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2.
BMJ Open ; 14(5): e076966, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38719327

ABSTRACT

OBJECTIVES: To estimate the economic burden of informal caregivers not in the labour force (NILF) due to caring for a person with arthritis in Australia, with projections of these costs from 2015 to 2030. DESIGN: Static microsimulation modelling using national survey data. SETTING: Australia nationwide survey. PARTICIPANTS: Participants include respondents to the Survey of Disability, Ageing and Carers who are informal carers of a person who has arthritis as their main chronic condition and non-carers. OUTCOME MEASURES: Estimating the economic impact and national aggregated costs of informal carers NILF to care for a person with arthritis and projecting these costs from 2015 to 2030 in 5-year intervals. RESULTS: On a per-person basis, when adjusted for age, sex and highest education attained, the difference in average weekly total income between informal carers and non-carers employed in the labour force is $A1051 (95% CI: $A927 to $A1204) in 2015 and projected to increase by up to 22% by 2030. When aggregated, the total national annual loss of income to informal carers NILF is estimated at $A388.2 million (95% CI: $A324.3 to $A461.9 million) in 2015, increasing to $A576.9 million (95% CI: $A489.2 to $A681.8 million) by 2030. The national annual tax revenue lost to the government of the informal carers NILF is estimated at $A99 million (95% CI: $A77.9 to $A126.4 million) in 2015 and is projected to increase 49% by 2030. CONCLUSION: Informal carers NILF are economically worse off than employed non-carers, and the aggregated national annual costs are substantial. The future economic impact of informal carers NILF to care for a person with arthritis in Australia is projected to increase, with the estimated differences in income between informal carers and employed non-carers increasing by 22% from 2015 to 2030.


Subject(s)
Arthritis , Caregivers , Cost of Illness , Humans , Australia , Caregivers/economics , Male , Female , Middle Aged , Arthritis/economics , Arthritis/therapy , Aged , Adult , Income , Surveys and Questionnaires , Young Adult
3.
Int J Rheum Dis ; 27(5): e15187, 2024 May.
Article in English | MEDLINE | ID: mdl-38742741

ABSTRACT

Thymic tumors are very rare neoplasms in children and account for less than 1% of mediastinal tumors in pediatric patients. One-third of the pediatric patients present with symptoms related to the compression of the tumor mass on the surrounding anatomic structures, and paraneoplastic syndromes such as myasthenia gravis, pure red cell aplasia, acquired hypogammaglobulinemia, and connective tissue disorders, which rarely occur in children with thymic tumors. Herein, we report a case of thymic carcinoma mimicking the symptoms of a connective tissue disease with symmetrical polyarthritis accompanying myositis, fever, weight loss, and malaise in a 15-year-old male patient. To our knowledge, this is the first case pediatric thymic carcinoma accompany with severe polyarthritis and myopathy, thus we have reviewed the current literature regarding the cases of thymic malignancies coexisting with paraneoplastic syndromes in children.


Subject(s)
Arthritis , Myositis , Paraneoplastic Syndromes , Thymoma , Thymus Neoplasms , Humans , Male , Myositis/diagnosis , Myositis/complications , Paraneoplastic Syndromes/diagnosis , Paraneoplastic Syndromes/etiology , Thymus Neoplasms/complications , Thymus Neoplasms/diagnosis , Adolescent , Arthritis/diagnosis , Arthritis/etiology , Thymoma/complications , Thymoma/diagnosis , Treatment Outcome , Thymectomy , Biopsy
4.
Clin Exp Rheumatol ; 42(5): 1097-1103, 2024 05.
Article in English | MEDLINE | ID: mdl-38743445

