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Introduction: Osteoarthritis (OA) and rheumatoid arthritis (RA) represent the most common forms of arthritis, which are mainly caused by mechanical and inflammatory components, respectively. Determination of synovial inflammation in synovial biopsies via the histopathological Krenn score may be crucial for correct diagnosis and treatment. Specifically, it remains unclear whether synovitis scores differ among multiple biopsy locations within a single joint. Materials and methods: Eighty synovial samples were taken from four standardized regions of the knee in 20 patients (ten primary OA, ten secondary OA) undergoing total knee arthroplasty (TKA) or total synovectomy. The Krenn synovitis score (grade 0–9) was determined in a blinded manner by two expert pathologists in all biopsies. Next to the inter-rater reliability, we evaluated the agreement of the determined scores among the four biopsy locations within each knee. Results: The inter-rater reliability between the two pathologists was very high (Cohen's kappa = 0.712; r = 0.946; ICC = 0.972). The mean synovitis score was significantly higher in knees with secondary than in primary OA (p = 0.026). Importantly, we found clear differences between the scores of the four different biopsy locations within the individual knee joints, with an average deviation of 10.6%. These deviations were comparable in knees with primary and secondary OA (p = 0.64). Conclusions: While we confirmed the synovitis score as a reliable and reproducible parameter to assess the histopathological synovitis grade in the knee, the considerable variability within the joint indicates that multiple synovial biopsies from different regions should be obtained to enable reliable results of the synovitis score. [ABSTRACT FROM AUTHOR]

En España, la prevalencia de diferentes enfermedades reumáticas se conoce principalmente a través de los estudios EPISER coordinados desde la Sociedad Española de Reumatología y que parten de encuestas en una muestra poblacional. Nuestro estudio tiene por objetivo describir la prevalencia en 2016 de las distintas enfermedades reumáticas en la población residente en el Baix Empordà según registros de codificación asistencial. Estudio observacional, descriptivo y transversal realizado sobre la población residente durante los años 2016-2017 en la comarca del Baix Empordà, donde una organización sanitaria integrada (Serveis de Salut Integrats Baix Empordà) gestiona todos los dispositivos asistenciales públicos con un sistema de información unificado. Se seleccionaron los pacientes ≥ 20 años y se analizó la codificación CIE-9-CM de sus contactos asistenciales en función de 11 agrupaciones diagnósticas de 28 enfermedades reumáticas. Las agrupaciones fueron: poliartritis, espondiloartritis, artritis microcristalinas, artrosis (excepto localización vertebral), reumatismos de partes blandas, fibromialgia, dolor vertebral crónico (incluyendo artrosis), osteoporosis, enfermedades del tejido conectivo, vasculitis y otros. La población estudiada se asignó a tres categorías: «con enfermedad reumática», «posible enfermedad reumática» y «sin enfermedad reumática». La muestra final fue de 71.785 personas, así distribuidas: «con enfermedad reumática» (n = 25.990; 36,2%); «posible enfermedad reumática» (n = 4.406; 6,1%) y «sin enfermedad reumática» (n = 41.389; 57,7%). El grupo «con enfermedad reumática» mostró un predominio de mujeres (59,8% vs. 44,9%) y mayor edad (59,1 ± 17,7 vs. 45,1 ± 16,2; p< 0,001) en comparación al grupo «sin enfermedad reumática». La presencia de enfermedad reumática aumentó progresivamente con la edad, siendo máxima en el grupo de 55-75 años. El 36,2% de nuestra población presenta algún tipo de enfermedad reumática. La prevalencia estimada de varias enfermedades reumáticas en la población del Baix Empordà coincide parcialmente con la estimada por el estudio EPISER 2016. La enfermedad reumática afecta en mayor proporción a mujeres, y es más frecuente en pacientes con edad superior a 45 años. In Spain, the prevalence of different rheumatic diseases is known mainly through the EPISER studies coordinated by the Spanish Society of Rheumatology and based on surveys in a population sample. The aim of our study is to describe the prevalence in 2016 of different rheumatic diseases in the population residing in Baix Empordà according to healthcare coding records. Observational, descriptive and cross-sectional study carried out on the population attended from 2016-2017 in Serveis de Salut Integrats del Baix Empordà, an organizational service that includes all the healthcare facilities in the Baix Empordà area with a unique information system. Patients ≥ 20 years of age were selected and the ICD9-CM coding of all their healthcare contacts was analysed according to 11 entities and 28 diseases. The entities were: polyarthritis, spondyloarthritis, microcrystalline arthritis, osteoarthritis, soft tissue rheumatism, fibromyalgia, chronic spinal pain, osteoporosis, connective tissue diseases, vasculitis and others. The studied population was assigned to the categories: "with rheumatic disease", "possible rheumatic disease" and "without rheumatic disease". In total, 71,785 patients were distributed as: 36.2% "with rheumatic disease (n = 25,990); 6.1% with "possible rheumatic disease" (n = 4,406) and 57.7% "without rheumatic disease" (n = 41,389). The group "with rheumatic disease" showed a predominance of women (59.8% vs. 44.9%) and older age (59.1 ± 17.7 vs. 45.1 ± 16.2; P <.001) compared to the group "without rheumatic disease". The presence of rheumatic disease increased progressively with age, being maximum in the group between 55-75 years. 36.2% of our population has some type of rheumatic disease. The estimated prevalence of some rheumatic diseases in the Baix Empordà population is partially consistent with that estimated by the EPISER 2016 study. Rheumatic disease affects women in a greater proportion and is more frequent in patients over 45 years of age. [ABSTRACT FROM AUTHOR]

This study aimed to examine the factors associated with cytomegalovirus (CMV) antigenemia and the time of onset of CMV antigenemia among patients with rheumatic diseases. A single-center, retrospective, observational study was conducted in our institution from January 2009 to December 2017. This study included patients with rheumatic diseases who had at least one CMV antigen measurement. Multivariate analysis and receiver operating characteristic analysis was performed. A total of 249 patients underwent CMV antigenemia assay, and 84 (33.7%) patients tested positive. When the association between CMV antigenemia and possible associated factors was investigated, multivariate analysis showed that daily steroid dose increased the odds of having CMV [odds ratio 16.25, 95% confidence interval (CI), 5.360–49.253]. In this study, the cutoff value of daily steroid dose found in this study (0.45 mg/kg/day) was reasonable in clinical practice, and the area under the curve of the steroid dose was 0.838 [95% CI 0.781–0.882], which was the largest of the known indicators. Moreover, the median time from the start of immunosuppressive therapy to the onset of CMV antigenemia was 30 (interquartile range, 21–44) days, and most of the daily steroid users (85.7%) developed CMV antigenemia within 60 days. The daily steroid dose is the most important factor associated with CMV antigenemia. Therefore, monitoring and treatment strategies based on the steroid dose, especially in the initial 2 months, are important. [ABSTRACT FROM AUTHOR]

