The Reliability of Ultrasound in the Assessment of Hyaline Cartilage in Rheumatoid Arthritis and Healthy Metacarpal Heads.

PURPOSE: i) To assess the inter- and intra-observer reliability of ultrasound (US) in the evaluation of the hyaline cartilage (HC) of the metacarpal head (MH) in patients with rheumatoid arthritis (RA) and in healthy subjects (HS) both qualitatively and quantitatively. ii) To calculate the smallest detectable difference (SDD) of the MH cartilage thickness measurement. iii) To correlate the qualitative scoring system and the quantitative assessment. MATERIALS AND METHODS: US examination was performed on 280 MHs of 20 patients with RA and 15 HS using a very high frequency probe (up to 22 MHz). HC status was evaluated both qualitatively (using a five-grade scoring system) and quantitatively (using the average value of the longitudinal and transverse measures). The HC of MHs from II to V metacarpophalangeal joint of both hands were scanned independently on the same day by two rheumatologists to assess inter-observer reliability. All subjects were re-examined using the same scanning protocol and the same US setting by one sonographer after a week to assess intra-observer reliability. RESULTS: The inter-observer agreement and intra-observer agreement were moderate to substantial (k = 0.66 and k = 0.73) for the qualitative scoring system and high (ICC = 0.93 and ICC = 0.94) for the quantitative assessment. The SDD of the MH cartilage thickness measurement was 0.09 mm. A significant correlation between the two scoring systems was found (r = -0.35; p < 0.001). CONCLUSION: The present study describes the main methodological issues of HC assessment. Using a standardized protocol, both the qualitative and the quantitative scoring systems can be reliable.

Ultrasound-Guided Procedures in Rheumatology Daily Practice: Feasibility, Accuracy, and Safety Issues.

BACKGROUND/OBJECTIVE: The aims of this study were to describe in detail the ultrasound (US)-guided procedures in our daily rheumatology practice, to evaluate the feasibility and accuracy of US-guided procedures, and to test the efficacy of our disinfection protocol in preventing infectious complications. METHODS: This was a cross-sectional and monocentric study. Information regarding patients' age, sex, body mass index, rheumatic disease, US pathological findings, aspirated and/or injected anatomical site, US equipment (ie, probe type and frequency), and needle type was consecutively collected for each US-guided procedure in a third-level rheumatology center. RESULTS: A total of 643 US-guided procedures were performed, with a mean of 5.2 procedures per working-day. In 94.2% of the patients, only one procedure was carried out, whereas in 5.8%, more than one. The mean time was 7 ± 2.5 minutes. Ultrasound-guided procedures were highly accurate (accuracy rate higher than 95%) and safe (adverse events were reported in 0.8%). Our disinfection protocol was effective in preventing infectious complications. Probes with frequency values between 8 to 13 MHz and 20-, 21-, and 22-gauge needles were the most frequently used at shoulder, knee, wrist, elbow, and ankle level. High-frequency linear probes (ranging between 18 and 22 MHz) and 23- and 25-gauge needles were used for injecting small joints of the hands and feet. Convex low-frequency probe (2-7 MHz) and 18- and 20-gauge needles were the most used for performing hip joint aspirations and/or injections. CONCLUSIONS: This study reports useful information for setting up a service providing US-guided procedures in rheumatology and supports the feasibility, accuracy, and safety of US-guided procedures.

One year in review 2017: spondyloarthritis.

The term spondyloarthritis (SpA) represents a condition characterised by a broad spectrum of clinical manifestations, laboratory abnormalities and imaging features; in particular, SpA is an inflammatory condition in which both peripheral and axial joints might be affected. The majority of people with this disease have either psoriatic arthritis or axial spondyloarthritis, which includes ankylosing spondylitis. Less common subgroups are enteropathic SpA, which is associated with inflammatory bowel diseases (Crohn's disease and ulcerative colitis), reactive arthritis, which can occur in people following gastrointestinal or genitourinary infections and undifferentiated SpA, that does not meet the diagnostic criteria of the other subgroups at onset, but that may evolve to do so later. Very interestingly, much of the emerging data show how SpA, during its course, tends to associate with the development of some comorbidities; in particular, with cardiovascular diseases, diabetes mellitus, osteoporosis and depressive disorders. Healthcare professionals in non-specialist settings do not always recognise the signs and symptoms of SpA, particularly spinal symptoms, which may be mistakenly attributed to other causes of low back pain, thus leading to significant delays in diagnosis and treatment of the disease itself and of its related comorbidities, with consequent disease progression and disability, compromising the health-related quality of life of patients. In this paper we reviewed the literature of the past year (Medline search of articles published from 1st March 2016 to 28th February 2017) with the aim of approaching the spectrum of SpA from some different points of view, to try to give the reader an insight into this clinically challenging group of rheumatic pathologies.

