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Resume La prise en charge des spondylodiscites infectieuses est complexe et multidisciplinaire. Survenant chez des patients souvent âges et comorbides, elle necessite une bonne collaboration entre rhumatologues, infectiologues, bacteriologistes et chirurgiens pour assurer une prise en charge optimale. La pierre angulaire reste l’antibiotherapie qui sera dans l’ideal introduite apres l’identification du germe causal. L’evaluation clinique et radiologique initiale permettront de choisir au mieux la strategie d’immobilisation. Un lever le plus precoce possible sera entrepris pour eviter les complications de decubitus. La presence d’anomalies neurologiques initiales ou de collections importantes fera discuter une prise en charge chirurgicale. Enfin, le monitoring de l’efficacite et de la tolerance du traitement sur le court, moyen et long terme sera indispensable pour attester de la guerison de l’infection et detecter de potentielles sequelles. Dans cette revue, nous detaillerons un a un ces differents temps de la prise en charge.

Resume Objectif Proposer des recommandations pour une utilisation pertinente de l’echographie dans la polyarthrite rhumatoide (PR) en pratique quotidienne, fondees sur les donnees de la litterature et l’opinion d’experts en echographie osteo-articulaire. Methodes A partir d’une analyse systematique de la litterature, un comite scientifique a selectionne des thematiques et questions pertinentes pour elaborer une premiere version des recommandations. Celles-ci ont ete soumises a un groupe d’experts en echographie osteo-articulaire selon une procedure Delphi, permettant l’elaboration d’une version preliminaire des recommandations qui ont ensuite ete reformulees et validees par un groupe d’experts elargi en evaluant leur pertinence, leur comprehensibilite et leur exhaustivite, au cours d’une reunion presentielle. Le degre d’accord des experts et la faisabilite de ces recommandations en pratique ont ete precises. Resultats A l’issue de 2 tours de Delphi, un consensus a ete obtenu sur 3 principes generaux, incluant les definitions des sites articulaires, tendineux et osseux a evaluer, et 10 recommandations. Elles soulignent l’interet de l’echographie pour aider au diagnostic de PR devant des arthralgies inflammatoires ou une oligoarthrite inclassee et pour evaluer l’etendue de l’atteinte inflammatoire et structurale initialement. Elles positionnent cet examen au cours du suivi et une fois la remission clinique obtenue avant d’envisager la decroissance therapeutique. Elles precisent son interet pour aider a la realisation des gestes techniques. Conclusion Ces 10 recommandations consensuelles devraient permettre une homogeneisation ainsi qu’une optimisation des pratiques cliniques, conduisant a ameliorer la prise en charge des patients presentant une PR.

International audience; To characterize Lyme arthritis, with a focus on management, and outcome. Observational retrospective multicentre study in Western France, of all consecutive cases of Lyme arthritis, documented by Borrelia burgdorferi IgG on ELISA serological testing, confirmed by Western blot, with or without positive Borrelia PCR in synovial fluid, with no alternative diagnosis. We enrolled 52 patients (29 males), with a mean age of 43 +/- 19.4 years. Most patients had monoarthritis (n = 43, 82.7%), involving the knee (n = 51, 98.1%), with a median delay between symptoms onset and Lyme arthritis diagnosis of 5 months (interquartile range, 1.5-8). Synovial fluid analysis yielded median white cell count of 16,000/mm(3) (9230-40,500), and positive PCR in 16 cases (39%), for B. burgdorferi sensu stricto (n = 5), B. garinii (n = 5), B. afzelii (n = 3), and undetermined (n = 3). All patients received antibiotics, for a median duration of 28 days (21-30), with doxycycline (n = 44, 84.6%), ceftriaxone (n = 6, 11.5%), or amoxicillin (n = 2). Twelve patients (23.1%) also received intra-articular injection of glucocorticoids as first-line treatment. Of 47 patients with follow-up, 35 (74.5%) had complete resolution of Lyme arthritis. Lyme arthritis in Western Europe may be due to B. burgdorferi ss, B. afzelii, or B. garinii. Clinical presentation is similar to Lyme arthritis in North America (i.e. chronic knee monoarthritis), with low sensitivity of synovial fluid PCR (39%).

