Relationship between sex and clinical and imaging features of early axial spondyloarthritis: results from a 48 month follow-up (Italian arm of the SPondyloArthritis Caught Early (SPACE) study).

OBJECTIVES: To assess the association between sex and clinical and disease activity indices, and X-rays and magnetic resonance imaging (MRI) features, in early-stage axial spondyloarthritis (axSpA). METHOD: Baseline data analysis was conducted on the Italian SPACE cohort, including patients with chronic back pain (duration ≥ 3 months and ≤ 2 years; onset < 45 years). Patients underwent MRI and X-rays of the sacroiliac joints (SIJs) to establish the diagnosis of axSpA, according to Assessment of SpondyloArthritis international Society criteria and physician's judgement. Clinical features, disease activity and functional indices, and images were collected at baseline and yearly during 48 months. Spinal and SIJ X-rays and MRI images were scored by two readers following Spondyloarthritis Research Consortium of Canada (SPARCC), modified Stoke Ankylosing Spondylitis Spinal Score, and modified New York criteria. Characteristics of axSpA patients according to sex (male/female) were compared over time using descriptive statistics. RESULTS: Ninety-one patients had axSpA (83.5% non-radiographic; 16.5% radiographic); 47.3% were male. Males were younger, with shorter duration of axial symptoms, and more frequently had HLA-B27 positivity, radiographic sacroiliitis with a bilateral/symmetric pattern, and more signs of spondylitis. Females more frequently showed peripheral/entheseal involvement and the non-radiographic phenotype. Males showed increased pelvic/spinal radiographic progression and more often had active sacroiliitis on MRI. Although the frequency of inflammatory corner lesions did not differ between males and females, localization varied, with more cervical/thoracic MRI-spine lesions in females and more lumbar lesions in males. We observed a significant downward trend of SPARCC SIJ/spine scores in all patients, irrespective of sex. More fat lesions were observed on MRI-spine in females and on MRI-SIJ in males. CONCLUSION: Sex was associated with distinct axSpA features: females showed low-grade radiographic sacroiliitis and spinal progression, and a higher prevalence of cervical and thoracic spine MRI signs.

Effect of an oral preparation containing hyaluronic acid, chondroitin sulfate, hydrolyzed collagen type II and hydrolyzed keratin on synovial fluid features and clinical indices in knee osteoarthritis. A pilot study.

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-1ß, 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<0.01), Lequesne (p=0.014) and VAS pain (p<0.01). On the contrary, no significant changes were found in the control group. The SF collected from the treated group showed a reduction of IL-8 (p=0.015), IL-6 and IL-10 levels, while no changes in cytokines were observed in the control group. This pilot study suggests that an oral administration of a preparation containing a combination of HA, CS and K can improve some clinical parameters and affect cytokine concentrations in SF in patients with knee OA.

SARS-CoV-2 infection in patients with autoimmune rheumatic diseases in northeast Italy: A cross-sectional study on 916 patients.

BACKGROUND: Whether patients with autoimmune rheumatic diseases (ARD) have a higher risk for SARS-CoV-2 infection (COVID-19) and how SARS-CoV-2 pandemic impacts on adherence to therapy has not been fully elucidated. We assessed the rate and clinical presentation of COVID-19, and adherence to therapy in a large cohort of patients with ARD followed-up in a tertiary University-Hospital in Northeast Italy. METHODS: Between April 9th and April 25th, 2020, after SARS-CoV-2 infection peak, a telephone survey investigating the impact of COVID-19 on patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), ANCA-associated vasculitis (AAV), and idiopathic inflammatory myopathies (IIM) was administered. Demographics, disease activity status, therapy, occupational exposure, and adherence to social distancing advise were also collected. RESULTS: 916 patients (397 SLE, 182 AAV, 176 SSc, 111 RA, 50 IIM) completed the survey. 148 patients developed at least one symptom compatible with COVID-19 (cough 96, sore throat 64, fever 64, arthromyalgias 59, diarrhea 26, conjunctivitis 18, ageusia/hyposmia, 18). Among the 916 patients, 65 (7.1%) underwent SARS-CoV-2 nasopharyngeal swab (18 symptomatic and 47 asymptomatic), 2 (0.21%) tested positive, a proportion similar to that observed in the general population of the Veneto region. No deaths occurred. 31 patients (3.4%) withdrew ≥1 medication, mainly immunosuppressants or biologics. Adoption of social distancing was observed by 860 patients (93.9%), including 335 (36.6%) who adopted it before official lockdown. CONCLUSIONS: COVID-19 incidence seems to be similar in our cohort compared to the general population. Adherence to therapy and to social distancing advise was high.

