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Objective To evaluate mid‐term radiographic and functional outcomes of tibial plateau fracture (TPF) patients treated with the open reduction internal fixation (ORIF) technique and to find predictive factors of clinical outcomes. Methods A retrospective, single‐center study was performed enrolling a consecutive series of patients with diagnosis of TPF. All subjects were treated by ORIF between January 2010 and December 2015 at our level‐1 healthcare trauma center. The inclusion criteria were: age between 18 and 75 years; ORIF technique used for articular TPF, type 41‐B and 41‐C, isolated or with associated injuries. The patients were divided in two groups, according to fracture patterns and compared. Their characteristics, radiographic and clinical outcomes were recorded. Radiographs 12 months after surgery were evaluated for reduction and alignment, and radiographs at 24 months to describe post‐traumatic osteoarthritis (PTOA). Functional outcomes were assessed using the visual analog scale (VAS), the Short Form 36 (SF‐36), the knee injury and osteoarthritis outcome score (KOOS), and the American Knee Society score (AKSS) questionnaires. Return to work and sport activities were also investigated. Univariate and multivariate analysis were performed, and the statistical significance was defined as two‐tailed P

The infrapatellar fat pad (IFP) is actively involved in knee osteoarthritis (OA). However, a proper description of which developmental modifications occur in the IFP along with age and in absence of joint pathological conditions, is required to adequately describe its actual contribution in OA pathophysiology. Here, two IFP sources were compared: (a) IFP from healthy young patients undergoing anterior-cruciate ligament (ACL) reconstruction for ACL rupture (n = 24); (b) IFP from elderly cadaver donors (n = 23). After histopathological score assignment to confirm the absence of inflammatory features (i.e., inflammatory infiltrate and increased vascularity), the adipocytes morphology was determined; moreover, extracellular matrix proteins were studied through histology and Second Harmonic Generation approach, to determine collagens content and orientation by Fast Fourier Transform and OrientationJ. The two groups were matched for body mass index. No inflammatory signs were observed, while higher area, perimeter, and equivalent diameter and volume were detected for the adipocytes in the elderly group. Collagen III displayed higher values in the young group and a lower total collagen deposition with aging was identified. However, collagen I/III ratio and the global architecture of the samples were not affected. A higher content in elastic fibers was observed around the adipocytes for the ACL-IFPs and in the septa cadaver donor-IFPs, respectively. Age affects the characteristics of the IFP tissue also in absence of a pathological condition. Variable mechanical stimulation, depending on age-related different mobility, could be speculated to exert a role in tissue remodeling.

Patients with psoriatic arthritis (PsA) have an increased prevalence of obesity, but mechanisms underlying this association remain unknown and it is unclear if obesity is the cause or effect of PsA. For PsA patients, comorbid obesity may influence their clinical response to systemic treatment, and especially targeted immunomodulators such as anti-tumor necrosis factor (TNF)α. Weight gain has also been associated with anti-TNFα treatment. Consequently, modification of the therapeutic approach may be needed for patients with an inadequate response to TNFα inhibitors. In recent years, interleukin (IL)-12/IL-23 inhibitors have entered clinical practice as a new class of drug for the treatment of PsA, with some data suggesting a lower effect of body weight on their effectiveness. Recent findings demonstrate effective and sustained responses in patients with PsA to ustekinumab, an IL-12/IL-23 inhibitor. This narrative review critically discusses the link between PsA, obesity, and response to therapy. The current role of ustekinumab in this setting is also discussed.

BackgroundLittle evidence is available about the impact of diet on disease activity of axial spondyloarthritis (axSpA). This study evaluated the impact of a 6-month nutritional advice based on the Mediterranean diet on the disease activity of axSpA.MethodsWe prospectively collected the information of a group of axSpA patients who were offered nutritional advice for a 6-month period, who were compared to axSpA patients followed at the same center who were not on a specific diet. A nutritionist gave suggestions for dietary modification at baseline and thereafter every 2 months until month 6. Adherence to the Mediterranean diet was evaluated with the PREDIMED questionnaire ranging from 0 (no adherence) to 10 (optimal adherence); disease activity was evaluated with ASDAS-CRP. A multivariable regression analysis was conducted to identify independent predictors of PREDIMED and of ASDAS-CRP improvement (improvement ≥ 20% of each score).ResultsA total of 161 patients were included: 81 receiving nutritional advice and 80 controls; 47 in the nutritional group and 63 controls had complete information until month 6. Overall, 40 (36.4%) were females, the mean age was 51.7 ± 1.3 years, and 58 (52.7%) were affected with psoriasis. No relevant change of anthropometric or laboratory measures was observed in either group. Adherence to the Mediterranean diet was moderate (PREDIMED score 6.7 ± 1.8 at baseline; 7.6 ± 2.1 at month 6) and improved more in the nutritional group compared to controls (p= 0.020). Predictors of a PREDIMED improvement ≥ 20% were receiving nutritional advice (OR 4.53, 1.36–15.1,p= 0.014), age (per 10-year increase OR 1.05, 1.02–1.68,p= 0.007), and BMI (OR 0.77, 0.63–0.9,p= 0.006). An ASDAS-CRP improvement ≥ 20% was more frequent in the nutritional group compared to controls (p= 0.020). A PREDIMED improvement ≥ 20% was associated with a ASDAS-CRP improvement ≥ 20% (OR 6.75,1.8–25.3,p= 0.005). Psoriasis and disease duration were negatively but not significantly associated to the ASDAS-CRP improvement.ConclusionsImproving adherence to the Mediterranean diet may have a beneficial impact on the activity of axSpA. Patients with a lower BMI and older patients are more prone to modify their diet towards the Mediterranean diet following nutritional advice. Patients with psoriasis may have a limited benefit from dietary improvement.Study registrationProtocol No. 52723, Padova Hospital Medical Ethical Committee (October 11, 2010).

The educational needs assessment tool (ENAT) is a seven-domain questionnaire assessing the educational needs (EN) of patients with rheumatoid arthritis (RA). The aim of this study was to validate the Italian version of the ENAT and to identify factors associated with EN in people with RA. The original English ENAT version was translated into Italian according to Beaton&rsquo, s method and subjected to Rasch analysis for validity testing. Socio-demographic and clinical variables were tested for associations with the ENAT domain scores using a multivariable linear regression model. The ENAT translated well into Italian and retained its construct validity. Some adjustments were needed when pooling the Italian and English datasets. The overall score of the ENAT had a high median: 82.8 (interquartile range (IQR): 57.5 to 100) i.e., 72.4% of the maximum score. The highest score was observed in the domain &ldquo, Arthritis process&rdquo, and the lowest was in &ldquo, Support systems&rdquo, Only gender was independently associated with EN (females having higher EN than males). The Italian ENAT is feasible for the use in the clinical setting and may help the health care practitioners to tailor educational interventions for RA patients. The characteristics of the patients, particularly female gender, may be associated with higher EN.

Osteoarthritis (OA) is one of the most common joint disorders. Evidence suggests that the infrapatellar fat pad (IFP) is directly involved in OA pathology. However, a comparison between OA versus non-OA IFP is still missing. Thus, the aim of this study was to compare IFP molecular, adipocytes and extracellular matrix characteristics of patients affected by OA, and patients undergoing anterior cruciate ligament (ACL) reconstruction. We hypothesized that not only inflammation but also changes in adipocytes and extracellular matrix (ECM) composition might be involved in OA pathogenesis. Fifty-three patients were enrolled. IFP biopsies were obtained, evaluating: (a) lymphocytic infiltration and vascularization, (b) adipocytes area and number, (c) adipo-cytokines and extracellular matrix gene expression levels, (d) IL-6 and VEGF protein production, (e) collagen fibers distribution. OA IFP was more inflamed and vascularized compared to ACL IFP. OA IFP adipocytes were larger and numerically lower (1.3-fold) than ACL IFP adipocytes. An increase of gene expression of typical white adipose tissue genes was observed in OA compared to ACL IFP. Collagen-types distribution was different in the OA IFP group compared to controls, possibly explaining the change of the biomechanical characteristics found in OA IFP. Statistical linear models revealed that the adipocyte area correlated with BMI in the OA group. In conclusion, inflammation and fibrotic changes of OA IFP could represent novel therapeutic targets to counteract OA.