Background No current guidelines are available for managing septic bursitis (SB). Objectives To describe the clinical characteristics and management of olecranon and prepatellar SB in five French tertiary care centres. Methods This is a retrospective observational multicentre study. SB was diagnosed on the basis of positive cultures of bursal aspirate. In the absence of positive bursal fluid, the diagnosis came from typical clinical presentation, exclusion of other causes of bursitis and favourable response to antibiotic therapy. Results We included 272 patients (median age of 53 years, 85.3% male and 22.8% with at least one comorbidity). A microorganism was identified in 184 patients (67.6%), from bursal fluids in all but 4. We identified staphylococci in 135 samples (73.4%), streptococci in 35 (19%) and 10 (5.5%) were polymicrobial, while 43/223 bursal samples remained sterile (19.3%). Forty-nine patients (18%) were managed without bursal fluid analysis. Antibiotic treatment was initially administered IV in 41% and this route was preferred in case of fever (P = 0.003) or extensive cellulitis (P = 0.002). Seventy-one (26%) patients were treated surgically. A low failure rate was observed (n = 16/272, 5.9%) and failures were more frequent when the antibiotic therapy lasted Conclusions Despite variable treatments, SB resolved in the majority of cases even when the treatment was exclusively medical. The success rate was equivalent in the non-surgical and the surgical management groups. However, a treatment duration of

Resume Objectifs La plupart des etudes retrouvent une majoration du risque de fractures vertebrales chez les patients acromegales, malgre une densite minerale osseuse normale. Nous avons etudie la prevalence des fractures vertebrales chez les patients acromegales de moins de 80 ans suivis au CHU de Nantes. Methode Etude transversale monocentrique realisee au CHU de Nantes de 1988 a 2018. Cinquante patients (18 femmes, 32 hommes) d’un âge median de 52,3 ans (27 -78 ans) ont ete inclus. Les fractures vertebrales etaient evaluees sur des radiographies conventionnelles des rachis lombaire et thoracique de face et de profil, selon la methode semi-quantitative de Genant. Nous avons egalement etudie les deformations vertebrales autres que les fractures, en utilisant 3 criteres : presence d’osteophytes, presence de pincement discal et aspect cuneiforme des vertebres. Nous avons analyse la densite minerale osseuse par absorptiometrie bi-photonique et le statut hormonal. Resultats Trois patients (6 %) presentaient une fracture vertebrale : une fracture de grade 1 et 2 fractures de grade 2 selon la classification de Genant, chez deux patients osteoporotiques et un patient osteopenique. Leurs deficits ante-hypophysaires etaient substitues. En considerant les deformations franches (osteophyte ou pincement discal ≥ grade 2 ou aspect cuneiforme), le rachis dorsal etait deforme chez 22 patients (44 %) et le rachis lombaire chez 21 patients (42 %). Conclusions Les patients acromegales presentaient une faible prevalence de fractures vertebrales, mais un nombre important de deformations vertebrales. Nous supposons que cette forte prevalence de deformations franches pourrait expliquer la forte prevalence de fractures vertebrales rapportee precedemment.

OBJECTIVE The aim of this study was to assess the magnetic resonance imaging (MRI) features associated with microbial pathogen detection by computed tomography (CT)-guided biopsy in patients with suspected septic spondylodiscitis. METHODS For the last 10-year period, we analyzed the medical records of patients who underwent MRI and CT-guided biopsy for suspected septic spondylodiscitis. Clinical characteristics were recorded. The following MRI features were assessed: edema or contrast enhancement of the intervertebral disc, adjacent vertebrae, epidural and paravertebral space, presence of abscess, and paravertebral edema size. A positive biopsy was defined by pathogen identification on bacterial analysis or the presence of granuloma on histology. Predictors of a positive biopsy were assessed with a logistic regression model. RESULTS We analyzed data for 61 patients (34 [56%] male; mean age, 59.9 ± 18.0 years); for 35 patients (57%), CT-guided biopsy was positive for a pathogen. The 4 MRI findings significantly associated with a positive biopsy were epiduritis, greater than 50% vertebral endplate edema, loss of intradiscal cleft, and abscess. The size of paravertebral edema was greater with a positive than negative biopsy (median, 15.9 [interquartile range, 11.3-21.3] vs 7.3 [4.6-12.9] mm; p = 0.004). On multivariable analysis, epiduritis was the only independent predictor of a positive biopsy (adjusted odds ratio, 7.4 [95% confidence interval, 1.7-31.4]; p = 0.006). CONCLUSIONS Epiduritis and the size of paravertebral edema on MRI are associated with detection of a microbial pathogen in suspected septic spondylodiscitis. For patients without these MRI signs, the need for further investigations such as enriched or prolonged cultures, a second CT-guided biopsy, or even surgical biopsy need to be discussed.

