Application of the OMERACT synovitis ultrasound scoring system in juvenile idiopathic arthritis: a multicenter reliability exercise.

OBJECTIVES: To evaluate the reliability of the OMERACT paediatric ultrasound (US) synovitis definitions and scoring system in JIA. METHODS: Thirteen sonographers analysed 75 images for the presence/absence of elementary lesions (binary scoring) and for grading synovitis, synovial hypertrophy, effusion and Doppler signals. Static US images of the second metacarpophalangeal joint (MCP-II), wrist, elbow, knee and ankle in JIA patients at different ages and different disease stages were collected with standardized scanning by two experienced sonographers. Intra- and inter-reader reliability were analysed with kappa coefficients. RESULTS: Intra-reader reliability was good for binary scoring (Cohen's kappa 0.62, range 0.47-0.75), synovitis and synovial hypertrophy; excellent for Doppler signals (quadratic weighted kappa 0.77, 0.66-0.86; 0.76, 0.61-0.84; and 0.87, 0.77-0.94, respectively); and moderate for effusion (0.55, 0.24-0.76). Inter-reader reliability was good for synovitis and synovial hypertrophy (Light's kappa 0.68, 95% CI: 0.61, 0.75 and 0.63, 0.54-0.71, respectively), excellent for Doppler signals (0.85, 95% CI: 0.77, 0.90), and moderate for binary scoring and effusion (0.48, 95% CI: 0.36, 0.64 and 0.49, 0.40-0.60, respectively). We obtained the best scores for the knee (0.71, 0.54-0.85) except for Doppler signals, with reliability higher for MCP-II. We found a trend toward better results in older children. CONCLUSIONS: This is the first study establishing the reliability of the OMERACT paediatric US synovitis definitions and scoring system in the five most commonly affected joints in JIA. The reliability was good among a large group of sonographers. These results support the applicability of these definitions and scoring system in clinical practice and multicentre studies.

Predictive factors of mortality in patients treated with tocilizumab for acute respiratory distress syndrome related to coronavirus disease 2019 (COVID-19).

COVID-19 patients (n = 34) suffering from ARDS were treated with tocilizumab (TCZ). Outcome was classified in two groups: "Death" and "Recovery". Predictive factors of mortality were studied. Mean age was 75.3, mean oxygen (O2) requirements 10.4 l/min. At baseline, all patients had multiple biological abnormalities (lymphopenia, increased CRP, ferritin, fibrinogen, D-dimer and liver enzymes). 24 patients (70.5%) recovered after TCZ therapy and 10 died (29.5%). Deceased subjects differed from patients in whom treatment was effective with regard to more pronounced lymphopenia (0.6 vs 1.0 G/l; p = 0.037), lower platelet number (156 vs 314 G/l; p = 0.0001), lower fibrinogen serum level (0.6 vs 1.0 G/l; p = 0.03), higher aspartate-amino-transferase (108 vs 57 UI/l; p = 0.05) and greater O2 requirements (11 vs 8 l/min; p = 0.003).

Biomarker variation in patients successfully treated with tocilizumab for severe coronavirus disease 2019 (COVID-19): results of a multidisciplinary collaboration.