Axial spondyloarthritis (axSpA) is a group of debilitating, chronic, rheumatic conditions characterized by inflammation and new bone formation, mainly involving the spine and the sacroiliac joints. The lack of biomarkers in axSpA is well known. Despite significant treatment advances in recent years thanks to the introduction of drugs with a new mode of action, such as new biologic and targeted synthetic disease-modifying antirheumatic drugs, no relevant improvement in the identification of disease biomarkers has been achieved. Common parameters, such as erythrocyte sedimentation rate and C-reactive protein, which are routinely used to measure systemic inflammation, are the sole markers available to date and are not adequate to assess disease activity in all patients. The aim of this study is to review the most promising serum biomarkers that may help treatment decision in axSpA via a proper assessment of disease activity and identification of negative prognostic factors.

Objectives: Our study aimed to identify: (1) the prevalence of spine and pelvis magnetic resonance imaging (MRI-spine and MRI-SIJ) inflammatory and structural lesions in patients (pts) with a diagnosis of axial spondyloarthritis (axSpA); (2) the predictive factors for a severe disease pattern with a higher probability of radiographic progression.Materials and Methods: Seventy-five pts with low back pain (LBP) (≥3 months, ≤2 years, onset ≤45 years) underwent physical examination, questionnaires, laboratory tests, X-rays, MRI-spine, and MRI-SIJ at baseline (T0) and during a 24-months follow-up. Two expert rheumatologists made axSpA diagnosis and classification (according ASAS criteria). MRI-spine, MRI-SIJ and X-rays were scored independently by 2 readers following the SPARCC, mSASSS, and mNY-criteria. According to ASAS criteria, 21 pts fulfilled imaging arm only and 29 clinical arm with/without imaging arm; 25 pts did not fulfill ASAS criteria.Results: At T0 the mean ± SD LBP onset was 28.51 ± 8.05 years, 45.3% pts were male, 38.7% were HLA-B27+; 56% showed bone marrow oedema (BMO) at MRI-spine and 64% at MRI-SIJ. Signs of enthesitis were found in 58% pts in the thoracic spine. Eighteen (24%) pts presented BMO at MRI-spine with a negative MRI-SIJ. The prevalence of BMO lesions and the SPARCC SIJ and spine score decreased during the follow-up in the 2 cohorts meeting ASAS criteria. An early onset of LBP, a lower use of NSAIDs, a BASDAI>4 were identified as predictors of spine structural damage; the high SPARCC SIJ score appeared to be a predictor of SIJ structural damage. A higher mSASSS was predicted by a lower age of onset of LBP. Predictor of higher SPARCC spine was a higher NSAIDs and of higher SPARCC SIJ score the HLA-B27 positivity with increased inflammatory biomarkers.Conclusions: At T0 a significant prevalence of BMO lesions was observed both in SIJ and spine, with predominant involvement of thoracic district. Since positive MRI-spine images were observed in the absence of sacroiliitis, these findings seem to be relevant in the axSpA diagnosis. Early age of disease onset, long duration of LBP, increased inflammatory biomarkers, higher use of NSAIDs, male gender, HLA-B27 positivity, SPARCC SIJ score>2 appeared predictors of radiological damage and activity.

BackgroundHip osteoarthritis (HOA) is the most common hip disorder and a major cause of disability in the adult population, with an estimated prevalence of end-stage disease and total hip replacement. Thus, the diagnosis, prevention, and treatment of the early stages of the disease in young adults are crucial to reduce the incidence of end-stage HOA.The purpose of this study was to determine whether (1) a relationship among the inflammatory status of labrum and synovium collected from patients with femoroacetabular impingement (FAI) would exist; and (2) to investigate the associations among the histopathological features of joint tissues, the pre-operative symptoms and the post-operative outcomes after arthroscopic surgery.MethodsJoint tissues from 21 patients undergoing hip arthroscopy for FAI were collected and their histological and immunohistochemical features were correlated with clinical parameters.ResultsSynovial mononuclear cell infiltration was observed in 25% of FAI patients, inversely correlated with the hip disability and osteoarthritis outcome score (HOOS) pain and function subscales and with the absolute and relative change in total HOOS. All the labral samples showed some pattern of degeneration and 67% of the samples showed calcium deposits. The total labral score was associated with increased CD68 positive cells in the synovium. The presence of labral calcifications, along with the chondral damage worsened the HOOS post-op symptoms (adjustedR-square = 0.76p= 0.0001).ConclusionsOur study reveals a relationship between the histologic labral features, the synovial inflammation, and the cartilage condition at the time of FAI.The presence of labral calcifications, along with the cartilage damage and the synovitis negatively affects the post-operative outcomes in patients with FAI.

The aim of this study was to evaluate the effect of an oral preparation containing a naturally occurring matrix of hydrolyzed collagen type II, chondroitin sulfate (CS), and hyaluronic acid (HA), and bioactive oligopeptides of natural hydrolyzed keratin (K) in patients affected by knee OA through the evaluation of synovial fluid (SF) and clinical changes before and after treatment. Thirty patients with knee OA and swollen joint were included in the study and submitted to arthrocentesis. Patients were randomized in two groups: 1) the treatment group (N.15) took a dietary supplement containing 120 mg HA, 240 mg CS and 300 mg K once a day for 4 weeks; 2) the control group (N.15) was only submitted to arthrocentesis. Patient symptoms were evaluated at the beginning and at the end of the study by the WOMAC self-assessment questionnaire, the Lequesne algofunctional index, and the VAS forms. SF changes were evaluated by measuring local inflammatory indices, cytokines IL-1β, IL-8, IL-6, IL-10 and GM-CSF. The group of patients treated with the oral supplement showed an improvement in the clinical indices WOMAC (p

Recently, infrapatellar fat pad (IFP) has been considered as a source of stem cells for cartilage regeneration in osteoarthritis (OA) due to their ability for differentiation into chondrocytes. However, stressful conditions, like that related to OA, may induce a pathogenic reprogramming. The aim of this study was to characterize the structural and functional properties of a new population of stem cells isolated from osteoarthritic infrapatellar fat pad (OA-IFP). Nine OA patients undergoing total knee arthroplasty were enrolled in this study (median age = 74 years, interquartile range [IQR] = 78.25-67.7; median body mass index = 29.4 Kg/m², IQR = 31.7-27.4). OA-IFP stem cells were isolated and characterized for morphology, stemness, metabolic profile and multi-differentiative potential by transmission electron microscopy, flow cytometric analysis, gene expression study and cytochemistry. OA-IFP stem cells displayed a spindle-like morphology, self-renewal potential and responsiveness (CD44, CD105, VEGFR2, FGFR2, IL1R, IL6R) to microenvironmental stimuli. Characterized by high grade of stemness (STAT3, NOTCH1, c-Myc, OCT-4, KLF4 and NANOG), the cells showed peculiar immunophenotypic properties (CD73+/CD39+/CD90+/CD105+/CD44-/+/CD45-). The expression of HLA-DR, CD34, Fas and FasL was indicative of a possible phenotypic reprogramming induced by inflammation. Moreover, the response to mechanical stimuli together with high expression level of COL1A1 gene, suggested their possible protective response against in vivo mechanical overloading. Conversely, the low expression of CD38/NADase was indicative of their inability to counteract NAD+-mediated OA inflammation. Based on the ultrastructural, immunophenotypic and functional characterization, OA-IFP stem cells were hypothesized to be primed by the pathological environment and to exert incomplete protective activity from OA inflammation. Keywords: Infrapatellar Fat Pad, osteoarthritis, stem cells, inflammation, reprogramming

Background The aim of this study was to assess the reliability of the videotape scoring system collected during knee arthroscopy for meniscal tears, and to test the consistency with intra-operative findings. Methods Fifty-seven patients undergoing arthroscopic treatment of meniscal tears were included in the analysis. The cartilage damage was assessed intra-operatively, at six sites, using the Outerbridge scoring system. The meniscal tears were graded according to the International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS) classification. The presence of synovial inflammation was scored, at four different sites, according to the macro-score method. The total cartilage, meniscal and synovial scores were calculated for each knee by the sum of the maximum grade of the lesions at each anatomic site. In order to assess the reliability of the arthroscopic scoring system, the videotapes recorded during the arthroscopy were reviewed by two independent observers one year after the surgery and compared with the scores completed by the surgeon during the operation. Results The total cartilage score showed substantial inter-rater and intra-rater reliability, and moderate consistency with the intra-operative score provided by the surgeon. The total meniscal score showed substantial inter-rater and intra-rater reliability, and good consistency with the intra-operative findings. The total synovial score showed substantial inter-rater agreement, substantial intra-rater reliability, and moderate consistency with intra-operative findings. Conclusions The videotape scoring system provided a reliable and reproducible system for recording the intra-operative state of the whole joint pathology in patients undergoing arthroscopic treatment of meniscal tears.