Patients with inflammatory rheumatic diseases (IRD) are at increased risk for worse COVID-19 outcomes. Identifying whether mRNA vaccines differ in immunogenicity and examining the effects of immunomodulatory treatments may support COVID-19 vaccination strategies. We aimed to conduct a longterm, model-based comparison of the humoral immunogenicity following BNT162b2 and mRNA-1273 vaccination in a cohort of IRD patients. Patients from the Swiss IRD cohort (SCQM), who assented to mRNA COVID-19 vaccination were recruited between 3/2021-9/2021. Blood samples at baseline, 4, 12, and 24 weeks post second vaccine dose were tested for anti-SARS-CoV-2 spike IgG (anti-S1). We examined differences in antibody levels depending on the vaccine and treatment at baseline while adjusting for age, disease, and past SARS-CoV-2 infection. 565 IRD patients provided eligible samples. Among monotherapies, rituximab, abatacept, JAKi, and TNFi had the highest odds of reduced anti-S1 responses compared to no medication. Patients on specific combination therapies showed significantly lower antibody responses than those on monotherapy. Irrespective of the disease, treatment, and past SARS-CoV-2 infection, the odds of higher antibody levels at 4, 12, and 24 weeks post second vaccine dose were, respectively, 3.4, 3.8, and 3.8 times higher with mRNA-1273 versus BNT162b2 (p < 0.0001). With every year of age, the odds ratio of higher peak humoral immunogenicity following mRNA-1273 versus BNT162b2 increased by 5% (p < 0.001), indicating a particular benefit for elderly patients. Our results suggest that in IRD patients, two-dose vaccination with mRNA-1273 versus BNT162b2 results in higher anti-S1 levels, even more so in elderly patients. [ABSTRACT FROM AUTHOR]

Objectives: Risk perception of the COVID-19 pandemic may affect chronic disease outcomes among patients with rheumatic diseases (RD). To describe and compare the perception of risk and effects of the COVID-19 pandemic on patients with RD from two health care centers compared with a control group. Methods: A retrospective case–control study was conducted. Patient respondents completed an online survey to measure risk perception and effects of the COVID-19 pandemic. The case group consisted of patients with a confirmed diagnosis of RD, coming from two third-level health care centers. The control group was a population group without RD from a public university. Results: A total of 3944 participants were included: 986 patients with an RD (cases) from the two hospital centers and 2958 controls without RD. A greater perception of risk severity and perception of contagion was observed in the group of patients with RD, OR: 1.70, 95% CI 1.44‒2.01 and OR: 2.0, 95% CI 1.79‒2.23, respectively; more significant deterioration in family life OR: 1.14, 95% CI 1.01‒1.29; greater economic impact, OR 3.94, 95% CI 3.48‒4.46; as well as negative emotions and feelings (alarmed, anxiety, depression, confusion, fear, isolation, and discrimination). This impact was maintained when the model was adjusted for comorbidities. Conclusion: In the face of an unexpected and catastrophic event such as the COVID-19 pandemic, patients with RD report apparently greater impact on their mental state and economic situation than the control population, as well as increased perception of discrimination. Key Points • The multidisciplinary analyses of risk perception are required to promote actions that can enhance the preparedness and responses of public efforts for possible future pandemics in a way that considers the specific needs of vulnerable people like patients with rheumatic diseases. • Identifying risk perceptions of possible effects of the pandemic, sources of communication, and opinions is essential to ensure self-care in rheumatic disease. • The impact of COVID-19 has been much greater for people with rheumatic disease, especially in terms of the perceived severity of the pandemic, impacts on family and economy, preventive behaviors, and uncertainty. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the clinical features and course of coronavirus disease 2019 (COVID-19) in individuals with rheumatic disease. Materials and Methods: This retrospective study was carried out at the Erciyes University rheumatology outpatient clinic from July 1 to August 1, 2021. The demographic and clinical data and summarized COVID-19 history, clinical course of COVID-19, fatigue, and pain levels of patients with rheumatic disease were obtained from our institutional electronic registration database and patient files. Results: Recruited participants were 106 individuals (83% female, %17 male) with rheumatic disease who had been confirmed by laboratory tests to have COVID-19 and recovered from the COVID-19 infection. Their mean age and body mass index (BMI) were 48.69±11.5 years and 29.89±6.76 kg/m2, respectively. Additionally, 21 (19.8%) had been hospitalized, and five (4.7%) had been admitted to the intensive care unit. The most common rheumatic diseases were axial spondyloarthritis (40; 37.7%) and rheumatoid arthritis (26 cases; 24.5%). Patients who received conventional synthetic disease-modifying drugs (csDMARDs) reportedly experienced more pain, fatigue, and headaches than those in the biologic agent and nonsteroidal anti-inflammatory drug (NSAID) groups. Conclusion: Our study results reveal similar symptoms and hospitalization rates among patients with rheumatic disease who recovered from COVID-19 and received either csDMARDs, biologic agents, or NSAIDs. However, patients in the csDMARD group reported more pain, fatigue, and headache compared to the other groups. [ABSTRACT FROM AUTHOR]

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The baseline inflammatory microenvironment in various organs of patients, which is shaped by pre-existing conditions and circulating drugs at the time before viral antigen exposure, may affect the severity of coronavirus disease-19 (COVID-19) infection and the nature of its complications. Inflammatory pseudotumor (IPT) of the spleen may represent one such complication that merits further investigation. We describe the case of a patient, who was under long-term treatment with a tumor necrosis factor inhibitor (TNFi), for psoriatic arthritis (PsA) and developed an inflammatory mass in the spleen, accompanied by systemic manifestations. This occurred with a history of four doses of nucleoside-modified messenger RNA (modRNA) vaccination for COVID-19 and shortly after a SARS coronavirus-2 (SARS-CoV-2) infection. Histologic examination of the splenectomy specimen supported by a large array of immunohistochemical stains and subsequent clinicopathological correlation indicated the diagnosis of splenic IPT in an immunologically altered background, due to modifying medication, immunization, and infection. Our case speculates that IPT may represent an adverse event related to immunogenicity of SARS-CoV-2, following antigen exposure (at first by sequential modRNA COVID-19 vaccinations and additionally by natural infection), despite the potentially protective effect of treatment with a TNFi., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Iliadis et al.)

Objectives: Fibromyalgia (FM) is a complex disorder involving pain dysregulation that can occur independently or alongside other rheumatological illnesses, complicating symptom interpretation. Consequently, this study aimed to evaluate the prevalence of secondary FM in patients with rheumatological diseases and its impact using the Revised Fibromyalgia Impact Questionnaire., Methods: This cross-sectional descriptive study was conducted at the Rheumatology Outpatient Department of King Fahad Military Medical Complex, Dhahran, from August 2023 to October 2023. Patients with primary rheumatological diseases other than FM were recruited. Secondary FM was diagnosed based on the 2016 revisions of the 2010/2011 FM diagnostic criteria. Data on the demographics of patients were collected through self-reported questionnaires., Results: Overall, 158 women (76%) and 50 men (24%) with a mean age of 45.7 (12.8) years participated in the study. Systemic lupus erythematosus was the primary diagnosis for most patients. Fisher's exact test (p=0.007) indicated a significant but weak association between osteoarthritis and FM. A family history of comorbidity was significantly associated with an FM diagnosis (p<0.043). Having a major life event, such as the death of a kin, was significantly associated with FM (p<0.032). A personal history of functional disorders was significantly linked to a diagnosis of concomitant FM., Conclusion: Concomitant FM is frequently undetected in patients with rheumatic diseases. Raising awareness of FM through educational programs may facilitate earlier diagnosis and more effective treatment., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Armed Forces Hospitals Eastern Province Institutional Review Board (IRB) issued approval AFHER-IRB-2024-013. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Alghanim et al.)