Objectives Patients with acromegaly appear to be at increased risk of vertebral fractures despite normal bone mineral density. We investigated the prevalence of vertebral fractures in a cohort of acromegalic patients under 80 years of age. Methods Monocentric cross-sectional study performed at Nantes University Hospital from 1988 to 2018. Fifty patients (18 females, 32 males) with a median age of 52.3 years (range: 27–78) were included. Radiological vertebral fractures were evaluated on conventional lumbar and thoracic spine radiographs using Genant's semiquantitative fracture assessment. We studied qualitative abnormalities of the spine using three criteria: osteophytes, disc-space narrowing and wedge-shaped vertebrae. We analysed bone mineral density and endocrine status. Results Three patients (6%) had a vertebral fracture: one grade 1 and two grade 2 according to Genant's assessment, with two osteoporotic and one osteopenic patients. They had no unsubstituted pituitary deficiency. Considering the frank deformations (osteophyte or disc narrowing ≥ grade 2 or wedge-shaped), the thoracic spine was deformed in 22 patients (44%) and the lumbar spine in 21 patients (42%). Conclusion Acromegalic patients had a low prevalence of vertebral fractures but had a significant amount of vertebral deformations. We speculate that this high prevalence of frank deformations could explain the previously reported high prevalence of vertebral fractures.

Objective To report on the characteristics and long-term course of rheumatic manifestations in Schnitzler syndrome (SchS). Methods A retrospective cohort study of patients with SchS followed between 2000 and 2020. Inclusion criteria included a diagnosis of SchS (Strasbourg criteria). All available bone scans were reviewed and scored according to the intensity and number of pathological sites. The scintigraphic score was compared with the clinical activity score, CRP level, and treatments. Results Twenty-five patients were included. Median age at diagnosis was 68 years. Eighty patients (72%) had SchS-related rheumatic pain. Most patients had a long-standing isolated rash before constitutional and/or rheumatic symptoms appeared. The monoclonal component level was usually very low (IgMκ in 22/25). Rheumatic pain predominated around the knees. Bone scans revealed abnormal tracer uptake in 15/18 (85%). The scintigraphic score correlated with clinical activity (r = 0.4, p r = 0.47, p p Conclusions Rheumatic manifestations are very prevalent in SchS. However, bone pain can be misleading and contribute to misdiagnosis. Bone scan abnormalities are very prevalent and correlate with disease activity and treatments. IL1-Ra has a dramatic and durable efficacy but may not be required in every patient early on.

Background Excessive bone formation in the entheses is one of the features of peripheral spondyloarthritis (SpA). Complex pathological mechanisms connecting inflammation, mechanical stress, and ossification are probably involved. We focused on bone morphogenetic protein (BMP)-2, -4, and -7 as possible mediators of this process. Methods BMP-2, -4, and -7 concentration was measured by ELISA in synovial fluids (SFs) of SpA (n = 56) and osteoarthritic (n = 21) patients. Mouse organotypic ankle cultures were challenged by a pro-inflammatory cocktail. Mouse primary chondrocytes, osteoblasts, or tenocytes were treated with TNF-α, interleukin (IL)-17, or IL-22 and/or subjected to cyclic stretch, or with recombinant BMP-2 or -4. Results In SpA SFs, if BMP-7 was barely detectable, BMP-2 concentration was higher and BMP-4 was lower than in osteoarthritic samples, so that BMP-2/BMP-4 ratio augmented 6.5 folds (p n = 21). Bmp-2/Bmp-4 ratio was similarly enhanced by cytokine treatment in explant and cell cultures, at mRNA level. In particular, simultaneous application of TNF-α and cyclical stretch induced a 30-fold increase of the Bmp-2/Bmp-4 ratio in chondrocytes (p = 0.027). Blockade of prostaglandin E2 and IL-6 production had almost no effect on the stretch-induced regulation of Bmp-2 or -4. Osteoinductive effects of BMP-4, and to a lesser extend BMP-2, were identified on cultured chondrocytes and tenocytes. Conclusions Our results first settle that BMP factors are locally deregulated in the SpA joint. An unexpected decrease in BMP-4 could be associated to an increase in BMP-2, possibly in response to mechanical and/or cytokine stimulations.

