Rheumatic Research Articles

Extract of Tinospora sinensis alleviates LPS-induced neuroinflammation in mice by regulating TLR4/NF-κB/NLRP3 signaling pathway

Ethnopharmacological relevanceThe dried rattan stem of Tinospora sinensis (Lour.) Merr. is valued for its efficacy of clearing heat and removing toxicity, calming and soothing the nerves. It is widely used in Tibetan medicine for the treatment of rheumatic and aging diseases. Studies have confirmed its anti-inflammatory and ameliorating effects on Alzheimer's disease; however, the anti-neuroinflammation efficacy and mechanism remain unclear. AimThis study aimed to explore the anti-neuroinflammation efficacy, major effective ingredients, and potential mechanism of extract of Tinosporae sinenisis (TIS). MethodsUPLC-Q-TOF/MS was used to identify the compounds of TIS and the plasma components of rats after gastric administration of TIS. C57BL/6 J mice were continuously intraperitoneally injected with lipopolysaccharide (LPS) (250 μg/kg) for 14 d to establish a neuroinflammation model. The effects of TIS (4.5 g/kg, 9 g/kg) on the learning and memory abilities in mice with neuroinflammation was evaluated using spontaneous activity, novel object recognition, and Morris water maze tests. Pathological changes in the hippocampus were observed using hematoxylin and eosin staining. Gene and protein levels of inflammatory factors in the brain were detected using qRT-PCR and ELISA kits. Iba-1 levels in the brain were detected using immunofluorescence to assess the degree of microglial activation. Network pharmacology, based on the components absorbed into plasma of TIS, was used to predict potential targets and pathways. Proteomics was used to study the differentially expressed proteins and related pathways in the brain tissue of mice with neuroinflammation. Finally, correlation analysis was performed on the results of network pharmacology and proteomics, and proteins related the anti-neuroinflammatory effect of TIS were detected by western blot. ResultsA total of 39 compounds were identified in TIS: genipingentiobioside, isocorydin, reticuline, (−)-argemonine, tinosineside A, tinosinenside A, and costunolide were absorbed into the plasma. After continuous intraperitoneal injection of LPS into C57BL/6 J mice, microglia in the brain tissue were activated and the gene and protein levels of IL-1β, TNF-α, IL-6, and iNOS were increased in the brain tissue, suggesting that the neuroinflammation model was successfully established. TIS reduced Iba-1 levels and gene expression and protein levels of inflammatory factors in the brain of mice with neuroinflammation. Furthermore, TIS improved the pathological changes in the hippocampus and learning and memory abilities caused by neuroinflammation. Network pharmacology has predicted that TNF, IL-1β, and IκBKB are closely related to neuroinflammation. Proteomics identified key differentially expressed proteins, including TNF, NF-κB2, NF-κBIA, and TLR4. Toll-like receptor (TLR), NF-κB, and NOD-like receptor (NLR) signaling pathways are involved in neuroinflammation-related pathways. Correlation analysis revealed TLR, TNF and NLR signaling pathways were closely related to the anti-neuroinflammatory effects of TIS. We observed that TIS alleviated neuroinflammation by inhibiting the TLR4/NF-κB/NLRP3 pathway. ConclusionThirty-nine compounds were identified from TIS, among which seven were absorbed into the plasma as prototype components. TIS alleviated LPS-induced neuroinflammation in mice, and its mechanism was related to inhibition of TLR4/NF-κB/NLRP3 signaling pathway.

High risk of misclassification of acute Parvovirus B19 infection into a systemic rheumatic disease.