Background: T-SPOT.TB ® , one of the screening tests for latent tuberculosis infection (LTBI), yields invalid results in human T-cell leukemia virus type 1 (HTLV-1)-positive patients with rheumatoid arthritis. However, the detailed mechanisms behind this invalidation are unclear. Additionally, it remains unclear whether T-SPOT.TB ® or QuantiFERON-TB (QFT) is more useful in HTLV-1-positive patients with rheumatic disease (RD)., Method: Among all of the HTLV-1-positive RD patients who visited our department between August 2012 and December 2022, 44 patients who were screened using T-SPOT.TB® were included in the analysis. QFT testing was performed in 33 of the 44 patients, and the results were compared with that of T-SPOT.TB®. Furthermore, we performed a culture experiment mimicking T-SPOT.TB® using peripheral blood mononuclear cells (PBMCs) obtained from HTLV-1-positive patients with RD. Additionally, T-cell subsets with autonomous product IFN-γ were analyzed using a flow cytometer., Results: Of the included patients, 13 (29.5%) were invalid for T-SPOT.TB® because of the increased number of negative control spots. The median HTLV-1 proviral load in the invalid group was higher than that in the valid group (2.45 vs. 0.49 copies/100 PBMCs, respectively, p = 0.002). QFT was performed in all 33 patients, including 13 patients who were invalid in T-SPOT.TB®. The main source of IFN-γ production was CD8+ T-cells in the T-SPOT.TB® mimic experiment. Furthermore, Tax-expressing CD4+ T-cells and Tax-specific cytotoxic CD8+ T-cells were more frequently observed in patients with invalid results than in patients with valid results. CD4+ T-cell depletion in the T-SPOT.TB® mimic experiment reduced the population of IFN-γ producing CD8+ T cells., Conclusion: T-SPOT.TB® may be invalidated by the interaction between Tax-expressing CD4+ T-cells and cytotoxic CD8+ T-cells. Moreover, HTLV-1-associated immune reactions due to contact between these cells may be unlikely to occur in QFT using whole blood. Therefore, our results reveal the superiority of QFT over T-SPOT.TB® as a screening test for LTBI in HTLV-1-positive patients with RD., Competing Interests: TH received honoraria for lectures from AbbVie GK, Eli Lilly Japan K.K., Pfizer Japan Inc., Asahi Kasei Pharma Corp., Bristol-Myers K.K., Chugai Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K.,Taisho Pharma Co., Ltdand Eisai Co. K. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kimura, Umekita, Iwao, Kawano, Hashikura, Hashiba, Hidaka, Sugata, Satou and Miyazaki.)

This study aimed to determine the incidence of post-chikungunya chronic rheumatism (pCHIK-CR) and its impact on quality of life (QoL) and chronic fatigue in adults seven years after the 2014-2015 CHIKV outbreak in Piedecuesta, Colombia. We evaluated 78 adults (median age: 30 years, IQR: 21.0; women 60.3%) with confirmed CHIKV infection. In 2022, participants underwent a GALS examination and completed surveys on disability, stiffness, health status, and fatigue. A rheumatologist evaluated patients who reported arthralgia, morning stiffness, and abnormal GALS examination. Chronic fatigue was defined as fatigue persisting for over six months. Seven years after infection, 14.1% of participants were classified as pCHIK-CR cases, 41.0% as having non-inflammatory pain, likely degenerative (NIP-LD), and 44.9% without rheumatic disease (Wo-RM). Patients with pCHIK-CR and NIP-LD exhibited significantly worse QoL compared to Wo-RM cases. Chronic fatigue prevalence increased from 8.6% in Wo-RM patients to 25.0% in NIP-LD and 54.6% in pCHIK-CR cases. This study implemented a comprehensive clinical assessment to objectively estimate and characterize the incidence of chronic rheumatological disease attributed to CHIKV infection. One in seven cases with CHIKV infection develops pCHIK-CR, which impacts both QoL and chronic fatigue. This study contributes to understanding the burden of these arboviruses in the medium term.

Objective: To explore the application of 18 F-flurodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in rheumatic diseases, to compare these different imaging features, and to describe the current PET/CT imaging status in clinical practice., Methods: A total of 486 cases in our department from January 2012 to December 2018 were enrolled in this study, and 18 F-FDG PET/CT examination was performed in all the patients. The clinical use of 18 F-FDG PET/CT was retrospectively analyzed to discuss the clinical application and its imaging characteristics of rheumatic diseases. Categorical data were used to ascertain prevalence statistics, whereas continuous data were used to delineate means and standard deviations. Independent sample t test, Chi square test and Mann-Whitney U test were used for statistical analysis. A P -value of < 0.05 was considered significant., Results: (1) From 2012 to 2018, totally 486 patients in the Department of Rheumatology and Immunology underwent 18 F-FDG PET/CT examination, accounting for 5.30% of the total number of PET/CT examinations in the whole hospital. In this study, 304 of the 486 patient were female (62.55%), 182 of them were male (37.45%), the average age of the patients was (53.21±18.81) years, and the proportion of the patients aged 45-65 (227/486, 46.71%) was the highest group. (2) Three leading purposes of the PET/CT examination in our department were to exclude cancers (55.56%), assist in diagnosis (24.60%) and evaluate the disease activity (19.84%). (3) Of the 486 patients who underwent 18 F-FDG PET/CT, 327 cases might indicate a differential diagnosis of rheumatic disease, of which, 292 cases were highly suggestive of diagnosis, including 61 cases of myositis, 60 cases of vasculitis, 37 cases of adult still's disease, 32 cases of IgG4 related diseases, 30 cases of rheumatoid arthritis, 22 cases of Sjögren's syndrome, 22 cases of systemic lupus erythematosus, and 9 cases of rheumatic polymyalgia; the remaining 35 cases only prompted the possibility of autoimmune disease. Of the 486 patients, 74 cases suggested the diagnosis of cancers, 25 cases indicated the diagnosis of infectious diseases, while 60 cases could not show any diagnostic values. Ten patients with rheumatic disease were followed up with a post-treatment repeat PET/CT, and the findings in remission showed reduced 18 F-FDG metabolic activity as well as a reduction in the extent of metabolic hypertrophic lesions., Conclusion: There are some typical sign of 18 F-FDG PET/CT for diffuse connective tissue diseases, therefore 18 F-FDG PET/CT has auxi-liary effect on the classification diagnosis of rheumatic diseases, especially for the exclusion of cancers.

Background: This study evaluated physicians' and patients' beliefs about biosimilars in Hong Kong, India, Pakistan, Singapore, Taiwan, and Thailand., Research Design and Methods: An online survey administered to physicians (dermatologists, n  = 119; gastroenterologists, n  = 148; rheumatologists, n  = 161) between 22 October 2021 and 7 January 2022, and patients ( n  = 90) with rheumatic or inflammatory bowel disease between 25 October 2021 and 12 April 2022., Results: Most (68%) physicians reported having a strong knowledge about biosimilars, yet 49% indicated that biosimilars are readily available to them. Physicians cited potential cost savings (81%) as the main benefit of biosimilars, and cost/coverage support (36%), patient support (25%), and increasing biosimilar awareness/education (24%) as main strategies for improving usage. Few (21%) patients reported having a strong knowledge about biosimilars. Patients cited offering alternatives in case of drug shortages (77%) as the main benefit of biosimilars, and cost/coverage support (53%), increasing awareness of product profile (22%), and providing biosimilars with a good efficacy profile/effective product (19%) as main strategies for improving usage., Conclusion: Programs focused on cost/coverage support, patient support, and biosimilar awareness could improve acceptance of biosimilars for chronic immune-mediated inflammatory diseases in Asian countries, thereby increasing patient access to essential biologic therapies.