Distinct tribological endotypes of pathological human synovial fluid reveal characteristic biomarkers and variation in efficacy of viscosupplementation at reducing local strains in articular cartilage.

OBJECTIVE: Viscosupplementation has been used for decades to treat mild to moderate osteoarthritis, yet it is unknown if the lubricating function of different pathological synovial fluids (SF) vary, or if they respond differentially to viscosupplementation. The objectives of this study were to (i) evaluate the friction coefficients and induced shear strains in articular cartilage when lubricated with pathological SF, (ii) identify the effect of hyaluronic acid (HA) supplementation on friction coefficients and shear strains, and (iii) identify SF biomarkers that correlate with lubricating function. METHOD: Human pathological SF was grouped by white blood cell count (inflammatory: >2000 cells/mm3, n = 6; non-inflammatory: <2000 cells/mm3, n = 6). Compositional analyses for lubricin and cytokines were performed. Friction coefficients and local tissue shear strain measurements were coupled using new, microscale rheological analyses by lubricating neonatal bovine cartilage explants with SF alone and in a 1:1 ratio with HA (Hymovis®). RESULTS: Friction coefficients were not significantly different between the inflammatory and non-inflammatory pathologies (p = 0.09), and were poorly correlated with peak tissue strains at the cartilage articular surface (R2 = 0.34). A subset of inflammatory SF samples induced higher tissue strains, and HA supplementation was most effective at lowering friction and tissue strains in this inflammatory subset. Across all pathologies there were clear relationships between polymorphonuclear neutrophil (PMN), IL-8, and lubricin concentrations with cartilage tissue strains. CONCLUSION: These results suggest that pathological SF is characterized by distinct tribological endotypes where SF lubricating behaviors are differentially modified by viscosupplementation and are identifiable by biomarkers.

Is it Useful to Repeat Magnetic Resonance Imaging of the Sacroiliac Joints After Three Months or One Year in the Diagnosis of Patients With Chronic Back Pain and Suspected Axial Spondyloarthritis?

OBJECTIVE: To investigate the value of repeated magnetic resonance imaging (MRI) of the sacroiliac (SI) joints in diagnosing chronic back pain patients in whom axial spondyloarthritis (SpA) is suspected and to examine determinants of positive MRI findings in SI joints. METHODS: Patients with chronic back pain (duration 3 months-2 years, age ≥16 years, age at onset <45 years) with ≥1 SpA feature who were included in the Spondyloarthritis Caught Early cohort underwent visits at baseline, at 3 months, and at 1 year. Visits included an evaluation of all SpA features and repeated MRI of SI joints. MRI-detected axial SpA positivity (according to the definition from the Assessment of SpondyloArthritis international Society) was evaluated by 2 or 3 well-trained readers who were blinded with regard to clinical information. The likelihood of a positive MRI finding at follow-up visits (taking into consideration contributing factors) was calculated by generalized estimating equation analysis. RESULTS: Of the 188 patients, 38.3% were male, the mean ± SD age was 31.0 ± 8.2 years, and the mean ± SD symptom duration was 13.2 ± 7.1 months. Thirty-one patients (16.5%) had positive MRI findings in the SI joints at baseline. After 3 months and after 1 year, the MRI results had changed from positive to negative in 3 of 27 patients (11.1%) and 11 of 29 patients (37.9%), respectively, which was attributable in part to the initiation of anti-tumor necrosis factor therapy. Status changes from negative to positive were seen in 5 of 116 patients (4.3%) after 3 months and in 10 of 138 patients (7.2%) after 1 year. HLA-B27 positivity and male sex were independent determinants of the likelihood of a positive MRI scan at any time point (42% in HLA-B27+ men and 6% in HLA-B27- women). If the baseline results were negative, the likelihood of a positive scan at follow-up was very low (≤7%). CONCLUSION: MRI-detected status changes in the SI joints were seen in a minority of the patients, and both male sex and HLA-B27 positivity were important predictors of MRI positivity. Our findings indicate that conducting MRI scans after 3 months or after 1 year in patients with suspected early axial SpA is not diagnostically useful.

