Lower hair cortisol concentration in adolescent and young adult patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Q-Fever Fatigue Syndrome compared to controls.

BACKGROUND: In patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), momentary cortisol concentrations in blood, urine, and saliva are lower compared to healthy controls. Long-term cortisol concentration can be assessed through hair, but it is unclear whether these concentrations are also lower. Additionally, it is unknown if lower cortisol extends to other patients suffering from persistent fatigue and how hair cortisol concentration (HCC) relates to fatigue levels. Therefore, this study examines HCC in fatigued patients with ME/CFS, Q fever Fatigue Syndrome (QFS), Post-COVID-19 condition (PCC), and Juvenile Idiopathic Arthritis (JIA). METHODS: Adolescent and young adult patients with ME/CFS (n=12), QFS (n=20), PCC (n=8), JIA (n=19), and controls (n=57) were included. Patients participated in a randomized cross-over trial (RCT) targeting fatigue through lifestyle and dietary self-management strategies. HCC was measured pre-post RCT in patients and once in controls, quantified using a LC-MS/MS-based method. Fatigue severity was measured with the Checklist Individual Strength-8. HCC was compared between groups with ANOVAs. Relations between HCC, fatigue severity, and other variables were investigated using linear regression analyses. RESULTS: The ME/CFS (p=.009) and QFS (p=.047) groups had lower HCC compared to controls. Overall, HCC was negatively associated with the presence of symptoms related to chronic fatigue syndromes (e.g., sleeping issues, often feeling tired, trouble thinking clearly; ß=-0.018, p=.035), except in the QFS group (ß=.063, p<.001). Baseline HCC did not predict fatigue improvement during the RCT (p=.449), and HCC increased during the trial (Mdif=.076, p=.021) regardless of clinically relevant fatigue improvement (p=.658). CONCLUSION: Lower cortisol concentration can also be observed in the long-term. Lower HCC is not limited to ME/CFS, as it was also observed in QFS. The role of cortisol may differ between these diagnoses and appears to be unrelated to fatigue levels.

Exploration of leech therapy in treating gouty rats and its uric acid lowering mechanism.

BACKGROUND: Gout is a hyperuricemia (HUA)-related inflammatory reaction in the joints. Leech therapy has been effective in the gout, but the exact mechanism is unclear. OBJECTIVES: In this study, an exploration of the therapeutic mechanism of leech therapy in HUA and gouty arthritis (GA) rats was done. MATERIAL AND METHODS: HUA and GA construction utilizing sodium urate crystal, the potassium form of oxygen oxazine acid, and adenine. Serum and tissues were collected to measure uric acid (UA), creatinine (Cr), and urea nitrogen (UN). Enzyme linked immunosorbent assay was executed to evaluate the levels of xanthine oxidase (XOD), interleukin-6 (IL-6)and tumor necrosis factor α (TNF-α). The expression of glucose transporter 9 (GLUT9), organic anion transporter 3 (OAT3), adenosine triphosphate (ATP)-binding cassette efflux transporter G2 (ABCG2) and the nuclear factor kappa B (NF-kB), interleukin-1ß (IL-1ß), Toll-like Receptor 2 (TLR2) were assessed by Western blot and visualized in immunohistochemistry staining. RESULTS: Leech therapy reduces the levels of UA, Cr, and UN as well as the liver and serum levels of XOD activity, increasing the expressions of GLUT9, ABCG2, and OAT3 in the kidney. Meanwhile, it reduces joint swelling and lowers the levels of TNF-α, IL-6, IL-1ß, TLR2, and NF-kB. CONCLUSIONS: Leech therapy regulates the metabolism of uric acid and treats gouty arthritis with an anti-inflammatory effect.

Itaconate is a metabolic regulator of bone formation in homeostasis and arthritis.