ABSTRACT

The relationship between intestinal microbiota and arthritis has garnered significant attention, with emerging evidence suggesting a potential association between dysbiosis and various forms of inflammatory arthropathies. While observational studies have provided valuable insights into microbiota alterations in patients with arthritis, establishing causality remains challenging. Observational data, influenced by multiple confounders such as environmental factors, medication effects, and dietary habits, are insufficient to conclusively determine whether microbiota changes are somehow causally linked to arthritis. The heterogeneity of results across independent studies further complicates interpretation. To further support this hypothesis, interventional randomised trials are deemed necessary, yet their implementation in this area presents significant technical limitations. Experimental animal models offer insights into potential pathogenic mechanisms linking dysbiosis to arthritis, including compromised intestinal barrier function, the role of microbiota-derived metabolites and molecular mimicry. However, conflicting findings underscore the complexity of hostmicrobiota interactions and the challenges in establishing causality.Efforts to modulate the microbiota for arthritis treatment or prevention have shown promise, yet efficacy and applicability remains uncertain. Antibacterial drugs, dietary interventions, probiotics, and faecal microbiota transplantation have been explored, but their clinical utility awaits further validation. In conclusion, while the association between intestinal microbiota and arthritis is increasingly recognised, establishing causality remains elusive.


Subject(s)
Dysbiosis , Gastrointestinal Microbiome , Humans , Animals , Probiotics/therapeutic use , Arthritis/microbiology , Fecal Microbiota Transplantation , Host-Pathogen Interactions , Risk Factors
5.
J Gerontol Nurs ; 50(5): 35-42, 2024 May.
Article in English | MEDLINE | ID: mdl-38691115

ABSTRACT

PURPOSE: To evaluate the long-term effect of a tablet-based, cognitive-behavioral group intervention (Tab-G) to improve daily walking for older adults with arthritis. METHOD: Using an experimental pretest/posttest repeated measure design, long-term effects on step count, fatigue, self-efficacy, and quality of life (QOL) were investigated. RESULTS: Results of repeated measures analysis of variance showed significant improvement in step counts (F[1, 37] = 4.18, p = 0.048), fatigue (F[1, 36] = 9.971, p = 0.003), self-efficacy (F[1,28] = 4.645, p = 0.04), and QOL (F[1, 29] = 6.147, p = 0.019) in the Tab-G group compared to the control group. There were significant time effects across four time points (baseline and Weeks 4, 8, and 10) in fatigue (F[3, 108] = 5.43, p = 0.002), self-efficacy (F[3, 84] = 5.433, p = 0.002), and QOL (F[3, 87] = 3.673, p = 0.015), but not in step counts (F[3, 111] = 0.611, p = 0.609). CONCLUSION: Findings demonstrate positive long-term effects on fatigue in older adults with arthritis. [Journal of Gerontological Nursing, 50(5), 35-42.].


Subject(s)
Arthritis , Cognitive Behavioral Therapy , Fatigue , Quality of Life , Self Efficacy , Humans , Aged , Female , Male , Pilot Projects , Arthritis/therapy , Arthritis/psychology , Cognitive Behavioral Therapy/methods , Walking , Aged, 80 and over , Computers, Handheld , Middle Aged
6.
Vet Rec ; 194 Suppl 1: 3-4, 2024 05.
Article in English | MEDLINE | ID: mdl-38700159

ABSTRACT

In a recent survey, Hannah Capon asked the owners of arthritic dogs what they would like vets to do differently. She'll be using her findings to help delegates at BVA Live better understand the owner experience of veterinary care and contextualise their approach accordingly.


Subject(s)
Veterinary Medicine , Dogs , Animals , Humans , Veterinary Medicine/organization & administration , Dog Diseases/prevention & control , Ownership , United Kingdom , Arthritis/veterinary , Veterinarians/psychology , Patient Care Planning
7.
Sci Rep ; 14(1): 10807, 2024 05 11.
Article in English | MEDLINE | ID: mdl-38734730

