Ultrasonography performed by an infectiologist in hip and knee prosthetic joint and native joint infections.

INTRODUCTION: Clinical ultrasonography (US) by infectiologists has only recently been developing, and as now there is little literature on the subject. Our study focuses on the conditions and diagnostic performance of clinical ultrasound imaging by infectiologists in cases of hip and knee prosthetic and native joint infection. METHODS: A retrospective study carried out between June 1st 2019 and March 31st 2021 in the University Hospital of Bordeaux, South-Western France. We measured US sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV), combined or not with the analysis of articular fluid, compared to the MusculoSketetal Infection Society (MSIS) score in prosthetic joints, or to expert diagnosis in native joints. RESULTS: Fifty-four patients underwent US by an infectiologist in an infectious disease ward, including 11 (20.4%) for native joint and 43 (79.6%) for prosthetic joint. Joint effusion and/or periarticular collection were highlighted in 47 (87%) patients, and US led to 44 punctures. In all patients (n = 54), Se, Sp, PPV and NPV of US alone were 91%, 19%, 64% and 57%, respectively. When US was combined with fluid analysis, Se, Sp, PPV, NPV were 68%, 100%, 100%, 64% in all patients (n = 54), 86%, 100%, 100%, 60% in acute arthritis (n = 17) and 50%, 100%, 100% and 65% respectively in non-acute arthritis (n = 37). CONCLUSION: These results suggest that US by infectiologists effectively diagnoses osteoarticular infections (OAIs). This approach has many applications in infectiology routines. Consequently, it would be interesting to define the contents of a first level of infectiologist competence in US clinical practice.

Clinical and immunological features of patients with cancer-associated systemic sclerosis: An observational study.

INTRODUCTION: Clinical and immunological features of patients with cancer-associated systemic sclerosis: an observational study. OBJECTIVE: Several studies have reported an increased incidence of cancer in patients with systemic sclerosis (SSc). The presence of RNA polymerase III antibodies (anti-RNA Pol 3) associates with an increased risk of cancer, but other risk factors need yet to be identified. We aimed to assess clinical and immunological predictive factors of cancer-associated SSc to guide clinicians when setting up selective cancer screening. METHODS: We conducted a monocentric, retrospective, observational study of SSc patients with and without associated malignancy. Clinical, laboratory and imaging data were collected, as well as SSc treatment. Subgroup analyses were performed according to the type of cancer and the time of diagnosis. RESULTS: Of 464 SSc patients, 74 (16%) had cancer, with breast (n=26) and lung cancer (n=13) being the most frequent. Diagnosis of cancer was made less than 3 years before or after SSc diagnosis for 23 patients (31%). In a multivariate analysis, anti-RNA Pol 3 and anti-SSA antibodies were significantly associated with an increased overall risk of cancer with an odds ratio (OR) of 4.12 (95% CI [1.6-10.7]; P<0.01) and 2.43 (95% CI [1.1-5.4]; P<0.05), respectively. Age at diagnosis of SSc and delay from the SSc diagnosis were also independent risk factors of cancer. Interstitial lung disease and anti-topoisomerase antibodies were associated with an increased risk of lung cancer and cancer occuring more than three years after SSc diagnosis. CONCLUSION: In addition to anti-RNA Pol 3 antibodies, anti-SSA antibodies associated with an increased risk of cancer in SSc patients. Interstitial lung disease was a risk factor specifically for lung cancer and cancers diagnosed more than 3 years after SSc diagnosis. For these patients, a systematic and regular cancer screening should be considered.

Presentation and Real-World Management of Giant Cell Arteritis (Artemis Study).

Background: Few studies of daily practice for patients with giant cell arteritis (GCA) are available. This French study aimed to describe the characteristics and management of GCA in a real-life setting. Methods: Cross-sectional, non-interventional, multicenter study of patients ≥50 years old who consulted hospital-based specialists for GCA and were under treatment. Patient characteristics and journey, diagnostic methods and treatments were collected. Descriptive analyses were performed. Results: In total, 306 patients (67% females, mean age 74 ± 8 years old) were recruited by 69 physicians (internists: 85%, rheumatologists: 15%); 13% of patients had newly diagnosed GCA (diagnosis-to-visit interval <6 weeks). Overall median disease duration was 13 months (interquartile range 5-26). Most patients were referred by general practitioners (56%), then ophthalmologists (10%) and neurologists (7%). Most common comorbidities were hypertension (46%), psychiatric disorders (10%), dyslipidemia (12%), diabetes (9%), and osteoporosis (6%). Initial GCA presentations included cranial symptoms (89%), constitutional symptoms (74%), polymyalgia rheumatica (48%), and/or other extra-cranial manifestations (35%). Overall, 85, 31, 26, and 30% of patients underwent temporal artery biopsy, high-resolution temporal artery Doppler ultrasonography, 18FDG-PET, and aortic angio-CT, respectively. All patients received glucocorticoids, which were ongoing for 89%; 29% also received adjunct medication(s) (methotrexate: 19%, tocilizumab: 15%). A total of 40% had relapse(s); the median time to the first relapse was 10 months. Also, 37% had comorbidity(ies) related to or aggravated by glucocorticoids therapy. Conclusion: This large observational study provides insight into current medical practices for GCA. More than one third of patients had comorbidities related to glucocorticoid therapy for a median disease duration of 13 months. Methotrexate and tocilizumab were the most common adjunct medications.