OBJECTIVES: Bone remodelling is a highly dynamic process dependent on the precise coordination of osteoblasts and haematopoietic-cell derived osteoclasts. Changes in core metabolic pathways during osteoclastogenesis, however, are largely unexplored and it is unknown whether and how these processes are involved in bone homeostasis. METHODS: We metabolically and transcriptionally profiled cells during osteoclast and osteoblast generation. Individual gene expression was characterised by quantitative PCR and western blot. Osteoblast function was assessed by Alizarin red staining. immunoresponsive gene 1 (Irg1)-deficient mice were used in various inflammatory or non-inflammatory models of bone loss. Tissue gene expression was analysed by RNA in situ hybridisation. RESULTS: We show that during differentiation preosteoclasts rearrange their tricarboxylic acid cycle, a process crucially depending on both glucose and glutamine. This rearrangement is characterised by the induction of Irg1 and production of itaconate, which accumulates intracellularly and extracellularly. While the IRG1-itaconate axis is dispensable for osteoclast generation in vitro and in vivo, we demonstrate that itaconate stimulates osteoblasts by accelerating osteogenic differentiation in both human and murine cells. This enhanced osteogenic differentiation is accompanied by reduced proliferation and altered metabolism. Additionally, supplementation of itaconate increases bone formation by boosting osteoblast activity in mice. Conversely, Irg1-deficient mice exhibit decreased bone mass and have reduced osteoproliferative lesions in experimental arthritis. CONCLUSION: In summary, we identify itaconate, generated as a result of the metabolic rewiring during osteoclast differentiation, as a previously unrecognised regulator of osteoblasts.

Melatonin hyalurosomes in collagen thermosensitive gel as a potential repurposing approach for rheumatoid arthritis management via the intra-articular route.

Despite the fact that several rheumatoid arthritis treatments have been utilized, none of them achieved complete joint healing and has been accompanied by several side effects that compromise patient compliance. This study aims to provide an effective safe RA treatment with minimum side effects through the encapsulation of melatonin (MEL) in hyalurosomes and loading these hyalurosomes in collagen thermos-sensitive poloxamer 407 (PCO) hydrogels, followed by their intra-articular administration in AIA model rats. In vitro characterization of MEL-hyalurosomes and PCO hydrogel along with in vivo evaluation of the selected formulation were conducted. Particle size, PDI and EE % of the selected formulation were 71.5 nm, 0.09 and 90 %. TEM micrographs demonstrated that the particles had spherical shape with no aggregation signs. Loading PCO hydrogels with MEL-hyalurosomes did not cause significant changes in pH although it increased its viscosity and injection time. FTIR analysis showed that no interactions were noted among the delivery system components. In vivo results revealed the superior effect of MEL-hyalurosomes PCO hydrogel over MEL-PCO hydrogel and blank PCO hydrogels in improving joint healing, cartilage repair, pannus formation and cell infiltrations. Also, MEL-hyalurosomes PCO hydrogel group showed comparable levels of TNF-α, IL1, MDA, NRF2 and HO-1 with the negative control group. These findings highlight the MEL encapsulation role in augmenting its pharmacological effects along with the synergistic effect of hyaluronic acid in hyalurosomes and collagen in PCO hydrogel in promoting joint healing.

Examination of Physical Functions, Activity and Participation in Children with Juvenile Idiopathic Arthritis.

AIMS: To examine physical functions, activity, and participation level, and associated factors with participation in children with juvenile idiopathic arthritis (JIA) across the International Classification of Functioning Disability and Health-Children and Youth. METHODS: 49 children (Girl/Boy:28/21) aged between 7 and 18 years (Mean: 13.4 ± 3.3) were included. To evaluate body structure/functioning; pain, fatigue, disease activity, and motor functions were assessed. Childhood Health Assessment Questionnaire and Juvenile Arthritis Biopsychosocial and Clinical Questionnaire were used to determine activity level. Child and Adolescent Scale of Participation was used to assess participation. RESULTS: Mild level of pain (2.0 ± 2.3), disease activity (2.0 ± 2.3), and fatigue (4.1 ± 4.0) were recorded. Decrease in motor functions was determined in 75% of children, while 61% of whom had activity-related disability. There was mild to moderate participation restrictions, and participation was significantly associated with age (r = -0.29), pain severity (r = -0.31), disease activity (r = -0.39), motor functions (r = 0.33), and activity level (r = -0.43), (p Ë‚ 0.05). CONCLUSIONS: Majority of children with JIA have deteriorations in physical functions, activity, and participation. Age, pain, disease activity, motor functions and activity level were associated with participation level. Children with JIA should be regularly evaluated multi-directional and they should be referred to rehabilitation programs to increase functionality and participation.

Serum GM-CSF level is a predictor of treatment response to tocilizumab in rheumatoid arthritis patients: a prospective observational cohort study.