ABSTRACT

This study assessed the association between arthritis, functional impairment, and nutritional risk (NR). Cross-sectional data were from the Canadian Longitudinal Study on Aging, a nationally representative sample of 45-85-year-old community-dwelling Canadians (n = 41,153). The abbreviated Seniors in the Community: Risk Evaluating for Eating and Nutrition II (SCREEN II-AB) Questionnaire determined NR scores (continuous), and high NR (score < 38); the Older American Resources and Services scale measured functional impairment. NR scores and status (low/high) were modelled using multiple linear and logistic regressions, respectively. Analyses adjusted for demographic characteristics, functional impairment, and health (body mass index, self-rated general and mental health). Additional analyses stratified the models by functional impairment. People with arthritis had poorer NR scores (B: - 0.35, CI - 0.48, - 0.22; p < 0.05) and increased risks of high NR (OR 1.11, 95% CI 1.06, 1.17). Among those with functional impairment, the likelihood of high NR was 31% higher in people with arthritis compared to those without arthritis (95% CI 1.12, 1.53). Among those with no functional impairment, the likelihood of high NR was 10% higher in people with arthritis compared to those without (95% CI 1.04, 1.16). These relationships differed based on the type of arthritis. Arthritis is associated with high NR in community-dwelling older adults, both with and without functional impairment. Findings highlight the need for further research on these relationships to inform interventions and improve clinical practices.


Subject(s)
Arthritis , Nutritional Status , Humans , Canada/epidemiology , Aged , Female , Male , Longitudinal Studies , Arthritis/epidemiology , Aged, 80 and over , Middle Aged , Aging , Cross-Sectional Studies , Risk Factors , Surveys and Questionnaires
8.
Int Immunopharmacol ; 133: 112032, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38608445

ABSTRACT

OBJECTIVE: The study aims to examine the effects of the COVID-19 pandemic on the prevalence of arthritis in the US using a specific generative AI tool. METHODS: The AI tool with Bing.com/copilot, designed to generate Python code, uses data from the Centers for Disease Control and Prevention (CDC) to visualize trends and uncover insights in four key areas: (1) The prevalence of arthritis in adults aged 18 years and older who have diabetes, (2) The prevalence of fair or poor health in adults aged 18 years and older who have arthritis, (3) The prevalence of activity limitations due to arthritis in adults aged 18 years and older with doctor-diagnosed arthritis, (4) The prevalence of arthritis in adults aged 18 years and older who are obese. This research did not require approval from an institutional review board or an ethics committee. RESULTS: The findings reveal a significant decline in the prevalence of arthritis among adults with conditions such as diabetes and obesity during the COVID-19 pandemic. There was also an observed improvement in activity limitations among patients with doctor-diagnosed arthritis. CONCLUSION: The study highlights the potential impact of the pandemic on chronic disease management, particularly arthritis. It underscores the importance of continued monitoring and care for patients with arthritis, especially during a global health crisis like the COVID-19 pandemic. The use of AI tools in generating insights from health data proves to be valuable in this context.


Subject(s)
Arthritis , COVID-19 , SARS-CoV-2 , Humans , COVID-19/epidemiology , Arthritis/epidemiology , Adult , Prevalence , Obesity/epidemiology , United States/epidemiology , Artificial Intelligence , Middle Aged , Adolescent , Male , Aged , Female , Young Adult , Diabetes Mellitus/epidemiology , Pandemics
9.
JMIR Public Health Surveill ; 10: e49433, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38598275

ABSTRACT

BACKGROUND: Improved life expectancy has increased the prevalence of older adults living with multimorbidities, which likely deteriorates their health-related quality of life (HRQoL). Understanding which chronic conditions frequently co-occur can facilitate person-centered care tailored to the needs of individuals with specific multimorbidity profiles. OBJECTIVE: The study objectives were to (1) examine the prevalence of multimorbidity among Korean older adults (ie, those aged 65 years and older), (2) investigate chronic disease patterns using latent class analysis, and (3) assess which chronic disease patterns are more strongly associated with HRQoL. METHODS: A sample of 1806 individuals aged 65 years and older from the 2021 Korean National Health and Nutrition Examination Survey was analyzed. Latent class analysis was conducted to identify the clustering pattern of chronic diseases. HRQoL was assessed by an 8-item health-related quality of life scale (HINT-8). Multiple linear regression was used to analyze the association with the total score of the HINT-8. Logistic regression analysis was performed to evaluate the odds ratio of having problems according to the HINT-8 items. RESULTS: The prevalence of multimorbidity in the sample was 54.8%. Three chronic disease patterns were identified: relatively healthy, cardiometabolic condition, arthritis, allergy, or asthma. The total scores of the HINT-8 were the highest in participants characterized as arthritis, allergy, or asthma group, indicating the lowest quality of life. CONCLUSIONS: Current health care models are disease-oriented, meaning that the management of chronic conditions applies to a single condition and may not be relevant to those with multimorbidities. Identifying chronic disease patterns and their impact on overall health and well-being is critical for guiding integrated care.