Background:Mediterranean diet (MD) proved to be beneficial on disease activity in patients affected by rheumatoid arthritis. A few data are available in other rheumatic conditions.Objectives:A prospective monocentric study was conducted to evaluate the effect of a nutritional intervention based on the MD and to investigate the impact of such modification on disease activity of axial spondyloarthitis (ax-SpA).Methods:Patients affected by ax-SpA randomized to a nutritional intervention arm (N) or a control arm (C) and were assessed at baseline (T0) and at month 6 (T6). Patients in N underwent a nutritional evaluation and received suggestions for dietary modification at T0, and then every 2 months. Adherence to the MD was evaluated with the PREDIMED questionnaire (range 0-10) [1]. A multivariable regression analysis was conducted to identify independent predictors of PREDIMED and of ASDAS-CRP improvement at T6.Results:Eligible patients (161) were randomized to either N (81) or C (80); 47 in N and 63 in C completed the study. No relevant change of anthropometric or laboratory measures was observed at T6 in either group. A ≥20%PREDIMED improvement was more frequent in N (22/47, 46.8%) compared to C (13/63, 20.6%) (pConclusion:A nutritional intervention is effective in improving adherence to the MD in ax-SpA. A higher adherence to the MD may have a beneficial impact on activity of ax-SpA. Patients with psoriasis may have a limited benefit from the dietary improvement.References:[1]Martínez-González, M.A. et al. A 14-item mediterranean diet assessment tool and obesity indexes among high-risk subjects: The PREDIMED trial.PLoS One2012,7.Table 1.Characteristics of the patients.All patientsNutritionControlsAll patientsNutritionControlsBaselineMonth 6Females, n, (%)40 (36.4)18 (38.3)22 (34.9)Age, years, mean±SD51.7±1.353.0±1.349.6±1.3HLA-B27 positivity, n (%)58 (52.7)22 (46.8)37 (57.1)Psoriasis, n (%)58 (50.7)26 (55.3)32 (50.8)Disease duration (years), mean±SD15.3±9.715.7±1015±9.5Duration of b/tsDMARD treatment overall, years, mean±SD5±4.15.8±4.54.5±3.8NSAID, n (%)76 (69.1)30 (63.8)46 (73)csDMARD, n (%)14 (12.7)5 (10.6)9 (14.3)BMI, Kg/meters2, mean±SD26.5±5.426.5±4.326.6±6.126.4±5.326.3±426.6±6.1ASDAS-CRP, mean±SD2.1±12.1±0.92.1±12±1.11.8±0.92.1±1.2BASDAI, mean±SD37.6±2337.4±23.237.7±22.939.3±24.137.3±23.641.2±24.6BASFI, mean±SD20.5±21.421.6±19.219.7±2319.8±19.619.1±18.820.5±20.4BASMI, mean±SD1.6±21.9±2.21.4±1.71.8±2.11.9±2.41.7±1.9Tender joint count, mean±SD1.1±2.30.8±2.11.4±2.50.9±20.8±20.9±1.9Swollen joint count, mean±SD0.3±1.30.4±20.1±0.50.2±1.30.3±1.80.2±0.8Leeds Enthesitis Index, mean±SD0.2±0.80.3±10.2±0.61.1±21.3±2.21±1.8CRP, mg/L, mean ±SD3.4±6.23.2±3.93.7±7.43.5±5.62.6±3.14.1±6.9LDL-c, mg/dl, mean ±SD130.8±36.5132.3±35129.7±38.4130.6±34.7125.7±34.8134.4±34.5PREDIMED score, mean ±SD6.7±1.87±2.16.6±1.67.6±2.18.6±1.96.8±2b/tsDMARD biological/targeted synthetic DMARDs; csDMARD conventional DMARDs. PREDIMED questionnaire to assess adherence to the Mediterranean diet.Disclosure of Interests:None declared.

The study aimed to evaluate biomarkers facilitating early diagnosis of axial spondyloarthritis (axSpA) and correlations between them and disease activity parameters and imaging indexes. Patients with low back pain (LBP) (≥3 months, ≤2 years, onset ≤45 years) participating in the Italian arm of the SpondyloArthritis-Caught-Early SPACE study underwent a physical examination, questionnaires, laboratory tests, X-rays and MRI of the spine and sacroiliac joints (SIJ). An expert rheumatologist formulated axSpA diagnosis in accordance with Assessment of SpondyloArthritis International Society (ASAS) criteria. Disease activity and physical functioning were assessed using imaging, clinical and serological indices. Spine and SIJ MRI and X-rays were scored independently by 2 readers using the SPARCC, mSASSS and NY-criteria. Patients were classified as: subjects with signs of radiographic sacroiliitis (r-axSpA), subjects with signs of sacroiliitis on SIJ-MRI but not on X-rays (nr-axSpA MRI SIJ+) or subjects with no signs of sacroiliitis on MRI/X-rays but with >2 SpA features and signs of bone oedema on MRI spine (nr-axSpA MRI SIJ-/undifferentiated SpA). Significant differences were found in the prevalence of radiographic sacroiliitis, active sacroiliitis on MRI and SPARCC SIJ scores. Biomarker levels were not significantly increased in any of the patient groups. The correlations between IL-17 and IL-23 and other indices were not significant; correlations were found between IL-22 and BASFI, BASG1, HAQ, VAS pain, between mSASSS and MMP3, and between the latter and hsCRP. Although not significantly higher in any of the three groups, IL-22, MMP3 and hsCRP values were correlated with some disease activity indexes and with mSASSS. Large observational studies are required to confirm these preliminary findings.

Osteoarthritis is a common chronic joint disorder affecting older people. The knee is the major joint affected. The symptoms of osteoarthritis include limited range of motion, joint swelling, and pain causing disability. There are no disease modifying drugs available, and treatments are mainly focused on pain management. Total knee replacement performed at the end stage of the disease is considered the only cure available. It has been found that obese people have an increased risk to develop not only knee but also hand osteoarthritis. This supports the concept that adipose tissue might be related to osteoarthritis not only through overloading. As matter of fact, obesity induces a low grade systemic inflammatory state characterized by the production and secretion of several adipocytokines that may have a role in osteoarthritis development. Furthermore, hypertension, impaired glucose, and lipid metabolism, which are comorbidities associated with obesity, have been shown to alter the joint tissue homeostasis. Moreover, infrapatellar fat pad in the knee has been demonstrated to be a local source of adipocytokines and potentially contribute to osteoarthritis pathogenesis. Here, we discuss the role of systemic and local adipose tissue in knee osteoarthritis. J. Cell. Physiol. 232: 1971-1978, 2017. © 2016 Wiley Periodicals, Inc.

The Osteoarthritis Quality of Life scale (OAQoL) is specific to individuals with osteoarthritis. The present study describes the adaptation of the OAQoL for use in the following five European languages: German, Hungarian, Italian, Spanish and Turkish. The study involved three stages in each language; translation, cognitive debriefing (face and content validity) and validation. The validation stage assessed internal consistency (Cronbach's alpha), reproducibility (test-retest reliability using Spearman's rank correlations), convergent and divergent validity (correlations with the Health Assessment Questionnaire, The Western Ontario and McMaster Universities Index of osteoarthritis and Nottingham Health Profile) and known group validity. The OAQoL was successfully translated into the target languages with minimal problems. Cognitive debriefing interviewees found the measures easy to complete and identified few problems with content. Internal consistency ranged from 0.94 to 0.97 and test-retest reliability (reproducibility) from 0.87 to 0.98. These values indicate that the new language versions produce very low levels of measurement error. Median OAQoL scores were higher for patients reporting a current flare of osteoarthritis in all countries. Scores were also related, as expected, to perceived severity of osteoarthritis. The OAQoL was successfully adapted for use in Germany, Hungary, Italy, Spain and Turkey. The addition of these new language versions will prove valuable to multinational clinical trials and to clinical practice in the respective countries.

