most frequent manifestation, despite this, its impact on health-related quality of life (HRQoL) has not been well stablished in these patients1. Pain, fatigue and functional disability contribute to HRQoL related to SLE2.ObjectivesWe aim to study the relation between joint and tendon involvement confirmed by contrasted MRI and these patient related outcomes (PRO).MethodsConsecutive SLE patients fulfilling SLICC criteria both symptomatic and asymptomatic for joint involvement were recruited. Gadolinium-enhanced MRI of non-dominant hand/wrist was performed in all subjects for joint and tendon evaluation. Different PRO: numeric scale (NE) of pain (0-10) and fatigue (0-3), Health Assessment Questionnaire (HAQ) and Fatigue Severity Scale (FSS-9) were collected and statistically analysed along with each MRI abnormality.Results83 subjects were recruited. Patients with synovitis, tenosynovitis, peritendonitis and bone marrow edema reported higher values in pain NE (6.03±2.57 vs 4.26±2.49, p 0.005; 6.56±1.95 vs 4.76±2.75, p 0.017; 8.80±1.30 vs 4.95±2.55, p 0.001; 6.47±2.62 vs 4.83±2.58, p 0.026); patients with synovitis reported higher values in fatigue EN (2.32±0.82 vs 1.91±0.84, p 0.035) and patients with tenosynovitis showed worse FSS-9 (61.50±1.73 vs 45.70±16.80, p 0.015) versus patients who did not show these abnormalities by MRI. Patients with synovitis and peritendonitis had a worse HAQ (1.14±0.69 vs 0.75±0.65, p 0.031; 1.69±0.07 vs 0.90±0.69, p 0.018).ConclusionSLE patients with joint and/or tendon involvement confirmed by contrast enhanced MRI have a worse HRQoL measured by pain, fatigue and functional disability.References[1]Ceccarelli F et al. Joint involvement in systemic lupus erythematosus: From pathogenesis to clinical assessment. Semin Arthritis Rheum. 2017;47:53-64[2]Piga M et al. Musculoskeletal manifestations as determinants of quality of life impairment in patients with systemic lupus erythematosus. Lupus. 2018 Feb;27(2):190-198AcknowledgementsGSK and societat Catalana de Reumatologia granted this work and we acknowledge them for their collaborationDisclosure of InterestsPATRICIA CORZO GARCIA Grant/research support from: GSK, Irene Carrión Barberà: None declared, Ivan Garcia-Duitama: None declared, Anna Agustí Claramunt: None declared, Salvatore Marsico: None declared, Jordi Monfort Grant/research support from: GSK, Tarek Carlos Salman Monte Grant/research support from: GSK

BackgroundAdvanced glycation endproducts (AGEs) are the result of non-enzymatic glycation of proteins, lipids or nucleic acids. In circumstances characterized by increased oxidative and carbonyl stress, such as chronic inflammation, AGEs can be formed more rapidly1, generating reactive oxygen species and activating inflammatory signaling cascades through their chief signaling receptor (commonly abbreviated as RAGE)2. This positive feedback of inflammation can play a role in the etiology of immune-mediated inflammatory diseases, more specifically in rheumatoid arthritis (RA), ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE).ObjectivesTo investigate whether the accumulated concentrations of AGEs in patients with SLE, RA or AS are significantly higher than in healthy patients.MethodsOne hundred thirteen consecutive patients fulfilling ACR/EULAR criteria for RA, 60 patients fulfilling ASAS/OMERACT MRI criteria for AS, 97 patients fulfilling ACR/SLICC criteria for SLE and 527 sex-matched healthy controls were recruited.in cross-sectional study. Exclusion criteria were pregnancy, diabetes mellitus, corticosteroid treatment ≥ 20mg/day and malignant neoplasm. Accumulated AGEs were non-invasively measured by skin autofluorescence (Age Reader Mu Connect, Diagnostics Technologies B.V) and demographic and clinical data were collected. AGEs comparisons between patients and controls were performed by multiple linear regression analysis adjusted by confunders, previously described in literature (age, smoking habit and cardiovascular risk-factors). Age was centered at 55 years.ResultsTable 1 shows some descriptive characteristics of our cohorts. AGEs adjusted mean was significantly increased in SLE patients compared with matched controls (95% CI [2.27, 2.76] vs [1.66, 1.89], pTable 1.Descriptive characteristics of the cohortsSLERAASPatientsControlsPatientsControlsPatientsControlsN=96N=189N=113N=240N=60N=99AGEs2.57 (0.65)1.98 (0.45)2.59 (0.58)2.00 (0.42)2.26 (0.46)1.90 (0.46)Age51.0 [43.0;61.0]56.0 [52.0;62.0]58.0 [54.0;65.0]61.0 [56.0;66.0]47.5 [41.0;55.0]53.0 [49.0;57.0]SmokerNo76 (79.2%)133 (70.4%)86 (76.1%)196 (81.7%)42 (70.0%)58 (58.6%)Yes20 (20.8%)56 (29.6%)27 (23.9%)44 (18.3%)18 (30.0%)41 (41.4%)Packs/year0.00 [0.00;10.8]2.50 [0.00;18.8]2.50 [0.00;18.0]0.00 [0.00;12.6]0.00 [0.00;7.88]14.9 [2.00;30.6]HypertensionNo74 (77.1%)116 (61.4%)77 (68.1%)146 (60.8%)53 (88.3%)75 (75.8%)Yes22 (22.9%)73 (38.6%)36 (31.9%)94 (39.2%)7 (11.7%)24 (24.2%)ObesityNo80 (83.3%)128 (67.7%)86 (76.1%)163 (67.9%)51 (85.0%)81 (81.8%)Yes16 (16.7%)61 (32.3%)27 (23.9%)77 (32.1%)9 (15.0%)18 (18.2%)DyslipidemiaNo85 (88.5%)104 (55.0%)79 (69.9%)108 (45.0%)51 (85.0%)55 (55.6%)Yes11 (11.5%)85 (45.0%)34 (30.1%)132 (55.0%)9 (15.0%)44 (44.4%)Continuous normal: mean (SD); Continuous non-normal: median [IQR]; Categorical: absolute (relative frequency)ConclusionAccumulated AGEs in all 3 pathologies are significantly higher than in the healthy controls. The different means of AGEs in each of the diseases, being higher in SLE and lower in AS, may suggest a different participation of AGEs in the immune-mediated mechanisms of each pathology.References[1]K. de Leeuw, R. Graaff et al., Accumulation of advanced glycation endproducts in patients with systemic lupus erythematosus, Rheumatology, Volume 46, Issue 10, October 2007, Pg 1551–1556.[2]Yan S., Ramasamy R. & Schmidt A. Mechanisms of Disease: advanced glycation end-products and their receptor in inflammation and diabetes complications. Nat Rev Endocrinol4, 285–293 (2008).Disclosure of InterestsNone declared