The Italian Society of Rheumatology clinical practice guidelines for the diagnosis and management of gout.

Gout is a chronic disease with an increased risk of premature death related to comorbidities. Treatment of gout has proved suboptimal and clinical practice guidelines (CPGs) are expected to have a key role in achieving improvement. Since new evidence has become available, the Italian Society for Rheumatology (SIR) has been prompted to update the 2013 recommendations on the diagnosis and management of gout. The framework of the Guidelines International Network Adaptation Working Group was adopted to identify, appraise (AGREE II), synthesize, and customize the existing gout CPGs to the needs of the Italian healthcare context. The task force consisting of rheumatologists from the SIR Epidemiology Unit and a committee with experience on gout identified key health questions to guide a systematic literature review. The target audience includes physicians and health professionals who manage gout in practice, and the target population includes adult patients suspected or diagnosed as having gout. These recommendations were finally rated by an external multi-disciplinary commission. From a systematic search in databases (Medline, Embase) and grey literature, 8 CPGs were selected and appraised by two independent raters. Combining evidence and statements from these CPGs and clinical expertise, 14 recommendations were developed and graded according to the level of evidence. The statements and potential impact on clinical practice were discussed and assessed. These revised recommendations are intended to provide guidance for the diagnosis and the treatment of gout and to disseminate the best evidence-based healthcare for this disease.

Cultures of a human synovial cell line to evaluate platelet-rich plasma and hyaluronic acid effects.

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.

Biomarkers, imaging and disease activity indices in patients with early axial spondyloarthritis: the Italian arm of the SpondyloArthritis-Caught-Early (SPACE) Study.

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.

Evidence-based algorithm for diagnosis and assessment in psoriatic arthritis: results by Italian DElphi in psoriatic Arthritis (IDEA).

Psoriatic arthritis (PsA) is a chronic inflammatory disease involving skin, peripheral joints, entheses, and axial skeleton. The disease is frequently associated with extrarticular manifestations (EAMs) and comorbidities. In order to create a protocol for PsA diagnosis and global assessment of patients with an algorithm based on anamnestic, clinical, laboratory and imaging procedures, we established a DElphi study on a national scale, named Italian DElphi in psoriatic Arthritis (IDEA). After a literature search, a Delphi poll, involving 52 rheumatologists, was performed. On the basis of the literature search, 202 potential items were identified. The steering committee planned at least two Delphi rounds. In the first Delphi round, the experts judged each of the 202 items using a score ranging from 1 to 9 based on its increasing clinical relevance. The questions posed to experts were How relevant is this procedure/observation/sign/symptom for assessment of a psoriatic arthritis patient? Proposals of additional items, not included in the questionnaire, were also encouraged. The results of the poll were discussed by the Steering Committee, which evaluated the necessity for removing selected procedures or adding additional ones, according to criteria of clinical appropriateness and sustainability. A total of 43 recommended diagnosis and assessment procedures, recognized as items, were derived by combination of the Delphi survey and two National Expert Meetings, and grouped in different areas. Favourable opinion was reached in 100% of cases for several aspects covering the following areas: medical (familial and personal) history, physical evaluation, imaging tool, second level laboratory tests, disease activity measurement and extrarticular manifestations. After performing PsA diagnosis, identification of specific disease activity scores and clinimetric approaches were suggested for assessing the different clinical subsets. Further, results showed the need for investigation on the presence of several EAMs and risk factors. In the context of any area, a rank was assigned for each item by Expert Committee members, in order to create the logical sequence of the algorithm. The final list of recommended diagnosis and assessment procedures, by the Delphi survey and the two National Expert Meetings, was also reported as an algorithm. This study shows results obtained by the combination of a DElphi survey of a group of Italian rheumatologists and two National Expert Meetings, created with the aim of establishing a clinical procedure and algorithm for the diagnosis and the assessment of PsA patients. In order to find accurate and practical diagnostic and assessment items in clinical practice, we have focused our attention on evaluating the different PsA domains. Hence, we conceived the IDEA algorithm in order to address PsA diagnosis and assessment in the context of daily clinical practice. The IDEA algorithm might eventually lead to a multidimensional approach and could represent a useful and practical tool for addressing diagnosis and for assessing the disease appropriately. However, the elaborated algorithm needs to be further investigated in daily practice, for evidencing and proving its eventual efficacy in detecting and staging PsA and its heterogeneous spectrum appropriately.