Background Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular (CV) disease. Adiponectin is involved in the metabolism of glucose and lipids with favourable effects on CV disease, especially its high molecular weight (HMW) isoform. Body composition changes are described in RA with various phenotypes including obesity. The effects of tocilizumab on serum adiponectin and body composition, especially fat mass, in patients with RA are not well determined. Methods Patients with active RA despite previous csDMARDs and/or bDMARDs and who were tocilizumab naïve were enrolled in a multicentre open-label study. They were evaluated at baseline, 1, 3, 6 and 12 months. Clinical assessment included body mass index (BMI) and anthropometric measurements. Lipid and metabolic parameters, serum adiponectin (total and HMW), leptin, resistin and ghrelin were measured at each time point. Body composition (lean mass, fat mass, % fat, fat in the android and gynoid regions) was evaluated at baseline, 6 and 12 months. Results One hundred seven patients were included. Both total and HMW adiponectin significantly increased from baseline to month 3, peaking respectively at month 3 (p = 0.0105) and month 1 (p p = 0.001). BMI and waist circumference significantly increased at month 6 and 12, as well as lean mass at month 6 (p = 0.0097). Fat mass, percentage fat and android fat did not change over the study period. Lipid parameters (total cholesterol and LDL cholesterol) increased while glycaemia, insulin and HOMA-IR remained stable. Serum leptin, resistin and ghrelin did not change during follow-up. Conclusions Tocilizumab treatment in RA patients was associated with a significant increase in total and HMW adiponectin, especially at the onset of the treatment. Tocilizumab also induced a significant gain in lean mass, while fat mass did not change. These variations in adiponectin levels during tocilizumab treatment could have positive effects on the CV risk of RA patients. In addition, tocilizumab may have an anabolic impact on lean mass/skeletal muscle. Trial registration The ADIPRAT study was a phase IV open-label multicentre study retrospectively registered on ClinicalTrials.gov under the number NCT02843789 (date of registration: July 26, 2016).

Resume Les tendinopathies calcifiantes de la coiffe sont une des causes les plus frequentes de douleurs chroniques de l’epaule, impactant generalement la vie quotidienne et professionnelle des patients. Apres l’echec du traitement de premiere intention associant antalgiques/AINS, kinesitherapie et infiltration de corticoides, un geste d’exerese de la calcification sous echographie est generalement propose. Cette revue reprend les differentes techniques utilisees : lavage a une ou deux aiguilles ou fragmentation seule, en detaillant leur mise en œuvre, leur efficacite et leurs complications. Les trois techniques ont une efficacite semblant equivalente bien que peu d’etudes comparatives soient disponibles. Les complications rapportees sont peu severes, essentiellement des malaises vagaux au cours du geste et une recrudescence des douleurs dans les 3 a 4 mois suivant le geste. De rares cas de bursites septiques ont ete rapportes (4 en tout). Enfin, bien que la technique soit quasi exclusivement etudiee au niveau de l’epaule, d’autres localisations (hanche, genou, coude) ont egalement ete traitees avec succes.

Compression of roots/nerves can disrupt some of their functions, but does not necessarily cause pain. This is illustrated by the frequency of nearly asymptomatic spinal stenosis or disc herniations. In fact, pain of radiculopathies (and nerve entrapments) may mostly be the consequence of intraneural oedema induced by microscopical venous stasis around roots/spinal ganglia (or nerves) not or poorly shown by imaging. This narrative review first lists arguments for a role of congestion of vasa-nervorum in the pathophysiology of radiculopathies, including those induced by disc herniation and spinal stenosis, but also other sources of overpressures in spinal venous plexuses (pregnancy, vena cava atresia and thrombosis, portal hypertension, epidural varices, arterio-venous fistula, vertebral hemangioma or hemangioblastoma). It also details sources of venous congestion around nerves outside the spine, from pelvis (May-Thurner syndrome, Nut-cracker syndrome) to buttocks (superior and inferior gluteal veins), and even thighs and legs. A better recognition of a preeminent role of venous congestion in radiculopathies, plexopathies, and nerve entrapments, should have major consequences: (i) discard the dogma that compression is mandatory to induce root/nerve suffering, since root/nerve adherences in two locations can impair blood flow in vasa-nervorum through root/nerve stretching; (ii) implementation of sensitive techniques to visualise impingement of blood flow around or within roots and nerves; (iii) better prevention of roots/nerves adherence, or arachnoiditis induced by extravascular fibrin deposition secondary to venous stasis.; (iv) optimizing treatments dampening clot formation and/or extravascular fibrin leakage in the intradural/peridural spaces, or around roots/nerves, like guided injection of tissue plasminogen activator.

The concept of fibromyalgia has progressed to achieve a certain consensus regarding the definition of the condition. We summarize what is known in 2020, be it in terms of diagnosis, with the criteria that have changed over the years, or at the level of the psychological profile, via the notions of “catastrophizing” and “coping” and post-traumatic syndrome. The importance of fatigue and sleep disorders is underlined, with the chronological sequence of post-traumatic syndrome, chronic fatigue, and then amplification of the pain and the onset of multiple associated symptoms. The etiopathogenic debate has been enriched thanks to neuro-imaging data to discover the start of the central neurological signature. The many associated symptoms are reanalyzed in the context of so-called sister conditions which form sometimes more or less separate entities, such as chronic fatigue syndrome or restless legs syndrome for example. What these conditions have in common is hypersensitivity, not just to pain, but also to all exteroceptive stimuli, from deep sensitivity in the neuro-vegetative system, the sense organs and certain functions of the central nervous system, to the psychological aspects and sleep control. In summary, it is possible to define fibromyalgia as a cognitive disorder of cortical integration of chronic pain, with amplification of painful and sensory nociception, decrease in the threshold for the perception of pain, and persistence of a stimulus that maintains the process in chronicity. Fibromyalgia is part of a group of chronic hypersensitivity syndromes of central origin, with a very wide range of means of expression.