Parvovirus B19 most frequently causes epidemics of erythema infectiosum in children but also affects adults often leading to rheumatologic manifestations. While the serum profile allows the diagnosis, manifestations may mimic autoimmune conditions. The aim was to evaluate the proportion of patients with acute Parvovirus B19 infection fulfilling classification criteria for rheumatic diseases (RA and SLE). We evaluated the clinical and serological features of 54 patients diagnosed with acute Parvovirus B19 infection seeking rheumatological attention between March and June 2024. The majority of patients were females (78%), with a mean (s.d.) age of 45 (13) years and 54% could not recall any known exposure. Fifty-one/54 (94%) had arthralgia, 27 (50%) arthritis (oligoarthritis in 67% of them), 24 (44%) fever, 19 (35%) skin rash and 7 (13%) purpura. Symptoms resolution generally occurred within 6 weeks. Complement levels were low in 14/33 (42%) tested patients, while the presence of serum ANA, anti-dsDNA, anti-phospholipids and rheumatoid factor was detected in 21/38 (55%), 10/26 (38%), 6/12 (50%) and 5/37 (13%) patients, respectively. Classification criteria for SLE were fulfilled in 93% of ANA-positive patients and RA criteria in 38% of patients with arthritis. Parvovirus B19 infection manifestations may vary and nearly all patients with positive serum ANA fulfil the classification criteria for SLE. The risk of misclassification in patients with viral infection should not be overlooked.

An observational study on the application of fast-track cardiac anesthesia using target-controlled infusion of sufentanil and propofol in valve replacement surgery.

The aim of this study was to evaluate the efficacy of fast-track cardiac anesthesia using target-controlled infusion of sufentanil and propofol in valve replacement surgery. The clinical data of 88 patients with rheumatic heart disease undergoing valve replacement surgery were retrospectively analyzed and grouped based on different treatment methods. Among them, 44 cases received fast-track cardiac anesthesia using target-controlled infusion of fentanyl and propofol from November 2019 to July 2021 were set as the control group, and 44 cases received fast-track cardiac anesthesia using target-controlled infusion of sufentanil and propofol from August 2021 to February 2022 were set as the study group. The study group showed shorter postoperative awakening time, extubation time, and hospital stay duration, and lower dosage of dopamine and nitroglycerin consumption compared to the control group (P < .05). At T5 and T6, both groups exhibited higher ACTH, cortisol (Cor), and C3a than at T0, and the study group showed significantly lower ACTH, Cor, and C3a at T5 and T6 than the control group (P < .05). At T7, the control group showed higher ACTH, Cor, and C3a than at T0, and ACTH, Cor, and C3a were significantly lower in the study group than in the control group at T7 (P < .05). Fast-track cardiac anesthesia using target-controlled infusion of sufentanil and propofol in valve replacement surgery has demonstrated favorable application effects, which stabilizes hemodynamics, alleviates myocardial damage, suppresses endocrine stress responses, and does not increase adverse reactions, thereby exhibiting good safety.

Hydroxychloroquine as an add-on therapy for the induction therapy of MPO-AAV: a retrospective observational cohort study.

The remission rate of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients who received standard induction therapy is far from satisfactory. Improving the remission rate of MPO-AAV patients is essential. Hydroxychloroquine (HCQ), one of the classic antimalarial drugs, has been widely used in various autoimmune rheumatic diseases. This retrospective observational cohort study is aimed to evaluate the efficacy and safety of HCQ during induction treatment for MPO-AAV. The medical records of patients diagnosed with MPO-AAV at Xiangya Hospital, Central South University from January 2021 to September 2023 were collected. They were assigned to the HCQ group or control group according to whether they used HCQ. The patients included were screened by propensity score matching. To evaluate whether MPO-AAV patients benefited from HCQ, we compared the prognosis of the two groups. The adverse effects of HCQ during follow-up were recorded. The composition ratio of complete remission, response and treatment resistance between HCQ group and control group were different statistically (P=.021). There was no significant difference between the two groups in 1-year renal survival (P=.789). The HCQ group had better 1-year patient survival than the control group (P=.049). No serious adverse effects were documented in the HCQ group. HCQ together with standard induction treatment may improve the remission rate of MPO-AAV patients, and HCQ had good safety in our study.