Spine and sacroiliac joints on magnetic resonance imaging in patients with early axial spondyloarthritis: prevalence of lesions and association with clinical and disease activity indices from the Italian group of the SPACE study.

Our aim was to determine the prevalence of spine and sacroiliac joint (SIJ) lesions on magnetic resonance imaging (MRI) in patients with early axial spondyloarthritis (axSpA) and their correlation with disease activity indices. Sixty patients with low back pain (LBP) (≥3 months, ≤2 years, onset ≤45 years), attending the SpA-clinic of the Unità Operativa Complessa Reumatologia of Padova [SpondyloArthritis-Caught-Early (SPACE) study], were studied following a protocol including physical examination, questionnaires, laboratory tests, X-rays and spine and SIJ MRI. Positive spine and SIJ MRI and X-rays images were scored independently by 2 readers using the SPARCC method, modified Stoke ankylosing spondylitis spine score and New York criteria. The axial pain and localization of MRI-lesions were referred to 4 sites: cervical/thoracic/lumbar spine and SIJ. All patients were classified into three groups: patients with signs of radiographic sacroiliitis (r-axSpA), patients without signs of r-axSpA but with signs of sacroiliitis on MRI (nr-axSpA MRI SIJ+), patients without signs of sacroiliitis on MRI and X-rays (nr-axSpA MRI SIJ-). The median age at LBP onset was 29.05±8.38 years; 51.6% of patients showed bone marrow edema (BME) in spine-MRI and 56.7% of patients in SIJ-MRI. Signs of enthesitis were found in 55% of patients in the thoracic district. Of the 55% of patients with BME on spine-MRI, 15% presented presented a negative SIJMRI. There was a significant difference between these cohorts with regard to the prevalence of radiographic sacroiliitis, active sacroiliitis on MRI and SPARCC SIJ score. The site of pain correlated statistically with BME lesions in thoracic and buttock districts. Since positive spine-MRI images were observed in absence of sacroiliitis, we can hypothesize that this finding could have a diagnostic significance in axSpA suspected axSpA.

Synovial fluid proteins are required for the induction of interleukin-1ß production by monosodium urate crystals.