One year in review 2016: systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a highly variable course and prognosis. The management of the disease is still a clinical challenge for the treating physicians as many aspects regarding the disease pathogenesis, clinical picture and outcomes remain to be elucidated. New and interesting data are emerging; here the recent literature on SLE pathogenesis, clinical and laboratory aspects, as well as treatments and comorbidities, are reviewed and the main findings summarised in order to provide a bird's eye on the relevant papers on these topics.

Scaffold-based cartilage treatments: with or without cells? A systematic review of preclinical and clinical evidence.

PURPOSE: Regenerative scaffold-based procedures are emerging as a potential therapeutic option for the treatment of chondral and osteochondral lesions. In general, we can summarize most of the recent developments to reach clinical application into 2 major trends: the use of different cell sources or the application of biomaterials as a cell-free approach. The aim of this systematic review was to analyze both preclinical and clinical studies on these new trends to understand how the available evidence supports the use of cell sources or justifies the cell-free approach for the scaffold-based treatment of cartilage lesions. METHODS: The research was performed using the PubMed database by looking at studies published in the English language referring to chondral or osteochondral defect repair with scaffold-based procedures until the end of 2013. The following strings were used: ("cartilage"[MeSH] AND "tissue scaffolds"[MeSH]). RESULTS: The search showed an increasing number of published articles each year for both scaffold-based approaches, identifying a total of 305 articles. Among clinical trials, 116 used cell-based scaffold treatments and 11 used scaffolds alone. In the preclinical setting, a scaffold/cell combination was the most used treatment approach (133 v 45 articles), with mesenchymal stem cells (MSCs) being the favorite cell type. Bone marrow was the most used cell source, but other sources are gaining interest. Among articles comparing scaffolds with or without cells, the majority reported superior results for cells (71 of 89 articles). In the clinical setting, most of the articles analyzed chondrocyte-based scaffolds, with only 7 studies using MSCs; all cells were from bone marrow. Despite the lower number of articles, cell-free scaffolds are gaining popularity, with a recent increase in published studies showing promising results. CONCLUSIONS: This systematic review underlined the difficulties in understanding the real need for cells to increase the scaffold-based cartilage healing potential because of the heterogeneity of products used as well as the design of the published studies. Scaffold and cell combinations were the most investigated option in the preclinical setting, showing generally superior results, but in the clinical setting, both strategies remain used. In particular, although chondrocytes are the most commonly used cell type, research showed increasing interest in the potential of MSCs for cartilage regeneration. However, the difficulties in managing cell cultures, together with the development of a new generation of materials able to exploit the intrinsic tissue regeneration ability, justifies the clinical use of cell-free scaffolds, with increasing literature and promising preliminary results. LEVEL OF EVIDENCE: Level IV, systematic review of Level I to IV studies.

Combination of denosumab and biologic DMARDs in inflammatory muscle-skeletal diseases and connective tissue diseases.