A Bayesian model to analyse the association of comorbidities with biosimilar treatment retention in a non-medical switch scenario in patients with inflammatory rheumatic musculoskeletal diseases

ObjectivesTo analyse clinical outcomes of a non-medical switch from originator adalimumab (ADA) to its ABP501 biosimilar (ABP) over 6 months in patients with inflammatory rheumatic musculoskeletal diseases (RMD) in relation to comorbidity as a risk factor for therapy discontinuation.MethodsRMD patients switching from originator ADA to ABP were identified from a large routine database from October 2018 onwards. Documented clinical data at the time of non-medical switching (baseline), and at 3 and 6 months were collected. Comorbidities were represented by the Charlson Comorbidity Index (CCI) at baseline and patients were categorized based on CCI > 0. Differences in the ABP retention rate over 6 months between patients with CCI = 0 and patients with CCI > 0 were analysed using Bayesian exponential regression.ResultsA total of 111 patients with axial spondyloarthritis (n = 68), rheumatoid arthritis (n = 23) and psoriatic arthritis (n = 15), were identified, 74.8% of whom had continued treatment with ABP after 6 months, while a smaller proportion had either switched to another ADA biosimilar (10.8%), switched back to originator ADA (7.2%), switched to a different biologic (3.6%), or dropped out (3.6%). At baseline, a CCI > 0 was found in 38% of patients. Cardiovascular comorbidities (40%) were most prevalent followed by diseases of the skin (33%), the gastrointestinal tract (20%) and the eye (20%). ABP treatment was continued after 6 months in 74% of patients with CCI = 0 and in 76% with CCI > 0. Bayesian analysis showed only a small difference (months) in the APB continuation rate between groups (estimate 0.0012, 95% credible interval (CrI) -0.0337 to 0.0361). Adjusting for age, sex, and disease subtype revealed somewhat shorter retention rates for patients with CCI > 0, but the distribution of the difference included 0 (estimate -0.0689, 95% CrI -0.2246 to 0.0234).ConclusionIn a non-medical switch scenario of RMD patients, there was no evidence for a considerable difference in ABP retention rates over 6 months between comorbidity groups.

The Potential Use of Arsenic Trioxide in the Treatment of Systemic Lupus Erythematosus.

Arsenic trioxide (ATO) is now part of the standard regimen for the treatment of newly diagnosed and relapsed acute promyelocytic leukemia. The availability of an oral form of ATO has greatly reduced the incidence of cardiotoxicity as compared to intravenous (IV) administration. Increasing evidence suggests that ATO has anti-inflammatory properties that may be useful for the treatment of autoimmune diseases. These include the modulation of Treg cell activation, Th1/Th2 and Th17/Treg balance, depletion of activated T cells and plasmacytoid dendritic cells, and influence of B-cell differentiation, leading to reduced autoantibody and cytokine production. ATO has also been shown to induce apoptosis of activated fibroblast-like synoviocytes through the generation of reactive oxygen species and alter the gut microbiota in collagen-induced arthritis. Despite the emergence of newer treatment modalities, the treatment of systemic lupus erythematosus (SLE), especially refractory manifestations, remains a challenge, owing to the paucity of effective biological and targeted therapies that are devoid of adverse effects. Oral ATO is an attractive option for the treatment of SLE because of the lower cost of production, convenience of administration, and reduced cardiotoxicity. This article summarizes the anti-inflammatory mechanisms of ATO and its potential application in the treatment of SLE and other rheumatic diseases.

Local anaesthetic to reduce injection pain in patients who are prescribed intramuscular benzathine penicillin G: a systematic review and meta-analysis