OBJECTIVES: Monosodium urate (MSU) crystal deposition in gouty joints promotes the release of inflammatory mediators, in particular interleukin (IL)-1ß. The induction of IL-1ß production by MSU crystals requires a co-stimulus. The objective of this study was to determine which part of the synovial fluid (SF) provides co-stimulation to MSU crystals to induce IL-1ß in macrophages. METHOD: The lipidic fraction (LF) and the protein fraction (PF) were isolated from the SF of patients with arthropathies. The PF was subfractionated according to different molecular weight (MW) ranges. THP-1 cells or human primary monocytes were stimulated with MSU crystals in the presence or absence of SF or SF fractions. IL-1ß and IL-8 production and IL-1ß mRNA expression were assessed by an enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR). RESULTS: Exposure of monocytes/macrophages to MSU crystals alone induced the moderate release of IL-8 but not of IL-1ß. The production of IL-1ß required the presence of both SF from patients with inflammatory arthritis (SFi) and MSU crystals. SF from patients with non-inflammatory arthritis, that is patients with osteoarthritis (OA), did not affect the IL-1ß production but slightly enhanced the secretion of IL-8. Both MSU crystals and SFi were required for the induction of the IL-1ß transcript, which was not expressed in the presence of either stimulus alone. SFi fractionation demonstrated that the MSU crystal co-stimulus was contained in the PF of SFi with MW > 50 kDa but not in the LF. CONCLUSIONS: This study shows that the SF of inflammatory arthritis patients, including gout patients, contains proteins required for the induction of IL-1ß by MSU crystals in macrophages whereas lipids are not involved.

Are Additional Tests Needed to Rule Out Axial Spondyloarthritis in Patients Ages 16-45 Years With Short-Duration Chronic Back Pain and Maximally One Spondyloarthritis Feature?

OBJECTIVE: To investigate whether HLA-B27 testing and imaging of the sacroiliac joints are needed in patients with ≤1 spondyloarthritis (SpA) feature, referred to a secondary care setting, after medical history collection, clinical examination, and measurement of acute phase reactants. METHODS: Baseline data from patients in the Spondyloarthritis Caught Early (SPACE) cohort visiting the rheumatology outpatient clinic of 5 centers across Europe (with back pain ≥3 months, ≤2 years, onset at ages <45 years) were used. All patients underwent a full diagnostic work-up: magnetic resonance imaging (MRI) and radiographs of the sacroiliac joints, HLA-B27 testing, and assessment of all other SpA features. Patients were diagnosed according to the treating rheumatologist and classified according to the Assessment of SpondyloArthritis international Society (ASAS) axial SpA criteria. RESULTS: Of the 354 patients, 133 (37.5%) showed 0 or 1 SpA feature after medical history collection, physical examination, and measurement of acute phase reactants (38 without SpA features, 95 with 1 SpA feature). Of the patients with ≤1 SpA feature, 18.4% (with 0 SpA features) and 17.9% (with 1 SpA feature) were diagnosed with axial SpA according to the rheumatologist after additional investigations (HLA-B27 testing and sacroiliac joint imaging). Additionally, 4 of 38 patients (10.5%) without SpA features fulfilled the ASAS axial SpA criteria (all according to the imaging arm only: 2 as MRI+/modified New York criteria (mNY)+, 1 as MRI+/mNY-, and 1 as MRI-/mNY+). Of the 95 patients with 1 SpA feature, 22 (23.2%) fulfilled the ASAS axial SpA criteria (all according to the imaging arm only: 3 as MRI+/mNY+, 15 as MRI+/mNY-, and 4 as MRI-/mNY+). CONCLUSION: In these patients in a secondary care setting with ≤1 SpA feature, axial SpA could not be ruled out without sacroiliac joint imaging and/or HLA-B27 testing.

The -308 TNFα and the -174 IL-6 promoter polymorphisms associate with effective anti-TNFα treatment in seronegative spondyloarthritis.