OBJECTIVE: Osteoporosis (OP) can complicate the course of rheumatic musculoskeletal diseases (RMDs) and connective tissue diseases (CTDs). Denosumab, a monoclonal antibody against RANK-L, showed beneficial effect in rheumatoid arthritis in inhibiting radiographic progression and erosive burden. We tested the efficacy, safety, and persistence on the treatment of the combination of biologic disease-modifying antirheumatic drugs (bDMARDs)/denosumab versus bDMARD in patients with RMD and CTD. METHODS: This is a retrospective evaluation of a single center, including patients with RMD/CTD (including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, systemic sclerosis, and overlap syndromes) treatment with bDMARD/denosumab, compared to age, gender, disease, bDMARD, and conventional synthetic disease-modifying antirheumatic drugs-matched controls. RESULTS: Twenty-eight bDMARD/denosumab patients and 49 bDMARD patients were eligible. Despite a statistically significant difference during the first-year efficacy (due to the different baseline timepoint), there was no difference in the efficacy profile in the second year of treatment and in the safety profile (including local, systemic, and serious adverse events). Moreover, no statistically significant difference in the persistence of bDMARD treatment over 2 years of evaluation was found. The combination of bDMARD and denosumab was not an independent predictor of disease flare or bDMARD treatment withdrawal. CONCLUSION: The combination of bDMARD and denosumab does not alter the efficacy and the safety profile of the bDMARD in patients with RMD/CTD. Future studies verifying the radiological disease inhibition could support denosumab use in RMD/CTD other than rheumatoid arthritis, when complicated by OP.

Baricitinib in the treatment of rheumatoid arthritis: clinical and ultrasound evaluation of a real-life single-centre experience.

BACKGROUND: Ultrasound (US) is useful in monitoring RA patients, with the US7 score allowing grey-scale and power-Doppler (PD) semi-quantitative evaluation of synovitis and teno-synovitis. We evaluated real-life efficacy and safety of Baricitinib, an oral selective JAK1-2 inhibitor, in RA patients using clinical, clinimetric, and US assessments. METHODS: Disease activity score in 28 joints calculated with C-reactive protein (DAS28-CRP), disease activity score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), simplified disease activity index (SDAI), visual analogue scale (VAS)-pain, health assessment questionnaire (HAQ), COCHIN scale, adverse events (AE), concomitant medications, laboratory parameters, and US7 were performed/recorded at baseline, 1, 3, and 6 months in RA patients starting Baricitinib. Responder/non-responder status was determined according to the EULAR Response Criteria at 3 months. SDAI clinical remission or low disease activity (LDA) were calculated at 3 and 6 months. RESULTS: In 43 enrolled patients, a significant improvement in disease activity and US7 components (except tendon PD) and a reduction of steroid dosage were observed. Responders at 3 months showed a significantly higher reduction of CDAI, SDAI, COCHIN scale, VAS-pain, and US7 synovialPD, compared with non-responders. At 3 and 6 months, remission/LDA was achieved by 12.8/53.8% and 21.6/51.3% patients, respectively. The csDMARD co-treatment was independently associated with remission/LDA at 3 months. Safety-related drop-outs were in line with literature data. The steroid dosage was associated with AE development at 6 months. CONCLUSION: The real-life data, also obtained with US evaluation, confirmed the Baricitinib efficacy in RA disease control, as well as the utility of assessment during the follow up of disease activity.

The Renal Resistive Index: A New Biomarker for the Follow-up of Vascular Modifications in Systemic Sclerosis.

OBJECTIVE: The aim of the present retrospective observational study was to evaluate the change of Renal Resistive Index (RRI) over time (ΔRRI) and under treatment in patients with systemic sclerosis (SSc) as well as to correlate these changes with disease complications. METHODS: Two hundred thirty patients [29 male, median age 57 (IQR 48-67) yrs] were enrolled. At baseline and follow-up (3.43, IQR 2.81-4.45 yrs), we collected the following data: disease variables, nailfold videocapillaroscopy (NVC) pattern, forced vital capacity (FVC), diffusing lung capacity for carbon monoxide (DLCO), systolic pulmonary arterial pressure (sPAP), presence of interstitial lung disease, RRI, evaluation of glomerular filtration rate, and new onset of pulmonary arterial hypertension (PAH). RESULTS: RRI value is high in SSc patients with digital ulcers and anticentromere antibodies, active and late NVC patterns, and limited cutaneous SSc. A significant correlation was observed between ΔRRI and ΔsPAP (R = 0.17, P = 0.02), with statistically higher ΔRRI (0.08 ± 0.02 vs 0.03 ± 0.05, P = 0.04) in patients complicated by PAH onset. No other new-onset complication was associated with ΔRRI. The receiver-operating characteristic curve analysis confirmed the predictive role of ΔRRI in development of new PAH (area under the curve 0.84, 95% CI 0.75-0.93, P = 0.02). In patients with SSc never exposed to sildenafil, ΔRRI was higher (0.04 ± 0.05) compared to both patients exposed to sildenafil during the study period (0.01 ± 0.05, P = 0.03) or in those exposed at the time of baseline evaluation (0.00 ± 0.05, P = 0.01). CONCLUSION: RRI and its variation in time are a reliable marker of SSc-related vasculopathy, both in renal and extrarenal compartments.