BACKGROUND: The aim of this prospective observational cohort study was to unveil the predictors of treatment response to tocilizumab (TCZ) therapy in rheumatoid arthritis (RA) patients, in terms of clinical characteristics and serum proinflammatory cytokines, especially to explore the predictive value of granulocyte macrophage-colony stimulating factor (GM-CSF). METHODS: Active adult RA patients with inadequate response to MTX intending to receive TCZ therapy were recruited prospectively in the study. A total of 174 severe RA patients were included for the identification of the associations between treatment response and the following characteristic features: demographics, medications, disease activity, serum proinflammatory cytokines and so on. RESULTS: Disease duration (OR = 0.996), tender joint count (TJC)/68 (OR = 0.943), neutrophil ratio (W4/baseline) (OR = 0.224), the high level of GM-CSF > 5 ng/ml (OR = 0.414) at baseline were the independent adverse predictors of good response assessed by clinical disease activity index (CDAI) at week 24 (W24) for TCZ therapy in RA patients. Moreover, DAS28-ESR (OR = 2.951, P = 0.002) and the high level of GM-CSF > 10 ng/ml at baseline (OR = 5.419, P = 0.002) were independent predictors of poor response, but not the high level of GM-CSF > 5 ng/ml (OR = 2.713, P = 0.054). The patients in the high GM-CSF group had significantly higher DAS28-ESR and serum levels of cytokines (IL-17A, IL-1ß, IL-6, TNF-α) at baseline, as well as significantly higher rate of non-good response (62.8% vs. 39.4%, P = 0.010) and poor response (27.9% vs. 9.1%, P = 0.004) than the low GM-CSF group at W24. In addition, poor responders had significantly higher levels of GM-CSF with concomitant increase in the serum levels of IL-17A and IL-1ß at baseline than those in moderate and good response groups, while serum levels of IL-6 and TNF-α at baseline were not significantly different in three response groups. CONCLUSION: The high levels of GM-CSF (> 5 ng/ml and > 10 ng/ml) at baseline were the independent predictors of non-good response and poor response to TCZ at W24 respectively. The high level of GM-CSF at baseline is a marker of high disease activity and a predictor of poor response to TCZ in severe RA patients, which may facilitate the development of individualized treatment strategies for refractory RA.

A systematic strategy for identifying causal single nucleotide polymorphisms and their target genes on Juvenile arthritis risk haplotypes.

BACKGROUND: Although genome-wide association studies (GWAS) have identified multiple regions conferring genetic risk for juvenile idiopathic arthritis (JIA), we are still faced with the task of identifying the single nucleotide polymorphisms (SNPs) on the disease haplotypes that exert the biological effects that confer risk. Until we identify the risk-driving variants, identifying the genes influenced by these variants, and therefore translating genetic information to improved clinical care, will remain an insurmountable task. We used a function-based approach for identifying causal variant candidates and the target genes on JIA risk haplotypes. METHODS: We used a massively parallel reporter assay (MPRA) in myeloid K562 cells to query the effects of 5,226 SNPs in non-coding regions on JIA risk haplotypes for their ability to alter gene expression when compared to the common allele. The assay relies on 180 bp oligonucleotide reporters ("oligos") in which the allele of interest is flanked by its cognate genomic sequence. Barcodes were added randomly by PCR to each oligo to achieve > 20 barcodes per oligo to provide a quantitative read-out of gene expression for each allele. Assays were performed in both unstimulated K562 cells and cells stimulated overnight with interferon gamma (IFNg). As proof of concept, we then used CRISPRi to demonstrate the feasibility of identifying the genes regulated by enhancers harboring expression-altering SNPs. RESULTS: We identified 553 expression-altering SNPs in unstimulated K562 cells and an additional 490 in cells stimulated with IFNg. We further filtered the SNPs to identify those plausibly situated within functional chromatin, using open chromatin and H3K27ac ChIPseq peaks in unstimulated cells and open chromatin plus H3K4me1 in stimulated cells. These procedures yielded 42 unique SNPs (total = 84) for each set. Using CRISPRi, we demonstrated that enhancers harboring MPRA-screened variants in the TRAF1 and LNPEP/ERAP2 loci regulated multiple genes, suggesting complex influences of disease-driving variants. CONCLUSION: Using MPRA and CRISPRi, JIA risk haplotypes can be queried to identify plausible candidates for disease-driving variants. Once these candidate variants are identified, target genes can be identified using CRISPRi informed by the 3D chromatin structures that encompass the risk haplotypes.