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Resume Objectifs Cette etude, menee dans une population de patients atteints de LES, avait pour objectifs (1) de decrire les atteintes articulaires echographiques (US), (2) d’estimer la correlation du nombre d’articulations cliniquement gonflees (NAG-C) et du SLEDAI clinique (SLEDAI-C) avec le NAG echographique (NAG-US) et le SLEDAI echographique (SLEDAI-US), (3) de mettre en evidence les caracteristiques specifiques des patients lupiques selon les observations en mode Doppler puissance (DP). Methode Nous avons inclus dans cette etude transversale multicentrique 151 patients adultes consecutifs atteints de LES. L’evaluation comprenait un examen clinique standardise des articulations, une echographie en mode B et en mode Doppler puissance (DP) sur 40 articulations et 26 tendons, en aveugle des resultats de l’examen clinique. La correlation entre l’examen clinique et l’echographie en mode B a ete calculee au moyen du coefficient de correlation intra-classe (ICC [Intervalle de confiance a 95 %]). Resultats Un taux tres eleve d’anomalies infracliniques echographiques a ete observe chez les patients asymptomatiques : l’existence d’au moins une manifestation echographique a ete retrouvee chez 85 % des patients qui ne presentaient aucun symptome articulaire. Parmi eux, 46 patients (87 %) avaient un antecedent d’atteinte articulaire. L’epanchement articulaire (108 patients), l’hypertrophie synoviale (HS, 109 patients) et la synovite (61 patients) etaient les anomalies les plus frequemment retrouvees. Un signal DP positif des articulations ou des tendons (grade > 1) a ete retrouve dans 44 % des cas (67/151). Des synovites ont ete detectees principalement aux articulations MCP et des poignets. Malgre la faible correlation de l’examen clinique au NAG-US en mode B, une bonne correlation du SLEDAI clinique au SLEDAI echographique a ete retrouvee. La comparaison des patients atteints de LES avec et sans signal DP n’a pas mis en evidence de caracteristiques specifiques du LES. Conclusion L’echographie est une methode d’imagerie qui a prouve son utilite pour l’evaluation des atteintes articulaires dans le LES mais qui ne modifiait pas de maniere significative le score SLEDAI.

Spondyloarthritis (SpA) is a common rheumatic disease characterized by enthesis inflammation (enthesitis) and ectopic ossification (enthesophytes). The current pathogenesis model suggests that inflammation and mechanical stress are both strongly involved in SpA pathophysiology. We have previously observed that the levels of sphingosine 1-phosphate (S1P), a bone anabolic molecule, were particularly high in SpA patients' serum compared to healthy donors. Therefore, we wondered how this deregulation was related to SpA molecular mechanisms. Mouse primary osteoblasts, chondrocytes, and tenocytes were used as cell culture models. The sphingosine kinase 1 (Sphk1) gene expression and S1P secretion were significantly enhanced by cyclic stretch in osteoblasts and chondrocytes. Further, TNF-α and IL-17, cytokines implicated in enthesitis, increased Sphk1 mRNA in chondrocytes in an additive manner when combined to stretch. The immunochemistry on mouse ankles showed that sphingosine kinase 1 (SK1) was localized in some chondrocytes; the addition of a pro-inflammatory cocktail augmented Sphk1 expression in cultured ankles. Subsequently, fingolimod was used to block S1P metabolism in cell cultures. It inhibited S1P receptors (S1PRs) signaling and SK1 and SK2 activity in both osteoblasts and chondrocytes. Fingolimod also reduced S1PR-induced activation by SpA patients' synovial fluid (SF), demonstrating that the stimulation of chondrocytes by SFs from SpA patients involves S1P. In addition, when the osteogenic culture medium was supplemented with fingolimod, alkaline phosphatase activity, matrix mineralization, and bone formation markers were significantly reduced in osteoblasts and hypertrophic chondrocytes. Osteogenic differentiation was accompanied by an increase in S1prs mRNA, especially S1P1/3 , but their contribution to S1P-impact on mineralization seemed limited. Our results suggest that S1P might be overproduced in SpA enthesis in response to cytokines and mechanical stress, most likely by chondrocytes. Moreover, S1P could locally favor the abnormal ossification of the enthesis; therefore, blocking the S1P metabolic pathway could be a potential therapeutic approach for the treatment of SpA. © 2019 American Society for Bone and Mineral Research.