OBJECTIVES: Acute respiratory distress syndrome (ARDS) related to SARS-CoV-2 is likely due to a cytokine storm characterised by a major release of pro-inflammatory cytokines, including interleukin-6 (IL-6). Blocking excessive IL-6 production might be the key to the COVID-19-ARDS treatment. Beneficial effects of IL-6 blockade using a humanised anti-IL-6 receptor antibody, tocilizumab (TCZ) were previously reported in patients with COVID-19 related ARDS. The aim of the study was to study the variation over time of several biomarkers, demonstrated to be predictors of poor prognostic, in subjects successfully treated with TCZ for severe COVID-19. METHODS: Retrospective analysis of a case series of patients with COVID-19-ARDS, evidenced by RT-PCR and lung CT-scan. Patients with increasing O2 requirements, within the window of opportunity for TCZ treatment (Day 7 to Day 17 after onset of symptoms) were treated with TCZ (2 infusions of 8 mg/kg). Demographic, biological and clinical data were collected from the patients' files. Serum levels of CRP, ferritin, fibrinogen, lymphocytes, platelets, creatinine, D-dimer and liver enzymes were assayed at the time of the first TCZ administration, then every two days for 8 days. RESULTS: 40 patients were treated with TCZ. Most of them had several comorbidities, and all had multiple biological abnormalities (lymphopenia, increased CRP, ferritin, fibrinogen, D-dimer, liver enzymes). 30 patients (75%) benefited from TCZ and 10 patients died. In the survivors, following TCZ administration CRP decreased dramatically as early as day 4 (-86.7%, p<0.0001) and returned to normal at day 6. Fibrinogen and lymphocyte count returned to normal values at day 6. Ferritin also decreased significantly. No significant change was observed for D-dimer (p=0.68) and other studied biomarkers (haemoglobin, leucocyte count, AST). CONCLUSIONS: In patients with COVID-19 acute respiratory distress syndrome, treatment with TCZ resulted in favourable evolution in 75% of the cases. Biomarkers of inflammation (CRP, ferritin, fibrinogen) decreased dramatically as early as the 4th day after TCZ injection. Lymphopenia, a predictor of poor prognostic, was reversed 6 days after TCZ injection.

The joint flanker effect and the joint Simon effect: On the comparability of processes underlying joint compatibility effects.

Previous studies observed compatibility effects in different interference paradigms such as the Simon and flanker task even when the task was distributed across two co-actors. In both Simon and flanker tasks, performance is improved in compatible trials relative to incompatible trials if one actor works on the task alone as well as if two co-actors share the task. These findings have been taken to indicate that actors automatically co-represent their co-actor's task. However, recent research on the joint Simon and joint flanker effect suggests alternative non-social interpretations. To which degree both joint effects are driven by the same underlying processes is the question of the present study, and it was scrutinized by manipulating the visibility of the co-actor. While the joint Simon effect was not affected by the visibility of the co-actor, the joint flanker effect was reduced when participants did not see their co-actors but knew where the co-actors were seated. These findings provide further evidence for a spatial interpretation of the joint Simon effect. In contrast to recent claims, however, we propose a new explanation of the joint flanker effect that attributes the effect to an impairment in the focusing of spatial attention contingent on the visibility of the co-actor.

Imaging Guidance Improves the Results of Viscosupplementation with HANOX-M-XL in Patients with Ankle Osteoarthritis: Results of a Clinical Survey in 50 Patients Treated in Daily Practice.

BACKGROUND: The objective of this survey was to assess retrospectively the interest of performing viscosupplementation using imaging guidance in patients suffering from ankle osteoarthritis (OA). PATIENTS AND METHODS: This is a multicenter retrospective survey using a standardized questionnaire. Fifty patients suffering from ankle OA and treated, in daily clinical practice, with a single intra-articular injection of a novel viscosupplement made of a combination of a non-animal cross-linked hyaluronan and mannitol, HANOX M-XL, were included in the survey. The injection procedure (imaging or landmark guidance), demographic data, patient's self-evaluation of pain, satisfaction, treatment efficacy, and tolerability were collected. Predictive factors of both efficacy and patient's satisfaction were investigated. RESULTS: The percentages of patients very satisfied/satisfied and not really satisfied/dissatisfied with the treatment were 68% and 32%, respectively. Efficacy was rated as very good, good, moderate, and poor by 38%, 30%, 12%, and 20% of the cases, respectively. Efficacy was unrelated to gender and age and was highly correlated with pain score (P < 0.0001). In satisfied patients, the decrease in consumption of analgesics/non-steroidal anti-inflammatory drugs was >75% in 64% of the cases. Efficacy was significantly different with regard to imaging guidance. There was a statistically significant difference in efficacy and satisfaction between landmark-guided and imaging-guided injections (P = 0.02). The success rate was 2.3 times higher in the imaging-guided group than in the landmark-guided group. No significant difference was found between patients injected under fluoroscopy or ultrasound guidance, despite a trend favoring ultrasound (P = 0.09). Tolerability was rated as very good/good in 47 patients, moderate in two, and poor in one and was unrelated to the type of guidance. CONCLUSION: This preliminary study suggests that the use of imaging guidance significantly optimizes the success rate of ankle viscosupplementation. No safety concern was observed. LEVEL OF EVIDENCE: III.