BackgroundChronic pain related to knee osteoarthritis (KOA) is a common health problem and functional magnetic resonance imaging (fMRI) is a useful technique which can determine different brain activation (1).ObjectivesThe main purpose of our study was to observe whether there is different risk to central sensitization and different brain activation in patients with KOA according to the treatment followed (conservative (CNV) Vs. total knee replacement (TKR))MethodsPatients diagnosed of primary KOA following a CNV treatment or undergoing TKR were recruited. The two groups were matched by age, sex and BMI. Clinical central sensitization was considered if patients presented spread tenderness, evaluated with an algometer, in more than 1 site of the extended peripatellar map (2) (notice that pain at points 3, 7 and 8 were not counted) fMRI testing involved pressure painful stimulation to the articular interline and to a commonly sensitized site (tibial surface, point 10).To evaluate the associations between central sensitization and the risk to undergo a TKR; logistic regression was performed to estimate OR and 95% confidence intervals (95%CI). Models were adjusted by sex, age and BMI (R (R v.3.5.2).Whole-brain activation maps were compared between groups using Statistical Parametric Mapping software (SPM12 http://www.fil.ion.ucl.ac.uk/spm).ResultsWomen have a significant higher risk to present central sensitization than men (OD 12,11 (95% CI 4,32-33,95) p-value:2,09*106), but no differences were observed between CNV and TKR group (OR TKR 0,69 (95% CI 0,24-1,98)) (Table 1). The differences observed in brain activation between the treatment groups in the interline fMRI test (point 7) did not correspond to any specific brain area. However, TKR group showed a higher activation that implicated the region of the amygdala and anterior hippocampus during the tibial fMRI test (point 10).Table 1.Central sensitization Odds Ratio (OR) with 95% Confidence Interval (95%CI)O.R. (95% CI)p-valueTreatment0.69 (0.24- 1.98)0,494Sex12.11 (4.32- 33.95)2,09*10-6Age0.72 (0.26- 1.97)0,525BMI1.88 (0.69- 5.17)0,219ConclusionPresenting central sensitization is not a risk for KOA patients to undergo a TKR, but the mechanism underlaying sensitization in both treatment groups might be different, with amygdala playing an important role in TKR patients. The amygdala is an important element of the brain systems that both express emotions and modulate pain. The activation of the amygdala in response to pressure stimulation on a sensitized knee site is interpreted as a failure of the descending pain inhibitory systems, and the occurrence of a major emotional response during the painful experience in patients that ultimately received TKR.References[1]Pujol, J. et al., 2017. Brain imaging of pain sensitization in patients with knee osteoarthritis. Pain, 158(9), pp.1831–1838.[2]Arendt-Nielsen L, Nie H, Laursen MB, Laursen BS, Madeleine P, Simonsen OH, Graven-Nielsen T. Sensitization in patients with painful knee osteoarthritis. Pain 2010;149:573-8Extended peripatellar map including the points tested for tenderness, and brain areas differently activated between both treatments groups during painful stimulation to point 7 (interline) and point 10 (tibial surface, a commonly sensitized site).Disclosure of InterestsNone declared

