Search

© Copyright Clinical and Experimental Rheumatology 2022., Objectives: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. Methods: We conducted a multicentre, international, retrospective cohort study. Results: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. Conclusions: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Multiscale homogenization represents a powerful tool to treat certain fluid-structure interaction problems involving porous, elastic, fibrous media. This is shown here for the case of the interacti ...

International audience; The coupling between the flow through a fibrous porous medium and that in a free-fluid region is studied. The flow dynamics inside the porous medium are described using the volume averaging method applied to the incompressible Navier−Stokes equations in the laminar regime. The two different flow domains are coupled via a penalization method that consists of varying the porous medium properties (porosity and permeability) continuously across the interface. This approach permits the use of the same set of the equations throughout the whole domain. The averaging method is validated against simulations which fully account for the presence of cylindrical fibers positioned at the bottom wall of a square driven cavity. Numerical experiments are carried out for two different Reynolds numbers, large enough to ensure that inertial effects inside the porous domain are not negligible. Good agreement is found when comparing the two approaches.

Marco A Cimmino,1 Massimiliano Parodi,1 Francesca Barbieri,1 Stefano Bombardieri,2 Giuseppe Zampogna,1 Annamaria Iagnocco,3 Alberto Batticciotto,4 Luca Maria Sconfienza,5,6 Luigi Sinigaglia,7 Fabrizio De Benedetti,8 Fabiola Atzeni,9 Piercarlo Sarzi-Puttini10 1Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Genoa, Italy; 2Rheumatology Unit, Santa Chiara Hospital, University of Pisa, Pisa, Italy; 3Academic Rheumatology Centre, Università degli Studi di Torino, Turin, Italy; 4Rheumatology Unit ASST-Settelaghi, Ospedale di Circolo – Fondazione Macchi, Varese, Varese, Italy; 5IRCCS Istituto Ortopedico Galeazzi, Milan, Italy; 6Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy; 7Rheumatology Unit, G. Pini Hospital, Milan, Italy; 8Division of Rheumatology, IRCCS, Bambin Gesù Paediatric Hospital, Rome, Italy; 9Rheumatology Unit, University of Messina, Messina, Italy; 10Rheumatology Unit, L. Sacco University Hospital, Milan, ItalyCorrespondence: Piercarlo Sarzi-PuttiniReumatology Department, L. Sacco University Hospital, ASST Fatebenefratelli – Sacco, Via G.B. Grassi, 74, Milan 20157, ItalyTel +39 02 39042208Email piercarlo.sarziputtini@gmail.comObjective: This open-label study evaluated the effects of combined tocilizumab (TCZ) and disease-modifying antirheumatic drugs (DMARDs) on magnetic resonance imaging (MRI) changes in synovial membrane enhancement, bone marrow edema (BME), and erosions in the wrist and hand joints of rheumatoid arthritis (RA) patients inadequately responding to DMARDs alone.Methods: The efficacy of intravenous TCZ 8 mg/kg administered every four weeks for 48 weeks was evaluated on six occasions. The primary endpoints were the changes in the extent and degree of wrist synovitis as measured using the RA MRI Score (RAMRIS) and dynamic, gadolinium-enhanced 0.2T MRI (DCE-MRI). A number of different parameters of DCE-MRI were evaluated.Results: Fifty-eight patients were treated, eight of whom (13.8%) discontinued the study prematurely. The mean RAMRIS significantly decreased after two weeks and the decrease was maintained for up to 48 weeks. By week 4, the mean RAMRIS synovitis score had significantly decreased from baseline (− 0.804± 1.575; p=0.018), but not the mean early enhancement (REE) or relative enhancement (RE). However, there were significant decreases in RE at week 24, in REE and Ntotal (total number of enhancing voxels)*IRE (initial rate of enhancement) at weeks 12, 24 and 48, and in Ntotal*ME (maximal enhancement) at weeks 24 and 48. Mean BME decreased from baseline to week 48, and bone erosions did not progress. The patients’ clinical parameters significantly improved from baseline until week 48.Conclusion: TCZ in combination with DMARDs improved wrist synovitis, BME and clinical parameters, without any progression in bone erosions. The RAMRIS for synovitis rapidly improved from as early as two weeks after the first TCZ infusion. (Funded by F. Hoffmann–La Roche; ACTRACE EudraCT No. 2009 012185-32).Keywords: tocilizumab, rheumatoid arthritis, wrist, synovitis, low-field MRI, dedicated MRI

Small-scale, deformable riblets, embedded within the viscous sublayer of a turbulent boundary layer and capable to adapt to the overlying motion, are studied. The wall micro-grooves are made of a linearly elastic material and can undergo small deformations; their collective behavior is assumed to occur over a large, elastic wavelength. The presence of two length scales allows for the use of a multiscale homogenization approach yielding microscopic problems for convolution kernels and parameters, which must then be employed in macroscopic boundary conditions to be enforced at a virtual wall through the riblets. The results found suggest that, in analogy to the case of rigid riblets, compliant, blade-like wall corrugations are more effective than triangular riblets in reducing skin friction drag, provided the spanwise periodicity of the indentations is sufficiently small for the creeping flow approximation to be tenable. (C) 2019 Elsevier Ltd. All rights reserved.