Subject(s)
Arthritis , Asthma , Hypersensitivity , Humans , Aged , Latent Class Analysis , Nutrition Surveys , Quality of Life , Chronic Disease , Republic of Korea/epidemiology
10.
BMC Health Serv Res ; 24(1): 466, 2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38614988

ABSTRACT

BACKGROUND: Evidence-based programs (EBPs) for older adults effectively improve health outcomes. However, there is a limited understanding of the unique needs of service providers as they consider adopting, implementing, and maintaining programs for older minority adults in low-income communities with limited aging services. METHODS: We conducted semi-structured interviews with key informants of community-based organizations (CBOs) to understand implementation and sustainability needs of CBOs within four racial and ethnically diverse Los Angeles County geographic areas. We performed thematic analysis of interview transcripts. RESULTS: Interviews were conducted with representatives from 25 senior-serving agencies providing aging-related EBPs. CBO representatives reported implementing EBPs in 8 domains: Falls Prevention (68%), Mental Health (64%), Caregiver Health (48%), Chronic Disease Management (48%), Diabetes Management (36%), Arthritis Management (28%), Physical Activity (24%), and Multiple Conditions Management (8%). Themes are presented using the six domains of the Bass and Judge framework for factors impacting successful and sustained EBP implementation. CBOs in low-income and diverse communities described unique challenges with tailoring interventions based on local community context (literacy, language), cultural context, and locally available resources (technology, safe community spaces, transportation) and faced resource-intensive administrative burdens through staff turnover, data collection, sustainable funding, and networking. CONCLUSIONS: Serving racial and ethnic communities has unique challenges that require tailored approaches and additional resources to ensure equitable access to EBPs for all communities. We describe suggestions for enhancing the effective adoption of EBPs among service agencies in under-resourced and diverse aging communities serving populations with aging-related health disparities.


Subject(s)
Arthritis , Racial Groups , Humans , Aged , Aging , Behavior Therapy , Data Collection
12.
Reumatol. clín. (Barc.) ; 20(4): 187-192, Abr. 2024. tab
Article in English | IBECS | ID: ibc-232371

ABSTRACT

Introduction and objectives: Magnetic resonance imaging (MRI) sensitivity and specificity seem to be less studied in enthesitis-related arthritis (ERA). We aimed to determine the ability of sacroiliac MRI to diagnose ERA patients. Materials and methods: We conducted a retrospective study including 44 patients with juvenile idiopathic arthritis (JIA). Each patient had a sacroiliac joint MRI. We divided patients into two groups: G1 patients with ERA and G2 patients with non-ERA subtype. Results: ERA was noted in 61% of the cases. Sacroiliac joints were painful in 15 patients (34%). MRI was normal in 25 patients (57%) (G1:11 versus G2:14) and showed bone marrow edema in the sacroiliac joints in 19 patients (34%) (G1=16 versus G2=3, p=0.005). Sacroiliac joints MRI's sensitivity and specificity in the ERA diagnosis were 61.54% and 82.35%, respectively. Positive and negative predictive values were 84.21% and 58.33%, respectively. Furthermore, sacroiliac joint pain in the clinical examination was able to predict sacroiliac bone edema in MRI with an odds ratio of 6.8 (95% CI 1.68–28.09; p=0.006). Conclusion: Our study showed that sacroiliac joint MRI has good specificity and positive predictive value in the diagnosis of ERA patients among JIA patients. This underlines the usefulness of sacroiliac joint MRI in the early diagnosis of ERA patients.(AU)