International audience; Micro-RNAs are an area of research exponentially expanding over the past years. These small sequences of 20-22 nucleotides have a strong role as post-transcriptional regulators of gene expression. Inflammatory arthritis pa-thophysiology involves various key players from innate to adaptive immunity, as well as various signalling pathways of inflammation. In this review, we discuss how micro-RNAs are involved in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and juvenile inflammatory arthritis, from pre-clinical phases to established diseases. We describe mi-RNAs key roles in fibroblast like synoviocytes migration, proliferation, apoptosis and cytokine production, in macrophages polarization, as well as in B cells and T cell proliferation and differentiation, with a special emphasis on Treg/Th17 imbalance. We finally discuss the application of these findings in pre-clinical models and highlight opportunities and limits of a therapeutic approach using mi-RNAs agonists or antagonists.

ObjectiveSteroid injections are common after an ultrasound-guided puncture and lavage (UGPL) of calcific tendonitis of the rotator cuff. However, steroids may prevent calcification resorption and negatively affect tendon healing. Our study was designed to determine whether saline solution was non-inferior to steroids in the prevention of acute pain reactions in the week following UGPL.MethodsThis was a randomised, double-blinded, controlled non-inferiority trial with 12-month follow-up. We included 132 patients (66 in each group) with symptomatic calcification measuring more than 5 mm. Patients received 1 mL of saline or steroid (methylprednisolone 40 mg) in the subacromial bursa at the end of UGPL. Primary outcome was the maximal pain during the week following the procedure with a prespecified non-inferiority margin of 10 mm (0–100 visual analogue scale). Secondary outcomes included pain at rest and during activity, function (disabilities of the arm, shoulder and hand score) and radiological evolution of the calcification over the 12-month follow-up.ResultsThe estimated mean difference in the first week’s maximal pain between these two groups was 11.76 (95% CI 3.78 to 19.75). Steroids significantly improved VAS pain at rest and during activities, as well as function at 7 days and 6 weeks. They did not change the rate of calcification resorption, which occurred in 83% and 74% of patients at 12 months in the saline and steroid groups.ConclusionNon-inferiority of saline when compared with steroids could not be established. However, steroid injection improved pain in the 6 weeks following the procedure, and function in the 3 months after, with no significant effect on calcification resorption.Trial registration numberNTC02403856.

The aim of our study was to describe spine immobilization in a multicentric cohort of vertebral osteomyelitis (VO), and evaluate its association with neurological complications during follow-up.We prospectively included patients from 2016 to 2019 in 11 centers. Immobilization, imaging, and neurological findings were specifically analyzed during a 6-month follow-up period.250 patients were included, mostly men (67.2%, n=168). Mean age was 66.7±15 years. Diagnosis delay was 25 days. The lumbo-sacral spine was most frequently involved (56.4%). At diagnosis, 25.6% patients (n=64) had minor neurological signs and 9.2% (n=23) had major ones. Rigid bracing was prescribed for 63.5% (n=162) of patients, for a median of 6 weeks, with variability between centers (P0.001). The presence of epidural inflammation and abscess on imaging was associated with higher rates of rigid bracing prescription (OR 2.33, P=0.01). Frailness and endocarditis were negatively associated with rigid bracing prescription (OR 0.65, P0.01, and OR 0.42, P0.05, respectively). During follow up, new minor or major neurological complications occurred in respectively 9.2% (n=23) and 6.8% (n=17) of patients, with similar distribution between immobilized and non-immobilized patients.Spine immobilization prescription during VO remains heterogeneous and seems associated inflammatory lesions on imaging but negatively associated with frailness and presence of endocarditis. Neurological complications can occur despite rigid bracing. Our data suggest that in absence of any factor associated with neurological complication spine bracing might not be systematically indicated. We suggest that spine immobilization should be discussed for each patient after carefully evaluating their clinical signs and imaging findings.