Abatacept retention and clinical effectiveness in patients with rheumatoid arthritis in a real-world setting in Taiwan.

AIM: To evaluate real-world abatacept retention and clinical outcomes in patients with rheumatoid arthritis in Taiwan. METHODS: This prospective, observational study enrolled patients with rheumatoid arthritis aged ≥20 years who received abatacept in real-world practice. The primary endpoint was the abatacept retention rate at 24 months. Patients were categorized into subgroups based on abatacept treatment status and previous biological disease-modifying antirheumatic drug (bDMARD) therapy. Risk factors affecting abatacept retention were determined by regression analysis. RESULTS: A total of 212 patients were enrolled. The overall abatacept retention rate at 24 months among all patients was 59.9% (95% confidence interval 53.0%-66.6%). Patients who were ongoing users of abatacept and bDMARD-naïve had the highest retention rate (76.3%); of these, 31.6% achieved low disease activity or remission after 2 years. Previous treatment with bDMARDs was associated with an increased risk of abatacept discontinuation (hazard ratio 1.99; p = .002). The most common reasons for abatacept discontinuation were drug switch (11.3%) and loss to follow-up (6.1%). Abatacept was well-tolerated with no new safety signals. CONCLUSION: The 24-month retention rate of abatacept was 59.9%; abatacept was associated with improved clinical outcomes and was well-tolerated in the real-world setting in Taiwan.

A survey exploring the nexus of psychological traits, nature connection, and quality of life among patients with rheumatoid arthritis.

Background: As the recognition of psychological factors in chronic illness management grows, this study examined the interplay of psychological traits - grit, self-efficacy, resilience, and nature-relatedness - and their collective impact on the Quality of Life (QoL) among patients with rheumatoid arthritis (RA) in Malaysia. Methods: A cross-sectional study was conducted among 222 patients with RA at a private hospital in Malaysia. Utilizing validated scales, including the Connor-Davidson Resilience Scale, Short Grit Scale, Nature Relatedness Scale, and Arthritis Self Efficacy Scale, data were collected. Pearson Product-moment Correlation analyses assessed the relationships between variables, and a multiple mediation analysis explored the mediating effects of resilience, grit, and self-efficacy on the relationship between nature-relatedness and QoL. Findings: Of the 222 participants (86% female, mean age = 56.03, S.D. = 13.42), the analysis revealed a significant mediating role of resilience in the relationship between nature-relatedness and QoL among RA patients (b = -.117, SE = .042, 95% BCa CI [-.208, -.046]). Although grit and self-efficacy positively correlated with QoL, they did not serve as significant mediators in the nature-relatedness - QoL relationship. This highlights the pivotal role of building a sense of resiliency among patients with RA. Interpretation: Individuals with RA are not only resilient in terms of their psychological traits such as grit, self-efficacy, and general resilience but also exhibit resilience in their connection and interaction with the natural environment (nature-relatedness). This holistic concept recognizes that fostering resilience in both psychological aspects and the context of one's environment is crucial for promoting overall well-being, particularly in the management of chronic illnesses like RA. It emphasizes the interconnectedness of psychological factors and environmental engagement in contributing to an individual's ability to cope and thrive despite health challenges.

Performance characteristics of genus or species-specific Polymerase Chain Reaction (PCR) for the microbial diagnosis of joint infections: A systematic review and meta-analysis.

Joint infections cause significant morbidity and mortality. Rapid diagnosis enables prompt initiation of appropriate antimicrobial therapy and surgical treatment. We conducted a systematic review and meta-analysis to evaluate the accuracy of genus- or species-specific polymerase chain reaction (PCR) in diagnosing joint infections. The literature databases were searched for articles from January 2010 to December 2022. The meta-analysis using the split component synthesis (SCS) method, included 20 studies with 2,457 adult participants. The pooled sensitivity, specificity, diagnostic odds ratio, and AUC of PCR were 49 % (95 % CI [37.9-60.2]), 95.7 % (95 % CI [91.6-97.8]), 21.32, and 0.82 respectively. Sensitivity was highest for sonicate fluid and lowest for periprosthetic tissue. The mean turnaround time to results was 4.7 hours (SD 1.1). PCR is a favourable option for diagnosing joint infections due to its rapid results, but it has low sensitivity. To enhance diagnostic yield, the test should be used in conjunction with other methods.