Objectives: The study aimed to evaluate biomarkers facilitating early axial-spondyloarthritis (axSpA) diagnosis and disease activity and imaging indices correlated. Materials and Methods: Seventy-five patients with low back pain (LBP) (≥3 months, ≤2 years, onset ≤45 years) participating in the Italian arm of the SpondyloArthritis-Caught-Early (SPACE) study underwent a physical examination, questionnaires, laboratory tests, spine, and sacroiliac joints (SIJ) X-rays and magnetic resonance imaging (MRI) at baseline and during a 24-months follow-up. Two expert rheumatologists formulated axSpA diagnosis and assessed fulfillment of Assessment of SpondyloArthritis International Society (ASAS) criteria. Disease activity and physical functioning were assessed using imaging, clinical, and serological indices. Spine and SIJ MRI and X-rays were scored independently by 2 readers following the Spondyloarthritis Research Consortium of Canada (SPARCC), mSASSS, and mNY-criteria. Patients were classified in accordance to ASAS criteria as: 21 patients classified according to axSpA imaging arm; 29 patients classified according to axSpA clinical ± imaging arm; 25 patients not fulfilling ASAS criteria. Results: At baseline biomarker levels were not significantly increased in any of the patient groups. Instead, a significant decrease of all functional and disease activity indices from baseline to 24 months was observed in all the three groups. In the same period, there were no significant variation in the serological markers values within each group. The correlations between IL-17 and IL-23 and clinical and functional indices were not significant. On the other hand, significant correlations were found between IL-22 and Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Patient Global Score (BASG1), Health Assessment Questionnaire (HAQ), Visual Analog Scale (VAS pain); MMP3 and mSASSS; MMP3 and hsCRP. Conclusions: Although not significantly higher in any of the cohorts, IL-22, MMP3, and hsCRP values correlated with some disease activity indices and with mSASSS. Further studies are warranted to confirm these preliminary findings.

Background Recently several studies have focused on the use of magnetic resonance imaging (MRI) that might facilitate early diagnosis and monitor the disease activity of axial spondyloarthritis (axSpA). Objectives Evaluate the prevalence of spine and pelvis MRI lesions in patients (pts) with low back pain (LBP) and suspected axSpA;investigate how MRI features evolve over time and relate to radiographic damage;identify the predictive factors for a more severe disease pattern with a higher probability of radiological progression. Methods Seventy-five pts with LBP (≥3 months, ≤2 years, onset ≤45 years) underwent a physical examination, questionnaires, laboratory tests, X-rays and MRI of the spine and sacroiliac joints (SIJ) at baseline (T0) and during a follow-up (FU) period of 24 months.Two expert rheumatologists defined axSpA diagnosis and assessed fulfilment of Assessment of SpondyloArthritis International Society ASAS criteria.Disease activity and physical functioning were assessed using: Bath Ankylosing Spondylitis Metrology Index (BASMI);Maastricht Ankylosing enthesitis Spondilities Score (MASES);Bath Ankylosing Spondylitis Disease Activity Index (BASDAI);Bath Ankylosing Spondylitis Functional Index (BASFI);Ankylosing Spondylitis disease activity score (ASDAS);Visual Analogue Scale (VAS pain);VAS night pain;VAS disease activity;Bath Ankylosing Spondylitis Patient Global Score (BASG1);BASG2;Health Assessment Questionnaire (HAQ);ESR;serum ultrasensitive CRP (hs-CRP).Spine and SIJ MRI and X-rays were scored independently by 2 readers following the SPARCC, mSASSS and score SIJ-mNY.Pts were classified in accordance ASAS criteria as:21 pts classified according to axSpA imaging arm;29 pts classified according to axSpA clinical±imaging arm;25 pts not fulfilling ASAS criteria.The Kruskal Wallis test was used to compare all indices during FU.A regression analysis was performed to identify the predictors of inflammation and radiological progression of the disease evaluated using mSASSS, score SIJ-mNY, SPARCC-SIJ and SPARCC-spine.The following independent variables were considered in this analysis:female sex,age of LBP onset,duration of LBP,presence of HLA-B27, elevated ESR/CRP, BASDAI>4, use of NSAIDs. Results The median LBP onset was 28.51±8.05 years, 45.3% were male, HLA-B27 was positive in 38.7% pts; 56% pts showed bone marrow edema (BME) in spine-MRI (19%,39%,33% in cervical/thoracic/lumbar region) and 61.3% pts in SIJ-MRI (respectively 58% on the right SIJ and 50% on the left SIJ).Signs of enthesitis were found in 62.7% pts (respectively 8%,58%,11% in the cervical/thoracic/lumbar spine).Eigtheen (24%) pts presented a negative BME SIJ-MRI with a positive BME spine-MRI.Predictive factors of increased radiological activity were, respectively, for a higher SPARCC-spine score, a higher use of NSAIDs and for a higher SPARCC-SIJ score, the presence of HLA-B27 and increased ESR/CRP.The prevalence of BME lesions on MRI and SPARCC-SIJ decreased during the FU period in the 2 cohorts that met the ASAS criteria for axSpA (Table 1, Figure 1a-b). Conclusion At T0 a significant prevalence of BME lesions was observed both for SIJ and the spine, with predominant involvement of thoracic district.Since positive spine-MRI images were observed in absence of sacroiliitis, we can hyphothesize that this finding could have a diagnostic significance in suspected axSpA.Further studies are warranted to assess in a more exhaustive manner the role of imaging in the monitoring of activity disease and radiological progression. Disclosure of Interests None declared

Background: The 5-item Compliance Questionnaire for Rheumatology (CQR5) allows the identification of patients likely to be high adherers (HAs) to anti-rheumatic treatment (i.e. taking ≥80% of their medications correctly), or “low” adherers (LAs). An Italian version of the questionnaire was validated (I-CQR5) [1]. Objectives: The objective was to investigate what factors are associated with high treatment adherence according to I-CQR5 in RA patients treated with biologic DMARDs (bDMARDs). Methods: RA patients (with disease duration >1 year, undergoing treatment with ≥1 self-administered biological disease-modifying anti-rheumatic drug (bDMARD), willing and capable of completing the questionnaire unaided) were enrolled in the study. I-CQR5 were anonymous and clinical data were collected from the local database. Factors included were demographic, social characteristics of the patients, clinical and treatment variables. Factors achieving a p Results: Among 604 RA patients, 193 patients were included in the validation analysis. Median age of the patients was 57 years (46-65), 142 (73.4%) were females, median disease duration was 15 years (9-21); 82 (42.7%) patients were treated with low dose bDMARDs; 174 (91.1%) patients were in low disease activity or remission (Fig.1). HAs were 40.9% (79/193) of patients: 100% (193/193) of patients treated with bDMARDs and 22.4% (57/193) of those treated with bDMARDs in combination with conventional synthetic DMARDs. Female gender, no employment, lower education level, positive Rheumatoid Factor and/or Anti-Citrullinated Peptides Antibodies, low bDMARD dose, higher patient-VAS were significantly more frequent in LAs compared with HAs. In the multivariate analysis, employment was also positively and significantly associated with high adherence: OR 2.89 (1.3-6.44), p=0.009 (Tab.1). Conclusion: As previously reported only one third of RA patients treated with bDMARDs were found to be HAs to treatment according to the I-CQR5. Employment status was the major determinant, increasing by almost 3-fold the likelihood of being adherent. Education level and female gender might be also taken into account as factors influencing treatment adherence. Reference: [1] Ometto F., et al. Treatment adherence in rheumatoid arthritis italian patients using a validated version of the 5-item compliance questionnaire for rheumatology (I-CQR5). EULAR18-4294. Disclosure of Interests: None declared

Background The most important pathogenetic calcium crystals that can be found in synovial fluid (SF) are calcium pyrophosphate (CPP) and basic calcium phosphate (BCP) crystals. We and others have demonstrated that a good portion of patients with osteoarthritis (OA) have these type of crystals in their SF and that they are associated with a higher inflammatory state independently from the disease severity [1]. Objectives The aim of this study was to investigate the levels of IL-1b, IL-8, IL-6, IL-10, CCL2 and OSMr in the SF of patients affected with OA considering the presence of CPP crystals and the positivity to the alizarin red test (a non-specific test for BCP crystals). A sub-analysis has been conducted subdividing patients according to their Kellgren-Lawrence (K-L) radiographic score. Methods Synovial fluid was collected from 69 OA consecutive patients diagnosed according to the EULAR criteria. Forty patients were negative to (CPP-) and 29 positive to (CPP+) CPP crystals. A standard analysis was performed for each sample including, white blood cell (WBC) count, differential cell count, crystal search under polarized light microscopy and alizarin red test. The cytokines were measured after appropriate dilutions by ELISA (Thermofisher) and expressed as pg/ml. The Mann-Whitney test was used to investigate differences between the groups of patients positive and negative to CPP; the Spearman rank test was used for correlations, while the Kruskal-Wallis to compare the groups according to the K-L score. Results With respect to the group of CPP-, the group of CPP+ patients had higher levels of WBC count (251.7±199.3 vs 176.3±161.8 cells/mm3; p=0.004), PMN% (5±7.1 vs 0.44±1.54; p Although no differences have been found analysing the variables in the groups subdivided by the K-L scores, all the cytokines showed higher levels in patients with a K-L score equal to 2. Conclusion Although associated with higher inflammatory SF indices and IL-1 and IL-8 levels, calcium crystals still play an undefined role in OA. More studies are warranted to evaluate if patients with calcium crystals in their SF might need a more specific treatment. Reference [1] Frallonardo P, Ramonda R, Peruzzo L, Scanu A, Galozzi P, Tauro L, et al. Basic calcium phosphate and pyrophosphate crystals in early and late osteoarthritis: relationship with clinical indices and inflammation. Clin Rheumatol. 2018Jun7. Disclosure of Interests Francesca Oliviero: None declared, Paola Galozzi: None declared, Marta Favero: None declared, Davide Tietto: None declared, Mariagrazia Lorenzin: None declared, Augusta Ortolan: None declared, Leonardo Punzi Consultant for: BMS, Fidia, Grunenthal, Menarini, Speakers bureau: BMS, Fidia, Grunenthal, Menarini, Anna Scanu: None declared, Roberta Ramonda: None declared