The genetic predisposition to a long-term efficacy of anti-tumor necrosis factor (TNF)α treatment in seronegative spondyloarthritis (SpA) was investigated by analysing the possible correlation between several single nucleotide gene polymorphisms and the retention rate of anti-TNFα therapies. We compared patients needing to switch the first anti-TNFα (Sw, No. 64) within at least 12 months of follow-up with patients not needing to switch (NSw, No. 123), observing at least 6 months of treatment to establish anti-TNFα failure, leading to treatment change. Response to treatment was evaluated by standardised criteria (BASDAI for axial involvement, DAS28-EULAR for peripheral involvement). The TNFα -308 A allele and the interleukin (IL)-6 -174GG homozygosis resulted as independent biomarkers predicting survival of the first anti-TNFα therapy in SpA patients (P=0.007, odds ratio (OR): 4.4, 95% confidence interval (CI)=1.5-13.1 and P=0.035, OR: 2.1, 95% CI=1.1-4.4). Also, the male gender (P=0.001, OR: 3.4, 95% CI=1.6-7.1) associated with the NSw phenotype, whereas no association was found either with the specific diagnosis or the predominant joint involvement.

Molecular mechanisms of pain in crystal-induced arthritis.

Crystal-induced arthritis (CIA) is characterized by an intense inflammatory reaction triggered by the deposition of monosodium urate, calcium pyrophosphate, and basic calcium phosphate crystals in articular and periarticular tissues. Severe, acute pain constitutes the most important clinical symptom in patients affected by these diseases. Pain along with redness, warmness, swelling, and stiffness in the affected joint arises abruptly in gout and disappears when the acute phase of the attack resolves. While an acute joint attack caused by calcium pyrophosphate crystals can mimic a gout flare, basic calcium phosphate crystal arthritis gives rise to a series of clinical manifestations, the most severe of which are calcific periarthritis, mostly asymptomatic, and a highly destructive arthritis known as Milwaukee shoulder syndrome, which is characterized by painful articular attacks. Pain development in CIA is mediated by several inflammatory substances that are formed after cell injury by crystals. The most important of these molecules, which exert their effects through different receptor subtypes present in both peripheral sensory neurons and the spinal cord, are prostaglandins, bradykinin, cytokines (in particular, interleukin (IL)-1ß), and substance P. The pharmacological treatment of pain in CIA is strictly associated with the treatment of acute phases and flares of the disease, during which crystals trigger the inflammatory response. According to international guidelines, colchicines, nonsteroidal anti-inflammatory drugs, and/or corticosteroids are first-line agents for the systemic treatment of acute CIA, while biologics, namely anti-IL-1ß agents, should be used only in particularly refractory cases.

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials for hand osteoarthritis.

Hand osteoarthritis (OA) is a very frequent disease, but yet understudied. However, a lot of works have been published in the past 10 years, and much has been done to better understand its clinical course and structural progression. Despite this new knowledge, few therapeutic trials have been conducted in hand OA. The last OARSI recommendations for the conduct of clinical trials in hand OA dates back to 2006. The present recommendations aimed at updating previous recommendations, by incorporating new data. The purpose of this expert opinion, consensus driven exercise is to provide evidence-based guidance on the design, execution and analysis of clinical trials in hand OA, where published evidence is available, supplemented by expert opinion, where evidence is lacking, to perform clinical trials in hand OA, both for symptom and for structure-modification. They indicate core outcome measurement sets for studies in hand OA, and list the methods and instruments that should be used to measure symptoms or structure. For both symptom- and structure-modification, at least pain, physical function, patient global assessment, HR-QoL, joint activity and hand strength should be assessed. In addition, for structure-modification trials, structural progression should be measured by radiographic changes. We also provide a research agenda listing many unsolved issues that seem to most urgently need to be addressed from the perspective of performing "good" clinical trials in hand OA. These updated OARSI recommendations should allow for better standardizing the conduct of clinical trials in hand OA in the next future.

Predictive factors for partial remission according to the Ankylosing Spondylitis Assessment Study working group in patients with ankylosing spondylitis treated with anti-TNFα drugs.