Three to 4-weekly intramuscular injections of benzathine penicillin G (BPG) for a prolonged period (e.g., 10 years, until age 40 years, or lifelong) are recommended for preventing group A streptococcal infections that cause recurrent acute rheumatic fever (ARF) and potential progression to rheumatic heart disease (RHD). The duration of treatment, frequency and local pain associated with BPG injections may lead to reduced compliance. Shorter courses of BPG are recommended for the treatment of syphilis and Streptococcal infections. We aimed to assess the effects of local anaesthesia in reducing injection pain in patients who are being treated with BPG. In this systematic review and meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Conference Proceedings Citation Index-Science and LILACS from database inception up to May 4, 2024, and performed additional searches for grey literature. Randomised controlled trials comparing BPG vs. BPG administered alongside local anaesthetics were included. Randomized controlled trials using BPG, irrespectively of indication, and testing any local anaesthetic agent for pain alleviation were considered eligible. We applied GRADE to assess the quality of evidence. Summary data were extracted from included trials. The primary outcome was injection pain, assessed through mean differences. A random-effects model was utilized to account for study heterogeneity. This study is registered with PROSPERO, CRD42022342437. Database searches identified a total of 3958 records, and 3 additional records were retrieved from grey literature searches. After removal of duplicates, screening of abstracts and full-text review, eight trials were included, combining a total of 489 patients (151 patients with RHD). Immediate pain level, as reported by patients, was of high intensity in most studies. Low intensity pain was still reported at 24h. Administration of lidocaine mixed with BPG was associated with a significant reduction in immediate post-injection pain (mean difference-3.84, 95% confidence interval-6.19 to-1.48, P=0.0001; 4 studies; I2=98%; GRADE: moderate quality), pain at 5 min (mean difference-2.85, 95% CI confidence interval-3.78 to-1.92, P<0.0001; 1 study; GRADE: moderate quality), and pain at 20 min (mean difference-1.85, 95% confidence interval-2.61 to-1.09, P<0.0001; 1 study; GRADE: moderate quality) on a 1 to 10 scale. One study assessed lidocaine cream applied to the skin prior to BPG injection and showed no significant reduction in injection pain (mean difference=-0.54, 95% CI confidence interval-1.17 to 0.09, P=0.13; 1 study; GRADE: low quality). Mepivacaine mixed with BPG in patients with syphilis showed a significant reduction of immediate post-injection pain (mean difference-2.19, 95% CI confidence interval-2.49 to-1.89, P<0.0001; 1 study; GRADE: moderate quality). Two studies assessed procaine mixed with BPG and reported: lower immediate pain levels or pain assessed at 1h (mean difference and 95% CI confidence intervals not provided, P=0.001 and P=0.008, respectively; 1 study; GRADE: low quality), or less immediate pain and pain at 24h on the buttock injected with procaine mixed with BPG (mean difference and 95% CI confidence intervals not provided, P<0.001 for both; 1 study; Grade: low quality). No severe adverse reactions were reported. In patients receiving intramuscular BPG injections, moderate quality quantitative evidence suggests that BPG injections diluted with lidocaine or mepivacaine may improve post-injection pain scores compared to BPG injections diluted with sterile water. Procaine may also have a benefit, but quality of evidence was lower. Most studies included small patient samples and assessed pain levels at different timepoints. Due to insufficient data we were not able to assess the impact of injection volume, and local anaesthetics' dose on pain intensity and duration of pain relief. WHO.

Adalimumab-induced manic episode in an adolescent with juvenile idiopathic arthritis

BackgroundJuvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatic disease in children, and adalimumab is one of the primary treatment options. Although it is widely used for inflammatory diseases, there is limited research on its safety and efficacy in patients with psychiatric disorders or in those with inflammatory diseases who also have comorbid psychiatric conditions.Case reportWe report a 12-year-old adolescent boy who presented with emotional instability for 1 year, exacerbated leading to hospital admission in the past month. Upon detailed evaluation after admission, it was found that the patient’s emotional fluctuations may be related to the use of Adalimumab. Follow-up after psychiatric inpatient treatment revealed that the patient did not experience emotional excitement again after discontinuing Adalimumab.ConclusionsAlthough tumor necrosis factor-α inhibitors have positive effects on the emotional, cognitive, and physical functions of patients with inflammatory diseases, their use may induce mood swings in patients with comorbid mood disorders. This is particularly important for adolescents with rapid mood changes, where greater caution is required. Further research is necessary to clarify the correlation between the adverse effects of these drugs and their impact on patients with bipolar disorder.