Introducción y objetivos: La sensibilidad y especificidad de la resonancia magnética parecen estar menos estudiadas en la artritis relacionada con entesitis (ERA). Nuestro objetivo era determinar la capacidad de la resonancia magnética de la articulación sacroilíaca para diagnosticar pacientes con ERA. Materiales y métodos: Realizamos un estudio retrospectivo que incluyó a 44 pacientes con artritis idiopática juvenil (AIJ). A cada paciente se le realizó una resonancia magnética de la articulación sacroilíaca. Dividimos a los pacientes en dos grupos: G1: pacientes con ERA y G2: pacientes con subtipo no ERA. Resultados: Se observó ERA en 61% de los casos. Las articulaciones sacroilíacas resultaron dolorosas en 15 pacientes (34%). La resonancia magnética fue normal en 25 pacientes (57%) (G1:11 vs. G2:14) y mostró edema de médula ósea en las articulaciones sacroilíacas en 19 pacientes (34%) (G1=16 vs. G2=3, p=0,005). La sensibilidad y especificidad de la resonancia magnética de articulaciones sacroilíacas en el diagnóstico de ERA fueron de 61,54 y 82,35%, respectivamente. Los valores predictivos positivos y negativos fueron 84,21 y 58,33%, respectivamente. Además, el dolor en la articulación sacroilíaca en el examen clínico fue capaz de predecir el edema del hueso sacroilíaco en la resonancia magnética con un odds ratio de 6,8 (IC 95%: 1,68 a 28,09; p=0,006). Conclusión: Nuestro estudio demostró que la resonancia magnética de la articulación sacroilíaca tiene buena especificidad y valor predictivo positivo en el diagnóstico de pacientes con ERA entre pacientes con AIJ. Esto subraya la utilidad de la resonancia magnética de la articulación sacroilíaca en el diagnóstico temprano de pacientes con ERA.(AU)


Subject(s)
Humans , Male , Female , Sacroiliitis/diagnosis , Arthritis , Magnetic Resonance Spectroscopy , Sacroiliac Joint/diagnostic imaging , Arthritis, Juvenile , Rheumatology , Rheumatic Diseases , Sensitivity and Specificity , Retrospective Studies
13.
Nihon Shokakibyo Gakkai Zasshi ; 121(4): 307-314, 2024.
Article in Japanese | MEDLINE | ID: mdl-38599841

ABSTRACT

Pouchitis is the most common long-term complication following ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis. Although several agents, including probiotics, steroids, and immunomodulators, have been used, the treatment of pouchitis remains challenging. Owing to the proven efficacy of biological therapy in inflammatory bowel disease, there is now growing evidence suggesting the potential benefits of biological therapy in refractory pouchitis. Here, we report the case of a 64-year-old woman with pouchitis due to ulcerative colitis who was successfully treated with ustekinumab (UST). The patient developed ulcerative pancolitis at the age of 35. Total colectomy and IPAA with J-pouch anastomosis were performed when the patient was 47 years old. Ileotomy closure was performed 6 months later. Postoperatively, the patient developed steroid-dependent pouchitis. Three years later, she developed steroid-induced diabetes. The patient has been taking 3mg of steroid for 20 years;therefore, her lifetime total steroid dose was 21g. The patient had over 20 episodes of bloody diarrhea a day. The last pouchoscopy in 20XX-9 revealed inflammatory stenosis with deep ulcerations of the afferent limb just before the ileoanal pouch junction. In July 20XX, when we took over her treatment, the policy of treatment was to withdraw her from steroids. Pouchoscopy revealed a widened but still tight afferent limb through which the scope could easily pass, and the ileoanal pouch still showed erosive ileitis without ulcers. Thiopurine administration and steroid tapering were initiated. Steroid tapering increased the erythrocyte sedimentation rate (ESR). As ESR increased, her arthritis exacerbated. Six months after the end of steroid administration, the patient consented to UST treatment. On April 20XX+1, the patient received her first 260-mg UST infusion. At this point, she experienced 14-15 episodes of muddy bloody stools. She had no abdominal pain;however, she experienced shoulder pain. Gradually, UST affected both pouchitis and arthritis. UST treatment was continued at 90mg subcutaneously every 12 weeks without abdominal pain recurrence. Eight months after the first UST infusion, nonsteroidal anti-inflammatory drugs were no longer necessary for shoulder pain. Follow-up pouchoscopy performed 14 months after UST optimization revealed a normal afferent limb without ulcerations in either segment. Pouchitis remission was maintained for over 2 years.