Infrared thermogram image guided discontinuous appearances of hyaluronic acid for classification of arthritic knee joints.

The liveliness of a human potentially depends on his/her smooth movability. To accomplish the work of daily life, the joints of the body need to be healthy. However, the occurrence of Rheumatoid arthritis and Osteoarthritis has a significant prevalence towards the immovability of humankind. Rheumatoid arthritis (RA) and Osteoarthritis (OA) mostly affect the joints of the hand and knee which result in lifelong pain, inability to climb, walk, etc. In the early stages, these diseases attack the synovial membrane and synovial fluid, and further it destroys the soft tissues and bone structure. By early diagnosis, we can start the treatment in the early stage which may cure these diseases with such extreme consequences. As per clinical studies of previous literature, it is observed that synovial fluid imbalance appears in the early stage of such diseases and Hyaluronic Acid (HA) concentration also decreases for that. Therefore, estimation of HA is a significant key to arthritis disease classification and grading. In this paper, we proposed a hybrid framework for classification of arthritic knee joints based on the analysis of the discontinuous appearances of the HA concentration using infrared imaging technology. To meet up the specific necessities, firstly we have proposed a modified K-Means clustering algorithm for extraction of the region of interest (ROI) i.e., the knee joint surface. Secondly, a mathematical formulation is proposed to calculate the concentration of HA from the segmented ROIs. This experimental process was implemented on the publicly available IR (Infrared) Knee Joint Dataset and for further evaluation of the novelty of mathematical formulation, we have extended the proposed work to the classification of healthy and arthritis affected knee joints depending on significant discriminative characteristics of the HA concentration with respect to the existing significant imaging features. Experimental results and analysis demonstrates that concentration of HA has the dominant potential for classifying healthy and arthritic knee joints using infrared holistic images. Our experimental analysis reveals that estimation and combination of the HA concentration features with conventional handcrafted and deep features increases the classification performance with an average accuracy of 91% and 97.22% respectively as compared to the each individual feature sets.

Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis.

Rheumatoid arthritis is a chronic inflammatory disease that shows characteristic diurnal variation in symptom severity, where joint resident fibroblast-like synoviocytes (FLS) act as important mediators of arthritis pathology. We investigate the role of FLS circadian clock function in directing rhythmic joint inflammation in a murine model of inflammatory arthritis. We demonstrate FLS time-of-day-dependent gene expression is attenuated in arthritic joints, except for a subset of disease-modifying genes. The deletion of essential clock gene Bmal1 in FLS reduced susceptibility to collagen-induced arthritis but did not impact symptomatic severity in affected mice. Notably, FLS Bmal1 deletion resulted in loss of diurnal expression of disease-modulating genes across the joint, and elevated production of MMP3, a prognostic marker of joint damage in inflammatory arthritis. This work identifies the FLS circadian clock as an influential driver of daily oscillations in joint inflammation, and a potential regulator of destructive pathology in chronic inflammatory arthritis.

Impact of Interleukin-6 Activation and Arthritis on Epidermal Growth Factor Receptor (EGFR) Activation in Sensory Neurons and the Spinal Cord.

In tumor cells, interleukin-6 (IL-6) signaling can lead to activation of the epidermal growth factor receptor (EGFR), which prolongs Stat3 activation. In the present experiments, we tested the hypothesis that IL-6 signaling activates EGFR signaling in peripheral and spinal nociception and examined whether EGFR localization and activation coincide with pain-related behaviors in arthritis. In vivo in anesthetized rats, spinal application of the EGFR receptor blocker gefitinib reduced the responses of spinal cord neurons to noxious joint stimulation, but only after spinal pretreatment with IL-6 and soluble IL-6 receptor. Using Western blots, we found that IL-6-induced Stat3 activation was reduced by gefitinib in microglial cells of the BV2 cell line, but not in cultured DRG neurons. Immunohistochemistry showed EGFR localization in most DRG neurons from normal rats, but significant downregulation in the acute and most painful arthritis phase. In the spinal cord of mice, EGFR was highly activated mainly in the chronic phase of inflammation, with localization in neurons. These data suggest that spinal IL-6 signaling may activate spinal EGFR signaling. Downregulation of EGFR in DRG neurons in acute arthritis may limit nociception, but pronounced delayed activation of EGFR in the spinal cord may be involved in chronic inflammatory pain.