The human meniscus plays a crucial role for transmission and distribution of load across the knee, as well as shock absorption, joint stability, lubrication, and congruity. The aim of this study was to compare the complex geometry, and unique ultrastructure and tissue composition of the meniscus in healthy (control) and pathological conditions to provide understanding of structural changes that could be helpful in the future design of targetted therapies and improvement of treatment indications. We analyzed meniscus samples collected from 3 healthy multi-organ donors (median age, 66 years), 5 patients with traumatic meniscal tear (median age, 41 years) and 3 patients undergoing total knee replacement (TKR) for end-stage osteoarthritis (OA) (median age, 72 years). We evaluated the extracellular matrix (ECM) organization, the appearance and distribution of areas of calcification, and modifications of cellular organization and structure by electron microscopy and histology. The ECM structure was similar in specimens from traumatic meniscus tears compared to those from patients with late-stage OA, showing disorganization of collagen fibers and increased proteoglycan content. Cells of healthy menisci showed mainly diffuse chromatin and well preserved organelles. Both in traumatic and in OA menisci, we observed increased chromatin condensation, organelle degeneration, and cytoplasmic vacuolization, a portion of which contained markers of autophagic vacuoles. Areas of calcification were also observed in both traumatic and OA menisci, as well as apoptotic-like features that were particularly prominent in traumatic meniscal tear samples. We conclude that meniscal tissue from patients with traumatic meniscal injury demonstrate pathological alterations characteristic of tissue from older patients undergoing TKR, suggesting that they have high susceptibility to develop OA.

Aim: Osteoarthritis (OA) is a whole joint pathology involving cartilage, synovial membrane, meniscus, subchondral bone, and infrapatellar fat pad (IFP). Synovitis has been widely documented in OA suggesting its important role in pathogenesis. The aim of this study was to investigate the role of different joint tissues in promoting synovitis. Materials and methods: Conditioned media (CM) from cartilage, synovial membrane, meniscus, and IFP were generated from tissues of five patients undergoing total knee replacement and used to stimulate a human fibroblast-like synoviocytes cell line (K4IM). Cytokines, chemokines, and metalloproteases release was analyzed in all CM by Bio-Plex Assay and sulfated glycosaminoglycan (GAG) content by dimethylmethylene blue assay. Gene expression of several markers was evaluated by real-time PCR in K4IM cells stimulated with the CM obtained from joint tissues. Results: CM from all tissues produced high levels of IL-6, IL-8, and CCL2. CCL21, MMP-3, and −13 levels were detected in all CM except IFP. MMP-10 was present only in CM of cartilage and synovial tissues. IL-1β, IL-15, TNF-α, CCL5, and CCL19 were undetectable. However, only K4IM cells stimulated by the CM from OA synovium showed an increase of IL-6, CXCL-8, CCL21, MMP10, and IL-1β expression. Conclusion: Our study showed that K4IM might be a suitable in vitro model for evaluating different cellular pathways in OA studies. Importantly, we demonstrated that in OA, all joint tissues might be involved in the progression of synovitis with a predominant role of synovial membrane itself compared to the other joint tissues.

Non-alcoholic fatty liver disease (NAFLD), potentially evolving into liver fibrosis (LF), is frequent in psoriasis (PsO), but data in psoriatic arthritis (PsA) are lacking. Our study aimed to investigate the prevalence of NALFD and LF in PsA/PsO and the contribution of arthritis in their onset.PsA and PsO patients were consecutively enrolled. Exclusion criteria were liver diseases causing fibrosis (except NAFLD), alcohol ≥ 20 g/day, daily use of non-steroidal anti-inflammatory drugs and current/previous methotrexate use. Clinical history, biochemical and clinimetrical data and insulin-resistance index HOMA (homeostatic model assessment) were assessed. Patients underwent a liver ultrasound to identify steatosis (therefore NAFLD) and transient elastography, to evaluate LF (stiffness≥ 7 kPa = fibrosis). Statistical analysis included basic statistics, logistic and linear regression analyses (to assess the contribution of arthritis to NAFLD and LF grading, respectively) and Spearman's correlations; p ≤ 0.05 was considered significant.Seventy-six patients were enrolled (PsA/PsO 43/33). MetS and LF prevalence were similar between PsA and PsO (35% vs 33%, p = 0.88; 31% vs 28%, p = 0.77, respectively). NAFLD was more frequent in PsO (65% vs 35%, p = 0.044). In multivariable models with NAFLD and LF grading as outcomes, arthritis was not a significant predictor, while HOMA was independently associated with both (OR 1.34; 95%CI 1.06, 1.69; beta 0.88; 95%CI 0.54, 1.21, respectively). Female sex was independently associated with LF grading (beta 1.81; 95%CI 0.05, 3.57).NAFLD was more frequent in PsO, but MetS and LF prevalence were similar in PsA and PsO. Insulin resistance is the main determinant of NAFLD and LF, while additional contribution of arthritis seems small. Key Points • The prevalence of metabolic comorbidities, including liver fibrosis, is overall quite similar between psoriatic arthritis and psoriasis. • NAFLD is more frequently found in psoriasis than psoriatic arthritis. • The contribution of arthritis in the onset of metabolic comorbidities seems small.

Osteoarthritis (OA) is the most common form of joint disease and a major cause of pain and disability in the adult population. Interestingly, there are patients with symptomatic OA displaying pain, while patients with asymptomatic OA that do not experience pain but show radiographic signs of joint damage. Pain is a complex experience integrating sensory, affective, and cognitive processes related to several peripheral and central nociceptive factors besides inflammation. During the last years, the role of infrapatellar fat pad (IFP), other than the synovial membrane, has been investigated as a potential source of pain in OA. Interestingly, new findings suggest that IFP and synovial membrane might act as a functional unit in OA pathogenesis and pain. The present review discuss the role of IFP and synovial membrane in the development of OA, with a particular focus on pain onset and the possible involved mediators that may play a role in OA pathology and pain mechanisms. Inflammation of IFP and synovial membrane may drive peripheral and central sensitization in KOA. Since sensitization is associated with pain severity in knee OA and may potentially contribute to the transition from acute to chronic, persistent pain in knee OA, preventing sensitization would be a potentially effective and novel means of preventing worsening of pain in knee OA.

The aim of this study was to identify the molecules and pathways involved in the cross-talk between meniscus and synovium that may play a critical role in osteoarthritis (OA) pathophysiology. Samples of synovium and meniscus were collected from patients with early and end-stage OA and cultured alone or cocultured. Cytokines, chemokines, metalloproteases, and their inhibitors were evaluated at the gene and protein levels. The extracellular matrix (ECM) changes were also investigated. In early OA cultures, higher levels of interleukin-6 (IL-6) and IL-8 messenger RNA were expressed by synovium and meniscus in coculture compared with meniscus cultured alone. RANTES release was significantly increased when the two tissues were cocultured compared with meniscus cultured alone. Increased levels of matrix metalloproteinase-3 (MMP-3) and MMP-10 proteins, as well as increased release of glycosaminoglycans and aggrecan CS846 epitope, were observed when synovium was cocultured with meniscus. In end-stage OA cultures, increased levels of IL-8 and monocyte chemoattractant protein-1 (MCP-1) proteins were released in cocultures compared with cultures of meniscus alone. Chemokine (C-C motif) ligand 21 (CCL21) protein release was higher in meniscus cultured alone and in coculture compared with synovium cultured alone. Increased levels of MMP-3 and 10 proteins were observed when tissues were cocultured compared with meniscus cultured alone. Aggrecan CS846 epitope release was increased in cocultures compared with cultures of either tissue cultured alone. Our study showed the production of inflammatory molecules by synovium and meniscus which could trigger inflammatory signals in early OA patients, and induce ECM loss in the progressive and final stages of OA pathology.