The Renal Resistive Index in systemic sclerosis: Determinants, prognostic implication and proposal for specific age-adjusted cut-offs.

BACKGROUND: Renal Resistive Index (RRI), reflects changes in both renal vascular and tubular-interstitial compartments and in systemic vascular compliance related to age and comorbidities. OBJECTIVES: a) To investigate determinants of RRI in SSc population, b) its association with SSc-related features and c) to test its prognostic impact on organ specific worsening or death. METHODS: 380 SSc patients ≥18 years were enrolled after giving informed consent. Baseline data on RRI, laboratory, instrumental and therapeutic features were retrospectively collected. Age-SSc adjusted cut-offs were created by dividing the population in age quartiles and considering RRI values >75th percentile as pathologic. Clinical follow-up was performed until last available visit or the development/worsening of specific internal organ involvement or death. RESULTS: RRI was independently predicted by age and systolic pulmonary arterial pressure on Echo. Therefore, we created Age-SSc adjusted pathologic RRI cut-offs, which were significantly associated with various disease related skin and lung fibrotic manifestations, as well as vasculopathic complications. After a mean follow-up of 3.6 ±â€¯2.6 years, RRI was one of the independent predictors (together with modified Rodnan skin score, interstitial lung disease, presence of dyspnoea and late nailfold-videocapillaroscopy pattern) for mortality, with 0.68 as best cut-off (sensitivity 88.5%, specificity 50.9%). CONCLUSION: If corroborated, Renal Resistive Index cut-offs might be used to evaluate renal and extrarenal involvement in SSc and could serve as predictors of mortality.

Platelet-rich plasma injections for the treatment of refractory Achilles tendinopathy: results at 4 years.

BACKGROUND: Chronic Achilles tendinopathy is responsible for a severe reduction in physical performance and persistent pain. There is currently a number of therapeutic options and the local administration of growth factors is an emerging treatment strategy. In particular, platelet-rich plasma (PRP) is a widely used way to provide a local regenerative stimulus for tendon healing. The aim of this study was to document the mid-term results obtained after treating recalcitrant Achilles tendinopathy with injections of high concentrate, leucocyte-rich PRP. MATERIALS AND METHODS: Twenty-seven patients (mean age: 44.6 years; 22 men and 5 women) affected by chronic mid-portion Achilles tendinopathy (7 bilateral, for a total of 34 tendons), refractory to previous treatments, were enrolled. Patients were treated with three ultrasound-guided intra-tendinous injections of PRP at 2-week intervals. Patients were prospectively evaluated at baseline, and then at 2, 6, and up to a mean of 54.1 months of follow-up (minimum 30 months), using the following tools: Blanzina, VISA-A, EQ-VAS for general health, and Tegner scores. RESULTS: The VISA-A score showed a significant improvement: the baseline score of 49.9±18.1 increased to 62.9±19.8 at 2 months (p=0.002), with a further improvement at 6 months (84.3±17.1, p<0.0005), and stable results at 4.5 years (90.0±13.9). The EQ-VAS score also showed a similar positive trend. An evaluation of the activity level confirmed these findings, showing a significant improvement in the Tegner score over time (p=0.017 for the final evaluation). The longer duration of symptoms before treatment was associated with a slower return to sport (p=0.041). DISCUSSION: PRP injections produced good overall results for the treatment of chronic recalcitrant Achilles tendinopathy with a stable outcome up to a medium-term follow-up. Longer symptom duration was related with a more difficult return to sporting activity.