Tofacitinib Regulates Endostatin via Effects on CD147 and Cathepsin S.

Angiogenesis is critical for rheumatoid arthritis (RA) progression. The effects of tofacitinib, a JAK-STAT inhibitor used for RA treatment, on angiogenesis in RA are unclear. We, therefore, evaluated the levels of angiogenic factors in two systems of a human co-culture of fibroblast (HT1080) and monocytic (U937) cell lines treated with tofacitinib and in serum samples from RA patients before and after six months of tofacitinib treatment. Tofacitinib reduced CD147 levels, matrix metalloproteinase-9 (MMP-9) activity, and angiogenic potential but increased endostatin levels and secreted proteasome 20S activity. In vitro, tofacitinib did not change CD147 mRNA but increased miR-146a-5p expression and reduced STAT3 phosphorylation. We recently showed that CD147 regulates the ability of MMP-9 and secreted proteasome 20S to cleave collagen XVIIIA into endostatin. We show here that tofacitinib-enhanced endostatin levels are mediated by CD147, as CD147-siRNA or an anti-CD147 antibody blocked proteasome 20S activity. The correlation between CD147 and different disease severity scores supported this role. Lastly, tofacitinib reduced endostatin' s degradation by inhibiting cathepsin S activity and recombinant cathepsin S reversed this in both systems. Thus, tofacitinib inhibits angiogenesis by reducing pro-angiogenic factors and enhancing the anti-angiogenic factor endostatin in a dual effect mediated partly through CD147 and partly through cathepsin S.

[IL-17A and IL-17F: from discovery to target of biologics - an illustrative example of translational research]. / IL-17A et IL-17F : de la découverte au ciblage thérapeutique - Un exemple de médecine translationnelle.

Interleukin (IL)-17A and then IL-17F have been discovered through their roles in chronic inflammatory diseases. These cytokines share 50% of sequence homology and bind to the same receptor made of the IL-17RA et IL-17RC chains. While they have rather similar pro-inflammatory effects, slight differences exist depending on the cell type considered or whether there is TNF or not. Indeed, there is a synergistic effect of TNF and IL-17A or IL-17F on many cell types. In addition, the interactions between immune and stromal cells also modulate their effects which vary according to stromal cell subtype. The identification of IL-17A and IL-17F roles in inflammatory diseases, as psoriasis, has led to the development of inhibitors of those cytokines. Anti-IL-17A, then anti-IL-17A/F and now anti-IL-17RA have been approved for different diseases and are particularly efficient in psoriasis. Their use is expending to other diseases like psoriatic arthritis and spondyloarthritis. Last, the recent understanding of the importance of stromal cells during chronic inflammation explains the relative inefficacy of such inhibitors in some other diseases.

Title: IL-17A et IL-17F : de la découverte au ciblage thérapeutique - Un exemple de médecine translationnelle. Abstract: L'interleukine (IL)-17A puis l'IL-17F ont été découvertes tour à tour pour leur rôle joué dans les maladies inflammatoires chroniques. Elles ont une homologie de séquence d'environ 50 % et partagent le même récepteur formé des chaînes IL-17RA et IL-17RC. Si elles ont des effets pro-inflammatoires assez similaires, il existe néanmoins quelques différences selon le type cellulaire considéré et selon la présence ou non de TNF, autre cytokine avec laquelle elles ont une synergie d'action. La troisième variable venant moduler leurs effets réside dans les interactions entre cellules immunes et cellules stromales, qui, là encore, varient selon le type de cellules stromales. La mise en évidence de leur rôle dans le psoriasis a notamment conduit au développement d'inhibiteurs de l'IL-17A, puis à la fois de l'IL-17A et de l'IL-17F et enfin d'un de leurs récepteurs. Ces inhibiteurs sont utilisés avec succès dans cette pathologie, et leur indication a été étendue progressivement au rhumatisme psoriasique et à certaines formes de spondylarthrite. Enfin, la récente compréhension de l'importance des cellules stromales dans la réaction inflammatoire chronique permet d'expliquer l'efficacité variable de ces biothérapies dans certaines pathologies.