Patients with rheumatic diseases (RD) are considered to be a high-risk population for infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The effectiveness of inactivated COVID-19 vaccinations (ICVs) was described as more effective than 95%. Despite this, no data on the immunogenicity and safety of the ICV in Han race stable RD patients in China. In this study, we sought to assess the safety and immunogenicity of the ICVs in RD patients in South China. A total of 80 adult stable RD patients were recruited. Following 14–35 days of immunization, cheiluminescence immunoassays (CLIA) were utilized to detect antibodies titers. An investigation into the relative parameters on the immunogenicity response to vaccination was carried out using logistic regression analysis. Compared to the HC group, the positive response of IgG and Nab in RD patients were lower than those in healthy control (HC) (P = .040 and P

Resumen: En la enfermedad reumática con afectación mitral, la insuficiencia es la forma de presentación más frecuente en gente joven. La posibilidad de reparación quirúrgica en la insuficiencia reumática depende fundamentalmente de factores anatómicos de la válvula, como son la flexibilidad del velo anterior y la presencia de lesiones calcificadas a nivel del aparato subvalvular, pero también de la experiencia del centro en reparación mitral compleja. Todo ello hace que esta patología infradiagnosticada haya quedado relegada a la sustitución protésica, ya que en muchos casos es remitida de forma tardía con una calcificación avanzada. Con el fin de desmitificar esta entidad, en el siguiente artículo abordaremos la insuficiencia mitral reumática y su tratamiento con las técnicas específicas reparadoras, así como la presentación de nuestra experiencia y una discusión de la patología con revisión de la literatura publicada hasta la fecha. Abstract: In rheumatic disease with mitral involvement, regurgitation is the most common form of presentation in young people. The possibility of surgical repair in rheumatic regurgitation depends on anatomical factors of the valve, such as the flexibility of the anterior leaflet and the presence of calcified lesions at the level of the subvalvular apparatus, but also on the experience of the center in complex mitral repair. All this means that this underdiagnosed pathology has been relegated to prosthetic replacement, since in many cases it is remitted late with advanced calcification. In order to demystify this entity, in the following article we will address rheumatic mitral regurgitation and its treatment with specific repair techniques, as well as the presentation of our experience and a discussion of the pathology with a review of the literature.

Rheumatic diseases, such as osteoarthritis and rheumatoid arthritis, affect over 750 million people worldwide and contribute to approximately 40% of chronic pain cases. Inflammation and tissue damage contribute to pain in rheumatic diseases, but pain often persists even when inflammation/damage is resolved. Mechanisms that cause this persistent pain are still unclear. Mitochondria are essential for a myriad of cellular processes and regulate neuronal functions. Mitochondrial dysfunction has been implicated in multiple neurological disorders, but its role in sensory processing and pain in rheumatic diseases is relatively unexplored. This review provides a comprehensive understanding of how mitochondrial dysfunction connects inflammation and damage-associated pathways to neuronal sensitization and persistent pain. To provide an overall framework on how mitochondria control pain, we explored recent evidence in inflammatory and neuropathic pain conditions. Mitochondria have intrinsic quality control mechanisms to prevent functional deficits and cellular damage. We will discuss the link between neuronal activity, mitochondrial dysfunction and chronic pain. Lastly, pharmacological strategies aimed at reestablishing mitochondrial functions or boosting mitochondrial dynamics as therapeutic interventions for chronic pain are discussed. The evidence presented in this review shows that mitochondria dysfunction may play a role in rheumatic pain. The dysfunction is not restricted to neuronal cells in the peripheral and central nervous system, but also includes blood cells and cells at the joint level that may affect pain pathways indirectly. Pre-clinical and clinical data suggest that modulation of mitochondrial functions can be used to attenuate or eliminate pain, which could be beneficial for multiple rheumatic diseases.

Objectives To explore clinical features of autoimmune inflammatory rheumatic disease (AIRD) patients with Pneumocystis jirovecii pneumonia (PJP) and identify potential risk factors and prognostic factors. Methods AIRD patients who had respiratory symptoms and underwent P. jirovecii detection were identified from the database in our department from November 2018 to October 2020. These patients were categorized into PJP and non-PJP groups according to the diagnostic criteria of PJP. Univariate and multivariate analyses were conducted. Results A total of 173 patients were enrolled and 46 of them had laboratory-confirmed PJP. Glucocorticoid increased the risk of PJP in a dose-dependent manner. In addition, shorter duration of immunosuppressive therapy (IST), combination therapy with CSA and chronic pulmonary comorbidities were also strongly associated with a higher risk of PJP. Combination of IgM and IgA could well identify AIRD patients with PJP from other AIRD patients with respiratory symptoms, with the optimal cut-off value of −0.96 g/l. Seven of 46 AIRD patients with PJP died (15.2%). A higher level of serum LDH, dyspnoea and ARDS, and the presence of extensive ground glass opacity (GGO) in radiologic examinations were more common in deceased patients. Conclusions AIRD patients with high-dose glucocorticoid treatment, recent initiation of IST, combination therapy with CSA and history of chronic pulmonary diseases had a greater risk of PJP infection. PJP patients with a higher level of serum LDH, dyspnoea, moderate and severe ARDS, and the presence of extensive GGO in radiologic examinations had poorer prognosis. Trial registration Chinese Clinical Trial Register; https://www.chictr.org.cn/ ; ChiCTR2100044095. [ABSTRACT FROM AUTHOR]

Le cancer est une problématique de santé publique majeure, et son dépistage est une problématique fréquente dans notre pratique courante. Le risque de cancer, chez les patients atteints de rhumatisme inflammatoire chronique (RIC), varie en fonction de leur terrain personnel, de la pathologie rhumatismale sous-jacente et des traitements pris au long cours. Cependant, à ce jour, aucune société savante rhumatologique n'a établi de recommandations spécifiquement dédiées au dépistage du cancer chez nos patients atteints de RIC. Dans cette revue, nous effectuons un état des lieux sur le risque de cancer au cours des RIC (en lien avec la maladie ou le traitement), le dépistage du cancer en population générale et chez les sujets immunodéprimés et, enfin, sur le dépistage des cancers au cours des RIC. Cancer is a major public health issue, and screening for cancer is a current situation in our routine practice. The risk of cancer in patients with rheumatic diseases varies according to their personal medical history, underlying rheumatic disease and treatment. However, to date, no rheumatological learnt society has established specific recommendations for cancer screening in our patients with rheumatic diseases. In this review, we provide an overview of the risk of cancer in rheumatic diseases (related to the disease itself or its treatment), cancer screening in the general population and in immunocompromised subjects, and cancer screening in rheumatic diseases. [ABSTRACT FROM AUTHOR]

Background: Non-criteria antiphospholipid antibodies (NC-aPL) are a relatively undefined subgroup of antiphospholipid antibodies (aPL). Knowledge about NC-aPL in adults is limited and even less is known in pediatric patients. Routine tests for antiphospholipid syndrome (APS)—a clinical state marked by the presence of aPL in association with vascular thrombosis—usually include lupus anticoagulant (LAC), anti-cardiolipin (aCL) and -beta-2 glycoprotein I (aβ2GPI). LAC is a functional screen for prothrombotic aPL, while the latter tests identify specific autoantibodies. Specific targets of NC-aPL include, but are not limited to, phosphatidylethanolamine, phosphatidylserine, and prothrombin. Presentation of cases: We present single-center data from eight pediatric patients with NC-aPL identified during a three-year period. All patients had presenting features raising suspicion for APS. Most patients were female with a primary rheumatic disease. One patient had a stroke. Another patient had alveolar hemorrhage and pulmonary hypertension. Raynaud's phenomenon, rashes involving distal extremities, and headaches were common. Most patients had a positive LAC, yet their routine aPL tests were negative, prompting testing for NC-aPL. Conclusions: Our findings suggest NC-aPL are associated with typical signs and symptoms of APS in pediatric patients. Pediatricians and pediatric subspecialists should consider NC-aPL when clinical suspicion is high and routine aPL tests are negative, particularly when LAC is positive. While guidelines for NC-aPL do not yet exist for children or adults, these autoantibodies have pathogenic potential. Actionable items could include evaluation for the presence of other (primary) rheumatic diseases, and consultation with hematologists and/or obstetricians regarding anticoagulation/platelet inhibition and thrombosis education. Future guidelines regarding NC-aPL will only be generated by gathering more data, ideally prospectively. [ABSTRACT FROM AUTHOR]