A macroscopic boundary condition to be used when a fluid flows over a rough surface is derived. It provides the slip velocity $\boldsymbol{u}_{S}$ on an equivalent (smooth) surface in the form $\boldsymbol{u}_{S}=\unicode[STIX]{x1D716}{\mathcal{L}}\boldsymbol{ : }{\mathcal{E}}$, where the dimensionless parameter $\unicode[STIX]{x1D716}$ is a measure of the roughness amplitude, ${\mathcal{E}}$ denotes the strain-rate tensor associated with the outer flow in the vicinity of the surface and ${\mathcal{L}}$ is a third-order slip tensor arising from the microscopic geometry characterizing the rough surface. This boundary condition represents the tensorial generalization of the classical Navier slip condition. We derive this condition, in the limit of small microscopic Reynolds numbers, using a multi-scale technique that yields a closed system of equations, the solution of which allows the slip tensor to be univocally calculated, once the roughness geometry is specified. We validate this generalized slip condition by considering the flow about a rough sphere, the surface of which is covered with a hexagonal lattice of cylindrical protrusions. Comparisons with direct numerical simulations performed in both laminar and turbulent regimes allow us to assess the validity and limitations of this condition and of the mathematical model underlying the determination of the slip tensor ${\mathcal{L}}$.

Background Anti-MDA5 antibodies are a known set of antibodies observed mainly in dermatomyositis, typically associated with cutaneous involvement, presence and often rapid progression (RP) of interstitial lung disease (ILD) and amyopathic muscle involvement. Despite the increased attention, described cohorts involves only a limited number of cases Objectives to define clinical characteristics of a large cohort of anti-MDA5 antibodies positive patients Methods Retrospective assessment of anti-MDA5 positive patients from centres referring to our group Results 82 anti-MDA5 positive cases (56 females) were collected. In median: onset age was 44 Y (IQR 22.57), diagnostic delay 4 Mo (IQR 1–10), follow-up 13 Mo (IQR 3–43). Fifty-three patients had ILD, that was RP in 24 cases (15 at ILD onset, 9 after ILD onset). Fifthteen ILD patients were admitted in Intensive Care Unit (ICU): 4 were treated with Extracorporeal-Membrane-Oxygenation, 7 with mechanical-invasive and 2 with mechanical-non-invasive ventilation. Forthy-nine patients had muscle involvement (39 symptomatic), 42 arthritis, 54 cutaneous involvement, 9 history of malignancy. Twelve patients died (ILD=7, ILD and sepsis=3, neoplasia=1, not specified=1), 7 of those in ICU Conclusions In our cohort, ILD was the most frequent finding. A RP of ILD was common, occurring also in ILD with symptomatic/chronic onset. The low rate of survival in ICU raised the problem of follow up and early treatment of ILD. In our cohort arthritis was common and muscle involvement mainly symptomatic. Finally, the high percentage of observed malignancies suggests a careful neoplastic screening and follow up Reference [1] Labrador-Horrillo M, et al. J Immunol Res2014;2014:290797. Disclosure of Interest None declared

The aim of this study was to identify possible correlations between nailfold microangiopathy severity, finger dermal thickness (DT) and fingertip blood perfusion (FBP) in systemic sclerosis (SSc) patients.Fifty-seven SSc patients and 37 healthy subjects were enrolled. All patients were evaluated by nailfold videocapillaroscopy (NVC) to classify and score the severity of microangiopathy. Both modified Rodnan skin score (mRss) and skin high-frequency ultrasound were used to detect finger DT. Laser Doppler flowmetry (LDF) was employed to detect FBP.A positive correlation was found between nailfold microvascular damage severity and both ultrasound-DT (p=0.028) and mRss values (p0.0001). In particular, both ultrasound-DT and mRss were found progressively higher in patients with 'Early', 'Active' or 'Late' NVC pattern of microangiopathy. A negative correlation was observed between nailfold microvascular damage severity and FBP (p0.0001), showing the lowest FBP of the patients with more advanced NVC patterns. A negative correlation was observed between FBP, and both ultrasound-DT (p=0.007) and mRss values (p=0.0002). SSc patients showed a higher ultrasound-DT at the level of the fingers, as well as a lower FBP than healthy subjects (p0.0001).This study demonstrates a relationship between nailfold microangiopathy severity, DT and FBP in SSc patients.