External Validation of the Machine Learning-Based Thermographic Indices for Rheumatoid Arthritis: A Prospective Longitudinal Study.

External validation is crucial in developing reliable machine learning models. This study aimed to validate three novel indices-Thermographic Joint Inflammation Score (ThermoJIS), Thermographic Disease Activity Index (ThermoDAI), and Thermographic Disease Activity Index-C-reactive protein (ThermoDAI-CRP)-based on hand thermography and machine learning to assess joint inflammation and disease activity in rheumatoid arthritis (RA) patients. A 12-week prospective observational study was conducted with 77 RA patients recruited from rheumatology departments of three hospitals. During routine care visits, indices were obtained at baseline and week 12 visits using a pre-trained machine learning model. The performance of these indices was assessed cross-sectionally and longitudinally using correlation coefficients, the area under the receiver operating curve (AUROC), sensitivity, specificity, and positive and negative predictive values. ThermoDAI and ThermoDAI-CRP correlated with CDAI, SDAI, and DAS28-CRP cross-sectionally (ρ = 0.81; ρ = 0.83; ρ = 0.78) and longitudinally (ρ = 0.55; ρ = 0.61; ρ = 0.60), all p < 0.001. ThermoDAI and ThermoDAI-CRP also outperformed Patient Global Assessment (PGA) and PGA + C-reactive protein (CRP) in detecting changes in 28-swollen joint counts (SJC28). ThermoJIS had an AUROC of 0.67 (95% CI, 0.58 to 0.76) for detecting patients with swollen joints and effectively identified patients transitioning from SJC28 > 1 at baseline visit to SJC28 ≤ 1 at week 12 visit. These results support the effectiveness of ThermoJIS in assessing joint inflammation, as well as ThermoDAI and ThermoDAI-CRP in evaluating disease activity in RA patients.

The Burden of Interstitial Lung Involvement in Rheumatoid Arthritis: Could Lung Ultrasound Have a Role in Its Detection? A Literature Review.

Lung involvement represents a fearful complication in rheumatoid arthritis (RA), potentially involving all compartments of the pulmonary system. Regarding interstitial lung disease (ILD), the HRCT represents the gold standard technique for its diagnosis; however, the examination is burdened by radiation exposure and high costs. In addition, although some risk factors for ILD are known, no algorithms exist to know which patients to submit to HRCT and when. In this context, lung ultrasound (LUS) showed promising results for at least 10 years, demonstrating correlation with high resolution computed tomography (HRCT) findings in other rheumatic diseases. Here, LUS may represent a screening test providing additional information to clinical examination and pulmonary function tests. The data deriving from LUS experience in other rheumatic diseases could steer the future towards the use of this technique also in RA patients, and in this review, we report the most relevant literature regarding LUS in RA-ILD.

What role do socioeconomic and clinical factors play in disease activity states in rheumatoid arthritis? Data from a large UK early inflammatory arthritis audit.

BACKGROUND: Persistently active rheumatoid arthritis (pactiveRA) may be due to the interplay between biological and non-biological factors. The role of socioeconomic factors remains unclear. OBJECTIVES: To explore which biological and non-biological factors associate with pactiveRA. METHODS: Adults with early RA in the National Early Inflammatory Arthritis Audit, recruited from May 2018 to October 2022, were included if having pactiveRA or persistently low RA (plowRA). The pactiveRA was defined as three consecutive Disease Activity Score-28 joints (DAS28) of >3.2 at baseline, 3 and 12 months. The plowRA was defined as DAS28 ≤3.2 at 3 and 12 months. Stepwise forward logistic regression was used to explore associations with pactiveRA (outcome). Age and gender were included a priori, with socioeconomic factors and comorbidities as exposure variables. RESULTS: 682 patients with pactiveRA and 1026 plowRA were included. Compared with plowRA, patients with pactiveRA were younger (58, IQR: 49-67) versus (62, IQR: 52-72), and included more women (69% vs 59%). The pactiveRA was associated with worse scores in patient-reported outcomes at baseline, and anxiety and depression screens. Overall, there was clear social patterning in pactiveRA, with age-by-gender interaction. Logistic regression indicated age, gender, social deprivation and previous or current smoking, were independently associated with pactiveRA, after controlling for disease severity markers (seropositivity). Depression, lung disease, gastric ulcers and baseline corticosteroid use, were also associated with pactiveRA (p<0.05 for all). CONCLUSION: Socioeconomic factors and deprivation were associated with pactiveRA, independent of clinical and disease characteristics. Identifying 'adverse' socioeconomic drivers of pactiveRA can help tailor interventions according to individual need.