BackgroundIt has been postulated that AGES could have a relevant role as inducers in the chronic inflammatory pathway present in various diseases1; among them, in immune-mediated diseases such as SLE, as well as that its concentration could be related to some parameters of the disease such as activity 2 or accumulated damage 3, showing studies discrepant results to date.ObjectivesTo describe correlations between the concentrations of AGEs measured by cutaneous autofluorescence and various parameters related to the disease in a population of SLE patients.MethodsAGE concentrations were measured by skin autofluorescence (Age Reader Mu Connect from Diagnoptics Technologies BV) in 66 SLE Caucasian patients and correlations with demographic and clinical data were analyzed, after adjusting for age, smoking and corticosteroids as possible confounding factors, according to previous data. Previous validation studies have shown that skin autofluorescence is strongly related to AGE levels in skin biopsies4. The indices were analyzed both as quantitative and categorized variables according to previously established categories or to medians/tertiles/quartiles depending on the distribution of the variable in our population.ResultsTable 1 shows some descriptive characteristics of our cohort. There were clinically and statistically significant differences in the values of AGEs according to the patient’s SLEDAI and SLICC. Specifically, it was observed that AGEs’ values in the population with severe activity according to SLEDAI was 0.61 (95% CI 0.85-2.046; p=0.045) points > than in those in remission (p=0.045); as well as AGEs‘ values in patients with SLICC ≥1 was 1.23 (95% CI 0.49-1.98; p=0.030) points > than in the group without cumulative damage. In all the models, the values of AGEs increased significantly with age, smoking and current treatment with corticosteroids, except for the model including the SLICC variable. Interactions in said model were explored, and it was observed that the concentration of AGES depended on the interaction between the value of SLICC and the intake of corticosteroids, so that differences were only observed between SLICC groups in those who took corticosteroids.Table 1.Descriptive characteristics of the cohort. c: categorized.AverageSD%Age5415BMI25.364.68SmokerNo68.2Yes31.8AGEs2.60.7Disease duration (years)1611DAS282.221.16cDAS28remission71.2low9.1moderate15.2high4.5SLEDAI54cSLEDAIremission21.2low16.7moderate51.5high10.6SLICC11cSLICC00.0148.5>130.3321.2FACIT Fatigue Scale1810Patient global assessment (PGA)3.02.4cPGA0-131.82-328.8>339.4Physician global assessment1.71.3cPhysician global assessment0-147.0>153.0Visual Analogue Scale (VAS)3.13.1cVAS034.81-430.3>434.8Health Assessment Questionnaire (HAQ)0.5270.551cHAQ033.30-0.7536.4>0.7530.3CorticoidsYes27.3No72.7ConclusionA correlation with elevated values of AGEs was observed in those SLE patients with higher scores in the indexes of activity (SLEDAI) and damage accrual (SLICC). The fact that the differences in SLICC are only observed in those patients treated with corticosteroids suggests that, maybe, only the accumulated damage related to taking corticosteroids could be mediated by AGEs.References[1]Medzhitov R. Origin and physiological roles of inflammation. Nature 2008;454:428–435.[2]Vytášek R, Šedová L, Vilím V. Increased concentration of two different advanced glycation end-products detected by enzyme immunoassays with new monoclonal antibodies in sera of patients with rheumatoid arthritis. BMC Musculoskelet Disord 2010;11:83.[3]leeuw K de, Graaff R, Vries R de, Dullaart RP, Smit AJ, Kallenberg CG, Bijl M. Accumulation of advanced glycation endproducts in patients with systemic lupus erythematosus. Rheumatology 2007;46:1551–1556.[4]Meerwaldt R, Links T, Graaff R, Thorpe SR, Baynes JW, Hartog J, Gans R, Smit A. Simple noninvasive measurement of skin autofluorescence. Ann N Y Acad Sci 2005;1043:290-298.Disclosure of InterestsNone declared

BackgroundJoint involvement in SLE is the most frequent manifestation and often it is the first clinical symptom. Despite this, it is not well characterised and demographic, serological and clinicotherapeutic correlations have not been well stablished1.ObjectivesWe aim to determinate if there is a demographic, clinic or serological profile related to inflammatory joint involvement of hand and/or wrist (sinovitis, bone marrow edema, erosions, tenosynovitis or peritendonitis) confirmed by contrasted MRI in SLE patients.MethodsConsecutive SLE patients fulfilling SLICC criteria both symptomatic and asymptomatic for joint involvement were recruited. Contrasted MRI of non-dominant hand/wrist was performed for joint and tendon evaluation. Sociodemographic, clinicotherapeutic and serological data were collected and statistically analysed along with each MRI abnormality.Results83 subjects were recruited. Erosions and synovitis were more frequent at advanced age (55±12.61 vs 45.06±12.18 years, p 0.001 and 52.78±12.99 vs 44.95±12.49 years, p 0.011). Synovitis is less frequent in patients with renal involvement (6.7% vs 24.3%, p 0.031). No other SLE organ-specific involvement showed statistical correlation. Neither SLE related autoantibodies (ANA, DNAds, Sm, RNP, Ro, La, antiphospholipid), complement fractions, ESR nor CRP correlated with MRI lesions, except for erosions which showed lower DNAds titers (15.94±49.56 vs. 27.23±62.41, p 0.008). Patients with bone marrow edema received more methotrexate (25% vs 6.3%, p 0.033), and those with erosions and peritendonitis received less mycophenolate (5.6% vs 22.9%, p 0.034; y 0% vs 12.8%, p 0.026). Peritendonitis was the only alteration related to higher SLEDAI (7±2.45 vs 3.64±3.34, p 0.018). None of the musculoskeletal abnormalities correlated with accrual damage.ConclusionSLE patients with joint and/or tendon abnormalities confirmed by MRI are usually older and have less renal involvement, receiving more methotrexate and less mycophenolate than those who do not show musculoskeletal involvement.References[1]Ceccarelli F et al. Joint involvement in systemic lupus erythematosus: From pathogenesis to clinical assessment. Semin Arthritis Rheum. 2017;47:53-64AcknowledgementsGSK and Societat Catalana de Reumatologia granted this work, we want to acknowledge them for their collaborationDisclosure of InterestsPATRICIA CORZO GARCIA Grant/research support from: GSK, Anna Agustí Claramunt: None declared, Ivan Garcia-Duitama: None declared, Irene Carrión Barberà: None declared, Salvatore Marsico: None declared, Jordi Monfort Grant/research support from: GSK, Tarek Carlos Salman Monte Grant/research support from: GSK