Expert Panel Consensus Statements on Vaccination for Adults with AIRD in India

Introduction: Due to notable distinctions in infection patterns, vaccine accessibility, and approaches to treatment among patients with autoimmune inflammatory rheumatic diseases (AIRD) in India compared to other regions globally, the Indian Rheumatology Association Vaccine (IRAVAC) group was formed to develop expert panel consensus statements on vaccination for adults with AIRDs in India. Methods: The IRAVAC group comprised seven rheumatologists, one epidemiologist, two infectious disease specialists, one clinical virologist, one specialist nurse, and a patient representative. The group determined the scope of the consensus statements, framed the research questions, and assigned a team of few members to review the evidence who designed the search strategy and conducted the systematic literature search and data extraction. Another group of members subsequently reviewed the articles for each vaccine, prepared a summary, generated draft statements, and assigned them an appropriate level of evidence. Eighty-eight such draft statements were circulated to the members of IRAVAC for review and deliberation. The draft statements were revised accordingly, and the final set of 48 statements on vaccinations for eight diseases was voted upon by the IRAVAC group, with a predefined 75% agreement set as a threshold for acceptance. It is envisaged that these consensus statements related to vaccination in AIRD would be helpful not only to rheumatologists in India but also to those in other countries.

Impact of Central Sensitization on Clinical and Functional Aspects of Psoriatic Arthritis.

Background/Objectives: Psoriatic arthritis (PsA) is an inflammatory rheumatic disease characterized by peripheral arthritis, enthesitis, spondylitis and psoriasis. The objective of this study was to examine the prevalence of central sensitization (CS) and its impact on the clinical and functional aspects of PsA. Methods: Adult patients with PsA according to the Classification of Psoriatic Arthritis (CASPAR) criteria were included in this cross-sectional observational study. The Central Sensitization Inventory (CSI) was used to assess the presence of CS. The study evaluated the impact of CS on individuals by analyzing many factors including demographic information, laboratory findings, clinical features, disease activity, quality of life, severity of sleeplessness, frequency of depression and anxiety. The patients were categorized into distinct groups based on the existence and intensity of CS, and a comparative analysis was conducted on their respective outcomes. Results: A total of 103 PsA patients with a mean age of 43.2 (SD: 6.7) years and including 42 (40.8%) males were included. The mean CSI score was 45.4 (SD: 15.1), and 67 (65.1%) patients had CS. The logistic regression analysis revealed that the variables Psoriasis Area Severity Index (PASI), General Anxiety Disorder-7 (GAD-7), and Insomnia Severity Index (ISI) exhibit considerable predictive power in relation to the outcome variable CS (p < 0.05). PASI was observed as the most important variable in predicting CS (OR 9.70 95% CI: 1.52-62.21). Conclusions: CS has demonstrable efficacy in influencing laboratory, clinical, and functional markers among individuals with PsA. When assessing pain sensitivity in these patients, it is important to take into account the presence of CS.

A biopsychosocial questionnaire for patients with primer Sjögren's syndrome: The BETY-Biopsychosocial Questionnaire.

The BETY-Biopsychosocial Questionnaire (BETY-BQ) is a scale developed to assess the biopsychosocial domains of patients with rheumatic diseases under a single roof. The study aimed to determine the validity and reliability of the BETY-BQ in patients with primary Sjögren's Syndrome (pSS). At enrollment and one week, 91 patients with pSS completed the BETY-BQ. Construct validity was measured by correlating the BETY-BQ total score responses with the Health Assessment Questionnaire (HAQ), Hospital Anxiety and Depression Scale (HADS), 36-Item Short-Form Health Survey (SF-36), EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), Primary Sjögren's Syndrome Quality of Life questionnaire (PSS-QoL), and Euro-QoL 5D (EQ-5D). The BETY-BQ correlated high to moderate with HAQ, bodily pain subscale of SF-36, Euro Qol-5D, PSS-QoL, HADS, and ESSPRI (0.776 to 0.557, p <0.05). Spearman's correlation coefficients between BETY-BQ total scores at baseline and average one week were very high (rho = 0.98, <0.001) and indicated substantial agreement between test-retest scores (ICC = 0.99, <0.001). Internal consistency reliability at baseline was 0.91 for the BETY-BQ. BETY-BQ is valid and reliable for assessing biopsychosocial status in patients with pSS and can be used to measure outcomes in pSS.

Wider recognition and greater understanding of postinfectious, antibiotic-refractory Lyme arthritis.