Resume Les tendinopathies calcifiantes de la coiffe des rotateurs sont dues a des depots d’apatite dans les tendons de l’epaule qui provoquent des douleurs chroniques invalidantes. Malgre la frequence de cette maladie qui concerne 10 a 42 % des epaules douloureuses, les mecanismes de cette mineralisation pathologique demeurent en grande partie inconnus. Dans les annees 1990, des etudes ont suggere un lien entre la formation de depots calciques et des cellules ayant l’aspect de chondrocytes identifiees a proximite des depots, dans une zone de fibrocartilage. On pensait a l’epoque que ces cellules etaient derivees des tenocytes, mais des cellules-souches de tendon capables de se differencier en chondrocytes ont ete isolees plus recemment. Les proprietes mineralisantes de ces cellules de type chondrocytaire, et notamment le role de la phosphatase alcaline, ne sont pas clairement etablis. Concernant la composition, ces depots contiennent de l’apatite carbonatee faiblement cristalline associee a des proteines, parmi lesquelles seule l’osteopontine a ete decrite comme un possible facteur de regulation. Lors de la resorption spontanee, la migration des cristaux d’apatite dans la bourse sous-acromiale provoque des douleurs severes et une limitation de mobilite. Des experiences in vivo et in vitro ont montre que les cristaux d’apatite pouvaient declencher un afflux de leucocytes et la secretion d’IL-1β et d’IL-18 en reponse a l’activation de l’inflammasome NLRP3. Neanmoins, les mecanismes conduisant a la resolution spontanee de cette inflammation et a la disparition de la calcification doivent encore etre elucides.

This review lists current evidences for a contribution of gut mycobiota to the pathogenesis of SpA and related conditions. Gut mycobiota has a small size as compared to bacterial microbiota, but an even greater inter- and intra-individual variability. Although most fungi (brought by food or air) are only transitory present, a core mycobiota of gut resident fungi exists, and interplays with bacteria in a complex manner. A dysbiosis of this gut mycobiota has been observed in Crohn's disease and sclerosing cholangitis, with decreased proportion of Saccharomyces cerevisiae and outgrowth of more pathogenic gut fungi. Fungal-induced lower number of commensal gut bacteria can promote translocation of some bacterial/fungal antigens through mucosae, and live fungi can also cross the epithelial border in Crohn's disease. This dysbiosis also lower the ability of bacteria to metabolize tryptophan into regulatory metabolites, consequently enhancing tryptophan metabolism within human cells, which might contribute to fatigue. Translocation of mycobiotal antigens like curdlan (beta-glucan), which plays a major role in the pathogenesis of SpA in the SGK mice, has been observed in humans. This translocation of fungal antigens in human SpA might account for the anti-Saccharomyces antibodies found in this setting. Contribution of fungal antigens to psoriasis and hidradenitis suppurativa would fit with the preferential homing of fungi in the skin area most involved in those conditions. Fungal antigens also possess autoimmune uveitis-promoting function. As genes associated with SpA (CARD9 and IL23R) strongly regulate the innate immune response against fungi, further studies on fungi contribution to SpA are needed.

Background: Calcific tendinitis of the rotator cuff is a frequent cause of shoulder pain. Ultrasound-guided percutaneous lavage (UGPL) is an effective treatment, but factors associated with good clinical and radiological outcomes still need to be identified. Purpose: To study the clinical, procedural, and radiological characteristics associated with improved shoulder function and the disappearance of calcification on radiograph after UGPL. Study Design: Case-control study; Level of evidence, 3. Methods: This is a post hoc analysis of the CALCECHO trial, a double-blinded randomized controlled trial conducted on 132 patients. The trial assessed the effect of corticosteroid injections after UGPL, and patients were randomly assigned to receive either corticosteroid or saline solution in the subacromial bursa. We analyzed all patients included in the randomized controlled trial as 1 cohort. We collected the patients’ clinical, procedural, and radiological characteristics at baseline and during follow-up (3, 6, and 12 months). Univariable analysis, followed by multivariable stepwise regression through forward elimination, was performed to identify the factors associated with clinical success (Disabilities of the Arm, Shoulder and Hand [DASH] score Results: Good clinical outcomes at 3 months were associated with steroid injections after the procedure (odd ratio [OR], 3.143; 95% CI, 1.105-8.94). At 6 months, good clinical evolution was associated with a lower DASH score at 3 months (OR, 0.92; 95% CI, 0.890-0.956) and calcium extraction (OR, 10.7; 95% CI, 1.791-63.927). A lower DASH at 6 months was also associated with a long-term favorable outcome at 12 months (OR, 0.939; 95% CI, 0.912-0.966). Disappearance of calcification at 3 and 12 months occurred more frequently in patients in whom communication was created between the calcification and the subacromial bursa during the procedure (OR, 2.728 [95% CI, 1.194-6.234] at 3 months; OR, 9.835 [95% CI, 1.977-48.931] at 12 months). Importantly, an association between calcification resorption and good clinical outcome was found at each time point. Conclusion: Assessing patients at 3 months seems to be an essential part of their management strategy. Calcium extraction and creating a communication between the calcific deposits and subacromial bursa are procedural characteristics associated with good clinical and radiological evolution.