BackgroundJoint involvement in SLE is the most frequent manifestation and shows a wide heterogeneity1. It has not a valid classification and it is often underestimated. Subclinical inflammatory musculoskeletal involvement is not well known2.ObjectivesWe aim to describe the prevalence of joint and tendon involvement in hand and wrist of SLE patients, either with clinical arthritis, arthralgia or asymptomatic and compare it with healthy subjects using contrasted MRI.MethodsSLE patients fulfilling SLICC criteria were recruited and classified as follows: group (G) 1: hand/wrist arthritis, G2: hand/wrist arthralgia, G3: no hand/wrist symptoms. Jaccoud arthropathy, CCPa and RF positivity, hand OA or surgery were excluded. Healthy subjects (HS) were recruited as controls: G4. Contrasted MRI of non-dominant hand/wrist was performed. Images were evaluated following RAMRIS criteria extended to PIP, Tenosynovitis score for RA and peritendonitis from PsAMRIS. Groups were statistically compared.Results107 subjects were recruited (G1: 31, G2:31, G3:21, G4:24). Any lesion: SLE patients 74.7%, HS 41.67%; p 0.002. Synovitis: G1: 64.52%, G2: 51.61%, G3: 45%, G4: 20.83%; p 0.013. Erosions: G1: 29.03%; G2: 54.84%, G3: 47.62%; G4: 25%; p 0.066. Bone marrow edema: G1: 29.03%, G2: 22.58%, G3: 19.05%, G4: 0.0%; p 0.046. Tenosynovitis: G1: 38.71%; G2: 25.81%, G3: 14.29%, G4: 0.0%; p 0.005. Peritendonitis: G1: 12.90%; G2: 3.23%, G3: 0.0%, G: 0.0%; p 0.07.ConclusionSLE patients have a high prevalence of inflammatory musculoskeletal alterations by contrasted MRI, even if asymptomatic. Not only tenosynovitis but peritendonitis is also present.References[1]Ceccarelli F et al. Joint involvement in systemic lupus erythematosus: From pathogenesis to clinical assessment. Semin Arthritis Rheum. 2017;47:53-64[2]Di Matteo A et al. Imaging of Joint and Soft Tissue Involvement in Systemic Lupus Erythematosus. Curr Rheumatol Rep. 2021;23:73AcknowledgementsThis work has been granted by GSK and Societat Catalana de Reumatologia and we want to acknowledge them for their collaborationDisclosure of InterestsPATRICIA CORZO GARCIA Grant/research support from: GSK, Ivan Garcia-Duitama: None declared, Anna Agustí Claramunt: None declared, Irene Carrión Barberà: None declared, Salvatore Marsico: None declared, Jordi Monfort Grant/research support from: GSK, Tarek Carlos Salman Monte Grant/research support from: GSK

Polyarteritis nodosa is a primary systemic necrotizing vasculitis whose evolution follows, in many cases, a chronic remitting-recurrent course with refractoriness to conventional immunosuppressants. We report here the clinical case of a 75-year-old patient with serologies suggestive of past hepatitis B virus infection who presented a flare of polyarteritis nodosa with great secondary functional impairment. She had not responded to several previous immunosuppressants and required high doses of glucocorticoids to control the flare. After the initiation of biological therapy with tocilizumab, the patient experienced a rapid and marked clinical and analytical improvement, going into clinical remission and being able to remarkably lower the corticosteroid dose and stop the rest of the immunosuppressants. There was no evidence of hepatitis B virus reactivation or changes in the titers of any of the parameters related to the aforementioned infection. This clinical case represents the first case reported in the literature about the successful and safe treatment of polyarteritis nodosa with tocilizumab in a patient with serologies suggestive of past hepatitis B virus infection.

[ES] La amplitud y diversidad de situaciones que se pueden plantear en estos trabajos de peritación, hacen que cualquier norma para regular su contenido omita casos que deben ser resueltos por el perito según su "leal saber y entender". Por la transcendencia y responsabilidad que se puede derivar de ellos, vamos a analizar algunos aspectos vinculados a su repercusión desde el punto de vista legal y profesional., [EN] The breadth and diversity of different situations that may arise in expert's surveys make any rules to regulate its content skip cases that must be solved by the surveyor/expert as its "best knowledge." On the importance and responsibility that can be derived from them, we will analyse some of the aspects related to its implications, in terms of legal and professional point of view.

Resume La maladie d'Alzheimer est une demence qui se manifeste a la fois par une alteration des fonctions cognitives et par des troubles psychocomportementaux. Une etude sur les reactions de la famille a la demence d'un parent doit envisager plusieurs points de vue : a) La charge familiale. Le poids de la maladie d'Alzheimer sur la famille est tres important. La prise en charge a des effets physiques et psychiques sur l'aidant qui peut presenter un etat anxieux, une depression, un ethylisme et qui a un risque de mortalite eleve ; b) Les reactions aux symptomes de la maladie. La famille doit supporter les symptomes de la maladie d'Alzheimer : les troubles cognitifs et surtout les troubles psychocomportementaux. Les reactions de la famille peuvent etre le deni, l'hyperprotection, le maternage, l'hyperinvestissement dans les soins ; c) Les relations avec l'institution geriatrique. Elles ne sont pas toujours paisibles. Des conflits peuvent eclater entre le patient, la famille et l'institution, surtout quand la famille ressent de la culpabilite et est ambivalente par rapport a l'institutionnalisation ; d) Les relations pathologiques famille–dement. Des relations pathologiques entre la famille et le parent peuvent apparaitre, dues a la pathologie psychique de l'aidant aggravee par la maladie d'Alzheimer du parent ; e) Le soutien apporte a la famille. Avant l'institutionnalisation, l'aidant familial doit etre soutenu dans le cadre du suivi geriatrique du patient. Des medicaments a visee cognitive et des psychotropes peuvent reduire les troubles du comportement. Le plus important est d'organiser et d'adapter les aides a domicile, avec si possible une prise en charge en centre de jour. Apres l'institutionnalisation, l'aidant doit continuer a etre soutenu. La fin de vie et la mort sont particulierement difficiles, parce que la comprehension des sentiments et des sensations de la personne demente reste toujours incertaine. Et il semble que le deuil d'un patient institutionnalise soit plus douloureux que le deuil apres une periode longue et stressante d'aide a domicile.