Background: Pulmonary complications of rheumatic diseases may cause functional impairment and increase mortality. However, reports regarding detection of lung involvement in children with treatment-naive, newly diagnosed rheumatic diseases are scarce. Herein, we aimed to describe the characteristics of such patients and explore the association between lung involvement and rheumatic disease. Methods: From January 2019 to June 2021, 48 pediatric patients with treatment-naive, newly diagnosed rheumatic diseases at Department of Rheumatology and Immunology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University were included with pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) findings, and 51 age-matched healthy controls were examined based on PFTs. Univariate and multivariable logistic regression analyses were used to investigate the clinical characters and laboratory parameters associated with lung involvement in these patients. Results: Asymptomatic patients had a faster respiratory rate and a higher ratio of forced expiratory volume in 1 s/forced vital capacity than the controls (P < 0.05). More patients than controls were observed to have a decreased DLCO below the lower limit of normal (18 of 45 [40.0%] vs. 6 of 36, respectively; P = 0.041). Among the 48 patients, 8 (16.7%) had abnormal HRCT findings and 27 (56.3%) had abnormal PFT results. Thirty-one (64.6%) patients had lung involvement. Logistic regression revealed that increases in the erythrocyte sedimentation rate (ESR) and CD4/CD8 ratio were associated with increased odds ratio of lung involvement (1.037, 95% CI: 1.003–1.072; 9.875, 95% CI: 1.296–75.243, respectively). Conclusions: Pediatric patients with treatment-naive, newly diagnosed rheumatic diseases are prone to pulmonary involvement. Increased ESR and CD4/CD8 are associated with elevated odds of lung involvement in patients. We recommend routine pulmonary evaluation in such patients, especially in high-risk patients, even in the absence of respiratory symptoms, once they are diagnosed with rheumatic disease. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency has been associated with autoimmune diseases and oral health. Knowledge about the association between vitamin D status and oral conditions in JIA is limited. We aimed to investigate vitamin D status in a cohort of Norwegian children and adolescents with JIA and possible associations between serum vitamin D levels, clinical indicators of oral health, and JIA disease characteristics. Methods: This multi-center, cross-sectional study, included individuals with JIA aged 4–16 years from three geographically spread regions in Norway. Demographic data, age at disease onset, disease duration, JIA category, disease status, medication, and vitamin D intake were registered. One blood sample per individual was analyzed for 25(OH) vitamin D, and the level of insufficiency was defined as < 50 nmol/L. A clinical oral examination was performed applying commonly used indices in epidemiological studies of dental caries, dental erosion, enamel defects, gingival bleeding, and oral hygiene. Serum vitamin D was used as exposure variable in multivariable regression analyses to estimate the associations between insufficient vitamin D level, JIA disease status, and oral conditions, with adjustments for age, sex, geographical region, BMI, seasonal blood sampling, and parental education. Results: Among the 223 participants with JIA, 97.3% were Caucasians, 59.2% were girls, and median age was 12.6 years. Median disease duration was 4.6 years, and 44.4% had oligoarticular JIA. Mean serum vitamin D level was 61.4 nmol/L and 29.6% had insufficient levels. Vitamin D levels did not differ between sexes, but between regions, iso-BMI categories, age groups, and seasons for blood sampling. Insufficient vitamin D levels were associated with dentin caries (adjusted OR 2.89, 95% CI 1.43–5.86) and gingival bleeding (adjusted OR 2.36, 95% CI 1.10–5.01). No associations were found with active JIA disease or more severe disease characteristics. Conclusion: In our study, nearly 30% had vitamin D insufficiency, with a particularly high prevalence among adolescents. Vitamin D insufficiency was associated with dentin caries and gingival bleeding, but not with JIA disease activity. These results point to the need for a multidisciplinary approach in the follow-up of children with JIA, including an increased focus on vitamin D status and oral health. [ABSTRACT FROM AUTHOR]

Objective: To review the evidence regarding the clinical effect of spa therapy for rheumatic diseases, with particular attention given to association protocols between balneotherapy and rehabilitation interventions, and to support the literature research and studies' selection with lexical analysis. Methods: A lexical analysis was performed considering a list of words representing diseases and outcome measures linked to the theme studied in our review. Then, two independent researchers conducted a literature search on PubMed using the string employed for lexical analysis, including Randomized Controlled Trials regarding spa therapy's clinical effects on patients affected by rheumatic diseases published in the last 30 years. After the exclusion of works that did not meet the eligibility criteria, 14 studies were included in the final scoping review. Results: Spa therapy has shown a favourable effect on pain, function and quality of life in patients with Osteoarthritis, Fibromyalgia and Rheumatoid Arthritis. Different treatment modalities and types of water have demonstrated beneficial long-term clinical improvement. Furthermore, the association between thermal therapy and rehabilitation treatments has shown better clinical outcomes, probably due to the synergistic effect between the peculiar properties of the thermal waters and the therapeutic exercise program, if conducted in the same context. Conclusions: The combination of balneotherapy and rehabilitative interventions seems to be effective in ameliorating several outcomes in patients with rheumatic diseases. However, due to the wide variety of methodologies and interventions employed, these findings need to be further investigated. The lexical analysis should represent an auxiliary support for an extensive evaluation of scientific literature. [ABSTRACT FROM AUTHOR]

Aim: This study aims to compare the prevalence of dental caries and the incidence of periodontally alveolar bone loss in individuals with rheumatic diseases (e.g., rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus and familial Mediterranean fever) with those of healthy individuals. Methodology: The study included 324 healthy individuals and 324 individuals with rheumatic diseases between the ages of 16 and 80 who were examined at Selçuk University, Faculty of Dentistry between 2017 and 2022. The intraoral examination and radiographic results of all patients recorded in the Patient Information Management System were analyzed and data were recorded by a single researcher. According to the intraoral visual examination and radiographic results of the patients, periodontal alveolar bone loss was evaluated as present or absent. DMF-T, DF-T, and D-T values were calculated by evaluating the number of decayed (D), missing (M), and filled (F) teeth of all patients on the radiographic records. Statistical analyses of the obtained data were performed with Chi)square test, Fisher exact test, and Mann–Whitney U tests, all of which are non-parametric tests. Results: From the results of statistical analysis of all data of rheumatic)diseased and healthy individuals, statistically significant differences were observed between the two groups in DF-T, D-T, M-T, and periodontal bone loss values (p = 0.022, p = 0.000, p = 0.006, and p = 0.000, respectively). Conclusion: Our study showed that the risk of caries and periodontal disease in individuals with rheumatic diseases is higher than that in healthy individuals. To confirm the results of this study, more detailed interventional studies are needed to evaluate microbiologically and biochemically the relationship between periodontitis and caries risk with rheumatoid diseases. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the differences between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with autoimmune rheumatic diseases (AIRD), and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) using single-cell RNA sequencing (scRNA-seq). Methods: From September 16 to December 10, 2021, we consecutively enrolled 445 participants (389 patients with AIRD and 56 healthy controls), of whom 236 were immunized with AZD1222 and 209 with mRNA-1273. The serum IgG antibodies to the SARS-CoV-2 receptor-binding domain was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells (PBMCs) were isolated from RA patients at 4-6 weeks after vaccination for scRNA-seq and further analyzed by CellChat. ScRNA-seq of PBMCs samples from GSE201534 in the Gene Expression Omnibus (GEO) database were also extracted for analysis. Results: The anti-SARS-CoV-2 IgG seropositivity rate was 85.34% for AIRD patients and 98.20% for healthy controls. The anti-SARS-CoV-2 IgG level was higher in patients receiving mRNA-1273 than those receiving AZD1222 (b: 35.25, 95% CI: 14.81-55.68, p=0.001). Prednisolone-equivalent dose >5 mg/ day and methotrexate use in AIRD patients, and non-anti-tumor necrosis factor-a biologics and Janus kinase inhibitor use in RA patients were associated with inferior immunogenicity. ScRNA-seq revealed CD16- monocytes were predominant in RA patients with high anti-SARS-CoV2-IgG antibodies, and enriched pathways related to antigen presentation via MHC class II were found. HLA-DRA and CD4 interaction was enhanced in high anti)SARS-CoV2-IgG group. Conclusions: mRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in AIRD patients. Enriched pathways related to antigen presentation via MHC class II in CD16- monocytes might be associated with higher anti-SARS-CoV2-IgG level in RA patients and further study is warranted. [ABSTRACT FROM AUTHOR]