The objective of this study was to evaluate the predictive factors for achieving partial remission (PR) in patients with ankylosing spondylitis (AS) treated with anti-TNFα. We longitudinally enrolled in a multi-center study 214 AS patients, classified according to New York criteria, treated with anti-TNFα drugs adalimumab (ADA), etanercept (ETA) and infliximab (INF) with at least 12 months of follow up. PR was reached when the score was <20 mm (on a visual analogue scale of 0-100 mm) in each of the following 4 domains: 1) patient global assessment (in the last week); 2) pain (spinal pain); 3) function [measured by the bath ankylosing spondylitis functional index (BASFI)]; 4) inflammation [mean of intensity and duration of morning stiffness, from the bath ankylosing spondylitis disease activity index (BASDAI)]. Two hundred fourteen AS patients (M/F=160/54; median age/range=43.2/19-78 years; median disease duration/ range=96/36-189 months) were treated with ADA (15.8%), ETA (28.9%) and INF (55.1%). At 12 and 24 months, high serum level of C reactive protein (CRP) (≥2 vs ≤0.8 mg/dL) were associated with higher rate of PR in AS patients treated with anti-TNFα drugs. At 24 months, PR was associated with shorter disease duration (≤36 vs ≥189 months) and higher erythrosedimentation rate (ESR) values (≥45 vs ≤17 mm/h). In male patients lower bath ankylosing spondylitis metrology index (BASMI) (≤2 vs ≥6) and absence of psoriasis were associated with higher PR rate only at 12 months. Other parameters assessed before treatment, such as BASDAI, BASFI, peripheral arthritis, inflammatory bowel disease and uveitis were not associated with PR. Our long-term longitudinal study in a setting of clinical practice showed that inflammatory parameters (i.e. CRP, ESR) and disease duration represent the most important predictive variables to achieve PR with an anti-TNFα treatment.

Pain and microcrystalline arthritis.

Microcrystals are responsible for some of the most common and complex arthropathies which are often accompanied by intense, severe pain and inflammatory reactions. The main pathogens are crystals of monosodium urate (MSU), responsible for the gout, calcium pyrophosphate (CPP), which deposits also in various clinical forms of arthopathies, and basic calcium phosphate associated with osteoarthritis. In this context, the microcrystal arthritis is characterized by multiple, acute attacks followed by chronic pain, disability, impaired quality of life, and increased mortality. Given their chronic nature, they represent an ever more urgent public health problem. MSU and CPP crystals are also able to activate nociceptors. The pain in mycrocrystalline arthritis (MCA) is an expression of the inflammatory process. In the course of these diseases there is an abundant release of inflammatory molecules, including prostaglandins 2 and kinins. Interleukin-1 represents the most important cytokine released during the crystal-induced inflammatory process. Therefore, clinically, pain is the most important component of MCA, which lead to functional impairment and disability in a large proportion of the population. It is fundamental to diagnose these diseases as early as possible, and to this aim, to identify appropriate and specific targets for a timely therapeutic intervention.

Effectiveness of treatment with viscosupplementation in temporomandibular joints with or without effusion.

The objective of this study was to determine whether the effectiveness of viscosupplementation with hyaluronic acid (HA) in patients with temporomandibular joint (TMJ) degenerative disorders depends on the presence of intra-articular effusion. In this study of case-control design, two groups of 25 patients were recruited: patients with a clinical diagnosis of painful chronic TMJ osteoarthritis and magnetic resonance imaging (MRI) signs of TMJ degeneration, with (effusion group) or without (no effusion group) MRI evidence of TMJ effusion. All patients underwent five weekly single-needle arthrocenteses plus medium molecular weight HA and 6 months of follow-up. Several clinical outcome parameters were assessed. For all variables, analysis of variance (ANOVA) for repeated measures was performed to assess the existence of significant within-group and between-group treatment effects. Over time, both groups showed significant improvements in all outcome parameters, which were maintained at the 6-month follow-up (P<0.05). Between-group comparisons showed that the treatment effects did not differ significantly for either the primary outcome variable (pain levels: F=0.849, P=0.548) or secondary outcome variables (chewing efficiency: F=0.854, P=0.544; functional limitation: F=1.35, P=0.226; mouth opening: F=0.658, P=0.707). The null hypothesis that there are no differences in treatment effectiveness between patients with and without effusion could not be rejected.