Hyaluronic acid is a glycosaminoglycan composed of disaccharides of glucuronic acid and N-acetylglucosamine. It is present at high concentrations in mammalian connective tissues. Since the length and concentration of HA decrease in osteoarthritis (AO), intraarticular HA injections began to be used in the early 1970s to restore the rheological properties of synovial fluid. Despite the widespread use of HA, many questions about its mechanism of action and properties remain to be clarified. A literature review presented in this article reveals that HA is a symptomatic slow-acting drug in osteoarthritis (SYSADOA) and that there is insufficient evidence to qualify it as a disease modifying osteoarthritis drug (DMOAD). HA is involved in many mechanisms of action ranging from interaction with mechanosensitive articular pain receptors to its ability to modulate extracellular matrix homeostasis. Although low molecular weight HA has a better safety profile and is slightly superior in in vitro studies and animal experimentation, clinical trials evaluating the efficacy of the drug show insufficient evidence to enable one type of HA to be recommended in preference to any other.

Resume Mme A., 75 ans, a ete hospitalisee pour une depression severe avec delire de persecution. Elle etait suivie pour un trouble bipolaire type I depuis plus de 40 ans. Le traitement instaure s’est revele inefficace compte-tenu de la mauvaise observance liee au delire de persecution. L’etat de Mme A. s’est aggrave progressivement, avec apparition de caracteristiques melancoliques. L’indication d’un traitement par ECT a ete posee mais la famille s’y est opposee. L’accord de la famille a ete tres difficile a obtenir. L’etat de Mme A. a necessite 22 seances d’ECT pour etre ameliore mais Mme A. a ete completement transformee par ce traitement, avec disparition des idees depressives et du delire de persecution. Sa famille ne l’avait pas connue ainsi depuis des annees.

Resume Dans cet article est rapportee l’experience d’un service de Gerontologie, dans le traitement des troubles psycho-comportementaux, au moyen d’un centre de jour interne. Plusieurs approches therapeutiques sont necessaires et peuvent etre rassemblees dans le centre de jour. Une etude sur son efficacite a ete effectuee au bout d’un an et ses resultats nous ont permis de preciser ses indications et ses limites. Ainsi, le centre de jour peut prendre en charge beaucoup de patients, y compris ceux qui presentent des alterations cognitives severes avec des troubles associes et il doit, de plus, jouer un role d’observation, d’analyse et de recherche de facon a optimiser les soins dans l’ensemble du service.

The international cooperation for development has been reducing inequalities between individuals and peoples for five decades. In this context, the architectural heritage has a great potential for the development of communities. However, cooperation projects related to architectural heritage present sometimes a problem, which is the evaluation of their results, because, in many cases, the degree in which the objectives have been achieved is hard to assess. This handicap contributes significantly to question the effectiveness of this type of projects over others. This difficulty in assessment is due to the lack of indicators that should quantify how the intervention contributes to the development and promotes economic growth but also helping individuals and communities to expand their life choices and adapt to change. In short, to demonstrate how the architectural heritage is integrated into the sustainable human development.

Objective: To analyse the role of the PTPN22 and CSK genes, previously associated with autoimmunity, in the predisposition and clinical phenotypes of giant cell arteritis (GCA). Methods: Our study population was composed of 911 patients diagnosed with biopsy-proven GCA and 8136 unaffected controls from a Spanish discovery cohort and three additional independent replication cohorts from Germany, Norway and the UK. Two functional PTPN22 polymorphisms (rs2476601/R620W and rs33996649/R263Q) and two variants of the CSK gene (rs1378942 and rs34933034) were genotyped using predesigned TaqMan assays. Results: The analysis of the discovery cohort provided evidence of association of PTPN22 rs2476601/R620W with GCA (PFDR=1.06E-04, OR=1.62, CI 95% 1.29 to 2.04). The association did not appear to follow a specific GCA subphenotype. No statistically significant differences between allele frequencies for the other PTPN22 and CSK genetic variants were evident either in the case/control or in stratified case analysis. To confirm the detected PTPN22 association, three replication cohorts were genotyped, and a consistent association between the PTPN22 rs2476601/R620W variant and GCA was evident in the overall meta-analysis (PMH=2.00E-06, OR=1.51, CI 95% 1.28 to 1.79). Conclusions: Our results suggest that the PTPN22 polymorphism rs2476601/R620W plays an important role in the genetic risk to GCA.

Conservation of historic buildings demands a special assessment method to ensure there is no damage to the existing structures. This concept must be adopted by all architects, engineers and technicians involved in historic building conservation. Floor and roof timber construction was widely extended in the vernacular buildings at Valencia. Floors were built usually by using timber joists, separated at 70 cm each, and with brick vaults between them. Timber roof structures consisted of rafters and rows for pitched roofs, with slopes inferior to 30o. A research group at the Polytechnic University of Valencia [1] has developed a NDT method of assessment of timber structures applied to the historic heritage. “Villa Ivonne”, a traditional building located at Meliana, close to Valencia (Spain) with timber roofs. It was used as a case study in which this method of assessment was applied. Besides the NDT measurements, visual inspection was done and its building timber structure system and pathology was studied. In this paper the NDT method is presented, by using ultrasonic, micro drilling and wood hardener devices. From the conclusions of these studies, pathology causes can be identified, and the subsequent repairs can be proposed.

Fermented sausages are considered self-stable products; nevertheless they have been implicated in several outbreaks. To increase food safety of fermented sausages and to cope with consumers’ demands for products with less chemical additives and less salt and fat content, biopreservation, understood to provide increased food safety and extension of shelf life by natural microbiota and/or their antimicrobial products, is considered an excellent alternative. Two major topics for biopreservation are considered in this chapter, lactic acid bacteria and their antimicrobial products and bacteriophages. Lactic acid bacteria have a long history of safe use, they are accepted by consumers as natural and health promoting and are the dominant natural microbiota of fermented meat products. Moreover, GRAS (Generally Recognized as Safe) bacteriophages used against specific food-borne pathogens do not disturb technological microbiota and could also be applied to the food environment.