Lyme disease, caused by Borrelia burgdorferi (Bb), can progress to Lyme arthritis (LA). While most patients with LA respond successfully to antibiotic therapy, a small percentage fail to improve, a condition known as antibiotic-refractory Lyme arthritis (ARLA). While T cell responses are known to drive ARLA, molecular mechanisms for ARLA remain unknown. In this issue of the JCI, Dirks et al. isolated disease-specific Th cells from patients with ARLA residing in Germany. A distinct TCR-β motif distinguished ARLA from other rheumatic diseases. Notably, the TCR-β motif was linked predominantly to HLA-DRB1*11 or 13 alleles, which differed from alleles in patients from North America. It also mapped primarily to T peripheral helper (Tph) cells, as opposed to classical Th1 cells. These findings provide a roadmap explaining how T cell responses necessary for control of an infection can, despite antibiotic therapy, drive a disadvantageous T cell response, resulting in a postinfectious, inflammatory arthritis.

Measuring Transition Readiness of Patients After Transfer from Pediatric to Adult Care in Rheumatology.

Transitional care is essential to maintain the continuity of care in younger patients with rheumatic diseases. In this study, we aimed to assess the transition readiness of rheumatology patients who had already transferred from pediatric to adult care using a questionnaire. We included young adult rheumatology patients who had already transferred to adult rheumatology care. The Transition Readiness Assessment Questionnaire (TRAQ) was used in the adult rheumatology clinic to assess the patients' readiness; a retrospective chart review was conducted to include diagnosis, age at diagnosis, age at transfer, and current age. Three hundred and ten patients (184 female and 126 male) participated in this study. The mean age at diagnosis, the mean age at transfer, and the mean age at the time of the study were 10.7 ± 4.29, 21.1 ± 1.69, and 24.0 ± 2.26 years, respectively. Most of the patients had familial Mediterranean fever, followed by arthritis, connective tissue disorders, and other diseases. Tracking health issues was the lowest-scored domain. Females scored significantly higher than males in the tracking health issue domain (P = .006) and managing health issue domain (P = .028) but not in the overall TRAQ score (P = .053). Patients in different diagnosis and transfer age groups scored similarly across the domains. In this study, females performed better than males in 2 domains of the TRAQ questionnaire. Diagnoses or transfer age groups were not associated with TRAQ outcomes.

An objective diagnosis of gout and calcium pyrophosphate deposition disease with machine learning of Raman spectra acquired in a point-of-care setting.

Raman spectroscopy is proposed as a next-generation method for the identification of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluid. As the interpretation of Raman spectra requires specific expertise, the method is not directly applicable for clinicians. We developed an approach to demonstrate that the identification process can be automated with the use of machine learning techniques. The developed system is tested in a point-of-care-setting at our outpatient rheumatology department. We collected synovial fluid samples from 446 patients with various rheumatic diseases from three centra. We analyzed all samples with our Raman spectroscope and used 246 samples for training and 200 samples for validation. Trained observers classified every Raman spectrum as MSU, CPP or else. We designed two one-against-all classifiers, one for MSU and one for CPP. These classifiers consisted of a principal component analysis model followed by a support vector machine. The accuracy for classification of CPP using the 2023 ACR/EULAR CPPD classification criteria was 96.0% (95% CI 92.3-98.3), while the accuracy for classification of MSU with using the 2015 ACR/EULAR gout classification criteria was 92.5% (95% CI 87.9-95.7). Overall, the accuracy for classification of pathological crystals was 88.0% (95% CI 82.7-92.2). The model was able to discriminate between pathologic crystals, artifacts, and other particles such as microplastics. We here demonstrate that potentially complex Raman spectra from clinical patient samples can be successfully classified by a machine learning approach, resulting in an objective diagnosis independent of the opinion of the medical examiner.

A Comprehensive Study of Risk Factors, Etiology, and Infarction Patterns in Cerebrovascular Accidents at a Tertiary Care Hospital in India.