Ehlers–Danlos syndrome (EDS) is a group of related connective tissue disorders consisting of 13 subtypes, each with its own unique phenotypic and genetic variation. The overlap of symptoms and multitude of EDS variations makes it difficult for patients to achieve a diagnosis early in the course of their disease. The most common form, hypermobile type EDS (hEDS) and its variant, hypermobile spectrum disorder (HSD), are correlated with rheumatologic and inflammatory conditions. Evidence is still needed to determine the pathophysiology of hEDS; however, the association among these conditions and their prevalence in hEDS/HSD may be explained through consideration of persistent chronic inflammation contributing to a disruption of the connective tissue. Aberrant mast cell activation has been shown to play a role in disruption of connective tissue integrity through activity of its mediators including histamine and tryptase which affects multiple organ systems resulting in mast cell activation disorders (MCAD). The overlap of findings associated with MCAD and the immune-mediated and rheumatologic conditions in patients with hEDS/HSD may provide an explanation for the relationship among these conditions and the presence of chronic inflammatory processes in these patients. It is clear that a multidisciplinary approach is required for the treatment of patients with EDS. However, it is also important for clinicians to consider the summarized symptoms and MCAD-associated characteristics in patients with multiple complaints as possible manifestations of connective tissue disorders, in order to potentially aid in establishing an early diagnosis of EDS. [ABSTRACT FROM AUTHOR]

As the coronavirus disease 2019 (COVID-19) pandemic continues worldwide, vaccination has been considered an effective measure to protect people from the COVID-19 and end the pandemic. However, for patients with rheumatic diseases (RD), concern for the induction of RD flare may combat the enthusiasm for vaccination. In general, current evidence doesn't support the increased risk of disease flare after COVID-19 vaccination. However, the disease flare of RDs may be triggered by COVID-19 vaccinations, especially for patients with high disease activity. Most of these flares after vaccination are mild and need no treatment escalation. Considering the benefits and risks, RD patients are recommended to receive the COVID-19 vaccination but should be vaccinated when the RDs are in stable states. [ABSTRACT FROM AUTHOR]

Objectives: COVID-19 pandemic has already had a tremendous impact on the process of human society; the survival of mankind and the healthy living environment deterioration with the influence will last for many years. This meta-analysis aims to assess the risk of COVID-19 in patients with rheumatic diseases. Methods: PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM) were systematically searched with no language restriction up to July 5, 2021. The pooled rates were synthesized by fixed effect model or random effect model depending on heterogeneity. Results: A total of 83 articles were included in this meta-analysis. The incidence of COVID-19 in patient with rheumatic diseases was 0.0190 (95% CI: 0.0136-0.0252), and the hospitalization rate, intensive care unit admission rate, mechanical ventilation rate, and case fatality rate of patients with rheumatic diseases infected with COVID-19 were 0.4396 (95% CI: 0.3899-0.4898), 0.0635 (95% CI: 0.0453-0.0836), 0.0461 (95% CI: 0.0330-0.0609), and 0.0346 (95% CI: 0.0218-0.0493), respectively. Conclusions: Our research shows that patients with rheumatic diseases have great risk of COVID-19. Differences in COVID-19 incidence, hospitalization rates, and mortality rates in regions were statistically significant. We still need to pay attention to the risk of COVID-19 in patients with rheumatic diseases. Key Points: • Although the risk of COVID-19 in patients with rheumatic diseases has been discussed in previous meta-analysis, their research directions were inconsistent, and few studies focus on prevalence or serious outcomes of COVID-19 in patient with rheumatic diseases, while the quality of these articles was variable. • The incidence of COVID-19 and serious clinical outcomes in patients with rheumatic diseases were still high along with differential risks in most regions. • The use of glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs did not affect the hospitalization rate and mortality in rheumatism patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background: We investigated how the non-medical switching (NMS) between Etanercept (ETN)/originator and SB4/biosimilar affects treatment efficacy in a rheumatic disease (RD) cohort, evaluating some laboratory parameters as loss of efficacy predictors after NMS. Methods: We enrolled 124 patients with RD (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis): 79 switchers from ETN/originator to SB4 and 45 naïve patients receiving SB4 (first biological treatment). At baseline, 6 (T1), and 12 months (T2), clinical and laboratory parameters were evaluated. Results: In naïve patients, TNF-α significantly increased at T1 in responders (NR) and non-responders (NNR). TNF-α was lower in NNR than in NR at T1 and T2. In NR and NNR, drug levels (DL) increased between T1 and T2. However, DLs were lower in NNR than in NR at T1 and T2. TNF-α was higher in switcher responders (SR) than in non-responders (SNR) at T1 and T2. In SNR, DLs were higher at baseline than in SR, but they decreased significantly at T1 and T2. Conclusions: We observed a decrease in DL and TNF-α levels after NMS in SNR. Moreover, in naïve patients, DL and TNF-α levels were higher in NR than in NNR. Monitoring DL and TNF-α levels may represent a future precision medicine approach to predict loss of efficacy after NMS. [ABSTRACT FROM AUTHOR]

Objective: Rheumatic mitral valve disease is often viewed as a historic disease in North America with limited contemporary data. We hypothesized that rheumatic pathology remains common and has worse short‐term outcomes and higher resource utilization compared to other mitral valve pathologies. Method: All patients undergoing mitral valve repair or replacement (2011–2019) were extracted from a regional Society of Thoracic Surgeons database. Resource utilization metrics included inflation‐adjusted hospital costs. Patients were stratified by mitral valve pathology for univariate analysis. Result: Out of the 6625 mitral valve procedures, 835 (12.6%) were from rheumatic disease, a proportion that incrementally increased over time (+0.39% per year, p =.032). Among 19 hospitals, there was high variability in number of rheumatic mitral operations (median: 22, interquartile range [IQR]: 5–80) and rate of rheumatic repairs (median: 3%, IQR: 0%–6%). Rheumatic patients were younger (62 vs. 65, p <.0001), more often female (75% vs. 43%, p <.001) and with greater burden of heart failure, multi‐valve disease, and lung disease, but less coronary disease. There were no differences in operative mortality (5.2% vs. 5.0%, p =.85) or major morbidity (22.2% vs. 21.8%, p =.83). However, resource utilization was higher for rheumatic patients, including more frequent transfusions (43% vs. 39%, p =.012), longer ICU (73 vs. 64 h, p <.0001) and postoperative length of stay (8 vs. 7 days, p <.0001). Conclusions: Rheumatic mitral disease accounts for a meaningful (12%) and rising percentage of mitral valve operations in the region, with high variability among hospitals. Rheumatic mitral surgery yielded similar short‐term outcomes compared to nonrheumatic pathology, but required greater resource utilization. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to assess the characteristics of inflammatory rheumatic disease (IRD) patients in Kuwait diagnosed with COVID‐19 and the factors linked with hospitalization, complications, and mortality. Methods: Data of IRD patients from Kuwait diagnosed with COVID‐19 between March 2020 and March 2021, submitted to the COVID‐19 Global Rheumatology Alliance physician‐reported registry, were included in our analysis. Data on patients' age, gender, smoking, diagnosis, IRD activity, and other comorbidities were collected. Statistical Package for the Social Sciences (SPSS), version 25, was used for statistical analysis. Results: A total of 52 patients were included, with a mean age of 55 years (±14). The majority of patients were ≤65 years (77%), female (77%), non‐smokers (80.8%), and diagnosed with rheumatoid arthritis (67.0%). Of the included patients, 19.2%, 9.6%, and 7.7% reported having methotrexate monotherapy, antimalarials monotherapy, and interleukin‐6 inhibitors monotherapy immediately before COVID‐19, respectively. Most of the included patients (92.3%) were either in remission or had minimal/low disease activity, while others (7.7%) had moderate disease activity. Forty‐three patients (82.7%) were hospitalized, while 11 patients (25.6%) required ventilation (invasive or non‐invasive). Ten of the ventilated patients (90.9%) received glucocorticoids as part of the local protocol to treat severe COVID symptoms, and 4 patients (7.69%) died. The duration till symptom‐free ranged between 0 to 30 days, with a mean value of 10 days (±6.5). Conclusion: The current study provides timely real‐world evidence regarding characteristics and potential risk factors linked to poor COVID‐19‐related outcomes in the IRD population in Kuwait. [ABSTRACT FROM AUTHOR]