August 2015 e113 Assessment of comorbidities in PAtients with symPtomAtic Knee osteoArthritis in sPAin: the emArtro study S. Gimenez Basallote; J. Vergara Martin; J.L. Llisterri Caro; G. Rodriguez Roca; J. Monfort Faure; F.J. de Abajo Iglesias; J. Rios Guillermo; L. Sanchez Bellmunt; M. Herrero Barbero; and J. Verges Milano Centro de Salud Limonar, Malaga, Spain; Centro de Salud Huercal de Almeria, Almeria, Spain; Centro de Salud Ingeniero Joaquin Benlloch, Valencia, Spain; Centro de Salud de la Puebla de Montalban, Toledo, Spain; Hospital del Mar, Barcelona, Spain; Hospital Universitario Principe de Asturias, Madrid, Spain; IDIBAPS, Hospital Clinic Barcelona, Barcelona, Spain; and Bioiberica, S.A., Barcelona, Spain Introduction: The primary outcome of the study is to assess the prevalence of comorbidities in symptomatic knee osteoarthritis (KOA) patients. Additionally, potential differentiating factors between KOA and non-osteoarthritic subjects will be assessed to detect a possible prognosis effect complementary to osteoarthritis. Here we present the protocol of the study that is being conducted at the moment. Material and Methods: It’s an observational, epidemiologic, multicenter, transversal study comparing comorbidities between subjects with and without KOA. The recruitment will be carried out by 65 investigators from different Spanish’s healthcare centers. 1150 subjects will be enrolled distributed in two groups: 575 KOA subjects selected and 575 sex and age-matched control subjects, without neither knee pain nor osteoarthritis. The results will be analyzed using descriptive statistics. Results: This study will provide new information about comorbidities in osteoarthritis which has become the leading cause of disability in the elderly and permanent disability caused by a rheumatic disease (RD) and one of the most frequent reasons for consultation. In other studies, it has been observed that the prevalence of comorbidities was significantly higher in osteoarthritis patients than controls (P < 0.0001) being hypertension, diabetes mellitus, chronic obstructive pulmonary disease, stroke and myocardial infarction the most prevalent osteoarthritis comorbidities. The ongoing study is in the follow-up period. Conclusions: Osteoarthritis is the most common RD, affecting 28% of those over 60 years, enduring pain, functional disability, decreased quality of life and causing significant social and economic burden. However, an important proportion of the economical costs of osteoarthritis compared to non-osteoarthritic population is due to an excessive use of sanitary resources which includes not only pharmacological treatment but also image and laboratory tests, management of treatment adverse reactions or rehabilitation and surgical interventions. The knowledge of comorbidities and concomitant medications in KOA patients will provide useful information to manage the disease more effectively and reduce its social and economic burden.

Background An aspect of pain in chronic diseases is the phenomenon of central sensitization (CS) manifested as pain hypersensitivity with anatomically spread hyperalgesia and enhanced temporal summation of pain after repeated stimulation. CS is a very common phenomena which occurs in OA and it has been clinically characterized using pressure pain stimulation 1 . One limitation on research is the subjectivity present in the pain assessment. Functional magnetic resonance imaging (fMRI) is an objective technique that maps neural activity in brain regions and demonstrates considerable anatomical resolution when mapping specific areas involved in pain perception 2 . However, there are little evidences on the study of CS phenomenon in OA by fMRI Objectives The aim of this study is to show fMRI evidence of pain CS in patients with knee OA compared with control subjects Methods We designed a cross-sectional, single blind study and compared OA patients following clinical and radiological ACR criteria vs healthy controls. All participants were recruited in the OA Unit at the Hospital del Mar during one year and a half. Clinical CS was assessed using extended version of the ArendtNielsen peripatellar map 1 (number of tender points, minimal pressure needed to suffer pain) and increased pain response to repeated stimulation (temporal summation). We used a three-step strategy: (1) identifying brain response to direct pulsed pressure stimulation on the painful knee (interline), (2) identifying brain response to pulsed pressure stimulation on a non-arthritic hyperalgesic area (anterior surface of the tibia) and (3) identifying brain response to painful contact heat stimulation on a healthy skin area (volar forearm). Results We included 60 OA patients and 30 controls (66.7+/ 7.8yrs and 62.8 +/ 7.7yrs, respectively). A total of 33 patients showed some evidence of CS which 19 met all criteria of CS. At interline test, there was no difference on fMRI outcomes. At tibial test we found significant differences on brain activity which involved greater activation, in sensitized patients, in primary somatosensory area, supramarginal gyrus, sensorymotor cortex and basal ganglia. Correlation between brain response and clinical CS assessment was significant on somatosensory cortex, suppramarginal gyrus, anterior cingulated cortex and ventral putamen nucleus, bilaterally. Finally, we found no significant differences on brain activation between groups on the painful heat stimulation Conclusions CS phenomenon is frequent in knee OA patients. Pressure on tibial bone looked adequate to discriminate between sensitized and non sensitized patients, unlike pressure on interline. The correlation maps involving fronto-subcortical activation could suggest that CS is related to learning and associative processes like associations between pain and daily activities References Arendt-Nielsen L, Nie H, Laursen MB, Laursen BS, Madeleine P, Simonsen OH, Graven-Nielsen T. Sensitization in patients with painful knee osteoarthritis. Pain 2010;149:573–581. Schweinhardt P, Lee M, Tracey I. Imaging pain in patients: is it meaningful? Curr Opin Neurol 19 2006 392-400. Disclosure of Interest None declared

Hyaluronic acid is a glycosaminoglycan composed of disaccharides of glucuronic acid and N-acetylglucosamine. It is present at high concentrations in mammalian connective tissues. Since the length and concentration of HA decrease in osteoarthritis (AO), intraarticular HA injections began to be used in the early 1970s to restore the rheological properties of synovial fluid. Despite the widespread use of HA, many questions about its mechanism of action and properties remain to be clarified. A literature review presented in this article reveals that HA is a symptomatic slow-acting drug in osteoarthritis (SYSADOA) and that there is insufficient evidence to qualify it as a disease modifying osteoarthritis drug (DMOAD). HA is involved in many mechanisms of action ranging from interaction with mechanosensitive articular pain receptors to its ability to modulate extracellular matrix homeostasis. Although low molecular weight HA has a better safety profile and is slightly superior in in vitro studies and animal experimentation, clinical trials evaluating the efficacy of the drug show insufficient evidence to enable one type of HA to be recommended in preference to any other.