Background Stroke is a debilitating cerebrovascular condition characterized by sudden neurological deficits. The incidence of stroke is rising in India, posing significant public health concerns. This study aims to examine the risk factors and etiology of stroke using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification and analyze infarct areas in cerebrovascular accidents (CVA) at a tertiary care hospital. Methodology This cross-sectional, hospital-based observational study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed to Be University), Pune, India, from January 2023 to January 2024. The study included 100 adult patients diagnosed with CVA based on clinical and radiological criteria. Patients aged 18 years and older were eligible, while those with a history of head trauma or those below 18 years were excluded. The investigation protocol included routine biochemical assessments and radiological investigations, such as computed tomography (CT), magnetic resonance imaging (MRI) with angiography or venography, and Doppler ultrasound of bilateral carotid arteries. Results The study population consisted of 100 patients, with 84 males (84%) and 16 females (16%). Age distribution showed 44% were over 60 years old, 23% aged 51-60 years, 15% aged 31-40 years, 14% aged 41-50 years, and 4% aged 21-30 years. Hypertension was the most prevalent risk factor, affecting 75% of patients, with a higher occurrence in males (62%), compared to females (13%). Smoking was observed in 51% of patients, and alcohol consumption was seen in 50%. Other significant risk factors included dyslipidemia (39%), diabetes mellitus (33%), chronic kidney disease (11%), ischemic heart disease (10%), atrial fibrillation (4%), valvular heart disease (4%), and pregnancy or postpartum conditions (2%). Ischemic stroke was predominant, occurring in 80% of patients, while hemorrhagic stroke occurred in 20%. High occurrences of ischemic strokes were noted in the frontal lobe (41%), parietal lobe (37%), occipital lobe (27%), and temporal lobe (26%), with the internal capsule region also showing significant numbers (27%). According to the TOAST classification, the most prevalent cause of stroke in this study was undetermined etiology with two or more causes, accounting for 32% of cases, followed by large artery atherosclerosis, which accounted for 30%. Cardioembolic stroke was identified in 11% of the patients, with 4% due to atrial fibrillation, 3% due to acute myocardial infarction, 3% due to rheumatic valvular heart disease, and 1% due to infective endocarditis. Conclusion This study highlights the significant prevalence of hypertension, smoking, alcohol consumption, and hyperhomocysteinemia as major risk factors for stroke. Ischemic strokes were predominant, with high occurrences in the cerebral lobes and gangliocapsular region. These findings emphasize the need for targeted prevention strategies, including managing hypertension and lifestyle modifications such as smoking cessation and reducing alcohol consumption, to mitigate the risk of stroke. Effective management of blood pressure, lipid levels, and blood glucose is crucial for stroke prevention. Recognizing gender-specific differences and addressing comorbidities through an integrated approach can enhance patient outcomes and reduce the burden of stroke.

South African Rheumatism and Arthritis Association 2024 guidelines for the use of biologic and targeted synthetic disease-modifying antirheumatic drugs.

Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) target a specific pathway of the immune system, and are usually prescribed after failure of conventional synthetic disease-modifying antirheumatic drug therapy. The choice of b/tsDMARD depends on the disease profile and comorbidities, patient preference, registered indications of the drugs, and risks associated with therapy. It is recommended that b/tsDMARDs for immune-mediated inflammatory rheumatic diseases are prescribed by a rheumatologist, and all patients must be included in the South African Rheumatism and Arthritis Association biologic registry. Knowledge of and vigilance for adverse events, particularly infections, associated with b/ts DMARD therapies are of paramount importance.

Pharmacotherapy of giant cell arteritis and polymyalgia rheumatica: Prospects for the use of monoclonal antibodies to interleukin 6