"Inflammatory or non-inflammatory pain in inflammatory arthritis - How to differentiate it?"

Pain is a significant issue in rheumatoid arthritis (RA) and psoriatic arthritis (PSA) and can have a negative impact on patients' quality of life. Despite optimal control of inflammatory disease, residual chronic pain remains a major unmet medical need in RA. Pain in RA can be secondary to inflammation but can also generate neuroendocrine responses that initiate neurogenic inflammation and enhance cytokine release, leading to persistent hyperalgesia. In addition to well-known cytokines such as TNFα and IL-6, other cytokines and the JAK-STAT pathway play a role in pain modulation and inflammation. The development of chronic pain in RA involves processes beyond inflammation or structural damage. Residual pain is often observed in patients even after achieving remission or low disease activity, suggesting the involvement of non-inflammatory and central sensitization mechanisms. Moreover, fibromyalgia syndrome (FMS) is prevalent in RA patients and may contribute to persistent pain. Factors such as depression, sleep disturbance, and pro-inflammatory cytokines may contribute to the development of fibromyalgia in RA. It is essential to identify and diagnose concomitant FMS in RA patients to better manage their symptoms. Further research is needed to unravel the complexities of pain in RA. Finally, recent studies have shown that JAK inhibitors effectively reduce residual pain in RA patients, suggesting pain-reducing effects independent of their anti-inflammatory properties.

Perioperative Short-Term Glucocorticoids Do Not Increase Incidence of Complications after Total Joint Arthroplasty in Patients with Rheumatoid Arthritis.

OBJECTIVES: The safety and analgesic efficacy of perioperative glucocorticoids have been established for patients without rheumatoid arthritis. Therefore, our study aims to investigate whether similar benefits can be observed in patients with rheumatoid arthritis undergoing total joint arthroplasty. Specifically, we aim to explore the impact of perioperative glucocorticoid use on postoperative complications, opioid consumption, incidence of hypotension, hyperglycemia, 30-day mortality, and 90-day re-admission in this patient population. METHODS: Approval for the study protocol was obtained from the Medical Research Ethics Committee at Sichuan University, aligning with the principles outlined in the Declaration of Helsinki. We retrospectively analyzed a consecutive series of patients with rheumatoid arthritis who underwent total joint arthroplasty at our medical center between November 2009 and April 2021 and who were not on chronic glucocorticoid therapy before surgery. Those who received glucocorticoids at any time during hospitalization were compared to those who did not in terms of acute complications within 90 days after surgery as well as postoperative rescue opioid consumption, hypotension, and hyperglycemia during hospitalization. The two groups were also compared in terms of overall duration of hospitalization, all-cause mortality within 30 days, and readmission for any reason within 90 days. Continuous data were assessed for significance using the independent-samples t test. Categorical data were assessed using the Pearson chi-squared test. RESULTS: Of the 849 patients included in the analysis, 598 administered perioperative glucocorticoids and 251 did not. Prior to surgery, the two groups did not differ significantly in any clinicodemographic variable that we examined. The incidence of acute postoperative complications (2.3% vs. 4.0%, p = 0.187) and acute postoperative infection (2.0% vs. 2.8%, p = 0.482) was comparable between those who received perioperative glucocorticoids and those who did not, but the former group exhibited a significantly lower incidence of rescue opioid use (17.9% vs. 44.6%, p < 0.001) as well as significantly lower total rescue opioid consumption (4.7 ± 2.1 mg vs. 8.9 ± 4.6 mg, p < 0.001). However, the two groups showed similar incidences of postoperative hypotension, hyperglycemia, 30-day mortality, and 90-day re-admission. CONCLUSION: Perioperative glucocorticoids may reduce the need for rescue opioids after total joint arthroplasty of rheumatoid arthritis patients, without increasing the incidence of acute complications, hypotension or hyperglycemia.