Chondroitin sulfate (CS) and 500-730 kDa hyaluronic acid (HA) are symptomatic slow-acting drugs for the treatment of osteoarthritis (OA). In addition, a growing body of evidence suggests a role for CS and this specific HA as modifiers of the course of OA. The therapeutic efficacy of CS and HA lies in their different mechanisms of action. Stromelysin-1 (metalloprotease-3 [MMP-3]) is a cartilage proteolytic enzyme, which induces cartilage destruction and acts as a mediator of the inflammatory response. However, there are few studies evaluating the in vitro effect of CS and HA on MMP-3 synthesis in human chondrocyte cultures from OA patients. Thus, the aim of the present study was to analyze the effect of CS and HA (500-730 kDa) on MMP-3 synthesis induced by interleukin-1beta (IL-1beta) in chondrocytes from patients with hip OA. Chondrocyte cultures were incubated for 48 h with IL-1beta (2.5 ng/ml) in the absence or presence of different HA 500-730 kDa (Hyalgan, Bioibérica Farma, Barcelona, Spain) concentrations, or alternatively, CS (Condro.san, Bioibérica Farma) at concentrations of 10, 50, 100, 150, 200 and 1,000 microg/ml. The results revealed that both CS and HA (500-730 kDa) inhibited MMP-3 synthesis induced by IL-1beta in human OA chondrocytes. Specifically, CS and HA (500-730 kDa) reduced MMP-3 expression levels at all tested concentrations. Therefore, our study provides new data on the mechanism of action of these drugs, which could help to explain their clinical efficacy in OA patients.

Chondroitin sulfate (CS) and hyaluronic acid (HA) are used in the symptomatic treatment of osteoarthritis (OA). Cholagenase-1 (MMP-1) and stromelysin-1 (MMP-3), are responsible for degradation of the extracellular matrix in OA. Few studies have determined the in vitro effect of CS and HA on MMP-1 synthesis and that of HA on MMP-3 expression in human OA chondrocyte culture. In the literature reviewed, there were no studies evaluating the effect of CS on MMP-3.To analyze the effect of CS and HA (500-730 kDa) on MMP-3 and MMP-1 synthesis induced by interleukin-1β (IL-1β) in OA chondrocytes.Chondrocytes were incubated for 48 hours with IL-1β (2.5 ng/ml) in the presence or absence of different HA concentrations (Hyalgan®, Bioibérica Farma) (10, 50, 100, 150, 200 and 1000 μg/ml). Functional evaluation of chondrocytes was performed by enzyme-immunoanalysis of MMP-1 and MMP-3 levels.CS and HA inhibited IL-1β-induced MMP-3 synthesis, without significantly modifying MMP-1. CS and HA reduced levels of MMP-3 expression at all the studied concentrations, with no statistically significant differences among these concentrations.The results of this study show for the first time that CS inhibits MMP-3 synthesis in OA cartilage. and corroborates the few existing data on the ability of HA to inhibit this enzyme.

Background: Bone scintigraphy used as a diagnostic technique frequently yields non-specific intense uptake by vertebrae. Bone biopsy may therefore be required to establish a diagnosis in cases of Paget’s disease of bone. The aim of the study was to ascertain the sensitivity and specificity of two new images—heart sign and clover sign—in Paget’s disease of bone. Methods: Two expert rheumatologists analyzed 294 bone scintigraphies of patients with vertebral involvement: 204 without and 90 with Paget’s disease. The presence or absence of the clover or heart signs was determined in each scintigraphy. A specificity and sensitivity study was performed with the data obtained. A study of concordance was made between two radiologists blinded to the real diagnosis. Each one analyzed 120 scintigraphies for the presence and absence of the signs: 40 with Paget’s disease and clover and/or heart signs (selected from the initial 90 cases), 40 with Paget’s disease with neither sign and 40 selected from the pool of 4000 scintigraphies of patients with vertebral involvement, with images easily mistaken for these signs (vertebral collapse, osteoarthritis and bone metastases). Kappa statistics were calculated. Findings: Sensitivity of both signs for Paget’s disease of bone was low: 44% (95% CI 34.0 to 55.3). However, specificity was excellent: 100% (95% CI 98.2 to 100). Inter-radiologist concordance was almost perfect: Kappa 0.86 (95% CI 0.77 to 0.95). Interpretation: The heart and clover signs are highly specific (probably pathognomonic) of Paget’s disease of bone. In cases with doubtful radiologic images, these findings on scintigraphic vertebral images may afford a definitive diagnosis of Paget’s disease of bone and thus obviate further confirmatory invasive diagnostic procedures.