The infrapatellar fat pad (IFP) is an intracapsular but extrasynovial structure, located between the patellar tendon, the femoral condyles and the tibial plateau. It consists of white adipose tissue, organised in lobules defined by thin connective septa. The aim of this study is the morphometric and ultrasonographic analysis of IFP in subjects without knee pathology during flexion‐extension movements. The morphometric study was conducted on 20 cadavers (15M, 5F, mean age 80.2 years). Ultrasound was performed on 24 volunteers with no history of knee diseases (5M, 19F, mean age: 45 years). The characteristics of the adipose lobules near the patellar tendon and in the deep portion of the IFP were evaluated. Numerical models were provided, according to the size of the lobules. At histological examination, the adipose lobules located near the patellar tendon were larger (mean area 12.2 mm(2) ± 5.3) than those at a deeper level (mean area 1.34 mm(2) ± 0.7, P 0.05). In the sagittal plane, the reduction of thickness of the superficial layer (with large adipose lobules) during flexion was 20.6%, whereas that of the deep layer (with small adipose lobules) was 1.3%. Numerical simulation of vertical loads, corresponding to flexion of the knee, showed that stress mainly developed within the interlobular septa and opposed bulging of the lobules. The characteristics of the lobular arrangement of the IFP (large lobules with superficial septa in the superficial part and small lobules with thick septa in the deep one), significant changes in the areas and perimeters of the superficial lobules, and the reduced thickness of the superficial layer during flexion all indicate the dynamic role played by the IFP in knee kinematics.

The aim of this study was to analyze the magnetic resonance imaging (MRI) volumetric and morphometric characteristics of the infrapatellar fat pad (IFP) and the suprapatellar fat pad (SFP) in normal controls, moderate and end-stage osteoarthritis (OA) patients. Forty-four MRI images of the three groups were collected: a) 17 patients undergoing meniscectomy with Outerbridge score 0 (control group); b) 15 patients undergoing meniscectomy with Outerbridge score 3/4 (moderate OA group); and c) 12 patients undergoing total knee replacement (end-stage OA group). Volume, depth, femoral and tibial arch lengths of IFP were quantified. The hypointense IFP signals were also scored. The SFP volume, oblique, antero-posterior and cranio-caudal lengths were determined. IFP and SFP characteristics were compared between groups. A decrease of IFP volume, depth, femoral, and tibial arch lengths in moderate and end-stage OA compared to controls were observed. A difference in IFP hypointense signal was found between groups. No differences were found in SFP characteristics between the groups. In controls and moderate OA patients, correlations were found among the different MRI characteristics of both IFP and SFP, while in the end-stage OA group correlations were found only in SFP. We evidenced differences of the IFP MRI morphometric characteristics between the groups analyzed, supporting an important role of IFP in OA pathology and progression. On the contrary, no differences were highlighted in SFP analysis suggesting that this fat pad is not clearly involved in OA, probably due to its peculiar localization and different function.

Background The 5-item Compliance Questionnaire for Rheumatology (CQR5) allows the identification of patients likely to be high adherers (HA) to anti-rheumatic treatment (i.e. taking ≥80% of their medications correctly), or “low” adherers (LA).1 We have previously validated an Italian version of the questionnaire (I-CQR5) following standardised guidelines. Objectives The objective was to investigate what factors are associated with high treatment adherence according to I-CQR5 in RA. Methods RA patients (disease duration >1 year, undergoing treatment with ≥1 self-administered biological or conventional synthetic disease-modifying anti-rheumatic drugs (bDMARDs, csDMARDs), capable of completing the questionnaire unaided) completed I-CQR5 on one occasion. I-CQR5 were anonymous and clinical data were retrieved anonymously from the local database. To investigate what factors were associated with high adherence, we included demographic and social characteristics, clinical and treatment information. Factors achieving a p Results Among 604 RA patients, 328 patients were enrolled, 18 questionnaires were incomplete. Median age of the patients was 57 years,48–67 females were 232 (82%), disease duration was 12 years;7–19 193 (64.3%) patients were treated with bDMARDs and 107 (54.6%) with csDMARD only; 270 (90.3%) were in low disease activity or remission (figure 1). HA were found to be 35.2% (109/310) of the patients.40.2% (79/193) were on bDMARDs and 22.4% (24/107) on csDMARDs. Older age, lower education level, higher prednisone daily dose, use of a csDMARD (particulary hydroxychloroquine and sulfasalazine) and higher patient-VAS were significantly more frequent in LA compared with HA (figure 1). In the multivariate analysis, bDMARD treatment and employment resulted independently associated with high adherence: OR 2.88 (1.36–6.1), p=0.006 and OR 2.36 (1.21–4.62), p=0.012 respectively (table 1). Conclusions Only one third of Italian RA patients were highly adherent to treatment according to I-CQR5. Treatment with bDMARDs and employment status were the major determinants of treatment adherence, increasing by almost 3-fold the likelihood of being highly adherent. Reference [1] Hughes L, et al. A 5 item version of the Compliance Questionnaire for Rheumatology (CQR5) successfully identifies low adherence to DMARDs. BMC Musculoskelet Disord2013;14:286. Disclosure of Interest None declared

Background The 5-item Compliance Questionnaire for Rheumatology (CQR5) allows the identification of patients likely to be high adherers (HA) to anti-rheumatic treatment (i.e. taking ≥80% of their medications correctly), or “low” adherers (LA). 1 Objectives The objective was to validate the construct of an Italian version of CQR5 in rheumatoid arthritis (RA). Methods Cross-cultural adaptation comprised: forward translation, synthesis of the translations, back-translation, expert committee assessment and field-testing. Validation was conducted administering the adapted version (I-CQR5) to RA patients (disease duration >1 year, treated with ≥1 self-administered disease-modifying anti-rheumatic drug, capable of completing the questionnaire unaided) on one occasion. Questionnaires were anonymous but contained self-reported data. Construct validity and reliability were assessed with Rasch analysis (Partial Credit model Parametrisation, PCM). Martin-Loef Likelihood ratio test assessed invariance for gender, age, education, social status and disease duration. Results The adaptation process was closed by the expert committee assessment. I-CQR5 is reported in Figure 1. Among 604 patients, 274 were included in the validation process, 6 questionnaires were incomplete. Median age was 57 years (48–67), females were 201 (77%), disease duration was 13.5 years (8.8–19.3), most patients lived with partner/family (159,75%) and had a middle/secondary school education (184,69%). HA were 93 (67%) and LA 179 (35%). Factor analysis revealed ordered thresholds in most items, 2 factors were sufficient to explain variability (Chi-square=0.46,p=0.5) (Tab.1). Item-fit statistics showed overall agreement of items with parametrisation (Infit statistics=0.6–1.4; excluding item no.5). Chi-square showed agreement with PCM parametrisation by item (excluding the item no.1). Martin-Loef likelihood ratio test confirmed unidimensionality (Chi-square 65.8, df=53,p=0.11) and Separation Reliability Index confirmed internal consistency (Patient Separation Index 0.91) (Tab.1). I-CQR5 was invariant to age (Chi-square=40.6, df=28,p=0.059), education level (Chi-square=49.9, df=42,p=0.187), social status (Chi-square=10.5, df=15,p=0.79), disease duration (Chi-square=13.6, df=36,p=0.220); Martin-Loef test was significant for gender (Chi-square=25.4, df=14,p=0.031). Conclusions I-CQR5 was well understood by patients and construct validity, unidimensionality and internal consistency were confirmed by factor analysis and PCM. Reference [1] Hughes L, et al. A 5 item version of the Compliance Questionnaire for Rheumatology (CQR5) successfully identifies low adherence to DMARDs. BMC Musculoskelet Disord2013;14:286. Disclosure of Interest None declared

The Infrapatellar Fat Pad (IFP) lies between patella, femur, meniscus and tibia and properly fills the space between these structures. This fatty structure facilitates distribution of synovial fluid and may act to absorb impulsive actions generated through the joint. In case of Osteoarthritis (OA), IFP is found to be affected by inflammation, hypertrophy and fibrosis. The aim of the present study is to analyze the correlation between microscopic characteristics and mechanical properties of the IFP in healthy and OA conditions. The microscopic anatomy of the IFP was analyzed through histological methods, whose results showed that the IFP affected by OA maintains similar lobules configuration but thicker interlobular septa. Geometrical data together with the morphological analysis of lobules and septa represented the basic data to provide numerical micro-models of the IFP. Numerical analyses were developed to evaluate the mechanical behavior considering the characteristic loading conditions as compressive, torsion and shear actions. The results were applied to identify the parameters of a homogenized hyperelastic constitutive formulation that interprets the IFP mechanics. The constitutive formulation was implemented within a finite element model of the knee, which was applied to evaluate the overall mechanical functionality of the knee structures. The results pointed out the actual mechanical relevance of IFP and the loss of proper stress-strain behavior of the OA IFP under mechanical loads.