Standardized Follow-up of Patients with Symptomatic Knee Osteoarthritis Treated with a Single Intra-articular Injection of a Combination of Cross-Linked Hyaluronic Acid and Mannitol.

OBJECTIVES: The objective of this study is to obtain pilot data from daily practice conditions of a viscosupplement made of a cross-linked high-molecular-weight hyaluronic acid (HA) combined with mannitol in patients with knee osteoarthritis (KOA). METHODS: The data of 40 consecutive patients, 29 women and 11 men, who were prospectively followed up for 6 months, using a standardized procedure, were retrospectively analyzed. All patients have received a single intra-articular injection of HAnox-M-XL (4.4 mL), viscosupplement made of a cross-linked HA (16 mg/mL) + mannitol (35 mg/mL), in the target knee. The primary outcome was safety. The secondary end points included 3- and 6-month change in the WOMAC pain (0-50) and WOMAC total (0-240) and patient's global assessment (PGA). Patient's self-assessment of treatment efficacy (0-3) and analgesic consumption were obtained at months 3 and 6. An intent-to-treat analysis was performed. RESULTS: Mean (SD) age was 60.7 (13.9) years, and mean BMI was 28.6 (5.0). Kellgren-Lawrence radiological grade was I/II and III/IV in 13 and 27 of the subjects, respectively. The average WOMAC pain and WOMAC total scores at baseline were 21.5 (9.8) and 89.9 (42.8), respectively. Thirty-nine patients completed the follow-up. HAnox-M-XL was well tolerated; two patients experienced knee pain after injection, which resolved within three days. No treatment-related severe adverse event was reported. Mean (SD) variations in WOMAC pain and WOMAC total scores were -8.2 (8.9) and -38.4 (35.6), respectively, at month 6 (P = 0.001). PGA decreased from 5.5 (2.0) to 3.0 (2.2) (P = 0.006). Efficacy was rated as good or very good in 76.9% of the cases. Most of the regular analgesics users decreased their consumption. CONCLUSION: Treatment with one injection of 4.4 mL HAnox-M-XL is effective to alleviate KOA symptoms over six months, without safety concern. Controlled trials are needed to confirm these pilot data.

Occurrence of Psoriatic Arthritis during Interferon Beta 1a Treatment for Multiple Sclerosis.

Interferon beta (IFN- ß ) is the first line therapy of relapsing-remitting multiple sclerosis. IFN- ß is a cytokine that can contribute to the development of systemic autoimmune disease including psoriasis. The development or the exacerbation of psoriasis during IFN- ß treatment has been previously observed. We report the occurrence of arthritis and dactylitis in a multiple sclerosis patient with preexisting psoriasis diagnosed as a psoriatic arthritis. The IL-23/Th17 pathway is involved in psoriasis and psoriatic arthritis and it has been suggested that IFN- ß therapy in patients with Th17-mediated disease may be detrimental. Together with previous similar reports, our case suggests that IFN- ß should certainly be used with caution in patients with concomitant systemic autoimmune disease with IL-23/Th17 involvement.

Evaluation of self-report questionnaires for assessing rheumatoid arthritis activity: a cross-sectional study of RAPID3 and RADAI5 and flare detection in 200 patients.