Background Collagenase-3 (MMP-13) is a human matrix metalloproteinase highly overexpressed in diseases where tissue repair and remodelling is needed, such as rheumatoid arthritis (RA), osteoarthritis (OA) and some cancers. However, its expression in normal tissues is limited to fetal ossification processes 1 . MMP-13 can digest fibrillar collagen, preferentially type II collagen, but also glomerular collagens and other components of the extracellular matrix (ECM) 2 . MMP-13 structures is composed of 4 domains: a hydrophobic pre-domine necessary for the secretion, a pro-domain involved in enzyme latency, a catalytic domain, and a hemopexin-like domain This last is essential for the substrate recognition and collagenolytic activity 3 Three different MMP-13 transcripts of 3.0, 2.5 and 2.2/2.0 kb have been described to be expressed in human cells. The 2.5kb transcript (isoform 205) corresponds to the MMP-13 original form, while the 3.0kb transcript (isoform 344) presents an insertion at the C-terminal produced by lack of exon 9B splicing. Finally, the smaller transcript of 2.2/2.0kb (isoform 209) presents a deletion (probably due to alternative splicing) of 88 amino acids, also affecting the C-terminal domain 4 . Objectives Our objective is to demonstrate the presence of these three MMP13 protein isoforms in human OA samples. Methods A specific peptide from each isoform was synthesized and two rabbits were immunized with each peptide. The antibodies recognizing each isoform were purified from the total antiserum by sulfolink column. On the other hand MMP-13 isoforms were synthesized in vitro in a Sf9 insect cells system, with a recombinant baculovirus containing MMP-13 transcripts cloned. The insect cells were culture to produce the respective isoforms, and they were purified by molecular exclusion chromatography. These proteins were used to test the specificity of the polyclonal antibodies obtained by Western Blot. Finally, ECM proteins were extracted from cartilage samples obtained from knee and hip arthrosic patients undergoing arthroplasty, using Guanidinium chloride (4M) method. The presence of the 3 isoforms in these samples was assay by western blot with the specific isoform polyclonal antibodies obtained. Results The purified polyclonal antibodies show immunoreactivity only in front of its specific isoform, showing that they are useful for the detection of each specific isoform in the samples. In all the samples tested, different intensities of the bands corresponding of each antibody were detected. No relative quantification could be performed due to the lack of a standard of each MMP-13 isoforms that allows us to compare the affinity of each polyclonal antibody to each specific isoform. Conclusions The MMP-13 mRNA isoforms are translated to protein in cartilage OA samples. The transcripts containing the deleted and the alternatively spliced exons differ from the original sequence in the region coding for the hemopexin-like domain 5 . This domain is necessary to cleave native triple helical collagens and provide to the protease its substrate specificity and affinity. The expression of 209 and 344 isoform could have clinical implications in OA if they present different subtracted recognition and/or speed of degradation, explaining some differences observed in the pathophysiology of the disease. References Mitchell PG et al (1996) Knauper V et al (1996) Freije JM et al (1994) Tardif G et al( 2003) Vera Knauper et al (1997) Disclosure of Interest None Declared

The purpose of this review is to describe the diverse aspects of depression in the elderly. The bibliographical research includes epidemiology, theoretical models, diagnosis and treatment. Many studies emphasize the need for an accurate diagnosis, given the risk of unrecognized depression. The therapeutic trial is used when there is uncertainty about the diagnosis, especially whether it is depression or dementia. A treatment and a long follow-up are necessary to prevent relapses and recurrences.

The solubilities of simple gases dissolved in normal fluids are examined in terms of a modified Pierotti cavity theory. If we assume that the effective diameters of solute and solvent molecules depend on temperature, it is possible to correct substantially the inaccuracy of the cavity term in Pierotti's theory. This temperature dependence is obtained by means of a correlative scheme that uses experimental thermal pressure coefficients and a hard sphere equation of state. This method generally improves the values of calculated Henry's constants as compared with those of the original method; for example, for 27 data points of five normal mixtures, the mean relative deviation between experimental and calculated Henry constants is reduced from 52% to 28%.

When Ru3(CO)12 is impregnated on silica and heated under vacuum a supported carbonyl complex, B, and subsequently a metallic ruthenium catalyst, D, are obtained. The catalytic activity of Ru3(CO)12 solutions for the isomerization and hydrogenation of 1-hexene has been compared with that of the heterogenized and heterogeneous systems. The isomerization activity follows the order homogeneous > heterogenized > heterogeneous, whilst the hydrogenation activity follows the reverse order. The influence of solvent, additives, and hydrogen pressure is described. The behaviour of the supported carbonyl complex resembles that of the heterogeneous catalyst more than that of the soluble carbonyl cluster.

A controlled study on a pragmatic type was performed on 30 patients of both sex, all having recurrent depressions. The efficacy of Clomipramine plus Lithium Carbonate was compared to that of Clomipramine plus placebo. The control consisted in a double-blind study with random sampling of patients. Results were recorded by an independant observer using a rating scale and were analysed statistically. In spite of the bias which was observed it seems possible to conclude. The association of Clomipramine plus Lithium Carbonate has no greater global antidepressive efficacy as compared with Clomipramine plus placebo which means that Lithium does not potentialize nor antagonize the anti depressant effect of Clomipramine. In respect of the number of patients : bipolar depressions (10 cases) unipolar (20 cases) it has not been possible to study the results in these 2 sub groups.

We report a case of a giant lymphocele following simple nephroureterectomy with delayed recognition. The unusual presentation and its management are discussed.

A case of diffuse lepromatous leprosy with lepra reaction type II-Lucio's phenomenon-in a 24 years old male patient is reported. The histological examination of the necrotic lesions and of the apparently normal skin showed the presence of dense perivascular and perianexial lymphohystiocitic infiltrates with great quantities of bacilli. The first biopsy did not show a picture a leuccocytoclastic vasculitis but only areas of necrosis. The immunofluorescence studies revealed on direct examination complement deposits on vessel walls. The complement levels in blood were lowered and circulating inmunecomplexes were also detected. These data confirm the opinion that Lucio's phenomenon is caused by circulating inmunecomplexes fixed on dermal vessel walls causing skin necrotic lesions.