A 46-year old man, affected by Darier’s disease (DD), was seen because of right hand pain, later extended to shoulders and ankles. Physical examination showed swelling and tenderness of the wrist, metacarpophalangeal and metatarsophalangeal joints, of the right Achilles tendon’s enthesis and of the left knee, with psoriatic-like lesions of the scalp. A diagnosis of seronegative spondyloarthritis, supported by HLA-B27 positivity and by the magnetic resonance imaging fi nding of hand synovitis and unilateral sacro-iliitis, was made. The correlation between DD, spondyloarthritis and psoriasis has been already anecdotally reported. Further observations may clarify if this association is more than casual.

Objective To investigate the timing of transition through different patterns of nailfold microvascular damage in patients with systemic sclerosis (SSc). Methods In this medium-term longitudinal study, 38 SSc patients (median disease duration 12 months) with the early scleroderma pattern of microangiopathy seen on baseline nailfold videocapillaroscopy (NVC) were followed up by NVC for a median of 84 months. The evolution of the NVC pattern over time was monitored and recorded. Results At the end of followup, the NVC pattern was still that of early scleroderma in 47% of the patients. The active scleroderma pattern was seen in 34%, the late scleroderma pattern in 13%, and a normal pattern in 5%. The mean± SD time of progression from the early to the active pattern and from the early to the late pattern was of 28 ± 20 months and 36± 29 months, respectively. In the subgroup of patients whose microangiopathy progressed from the early to the late NVC pattern, the time of progression from the early to the active pattern was only 8± 1 months (P = 0.01), demonstrating that there is a subset of patients with rapid progression of microangiopathy. Clinical symptoms progressed in accordance with the nailfold morphologic changes in 60% of the SSc patients. Conclusion The results of this longitudinal study demonstrate dynamic transition of microvascular damage through different NVC patterns of microangiopathy in ∼50% of SSc patients. It is recommended that patients exhibiting rapid progression from the early to the active NVC pattern (

Objectives To study with MRI the hands of consecutive PMR patients, who were not selected on the basis of peripheral arthritis, with a correlation to clinical and laboratory findings. Methods Twenty-six hands of 15 PMR patients and 26 hands of 13 healthy controls were studied by extremity-dedicated MRI for the presence of synovitis, tenosynovitis, soft-tissue oedema, bone marrow oedema and erosions. Results Sixteen (61.6%) of the 26 PMR hands and 4 (15.4%) of the 26 control hands showed tenosynovitis (P = 0.001). Extensor tendon tenosynovitis was seen in 9 (34.6%) of the 26 PMR hands, but in only 1 (3.8%) control hand (P = 0.002) and flexor tenosynovitis was seen in 12 (46.1%) of the 26 PMR hands and in 4 (15.4%) of the 26 control hands (P = 0.03). All other features were similar in the two groups. Conclusions Our data support the view that tenosynovitis, especially of the extensor tendons, is a frequent event in PMR, unrelated to clinical involvement of the hand. This finding is in agreement with the concept of PMR as a disease of extra-articular structures.

Despite the ubiquity of fluid flows interacting with porous and elastic materials, we lack a validated non-empirical macroscale method for characterizing the flow over and through a poroelastic medium. We propose a computational tool to describe such configurations by deriving and validating a continuum model for the poroelastic bed and its interface with the above free fluid. We show that, using stress continuity condition and slip velocity condition at the interface, the effective model captures the effects of small changes in the microstructure anisotropy correctly and predicts the overall behaviour in a physically consistent and controllable manner. Moreover, we show that the performance of the effective model is accurate by validating with fully microscopic resolved simulations. The proposed computational tool can be used in investigations in a wide range of fields, including mechanical engineering, bio-engineering and geophysics., Main paper: 28 pages, 14 figures; Supplementary appendicies: 7 pages; under consideration for publication in Roy. Soc. Proc. A