Introduction: Joint inflammation, which causes pain and swelling, is common in rheumatic diseases. In Saudi Arabia, large multicenter studies on the prevalence of rheumatic diseases and the common beliefs about these diseases are lacking. Our study aimed to investigate the false beliefs about rheumatic diseases in Saudi Arabia. Materials and Methods: A cross-sectional questionnaire-based study was carried out in Riyadh, Saudi Arabia, from December 2019 to January 2020, to assess the understanding and misconceptions of rheumatic disorders in the study population. The statistical analysis was performed using the Fisher's exact test and the Chi-squared test, and binary logistic regression was employed for dichotomous variables. Results: Five hundred and eleven respondents were recruited in the study, with a mean age of 26.9 years; 76.9% of respondents were female. 89.4% of the respondents were Saudi nationals; 75.2%, 20.3%, and 4.5% of respondents had bachelor's, prebachelor's, and master's degrees, respectively. The most frequently reported rheumatic disease was rheumatoid arthritis (66%), followed by myositis (13.3%). Most of the respondents (77%) in this study were aware of rheumatic diseases. Conclusion: Most of the respondents were aware of rheumatic diseases. However, a more exhaustive multicentric survey with a wider population-based survey is needed to provide substantial data and help rheumatologists overcome patients' misconceptions and improve outcomes. [ABSTRACT FROM AUTHOR]

Herbal formulae have been used in China for thousands of years but have unclear clinical positioning and unknown characteristic indications make it difficult to determine their specific application in various diseases, which seriously hamper their clinical value. Identifying the precise clinical positioning and clinical advantages of similar formulae for related diseases is a critical issue. To develop a methodology based on modular pharmacology to determine the clinical advantages and precise clinical position of similar formulae. In this study, we proposed a modular-based network proximity approach to explore drug repositioning and clinical advantages of three formulae, Shirebi tablets (SRB), Yuxuebi capsules (YXB), and Wangbifukang granules (WBFK), for rheumatic disease. First, we constructed a rheumatology target network, and modules were obtained using the cluster tool molecular complex detection (MCODE). Based on the modular interaction map established by a quantitative approach for inter-module coordination and its transition (IMCC), using a targeting rate (TR) matrix to identify targeted modules of three formulae. Moreover, the network proximity Z-score and Jaccard similarity coefficient were used to identify potential optimal symptomatic indications and related diseases using three formulae. At the same time, the driver genes for SRB and gouty arthritis were identified by flow centrality and shortest distance, and the epresentative driver genes were validated by in vivo experiments. 32 modules were obtained using the MCODE method. 4, 4, and 14 characteristic targeted modules of SRB, YXB, and WBFK, respectively, were identified using a targeting rate (TR) matrix. Module 2, 16, and 19 were targeted by both SRB and WBFK. The common effects of SRB and WBFK focused on inflammatory response and innate immune response, YXB was found to be involved in the collagen catabolic process, transmembrane receptor protein serine/threonine kinase signaling pathway. Moreover, potential optimal symptomatic indications and representative related diseases were identified for three formulae: SRB was significantly associated with GA (Z = −20.26); YXB was significantly associated with AS (Z = −4.532), MI (Z = −29.11), RhFv (Z = −6.945), OA (Z = −39.97), and GA (Z = −13.03); and WBFK was significantly associated with MI (Z = −205.5), SLE (Z = −37.65), RhFv (Z = −42.45), and GA (Z = −17.24). Finally, 8 driver genes for SRB and gouty arthritis were identified,the representative driver genes TRAF6 and NFE2L1 were validated by in vivo experiments. The modular-based network proximity approach proposed in this study may provide a new perspective for the precise drug repositioning and clinical advantages of similar formulae in disease treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Patients on immunosuppressive therapy for rheumatic diseases are at increased risk of infection. Although infections of the central nervous system (CNS) are less common compared with other sites, patients on broadly immunosuppressive and biologic immunomodulatory agents may be susceptible to more severe, disseminated forms of infection, including of the CNS. Certain key principles regarding infection risk apply across immunosuppressive therapies, including increased risk with higher doses and longer duration of therapy and with combination therapy. Providers should be aware of the CNS infection risk related to immunosuppressant use to help guide best practices for screening and prophylaxis.

BackgroundEvidence-based recommendations for vaccination of patients with pediatric rheumatic diseases (PRDs) are available, their implementation in practice is unknown.ObjectivesTo analyze real-life vaccination coverage in children with PRDs and identify reasons for incomplete vaccination.MethodsUp-to-date information on vaccination status of Slovak children followed at a tertiary pediatric rheumatology center was retrieved from pediatricians over an 18-month period and compared to the standard Slovak Immunization Schedule. Reasons for missed vaccinations were analyzed retrospectively.ResultsVaccination records of 156 patients (median age 10 years, 2–18) with PRDs (JIA n = 108, systemic diseases n = 21, autoinflammatory diseases n = 16, uveitis n = 9, others n = 2) were available for analysis. 117 (75.0%) were completely vaccinated, 2 (1.3%) had not received any vaccine due to reasons unrelated to PRD. 37 (23.7%) remaining patients missed altogether 48 mandatory vaccinations. In 58.3% (n = 28, in 24 patients) no PRD related reasons for missing vaccinations were identified. Only 20 vaccinations (18 live-attenuated and 2 non-live in 19 patients) were missed due to ongoing immunosuppressive treatment or PRD activity. Patients aged 11–14 years were more likely to be incompletely vaccinated than other age groups (48.8% vs. 15.9%, p < 0.001), mainly due to missed MMR booster. Systemic immunosuppressive treatment was a significant predictor for incomplete vaccination status (OR 5.03, 95% CI 1.13–22.31, p = 0.03).ConclusionFull vaccination is possible in a high proportion of PRD patients. In addition to immunosuppressive therapy, reasons unrelated to PRDs are a frequent and possibly inadequate cause of missed vaccinations. Periodic vaccination status assessments are needed in pediatric rheumatology care.