The current prospective observational study aimed to evaluate the long-term (24 months), real-life effectiveness of ustekinumab in psoriatic arthritis (PsA). Consecutive patients with moderate-severe PsA and active psoriasis who begun ustekinumab treatment were evaluated prospectively (January 2015–March 2017). Clinimetric scores and biochemical values were assessed at baseline (T0), at 6 (T6), 12 (T12), and 24 (T24) months. Friedman test and generalized linear models were used to compare variables over time. Regression analysis to identify determinants of minimal disease activity (MDA) at T6 and of treatment discontinuation was conducted. Sixty-five patients (43.1% men; age 49.4 ± 11.6 years) were enrolled; ustekinumab was prescribed as a first (20%), second (33.8%), third (26.5%), fourth (15.4%), or fifth (4.6%) line biological therapy. Significant decrease in tender/swollen joints, Visual Analogue Scale of pain (VASp) and general health (VASgh), Disease Activity in PsA (DAPSA), Psoriasis Area Severity Index (PASI), Leeds Enthesitis Index (LEI), Health Assessment Questionnaire modified for spondyloarthritis (HAQ-S), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) was achieved. MDA was reached by 30.7, 47.0, and 34.0% of patients respectively at T6, T12, and T24. In multivariable models, mono-oligoarthritis was independently associated to MDA at T6 (OR 9.02; 95% CI 1.41, 57.71), while baseline CRP (OR 1.12; 95% CI 1.00, 1.26) and LEI (OR 0.50; 95% CI 0.25, 0.97) to ustekinumab discontinuation. More patients used disease-modifying antirheumatic drugs at T0 (35.3%) than at T24 (8.5%). Only nine episodes of infection and no serious adverse events were registered. In a real-life clinical setting, ustekinumab was safe and effective in PsA. Comedication tapering was often possible.

The infrapatellar pad, a fibro-adipose tissue with peculiar microscopic and mechanical features, is gaining wide attention in the field of rheumatological research. The purpose of this descriptive review is to summarize the most recent published evidence on the anatomic, physiologic and biomechanical inter-relationship between the infrapatellar fat pad and the knee synovial membrane. As an extrasynovial tissue, the infrapatellar fat pad does not directly interact with the articular cartilage; based on its location in close contact with the synovial membrane, and due to the metabolic properties of adipose tissue, it may influence the behavior of the synovial membrane. In fact, considering evidence of macroscopic and microscopic anatomy, the infrapatellar fat pad is the site of insertion of the infrapatellar and medial synovial plicae. Also biochemically, there is much evidence highlighting the interaction among these two structures; in the case of inflammation, the mutual interplay is ascribable to the release of pro-inflammatory mediators stimulating the proliferation of inflammatory cells and promoting tissue modifications in both. All these assumptions could support the emerging idea that the infrapatellar fat pad and the synovial membrane may be considered a morpho-functional unit.

The aim of this study was to assess the frequency of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluids (SFs) aspirated from wrist and finger joints of patients with previously diagnosed joint diseases. We reviewed the results of SF analysis of 1593 samples and identified 126 patients with effusions in the small joints of the hands and wrists. We reported from patients' medical files data about sex, age, diagnosis, disease duration and the microscopic SF results. The prevalence of CPP crystals in SF was 85.71% in CPP-crystals arthritis (CPP-CA), 19.35% in rheumatoid arthritis (RA), 13.89% in osteoarthritis (OA) and 0% in psoriatic arthritis (PsA), spondyloarthritis (SpA), gout and miscellanea. The prevalence of MSU crystals in SF was 83.3% in gout, 10% in PsA, 2.8% in OA and 0% in RA, SpA, miscellanea and CPP-CA. Consistent with previously reported data concerning the big joints, microcrystals can be frequently found also in the small joints of patients with previous diagnosis. The finding underlines the importance of analyzing SF from the hand and wrist joints in the attempt to identify comorbidities associated with the presence of crystals and to develop targeted treatment strategies.

Synovial inflammation plays an important role in osteoarthritis (OA) pathogenesis. Different biological compounds have been tested mainly on chondrocytes, to treat early stages of OA. However, because OA has been recently defined as "an organ" pathology, investigation on synoviocytes is also needed. Therefore, the aim of the present study was to validate a human fibroblast-like synoviocytes cell line (K4IM) to test the effects of platelet-rich plasma (PRP) and hyaluronan (HA) on anabolic and catabolic gene expression and on HA secretion from cell cultures. In order to determine the effect of PRP and HA, K4IM cells were maintained in culture with or without TNF-α stimulation. In the presence of PRP, unstimulated K4IM cells presented the same expression of IL1B, IL6, CXCL8, VEGF, TIMP1, and hyaluronic synthase isoform HAS3 as primary human synoviocytes, while HA addition did not change their expression pattern, which was similar to control cells. Stimulated cells expressed significantly higher values of IL1B, CXCL8, and VEGF compared with unstimulated ones. PRP did not show any modification, except for VEGF, while HA addition modulated IL1B expression. PRP did not modulate HA release of both stimulated and unstimulated cells. Our study showed the possibility to use K4IM synoviocytes as an in vitro model to test biological compounds useful for the treatment of early OA. Primary cells reflect the phenotype of cells in vivo, but limited recovery from biopsies and restricted lifespan makes experimental manipulation challenging. Therefore, despite cell lines present some limitations, they could be used as an alternative for preliminary experiments.

Background Resveratol (RES) and its natural precursor polydatin (PD) are polyphenol compounds that display a broad variety of beneficial effects including anti-apoptotic and anti-inflammatory properties. Objectives This study aimed to investigate the role of RES and PD in the inflammatory process induced by monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in vitro. Their effect was evaluated though IL-1β, NLRP3 inflammasome, reactive oxygen species (ROS), nitric oxide (NO) and the phagocytosis index assessment. Methods A monocytic cell line (THP-1) was primed for 3 hours with phorbol myristate acetate (PMA) (100ng/ml) and stimulated with synthetic MSU (0.05mg/ml) and CPP (0.025mg/ml) crystals. RES and PD were added to cultures at, respectively, 100μM and 200μM. Experiments were carried out either adding RES and PD along with crystals, or pretreating cells (2 hs) with polyphenols and removing them before crystal stimulation. IL-1β were evaluated in cell supernatants and at intracellular level by ELISA assay. IL-1β and NLRP3 expression was assessed by RT-PCR. Reactive oxygen species (ROS) and NO were measured by cytometric analysis using fluorogenic probes (CellROX Deep Red Reagent and DAF-FM, respectively). Crystal phagocytosis index was calculated at different time points using polarized light microscopy. Results RES and PD inhibited IL-1b induced by crystals both at extracellular and intracellular level. This inhibition was more pronounced after polyphenol cell pretreatment. In this case cytokine production was completely suppressed both in control and in stimulated cells. Cell pretreatment was extremely effective also in reducing mRNA expression of IL-1 after crystal stimulation while NLRP3 expression was to some extent affected by RES. RES and PD had a slight inhibitory effect on crystal phagocytosis when added along with the stimulus, while pretreated cells did not show any difference in the phagocytosis index. ROS production induced by MSU crystals was more pronounced (4 fold increase) with respect to CPP crystals (2 fold increase). RES was more effective than PD in inhibiting ROS production (p Conclusions Our results demonstrated that RES and PD are effective in inhibiting crystal-induced inflammation affecting IL-1 production and NLRP3 expression and activation. Data obtained after cell pretreatment allow us to hypothesize that these polyphenols act on specific signaling pathway preventing inflammation, and that this action is independent from crystal phagocytosis. Disclosure of Interest None declared