Objective.To evaluate the longterm effects of endothelin-1 (ET-1) antagonism on peripheral blood perfusion (PBP) in patients with systemic sclerosis (SSc).Methods.Twenty-six patients with SSc already receiving cyclic intravenous iloprost (ILO) for severe Raynaud phenomenon were enrolled. Thirteen patients continued the treatment for a further 3 years (ILO group) and 13 patients, because of the appearance of digital ulcers, received in addition bosentan (BOS; 125 mg twice/day) for 3 years (ILO + BOS group). Both PBP at fingertips and nailfold microangiopathy were evaluated yearly by laser Doppler flowmetry and nailfold videocapillaroscopy, respectively.Results.A progressive significant increase of PBP was observed in the ILO + BOS group during the 3 followup years (p = 0.0007, p = 0.0002, p = 0.01, respectively). In contrast, an insignificant progressive decrease of PBP was observed in the ILO group. Difference of perfusion between the PBP evaluations at basal temperature and at 36°C (to test capillary dilation capacity), was found progressively decreased during the 3-year followup only in the ILO group (p = 0.05, p = 0.26, p = 0.09, respectively). A progressive increase of nailfold capillary number was observed only in the ILO + BOS group after 2 and 3 years of followup (p = 0.05).Conclusion.Longterm treatment of SSc patients with ET-1 antagonism, in combination with ILO, seems to increase fingertip blood perfusion, as well as both capillary dilation capacity and number.

The objective of this prospective study was to investigate the transition from primary (PRP) to secondary (SRP) Raynaud’s phenomenon (RP), in a large cohort of patients affected by isolated RP. A total of 2065 patients with RP were investigated by clinical interview, laboratory examinations, and nailfold videocapillaroscopy (NVC). Patients with negative NVC at first visit were yearly followed to monitor either the appearance of specific morphological alterations at NVC, or clinical manifestations of an underlying disease. Capillary abnormalities at NVC were scored, as well as the qualitative patterns of microangiopathy (Early, Active and Late). NVC was found negative at first visit in 1500 subjects; among them, 412 patients were evaluable and they were followed for a mean time of 5±4 years (range 2-13 years). Sixty-eight patients (16%) achieved a diagnosis of SRP during follow-up, showing normal or not specific capillary alterations at NVC 4% of patients (the diagnosis was undifferentiated connective tissue diseases), Early scleroderma-pattern 57%, Active scleroderma-pattern 7%, Late scleroderma-pattern 12%, and scleroderma-like pattern 18% of patients. The time of transition from normal/not specific capillary alterations to Early scleroderma-pattern was 4.4±3.8 years. Enlarged capillaries (diameter between 20 and 50 microns) and mild reduction of capillary density were found the more frequent markers at first NVC visit in patients who progressed to a scleroderma pattern (P=0.01). This study demonstrates in a large cohort, that almost 16% of patients initially diagnosed as affected by RP with negative NVC may transit to SRP during a mean follow-up of 4.4 years. PRP patients showing major notspecific alterations of nailfold capillaries at first NVC should be strictly monitored at least once a year since at higher risk of transition to SRP.

Objective.This study evaluates possible correlations between the pattern of antinuclear antibodies (ANA) on indirect immunofluorescence (IIF) testing and nailfold microangiopathy stage (early, active, and late stage) in systemic sclerosis (SSc). Patients with SSc were followed prospectively to monitor progression of microvascular damage.Methods.The ANA pattern on IIF was searched in 42 patients with SSc showing an early pattern of nailfold microangiopathy at baseline, and was followed using nailfold videocapillaroscopy (NVC) for a median time of 91 months.Results.Among patients whose microangiopathy showed a rapid progression from early to late pattern on NVC, the IIF pattern was fine-speckled + nucleolar (Scl-70+) in 44%, centromeric in 33%, nucleolar in 11%, and homogeneous in 11% of patients with SSc. Antitopoisomerase I antibodies were significantly more frequent (57%) in patients with late pattern of microangiopathy on NVC. The median time of progression from early to active disease was significantly lower in patients with both fine-speckled + nucleolar and nucleolar ANA positivity. The severity of microangiopathy was higher in patients with the nucleolar pattern on IIF. Patients already showing a slight reduction of capillary number at baseline were likely to have either the nucleolar or the fine-speckled + nucleolar pattern on IIF. Of note, 37% of patients still showing the early microangiopathy pattern on NVC at the end of the followup were ANA-negative.Conclusion.ANA-negative patients with SSc display a slower progression of nailfold microangiopathy characterized by the early pattern on NVC. Progression to the late NVC pattern (more advanced stage of microvascular damage) seems to be associated with a different autoantibody pattern on IIF (fine-speckled + nucleolar pattern being the most prevalent).