The development and progression of immune-mediated rheumatic disease (IMRD) involves dysfunction of innate and adaptive immune cell populations leading to altered responses including inflammasome activation, dysregulated cytokine networks, increased immune cell numbers and multifaceted cell-cell communication. Several rheumatic diseases are further characterized by the presence of autoantibodies, immune complex mediated complement activation and the deficit of peripheral immune tolerance due to reduced regulatory T-lymphocyte cell function. Ultimately, in rheumatic disease the loss in cellular and tissue homeostasis culminates in the advancement of chronic inflammation. The three members of the NR4A subfamily of nuclear receptors are immediate early genes, and act as potent transcriptional responders to changes in the cellular and tissue microenvironment. Subfamily members are rapidly expressed in diseases characterized by inflammation and function to control the differentiation and activity of innate and adaptive immune cells in a cell-type and cell-context specific manner. Rheumatic disease including rheumatoid-, psoriatic-, osteo-arthritis and systemic sclerosis display altered NR4A1-3 activity in controlling immune cell migration and function, production of paracrine signaling molecules, synovial tissue hyperplasia, and regulating cartilage turn-over in vivo. Additionally, NR4A1-3 activities mediate cytokine, prostanoid and growth factor signaling to control angiogenesis, modulate the regulatory functions of mesenchymal stromal cells, alter the activation status of dendritic cells, influence the generation of peripheral myeloid and T-lymphocyte lineages and promote the maintenance of functional regulatory T-cells. Further reports uncover the potential of moderating NR4A 1-3 receptors as therapeutic targets in altering immune tolerance, pathological angiogenesis and controlling inflammation in several models of disease.

Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that attacks various organ systems with a variety of clinical implications, ranging from mild skin and mucosal manifestations to severe central nervous system manifestations and death. Cases of SLE have been documented nearly two centuries ago when scholars used the terms ‘erythema centrifugum’ and ‘seborrhea congestiva’ to describe the discoid skin lesions and the butterfly or malar rash in SLE. Since then, knowledge about this disease has developed rapidly, especially knowledge related to the underlying pathogenesis of SLE. To date, it is known that immune system dysregulation, supported by genetic and environmental predisposition, can trigger the occurrence of SLE in a group of susceptible individuals. Various inflammatory mediators, cytokines and chemokines, as well as intra- and intercellular signaling pathways, are involved in the pathogenesis of SLE. In this review, we will discuss the molecular and cellular aspects of SLE pathogenesis, with a focus on how the immune system, genetics and the environment interact and trigger the various clinical manifestations of SLE.

• CMV infection status can be difficult to discriminate. • The first study of CMV specific multi-cytokine immune responses in RD patients. • CMV antigen-specific IFN-γ, TNF-α had higher AUCs. • Combined noninvasive biomarkers may effectively differentiate infection status. To explore Cytomegalovirus (CMV) antigen-specific multi-cytokine immune responses in patients with rheumatic disease (RD) under different CMV infection status. A total of 60 RD patients in our center from March 2023 to August 2023 were enrolled. The patients were divided into latent CMV infection and active CMV infection, the latter was classified as subclinical CMV infection or CMV disease based on presence or absence of symptoms related to CMV. Whole blood was collected and stimulated with QuantiFERON-CMV antigen. The levels of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, IL-17 and CXCL-2 in supernatant were measured by Luminex Assays. The receiver operating characteristic curve was used to evaluate the diagnostic accuracy of cytokine for distinguishing different CMV infection status. The proportion of patients with severe lymphopenia was lowest in the latent CMV infection group, while there were no significant differences in medication usage in different CMV infection status. After stimulation with QF-CMV antigens, the levels of IFN-γ, TNF-α and IL-2 in the CMV disease group were significantly lower than those in the latent CMV infection group. CMV antigen-specific IFN-γ, TNF-α levels and severe lymphopenia together provided the best discriminatory performance for distinguishing between latent and either active CMV infection patients (AUC = 0.854) or CMV disease patients (AUC = 0.935). Noninvasive peripheral blood biomarkers (the combination of CMV antigen-specific IFN-γ, TNF-α levels and severe lymphopenia) may have the potential to diferentiate different status of CMV infection in RD population. [ABSTRACT FROM AUTHOR]

Objectives Although evidence is accumulating globally, data on outcomes in rheumatic disease and COVID-19 in Ireland are limited. We used data from the COVID-19 Global Rheumatology Alliance (C19-GRA) to describe time-varying COVID-19 outcomes for people with rheumatic disease in Ireland. Methods Data entered into the C19-GRA provider registry from Ireland between 24 March 2020 and 9 July 2021 were analysed. Differences in the likelihood of hospitalization and mortality according to demographic and clinical variables were investigated using Chi-squared test or Fisher's exact test, as appropriate. Trends in odds of hospitalization and mortality over time were investigated using logistic regression with the time period as a categorical variable. Results Of 212 cases included, 59.4% were female and median age was 58.0 years (range 13–96). Of the 212 cases, 92 (43%) were hospitalized and 22 (10.4%) died. Increasing age, a diagnosis of gout, ever smoking, glucocorticoid use, having comorbidities and specific comorbidities of cancer, cardiovascular and pulmonary disease were more common in those hospitalized. A diagnosis of inflammatory arthritis, csDMARD and/or b/tsDMARD use were less frequent in those hospitalized. Increasing age, a diagnosis of gout, ever smoking, having comorbidities and specific comorbidities of obesity, cardiovascular and pulmonary disease were more common in those who died. Odds of hospitalization or mortality did not change over time. Conclusion No temporal trend was observed in either COVID-19-related hospitalization or mortality outcomes for people with rheumatic disease in Ireland. [ABSTRACT FROM AUTHOR]

Recent advances in gene expression analysis techniques and increased access to technologies such as microarrays, qPCR arrays, and next-generation sequencing, in the last decade, have led to increased awareness of the complexity of the inflammatory responses that lead to pathology. This finding is also the case for rheumatic diseases, importantly and specifically, rheumatoid arthritis (RA). The coincidence in major genetic and epigenetic regulatory events leading to RA's inflammatory state is now well-recognized. Research groups have characterized the gene expression profile of early RA patients and identified a group of miRNAs that is particularly abundant in the early stages of the disease and miRNAs associated with treatment responses. In this perspective, we summarize the current state of RNA-based biomarker discovery and the context of technology adoption/implementation due to the COVID-19 pandemic. These advances have great potential for clinical application and could provide preclinical disease detection, follow-up, treatment targets, and biomarkers for treatment response monitoring. [ABSTRACT FROM AUTHOR]

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Objective: TURKBIO registry, established in 2011, is the first nationwide biological database in Turkey. This study aimed to provide an overview of TURKBIO data collected by June 2018. Methods: The registry included adult patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), nonradiographic axial spondyloarthritis (nr-AxSpA), and psoriatic arthritis (PsA). Demographic and clinical features, disease activity markers, and other follow-up parameters, current and previous treatments, and adverse events were registered electronically at each visit using open-source software. The registration of patient-reported outcome measures was carried out electronically by the patients using touch screens. Results: TURKBIO registry included a total of 41,145 treatment series with biologicals. There were 2,588 patients with axSpA (2,459 AS and 129 nr-axSpA), 2,036 with RA, and 428 with PsA. The total number of patients, including those with other diagnoses, was 5,718. In the follow-up period, the number of patients and also visits steadily increased by years. The yearly mean number of visits per patient was found to be 2.3. Significant improvements in disease activity and health assessment parameters were observed following the biological treatments. Biologics were often given in combination with a conventional synthetic disease-modifying antirheumatic drug in patients with RA. Infections were the most commonly seen adverse events, followed by allergic reactions. Tuberculosis was observed in 12 patients, malignancy in 18, and treatment-related mortality in 31. Conclusion: TURKBIO provided a valuable real-life experience with the use of biologics in rheumatic diseases in Turkey. [ABSTRACT FROM AUTHOR]