Role of stress in the development of rheumatoid arthritis: a case-control study.

OBJECTIVES: The primary objective of this study was to assess the stressful life events preceding the onset of symptoms in RA. The secondary objectives were to assess how early RA patients perceive stress and cope with stressors. METHODS: A case-control study was performed, comparing patients recently diagnosed with RA to age- and gender-matched control subjects recently hospitalized for an unplanned surgical procedure not known to be influenced by stress. The Social Readjustment Rating Scale assessed the cumulative stress induced by stressful life events in the year preceding the onset of symptoms. Coping strategies, stress and anxiety symptoms were evaluated using validated psychological scales. RESULTS: Seventy-six subjects were included in each group. The mean Social Readjustment Rating Scale score was twice as high in cases compared with controls [respectively, 167.0 (172.5) vs 83.3 (124.4), P < 0.001]. The association between cumulative stress and RA was statistically significant only in women, with a dose-dependent association between stress and RA. While female patients with RA attributed more often the onset of symptoms to a life event than female controls (70.2 vs 24.5%, P < 0.001), no significant difference was found when comparing male RA patients with male controls (26.9 vs 18.5%, respectively, P = 0.46). Increased perceived stress score (P = 0.04) and coping based on emotions (P = 0.001) were found in cases compared with controls. CONCLUSION: Patients with early RA reported more life events in the year preceding the onset of symptoms than controls. Gender specificities were found with a significant association between cumulative stress and RA only in women.

Real-World 1-Year Retention Rate of Subcutaneous Tocilizumab Treatment in Patients with Moderate to Severe Active Rheumatoid Arthritis: TANDEM Study.

INTRODUCTION: Drug retention is particularly relevant to assess long-term treatments. This real-world study mainly aimed to describe 1-year retention rate (RR) of subcutaneously administered tocilizumab (TCZ-SC) in patients with moderate to severe active rheumatoid arthritis (RA). METHODS: This non-interventional, prospective, multicenter study (NCT02608112) was conducted in patients with RA initiating TCZ-SC treatment, with an 18-month follow-up. RR was estimated at month 12 in the overall population and baseline subgroups (combination with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) or not, age, body mass index, methotrexate dose), using the Kaplan-Meier method. Patient compliance to TCZ-SC was described using the 5-item Compliance Questionnaire for Rheumatology (CQR5). RESULTS: At inclusion 75% of the 285 analyzed patients were women, mean RA duration was 9 ± 9 years, previous RA treatments included biological agents (63%) and/or csDMARDs (94%), mean Disease Activity Score 28 joints-Erythrocyte Sedimentation Rate (DAS28-ESR) was 4.8 ± 1.2. TCZ-SC RR at month 12 was estimated to be 64% (95% CI 58%-69%) with no statistical differences between subgroups. Clinical results improved with TCZ-SC; the proportion of patients treated with combined glucocorticoids decreased from 49% to 22% at month 12. At each follow-up time, at least 80% of patients were high adherers to TCZ-SC (at least 80% of theoretical injections). Among the 286 patients with at least one TCZ-SC injection, 25 patients (9%) experienced serious adverse events related to TCZ-SC with no differences according to patient age. CONCLUSIONS: This real-world study corroborates the RR at month 12 previously shown in interventional studies on TCZ-SC. Our data suggest there are no differences according to patient's profile (age, BMI), methotrexate doses, and TCZ-SC use. TRIAL REGISTRATION: NCT02608112.

Adult-onset Still's disease biological treatment strategy may depend on the phenotypic dichotomy.

OBJECTIVES: Adult-onset Still's disease (AOSD) phenotype appears to be dichotomized in systemic or chronic articular forms. As biologicals and particularly interleukin (IL)-1 and IL-6 blockers play a more and more prominent role in the treatment, their place requires clarification. This study aimed to identify factors predictive of treatment response to anakinra or tocilizumab and investigate whether the choice of biotherapy and delays in the initiation of biotherapy influenced the likelihood of steroid discontinuation. METHODS: A multicenter exploratory retrospective study included all patients diagnosed with AOSD and receiving biological treatments in three regional hospitals until 2018. Clinical and biological characteristics at diagnosis and treatment-related data were collected. The nonparametric Mann-Whitney test was used to perform univariate analysis for quantitative variables, and Fisher's exact test was used for qualitative variables. RESULTS: Twenty-seven patients were included. All but one patient achieved remission with either anakinra or tocilizumab. Treatment responses depended on disease phenotype: the presence of arthritis and a chronic articular phenotype were associated with a substantial response to tocilizumab with p = 0.0009 (OR 36 [2.6-1703]) and p = 0.017 (OR 10 [1.22-92.6]), respectively, whereas the systemic form and the absence of arthritis were associated with a substantial response to anakinra with p = 0.0009 (OR 36 [2.6-1703]) and p = 0.017 (OR 10 [1.22-92.6]), respectively. Tocilizumab increased the likelihood of corticosteroid withdrawal (p = 0.029) regardless of delays in initiation or when it was initiated relative to other treatment in the overall therapeutic strategy. CONCLUSION: This study highlights the therapeutic implications of the phenotypic dichotomy of AOSD and should help us better codify AOSD treatment.