Objectives: MRI has been proposed as the imaging method of choice to evaluate the long-term outcome in patients with early arthritis. The role of dynamic MRI, performed at presentation, in predicting the outcome of patients with early arthritis has been addressed in the present study. Methods: 39 patients with early arthritis, involving at least one wrist, were studied with clinical visits and laboratory investigations, every 3 months. Dynamic MRI was performed with a low-field (0.2T), extremity-dedicated machine (Artoscan, Esaote, Genova, Italy) equipped with a permanent magnet and with a dedicated hand and wrist coil. During the intravenous injection of Gd-DTPA, twenty consecutive fast images of 3 slices of the wrist were acquired. The synovial contrast enhancement ratio was calculated both as rate of early enhancement (REE) per second during the first 55” and as relative enhancement (RE) at t seconds. Results: In our cohort of patients, REE and RE were significantly lower than those observed in a historical cohort of 36 patients with active rheumatoid arthritis. In univariate analysis, low RE predicted complete remission of arthritis. In multivariate analysis, fulfillment of RA criteria during follow-up was predicted by high RE. The need for immunosuppressive treatment at the end of follow-up was predicted by both low RE and high REE. Conclusions: Dynamic MRI may be used to predict several outcomes of early arthritis involving the wrist

BACKGROUND AND PURPOSE: A growing body of evidence suggests the involvement of the brain in FM. The purpose of this proton MRS study was to test the hypothesis that there are metabolic alterations in some brain regions processing pain (VLPFC and thalamus) in patients with FM compared with HC. MATERIALS AND METHODS: Twelve patients with FM (30–54 years of age; mean age, 43.2 years), and 12 HC, matched for age and sex, underwent 1 session of single-voxel MRS performed on a 3T MR imaging scanner. MRS spectra were acquired with a PRESS for localization. The raw data from each spectrum was evaluated with an LCModel. T tests were used to evaluate differences of brain metabolites between groups. The Pearson correlation tested the relationship of metabolite ratios and clinical symptoms. RESULTS: Glx/Cr and Glu/Cr ratios within the VLPFC of both sides were significantly higher in patients than in HC (P < .01). No significant differences of metabolites between groups were found in the thalami. Positive correlations were found between Glu/Cr in the left thalamus and the VAS for pain (r = 0.730, P = .007) and between mIns/Cr in the right VLPFC and the VAS for pain (r = 0.607, P = .037) and the FIQ (r = 0.719, P = .008). CONCLUSIONS: The presence of elevated Glu/Cr levels in VLPFC strengthens the opinion that a complex neurophysiologic imbalance of different brain areas involved in pain processing underlies FM. These data may be useful in the diagnosis and development of more effective pharmacologic treatments.

Objective: To assess the clinical characteristics of gout and its diagnostic approach in a group of Italian patients. Methods: In a retrospective analysis, we evaluated 72 consecutive gouty patients examined in the years 2000-2007.We recorded demographic data, family history, comorbidities and disease characteristics (seasonality of the attacks, joints affected, serum uric acid concentration, and treatment). Result: 63/72 (87.5%) patients were men and 9 women, with mean age 61.9±13.7 years. 8/72 (11.1%) patients reported a familial history of gout. The first attack occurred mainly in the months of June, July and December. The first metatarsophalangeal joint was affected in 59.7% of patients and the hand in 25%. Treatment changed over the follow- up period, with a decreased use of NSAIDs (p

To the Editor: Olech, et al 1 recently used extremity-dedicated magnetic resonance imaging (MRI) to highlight hand lesions in patients with rheumatoid arthritis (RA) in comparison with controls. They noted that the second and third metacarpal heads were more often eroded in RA. Bone lesions, morphologically identical with erosions, were also common in controls at the same locations. A similar observation was made by Tan, et al , who linked it to anatomical causes2. The term “lesion” in MRI studies of the joints encompasses bone edema, erosions, and cysts3. According to the OMERACT definition4, an erosion is a sharply marginated bone lesion, of typical juxtaarticular localization and specific signal characteristics, which is … Address correspondence to Prof. M.A. Cimmino; E-mail: cimmino{at}unige.it

Microvascular involvement is a key feature of systemic sclerosis (SSc). Nailfold capillaroscopy is widely used to evaluate capillary morphology. As well as laser Doppler flowmetry (LDF), it is a technique for measuring the peripheral microvascular perfusion.1 2 The aim of this study was to investigate possible correlations between fingertip blood perfusion (FBP) by LDF and different degrees of microvascular damage by nailfold videocapillaroscopy (NVC) in SSc patients. Forty-six SSc patients (mean±SD age 65±13 years) and 16 healthy subjects …