Objectives The aim of this study was to show the usefulness of a mid-infrared fibre evanescent wave spectroscopy point of care device in the identification of septic arthritis patients in a multicentre cohort, and to apply this technology to clinical practice among physicians. Methods SF samples from 402 patients enrolled in a multicentre cohort were frozen for analysis by mid-infrared fibre evanescent wave spectroscopy. The calibration cohort was divided into two groups of patients (septic arthritis and non-septic arthritis) and relevant spectral variables were used for logistic regression model. Model performances were tested on an independent set of 86 freshly obtained SF samples from patients enrolled in a single-centre acute arthritis cohort and spectroscopic analyses performed at the patient’s bedside. Results The model set-up, using frozen–thawed SFs, provided good performances, with area under the curve 0.95, sensitivity 0.90, specificity 0.90, positive predictive value 0.41 and negative predictive value 0.99. Performances obtained in the validation cohort were area under the curve 0.90, sensitivity 0.92, specificity 0.81, positive predictive value 0.46 and negative predictive value 0.98. The septic arthritis probability has been translated into a risk score from 0 to 4 according to septic risk. For a risk score of 0, the probability of identifying a septic patient is very low (negative predictive value of 1), whereas a risk score of 4 indicates very high risk of septic arthritis (positive predictive value of 1). Conclusion Mid-infrared fibre evanescent wave spectroscopy could distinguish septic from non-septic synovial arthritis fluids with good performances, and showed particular usefulness in ruling out septic arthritis. Our data supports the possibility of technology transfer. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT02860871.

Background Calcific tendonitis of the rotator cuff is due to carbonated apatite deposits in the shoulder tendons. During the evolution of the disease, an acute inflammatory episode may occur leading to the disappearance of the calcification. Although hydroxyapatite crystal-induced inflammation has been previously studied with synthetic crystals, no data are available with calcifications extracted from patients suffering from calcific tendinopathy. The objective of the study was to explore the inflammatory properties of human calcifications and the pathways involved. Methods Human calcifications and synthetic hydroxyapatite were used in vitro to stimulate human monocytes and macrophages, the human myeloid cell line THP-1, and human tenocytes. The release of IL-1β, IL-6, and IL-8 by cells was quantified by ELISA. The gene expression of pro- and anti-inflammatory cytokines was evaluated by quantitative PCR. NF-kB activation and NLRP3 involvement were assessed in THP-1 cells using a NF-kB inhibitor and a caspase-1 inhibitor. The inflammatory properties were then assessed in vivo using a mouse air pouch model. Results Human calcifications were able to induce a significant release of IL-1β when incubated with monocytes, macrophages, and THP-1 only if they were first primed with LPS (monocytes and macrophages) or PMA (THP-1). Stimulation of THP-1 by human calcifications led to similar levels of IL-1β when compared to synthetic hydroxyapatite although these levels were significantly inferior in monocytes and macrophages. The patient’s crystals enhanced mRNA expression of pro-IL-1β, as well as IL-18, NF-kB, and TGFβ when IL-6 and TNFα expression were not. IL-1β production was reduced by the inhibition of caspase-1 indicating the role of NLRP3 inflammasome. In vivo, injection of human calcifications or synthetic hydroxyapatite in the air pouch led to a significant increase in membrane thickness although significant overexpression of IL-1β was only observed for synthetic hydroxyapatite. Conclusions As synthetic hydroxyapatite, human calcifications were able to induce an inflammatory response resulting in the production of IL-1β after NF-kB activation and through NLRP3 inflammasome. In some experiments, IL-1β induction was lower with human calcifications compared to synthetic apatite. Differences in size, shape, and protein content may explain this observation.

Additional file 1: Supplementary Figure S1. IL-1β release after 6h stimulation of CD14+ monocytes, MCSF-Macrophages, GM-CSF/IFNγ-Macrophages by crystals at 250, 500 and 1000 ng/ml in presence of LPS (lipopolysaccharide) and parallel cell death rate. sHA= synthetic hydroxyapatite, CAL = human calcification CT= control group without crystal; LPS= lipopolysaccharide. n = 3. * p≤ 0,05. Supplementary Figure S2. Western Blot raw images of sHA (positive control) and three patients. Cleaved IL-1β was studied in cellular lysates (CL) and in supernatants (SN). iNF-κB= NF-κB inhibitor; iCasp1= caspase-1 inhibitor; inh= inhibitor; sHA= synthetic hydroxyapatite; CAL= human calcification; CT = control condition without crystals. Supplementary Table 1. Primers used for quantitative Polymerase Chain Reaction.