Abatacept monotherapy compared with abatacept plus disease-modifying anti-rheumatic drugs in rheumatoid arthritis patients: data from the ORA registry.

BACKGROUND: Retention rate, efficacy, and safety of abatacept (ABA) was compared between patients with rheumatoid arthritis receiving ABA as monotherapy to those in combination ABA + conventional synthetic DMARD (csDMARD). METHODS: The patients were obtained from the ORA registry. The retention rate was analysed in two ways: (1) therapeutic strategy retention, in which the addition of a csDMARD was considered to indicate failure of the monotherapy strategy; and (2) ABA retention, which was assessed by the discontinuation of ABA regardless of other treatment modifications. Efficacy and safety were compared between ABA initiated alone and ABA used in combination with a csDMARD. RESULTS: The retention rate at month 6 (M6) was evaluated in 569 patients. A significant difference was identified in the retention rate between the ABA monotherapy strategy and the ABA + csDMARD strategy (58.5 % [110/188] vs. 68 % [258/381], respectively, p = 0.031). No significant difference was identified in the ABA retention rate initiated either as a monotherapy or in combination with csDMARDs (75 % [142/188] vs. 76 % [291/381], respectively, p = 0.824). Data regarding ABA efficacy were available for 444 patients. There was no significant difference in the responder proportion after 6 months of treatment between ABA monotherapy and ABA + csDMARD treatment (60.2 % [88/146] vs. 60 % [179/298], respectively, p = 0.967). CONCLUSIONS: This "real-life" analysis, which is relevant for bedside practice, emphasised the satisfactory efficacy and safety of ABA used in monotherapy, which provides an acceptable alternative when csDMARDs are undesirable.

IgE Inhibits Toll-like Receptor 7- and Toll-like Receptor 9-Mediated Expression of Interferon-α by Plasmacytoid Dendritic Cells in Patients With Systemic Lupus Erythematosus.

OBJECTIVE: Plasmacytoid dendritic cells (PDCs) play a central role in pathogenesis of systemic lupus erythematosus (SLE) through their unique ability to produce large amounts of type I interferon (IFN) upon Toll-like receptor 7 (TLR-7) and TLR-9 triggering. PDCs express specific surface regulatory receptors involved in negative regulation of IFNα secretion. These receptors use the γ-chain of high-affinity Fc receptor (FcR) for IgE, FcɛRI. We undertook this study to test our hypothesis that IgE engagement of FcɛRI on PDCs may impact IFNα production in SLE patients. METHODS: Serum levels of total IgE were measured in healthy volunteers, SLE patients, and patients with IgE-dependent allergic disorders. FcɛRI expression on PDCs from SLE patients was evaluated by flow cytometry. Purified PDCs were incubated with monoclonal IgE for 24 hours, then stimulated for 18 hours with TLR agonists or immune complexes (ICs). IFNα production by PDCs was detected by quantitative real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. Expression of TLR-7, TLR-9, and IFN regulatory factor 7 (IRF-7) in PDCs was quantified by quantitative real-time PCR. RESULTS: We observed significantly higher IgE levels in SLE patients with quiescent disease than in those with active disease. In SLE patients, IgE levels correlated inversely with disease activity. IgE levels were not associated with the presence of antinuclear IgE. Purified PDCs treated for 24 hours with monoclonal IgE up-regulated FcɛRI expression in an IgE dose-dependent manner. IgE-treated PDCs significantly decreased IFNα secretion and down-regulated CCR7 expression upon stimulation with TLR-7 and TLR-9 ligands and ICs from lupus patients. IgE treatment down-regulated expression of TLR-9 and IRF-7. CONCLUSION: Our results support the notion that IgE plays a protective role in SLE pathogenesis through the modulation of inflammatory response by PDCs.

Nonspecific low back pain: assessment of available medications.

Many medications have been evaluated for the treatment of nonspecific low back pain. The only medications proven to be more effective than a placebo in chronic low back pain are nonsteroidal antiinflammatory drugs (NSAIDs), the acetaminophen-tramadol combination, antidepressants other than selective serotonin reuptake inhibitors, and some types of spinal applications of glucocorticoids or local anesthetics. However, the efficacy of these drugs in inducing pain relief is limited, and NSAIDs are the only drugs that also improve function. Nevertheless, the outcome of nonspecific low back pain is favorable in most cases, even in placebo-treated patients. In addition, treatment effects vary dramatically across studies. One factor in this variability is the heterogeneity of patient populations. To improve the uniformity of patient populations enrolled in therapeutic trials, the selection criteria should take into account the nociceptive, dysfunctional, and possible neuropathic components of the pain syndrome.