Giant cell arteritis (GCA) and polymyalgia rheumatica (RPM) are immune-mediated rheumatic disease (IMRDs), which typically develop in people over 50 years of age. Currently, GCA and PMR are considered within a single complex autoimmune-autoinflammatory pathology, defined as “GCA-PMR spectrum disease”. This was reflected in the development of general recommendations for pharmacotherapy within the framework of the “treat-to-tar get” strategy, although specific approaches to the treatment of patients with GCA and RPM differ depending on the clinical and pathogenetic characteristics of each nosological form. Glucocorticoids (GCs) are central to the treatment of GCA and RPM. Attention is drawn to the paradoxical discrepancy between the high effectiveness of GCs in the short term and the increasing severity of pathology associated with persistent inflammatory activity and the accumulation of organ damage induced by GCs in the long term, which indicates the need to improve therapy, primarily in the direction of optimizing the use of GCs. New opportunities for pharmacotherapy of GCA and RPM (as well as other IMRDs) are associated with the use of biologic agents that block the activity of cytokines involved in the immunopathogenesis of diseases, and in recent years, JAK (Janus kinase) inhibitors. Among pharmacological “targets,” special attention is drawn to interleukin (IL) 6, a pleiotropic cytokine involved in the development of inflammation, immune response, immunometabolism, cancerogenesis, vascular wall remodeling, etc. Currently, several biologic agents have been developed that are specific to both IL-6 receptor and IL-6: humanized monoclonal antibodies (mAbs) to the IL-6 receptor (tocilizumab), and human mAbs to IL-6 receptor (sarilumab and levilimab (BIOCAD)), humanized mAbs to IL-6 olokizumab (R-PHARM), etc. The article summarizes data regarding the effectiveness and safety of tocilizumab in GCA and RPM, recommendations for the use of IL-6 inhibitors in these diseases and discusses the prospects for further research.

Clustering Methods in Rheumatic and Musculoskeletal Disease Research: An Educational Guide to Best Research Practices.

Clinical manifestations and disease progression often exhibit significant variability among patients with rheumatic diseases, complicating diagnosis and treatment strategies. A better understanding of disease heterogeneity may allow for personalized treatment strategies. Cluster analysis is a class of statistical methods that aims to identify subgroups or patterns within a dataset. Cluster analysis is a type of unsupervised learning, meaning there are no outcomes or labels to guide the analysis (ie, there is no ground truth). This makes it difficult to assess the accuracy or validity of the identified clusters, and these methods therefore require thoughtful planning and careful interpretation. Here, we provide a high-level overview of clustering, including different types of clustering methods and important considerations when undertaking clustering, and review some examples from the rheumatology literature.

Emerging Role and Mechanism of Mesenchymal Stem Cells-Derived Extracellular Vesicles in Rheumatic Disease.

Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from mesoderm. Through cell-to-cell contact or paracrine effects, they carry out biological tasks like immunomodulatory, anti-inflammatory, regeneration, and repair. Extracellular vesicles (EVs) are the primary mechanism for the paracrine regulation of MSCs. They deliver proteins, nucleic acids, lipids, and other active compounds to various tissues and organs, thus facilitating intercellular communication. Rheumatic diseases may be treated using MSCs and MSC-derived EVs (MSC-EVs) due to their immunomodulatory capabilities, according to mounting data. Since MSC-EVs have low immunogenicity, high stability, and similar biological effects as to MSCs themselves, they are advantageous over cell therapy for potential therapeutic applications in rheumatoid arthritis, systemic erythematosus lupus, systemic sclerosis, Sjogren's syndrome, and other rheumatoid diseases. This review integrates recent advances in the characteristics, functions, and potential molecular mechanisms of MSC-EVs in rheumatic diseases and provides a new understanding of the pathogenesis of rheumatic diseases and MSC-EV-based treatment strategies.

Anxiety and Work Disability in Patients With Immune-Mediated Inflammatory Diseases: A Cross-Sectional Study From a Single Center.

Immune-mediated inflammatory diseases (IMIDs) are chronic diseases that are associated with an inflammatory process with unclear etiology and occur in genetically predisposed individuals. In this study, inflammatory bowel disease (IBD) and rheumatic disease (RD) were examined. The aim of the research is to evaluate the relationship between IMID and state anxiety and work impairment in patients. A cross-sectional study was conducted in an outpatient clinic for rheumatology and gastroenterology at an Italian university hospital. A total of 476 patients (261 IBD and 215 RD) were considered. Patients diagnosed with IBD demonstrated significantly higher levels of anxiety, encompassing both trait and state anxiety, compared to those with RD ( p <.001). While trait anxiety exhibited a modest positive correlation with work productivity loss ( r =.163; p =.046), activity impairment showed a positive correlation with both state anxiety ( r =.243; p <.001) and trait anxiety ( r =.206; p =.002). The impact of anxiety on job performance and daily activities should not be underestimated, as it may elevate the risk of unemployment and absenteeism and lead to increased societal costs.