Osteoarthritis (OA) is characterized by chronic degeneration of joints, involving mainly the articular cartilage and the underlying bone, and severely impairing the quality of life of the patient. Although with limited efficacy, currently available pharmacological treatments for OA aim to control pain and to retard disease progression. Salmon calcitonin (sCT) is a drug which has been shown to have therapeutic effects in experimental arthritis by inhibiting both bone turnover and cartilage degradation and reducing the activities of matrix metalloproteinases (MMP). High molecular weight hyaluronic acid (HA) is used as a lubricant in OA therapy, and, interestingly, HA polymers may normalize the levels of MMP-1, -3 and -13. We demonstrated that sCT rapidly clears from the knee joint of rat animal model, after intra-articular (i.a.) administration, and it induces systemic effects. Here, sCT was conjugated to HA (200kDa) with the aim of prolonging the residence time of the polypeptide in the joint space by reducing its clearance. An aldehyde derivative of HA was used for N-terminal site-selective coupling of sCT. The activity of sCT was preserved, both in vitro and in vivo, after its conjugation and the i.a. injection of HA-sCT did not trigger any systemic effects in rats. The efficacy of HA-sCT treatment was tested in a rabbit OA model and clear chondro-protective effect was proven by macro- and microscopic assessments and histological findings. Our results indicate that HAylation of sCT increases the size of the polypeptide in a stable covalent manner and delays its passage into the blood stream. We conclude that HA conjugation prolongs the anti-catabolic effects of sCT in joint tissues, including the synovial membrane and cartilage.

Background and aims: Knee osteoarthritis (KOA) is a common cause of disability and pain in adults. Obesity is increasingly recognized as the primary modifiable risk factor for the onset and progression of KOA. The mechanisms that link the two conditions are still not fully clarified but recent data suggest an important role mediated by the infrapatellar fat pad (IFP). Accordingly, we aimed to determine the histomorphological characteristics of IFP in individuals affected by KOA and compare them to those obtained from lean healthy individuals using a histological scoring system. Moreover, we determined the expression of certain adipocytokines in IFP of KOA subjects. Materials and Methods: We enrolled 28 subjects (BMI 35.5±5 kg/m2) undergoing total knee replacement for OA. The controls were represented by IFP and adjacent synovial membrane specimens sampled from bodies or bodies part of 8 healthy subjects without history of osteoarthritis involved in the Body Donation Program ‘Donation to Science’ held by the University of Padova. The microscopic anatomy of IFP was analyzed through histological and morphometrical methods. The histology of the synovial membrane adjacent to the IFP was also analyzed. We determined mRNA expression using Quantitative real time PCR for adipokines (leptin, adiponectin, Peroxisome proliferator-activated receptor gamm, fatty acid binding protein4) and cytokines (Interleukin 6 [IL-6], Tumor necrosis factor alfa[TNF-α], Monocyte chemoattractant protein-1[MCP-1], Vascular endothelial growth factor [VEGF]) in the IFP specimens of KOA subjects. Results: All the evaluated IFPs showed microscopical characteristics similar to white adipose tissue. IFPs were organized in adipose lobuli separated by fibrous septa. No differences were detected in the mean diameter of the adipose lobuli of the IFP in KOA patients and controls. Mononuclear infiltration was present in 22 KOA patients while it was not observed in any of the IFP used as control (p = 0.001). The average number of vessels and the thickness of interlobular septa were significantly higher in KOA patients compared to controls (p < 0.0001 and p = 0.004 respectively). BMI correlated positively with the thickness of the interlobular septa in IFP (p= 0.02, r= 0.42). Concerning synovial membrane, the presence of lymphocytic infiltration and hyperplasia was statistically higher in KOA compared to controls (p

Bartter's and Gitelman's syndromes are two different genetic renal diseases, but are both characterised by hypokalaemia and metabolic alkalosis. Bartter's syndrome is characterised by multiple gene mutations (Na-K-2Cl cotransporter; K(+) channels renal outer medullary potassium channel (ROMK); Cl channels, chloride channel Kb (ClCNKb); regulatory protein Barttin; and Ca(2+) -sensing receptor, CaSR) at the thick ascending limb of Henle's loop, while Gitelman's syndrome is caused by a mutation in the gene encoding the renal thiazide sensitive Na(+)-Cl(-) cotransporter, located in the apical membrane of the distal convoluted tubule. The co-existence of hypokalaemia with hypomagnesaemia and hypocalciuria represents the biochemical hallmark of Gitelman's syndrome that distinguishes it from Bartter's syndrome. Calcium pyrophosphate deposition (CPPD) including chondrocalcinosis has been frequently reported in association with Bartter's syndrome. Some authors postulate that these cases were probably due to Gitelman's syndrome and not due to Bartter's syndrome as all patients had hypomagnesaemia. This electrolyte disorder seems to induce CCP crystal deposition. To date, no cases of CPPD have been reported in patients who had Bartter's syndrome without hypomagnesaemia. CPPD may be found in other conditions associated with hypomagnesaemia, such as short bowel syndrome or tacrolimus therapy in liver transplantation patients. As acute CPP crystal arthropathy or pseudogout can be the onset presentation of Gitelman's syndrome, CPPD should be considered a major feature of this disease. Rheumatologists should be aware of the association between Gitelman's syndrome and CPPD, and should consider this metabolic disorder when CPPD occurs in younger patients.

This study aimed to apply the recently proposed Oslo hand osteoarthritis magnetic resonance imaging (MRI) scoring system to evaluate MRI findings in a cohort of patients affected by long-standing erosive hand osteoarthritis (EHOA). Eleven female EHOA patients (median 59 [interquartile range 62-52] years, disease duration 9.5 [interquartile range 13-3.75] years) underwent MRI (1.5 T) of the dominant hand, and synovitis, bone marrow lesions (BMLs), joint space narrowing, osteophytes, cysts, malalignment, and erosions were scored using the Oslo scoring system. Intra- and inter-reader reliability were assessed. The patients also underwent X-ray examination, and bone features were evaluated using the same scoring system. Pain and tenderness were assessed during a physical examination. Spearman's non-parametric test was used to analyze the correlations between variables. MRI intra- and inter-reader reliability were found between good and moderate for many features. No statistical differences were found between the radiographs and MRI with regard to detection of JSN, malalignment, and bone erosions. Synovitis was detected in 39.8 % of the 80 joints examined (in a mild form in 80 %), erosions were found in 51.1 %, and BMLs were identified in 20.5 and 23.9 % at the distal and the proximal side, respectively. BMLs at both the proximal and distal ends were correlated with tender joints (BML distal p = 0.0013, BML proximal p = 0.012). The presence of synovitis was correlated with tenderness (p = 0.004) and erosions at both the distal and proximal joints (p = 0.004). The presence of erosions correlated with tender joints (p

Osteoarthritis (OA), a disease that mainly targets cartilage, also affects ligaments, the subchondral bone and synovium, and, according to recent definitions, it is a disease of the joint as an organ.1 Its most characteristic radiographic features are joint space narrowing, bone sclerosis and osteophytes;2 bone erosions, and in particular subchondral bone erosions, have also been found in some patients.3 Bone erosions that classically affect the interphalangeal (IP) joints identify a disease subset called erosive osteoarthritis (OA).4 The particular localisation of erosive OA is considered so characteristic of the disease that the term has been used, since it was first described by Peter et al ,5 almost interchangeably with erosive hand OA. A growing body of evidence, however, suggests that it is time to re-evaluate the definition, since the term erosive OA can be appropriately applied to other OA localisations including at the thumb base (TB)6 and facet joints.7 These different disease subsets share not only the same classic radiographic features, such as subchondral bone erosions, but also the severity …

This review summarises recent evidence about the interaction between bone, the immune system and cartilage in disabling conditions such as osteoarthritis, rheumatoid arthritis and spondyloarthritis. These topics have been recently discussed at the 'OsteoRheumatology' conference held in Genoa in October 2014. The meeting, at its 10th edition, has been conceived to bring together distinguished international experts in the fields of rheumatic and metabolic bone diseases with the aim of discussing emerging knowledge regarding the role of the bone tissue in rheumatic diseases. Moreover, this review focuses on new treatments based on underlying the pathophysiological processes in rheumatic diseases. Although, a number of issues still remain to be clarified, it seems quite clear that in clinical practice, as well as in basic and translational research, there is a need for more knowledge of the interactions between the cartilage, the immune system and the bone. In this context, 'OsteoRheumatology' represents a potential new discipline providing a greater insight into this interplay, in order to face the multifactorial and complex issues underlying common and disabling rheumatic diseases.