Subject(s)
Arthritis , Colitis, Ulcerative , Colonic Pouches , Pouchitis , Proctocolectomy, Restorative , Female , Humans , Middle Aged , Arthritis/complications , Arthritis/surgery , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/surgery , Colitis, Ulcerative/complications , Pouchitis/drug therapy , Pouchitis/etiology , Proctocolectomy, Restorative/adverse effects , Shoulder Pain/complications , Shoulder Pain/surgery , Steroids/adverse effects , Ustekinumab/therapeutic use
14.
Rheum Dis Clin North Am ; 50(2): 161-179, 2024 May.
Article in English | MEDLINE | ID: mdl-38670719

ABSTRACT

The differential diagnosis of inflammatory arthritis as an immune-related adverse event can be challenging as patients with cancer can present with musculoskeletal symptoms that can mimic arthritis because of localized or generalized joint pain. In addition, immune checkpoint inhibitors can exacerbate joint conditions such as crystal-induced arthritis or osteoarthritis, or induce systemic disease that can affect the joints such as sarcoidosis. This distinction is important as the treatment of these conditions can be different from that of immune-related inflammatory arthritis.


Subject(s)
Arthritis , Immune Checkpoint Inhibitors , Humans , Immune Checkpoint Inhibitors/adverse effects , Diagnosis, Differential , Arthritis/diagnosis , Arthritis/chemically induced , Arthritis/drug therapy , Sarcoidosis/chemically induced , Sarcoidosis/diagnosis , Sarcoidosis/immunology , Neoplasms/drug therapy , Neoplasms/immunology , Osteoarthritis/drug therapy , Osteoarthritis/immunology , Crystal Arthropathies/diagnosis , Crystal Arthropathies/immunology
15.
Rheum Dis Clin North Am ; 50(2): 269-279, 2024 May.
Article in English | MEDLINE | ID: mdl-38670725

ABSTRACT

The introduction of immune checkpoint inhibitors (ICIs) has changed the landscape of the treatment of cancer. Several immune-related adverse events (irAEs) have now been described such as ICI-inflammatory arthritis (IA), sicca syndrome, polymyalgia rheumatica, myositis, and vasculitis as a consequence of immune activation. The onset of the ICI-IA can vary from after the first infusion of ICIs to a delayed presentation a year or more after ICI initiation. Ultimately, baseline patient and tumor characteristics, the types of immunotherapies used, pre-existing autoimmune diseases, and/or other irAEs, as well as patient preferences will all shape the discussions around ICI-IA management.


Subject(s)
Arthritis , Immune Checkpoint Inhibitors , Humans , Immune Checkpoint Inhibitors/adverse effects , Arthritis/chemically induced , Arthritis/drug therapy , Neoplasms/drug therapy , Neoplasms/immunology , Immunotherapy/adverse effects , Immunotherapy/methods
16.
Rheum Dis Clin North Am ; 50(2): 325-335, 2024 May.
Article in English | MEDLINE | ID: mdl-38670730

ABSTRACT

Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) is an immune-related adverse event that can occur as a result of receiving ICIs for cancer treatment. Thus far, ICI-IA has been described variably in the literature, in part due to varying presentations that evolve over time, as well as a lack of standardized definitions and classification. This scoping review aggregates various descriptions of ICI-IA, highlighting the most prominent attributes of ICI-IA from categories such as symptoms, signs, imaging, and laboratory findings as well as discussing potential mimic conditions.