OBJECTIVES: To assess the validity of the two self-report questionnaires RAPID3 and RADAI5 for measuring the activity of rheumatoid arthritis (RA) in everyday practice, comparatively to the DAS28, CDAI, and SDAI. To determine cutoffs for flare detection based on patients' and physicians' opinions. METHODS: The RAPID3 and RADAI5 questionnaires were completed by 200 consecutive patients with RA. The DAS28, CDAI, and SDAI were computed in each patient. Patients and physicians stated whether a flare was occurring. Pairwise Spearman correlation coefficients were computed between the two scores and three indices. The kappa coefficient was used to assess agreement between the patients and physicians regarding the presence of a flare. Receiver-operating characteristic (ROC) curves were constructed to determine cutoffs for flare detection. RESULTS: The 200 patients had a mean age of 57 ± 11.5 years, a mean RA duration of 13 ± 8.3 years, a mean DAS28 of 3.61 ± 1.43, a mean CDAI of 12.7 ± 9.89, and a mean SDAI of 13.4 ± 10.45. The mean RAPID3 and RADAI5 scores were 3.45 ± 2 and 3.93 ± 2.18, respectively. The RAPID3 and RADAI5 scores correlated significantly with the three composite activity indices, with ρ values ranging from 0.64 to 0.74. The flare rate was 35% according to the patients and 22% according to the physicians, with moderate agreement between patients and physicians (κ=0.44). Flare cutoffs with satisfactory sensitivity and specificity values were obtained for the two scores and three indices. For the three indices, flare cutoffs according to the physicians were within the range indicating moderate disease activity: 4.04 for the DAS28, 14.5 for the CDAI, and 16.7 for the SDAI. The RAPID3 and RADAI5 flare cutoffs according to the physicians and patients were similar, 4.27 and 4.33 for RAPID3 and 4.5 and 4.7 for RADAI5, respectively. CONCLUSION: These results confirm the validity of the RAPID3 and RADAI5 self-report questionnaires and support their widespread use in everyday practice in patients with RA. The self-report questionnaire scores correlate with the composite activity index values and allow the detection of activity peaks or flares.

Aortic involvement in giant cell arteritis: current data.

Aortitis due to giant cell arteritis (GCA) is rare but probably underestimated given the frequent paucity of symptoms. Thus, early studies relied on the occurrence of complications to estimate the prevalence of GCA aortitis. With this method, aortitis was a feature in 3 to 18% of GCA patients. Since then, the introduction of modern imaging techniques has established that aortitis is more common than previously thought. Aortitis should be considered in patients with atypical clinical presentations of GCA consisting, for instance, in isolated laboratory evidence of systemic inflammation or a relapse during treatment. Aortitis may be difficult to diagnose, as temporal artery biopsy has limited sensitivity in patients with predominant large-vessel involvement. Positron emission tomography (PET) and magnetic resonance imaging (MRI) are both highly effective for the early diagnosis of aortitis. Case-series evaluating PET in patients with GCA found evidence of aortitis in over half the cases, with predominant involvement of the thoracic aorta. To date, no evidence is available about the potential usefulness of PET or MRI in monitoring patients with GCA aortitis over time. Involvement of the aorta and other large arteries does not change the treatment strategy, which rests on corticosteroid therapy. Administration of a corticosteroid-sparing drug should be considered, most notably when a relapse occurs. Aortitis is associated with an increased risk of aneurysm of the thoracic aorta. Consequently, all GCA patients should be monitored for aneurysm at regular intervals, even after treatment discontinuation. The recommended strategy is an annual evaluation including a chest radiograph, echocardiogram, and abdominal Doppler sonogram; these imaging studies can be replaced by contrast-enhanced computed tomography of the chest and abdomen.

Septic arthritis of the acromioclavicular joint.

The acromioclavicular joint is rarely the site of septic arthritis. We conducted a retrospective review at our rheumatology department, which identified five cases within the last 6 years. All five patients were males, and their mean age was 63 years. Risk factors were consistently identified and included intravenous substance abuse, prior joint disease, a recent history of intraarticular injections, and a remote history of surgery. Joint aspiration was performed in all five patients and provided the organism in two patients. Blood cultures recovered Staphylococcus aureus in three patients, a coagulase-negative Staphylococcus in one patient, and no organism in one patient. Ultrasonography and/or magnetic resonance imaging established the early diagnosis in four patients and ruled out concomitant involvement of the glenohumeral joint. Only about 20 cases of septic arthritis of the acromioclavicular joint have been reported to date. This rare infection must be diagnosed rapidly to prevent joint destruction. The treatment is that usually recommended for septic arthritis.