Subject(s)
Arthritis , Immune Checkpoint Inhibitors , Humans , Immune Checkpoint Inhibitors/adverse effects , Arthritis/drug therapy , Arthritis/chemically induced , Neoplasms/drug therapy , Neoplasms/immunology
17.
Crit Rev Immunol ; 44(5): 59-70, 2024.
Article in English | MEDLINE | ID: mdl-38618729

ABSTRACT

We investigated the potential arthritis-inducing effects of Phillygenin and its underlying mechanisms. RAW264.7 cells were stimulated with lipopolysaccharide to induce inflammation. Phillygenin was found to reduce arthritis score, histopathological changes, paw edema, spleen index, and ALP levels in a dose-dependent manner in a model of arthritis. Additionally, Phillygenin was able to decrease levels of inflammation markers in serum samples of mice with arthritis and also inhibited inflammation markers in the cell supernatant of an in vitro model of arthritis. Phillygenin increased cell viability and JC-1 disaggregation, enhanced calcien-AM/CoCl2, reduced LDH activity levels and IL-1a levels, and inhibited Calcein/PI levels and iron concentration in an in vitro model. Phillygenin was also found to reduce ROS-induced oxidative stress and Ferroptosis, and suppress the NLRP3 inflammasome in both in vivo and in vitro models through AMPK. In the in vivo model, Phillygenin was observed to interact with AMPK protein. These findings suggest that Phillygenin may be a potential therapeutic target for preventing arthritis by inhibiting NLRP3 inflammasome and Ferroptosis through AMPK. This indicates that Phillygenin could have disease-modifying effects on arthritis.


Subject(s)
Arthritis , Ferroptosis , Lignans , Humans , Animals , Mice , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , AMP-Activated Protein Kinases , Inflammation
18.
Mol Med ; 30(1): 48, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594612

ABSTRACT

BACKGROUND: Immune-mediated arthritis is a group of autoinflammatory diseases, where the patient's own immune system attacks and destroys synovial joints. Sustained remission is not always achieved with available immunosuppressive treatments, warranting more detailed studies of T cell responses that perpetuate synovial inflammation in treatment-refractory patients. METHODS: In this study, we investigated CD4 + and CD8 + T lymphocytes from the synovial tissue and peripheral blood of patients with treatment-resistant immune-mediated arthritis using paired single-cell RNA and TCR-sequencing. To gain insights into the trafficking of clonal families, we compared the phenotypes of clones with the exact same TCRß amino acid sequence between the two tissues. RESULTS: Our results show that both CD4 + and CD8 + T cells display a more activated and inflamed phenotype in the synovial tissue compared to peripheral blood both at the population level and within individual T cell families. Furthermore, we found that both cell subtypes exhibited clonal expansion in the synovial tissue. CONCLUSIONS: Our findings suggest that the local environment in the synovium drives the proliferation of activated cytotoxic T cells, and both CD4 + and CD8 + T cells may contribute to tissue destruction and disease pathogenesis.


Subject(s)
Arthritis , CD8-Positive T-Lymphocytes , Humans , CD8-Positive T-Lymphocytes/metabolism , Arthritis/metabolism , Arthritis/pathology , Synovial Membrane , Clone Cells , Amino Acid Sequence , CD4-Positive T-Lymphocytes/metabolism
19.
Haemophilia ; 30 Suppl 3: 120-127, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38578694

ABSTRACT

Gene therapy and universal use of safer, more effective, and personalised prophylactic regimens (factor, and nonfactor) are expected to prevent joint bleeding and promote joint health in persons with haemophilia (PwH). Growing evidence suggests that subclinical bleeding, with active and inactive synovial proliferation, continues and haemophilic arthropathy remains a major morbidity in PwH despite early institution of joint prophylaxis. Joint health assessment is evolving with physical examination scores complementing imaging scores. Point-of-care ultrasound is emerging as a safe, cost-effective, and readily available tool for acute determination of musculoskeletal abnormalities, serial evaluation of joints for sonographic markers of haemophilic arthropathy, and in providing objective insight into the efficacy of new therapies. In acute haemarthrosis, arthrocentesis expedites recovery and prevent the vicious cycle of bleed-synovitis-rebleed. When synovial proliferation develops, a multidisciplinary team approach is critical with haematology, orthopaedics, and physiotherapy involvement. Synovectomy is considered for patients with chronic synovitis that fail conservative management. Non-surgical and minimally invasive procedures should always be offered and considered first. Careful patient selection, screening and early intervention increase the success of these interventions in reducing bleeding, pain, and improving joint function and quality of life. Chemical synovectomy is practical in developing countries, but radioactive synovectomy appears to be more effective. When surgical synovectomy is considered, arthroscopic/minimally invasive approach should be attempted first. In advanced haemophilic arthropathy, joint replacement and arthrodesis can be considered. While excited about the future of haemophilia management, navigating musculoskeletal challenges in the aging haemophilia population is equally important.


Subject(s)
Arthritis , Hemophilia A , Synovitis , Humans , Hemophilia A/complications , Hemophilia A/therapy , Hemophilia A/diagnosis , Quality of Life , Hemarthrosis/diagnosis , Hemarthrosis/etiology , Hemarthrosis/therapy , Synovitis/diagnosis , Synovitis/etiology , Synovitis/therapy , Aging , Arthrodesis
20.
Front Immunol ; 15: 1331959, 2024.
Article in English | MEDLINE | ID: mdl-38558818

ABSTRACT

Introduction: Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) poses a major clinical challenge to ICI therapy for cancer, with 13% of cases halting ICI therapy and ICI-IA being difficult to identify for timely referral to a rheumatologist. The objective of this study was to rapidly identify ICI-IA patients in clinical data and assess associated immune-related adverse events (irAEs) and risk factors. Methods: We conducted a retrospective study of the electronic health records (EHRs) of 89 patients who developed ICI-IA out of 2451 cancer patients who received ICI therapy at Northwestern University between March 2011 to January 2021. Logistic regression and random forest machine learning models were trained on all EHR diagnoses, labs, medications, and procedures to identify ICI-IA patients and EHR codes indicating ICI-IA. Multivariate logistic regression was then used to test associations between ICI-IA and cancer type, ICI regimen, and comorbid irAEs. Results: Logistic regression and random forest models identified ICI-IA patients with accuracies of 0.79 and 0.80, respectively. Key EHR features from the random forest model included ICI-IA relevant features (joint pain, steroid prescription, rheumatoid factor tests) and features suggesting comorbid irAEs (thyroid function tests, pruritus, triamcinolone prescription). Compared to 871 adjudicated ICI patients who did not develop arthritis, ICI-IA patients had higher odds of developing cutaneous (odds ratio [OR]=2.66; 95% Confidence Interval [CI] 1.63-4.35), endocrine (OR=2.09; 95% CI 1.15-3.80), or gastrointestinal (OR=2.88; 95% CI 1.76-4.72) irAEs adjusting for demographics, cancer type, and ICI regimen. Melanoma (OR=1.99; 95% CI 1.08-3.65) and renal cell carcinoma (OR=2.03; 95% CI 1.06-3.84) patients were more likely to develop ICI-IA compared to lung cancer patients. Patients on nivolumab+ipilimumab were more likely to develop ICI-IA compared to patients on pembrolizumab (OR=1.86; 95% CI 1.01-3.43). Discussion: Our machine learning models rapidly identified patients with ICI-IA in EHR data and elucidated clinical features indicative of comorbid irAEs. Patients with ICI-IA were significantly more likely to also develop cutaneous, endocrine, and gastrointestinal irAEs during their clinical course compared to ICI therapy patients without ICI-IA.


Subject(s)
Antineoplastic Agents, Immunological , Arthritis , Kidney Neoplasms , Melanoma , Humans , Antineoplastic Agents, Immunological/therapeutic use , Retrospective Studies , Arthritis/drug therapy , Melanoma/drug therapy , Kidney Neoplasms/drug therapy
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