Rheumatic Research Articles

Extracorporeal membrane oxygenation: unmet needs and perspectives.

Extracorporeal Membrane Oxygenation (ECMO) has become an essential lifesaving intervention for individuals with severe cardiovascular and respiratory failure. Its application is expanding across several therapeutic contexts, surpassing conventional indications. The COVID-19 pandemic has significantly stressed worldwide health systems to manage acute respiratory failure. ECMO has been employed as a vital intervention, particularly for patients with severe COVID-19-induced acute respiratory distress syndrome (ARDS). ECMO is applicable throughout pregnancy. The principal indications for ECMO in pregnant women align with those in the general population. However, pregnancy complicates issues, necessitating consideration of both mother's and infant's well-being. Patients with systemic rheumatic diseases are prone to experience life-threatening complications. While a majority of these patients respond to immunosuppressive drugs, a small percentage suffer organ failure and may benefit from ECMO as a bridge to recovery. The article addresses coagulation therapies, highlighting the necessity of precise anticoagulation to avert both bleeding and thrombosis, particularly in patients requiring extended ECMO support. Additionally, the pharmacokinetics of antibiotics in ECMO patients are summarized, including the influence of the ECMO circuit on drug metabolism. Survey-based research offers valuable insights into ECMO use, procedures, and challenges. The paper evaluates current survey-based research and ECMO guidelines, highlighting clinical practice, training, and resource availability discrepancies across ECMO centers globally. Particular focus is placed on the rehabilitation requirements of ECMO survivors, acknowledging the importance of early mobilization and post-discharge care in improving long-term outcomes and quality of life.

Elevated Trans-mitral Pressure Gradient Predicts Surgery in Young People with Moderate-Severe Rheumatic Mitral Regurgitation.

Mitral regurgitation (MR) is the most common lesion in children with rheumatic heart disease (RHD). Progression of RHD results in the need for surgical intervention, the timing of which is dictated by left ventricular dilatation and the onset of heart failure symptoms. We sought to determine whether elevation in trans-mitral pressure gradient (TMPG) in those with moderate or severe rheumatic MR without significant mitral stenosis (MS) could predict the need for future surgical intervention. Echocardiographic studies were reviewed for 116 children and young people with moderate or severe rheumatic MR. Those with significant mitral stenosis or concurrent aortic valve disease were excluded. Trans-mitral pressure gradient was measured at baseline and details of mitral valve surgical intervention were retrieved from a registry database. Time to future surgery (up to six years) was compared between those with TMPG < 5mmHg and TMPG ≥ 5mmHg. Survival curves demonstrated an increased risk of surgery for those with TMPG ≥ 5mmHg with Cox proportional regression analysis providing a hazard ratio of 5.8. The proportion free from mitral valve surgery at one year for the TMPG < 5mmHg group was 0.94 (95% CI 0.86-0.97), compared to 0.62 (95% CI 0.42-0.77) in the ≥ 5mmHg group. Trans-mitral pressure gradient is a strong predictor of future mitral valve surgery in children and young people with significant rheumatic MR without MS. This non-invasive measure could be used to signal the need for more aggressive monitoring in order to optimize the timing of intervention.

Mitral valve infective endocarditis as a manifestation of disseminatedCryptococcus neoformans infection: a case report

Infective endocarditis is a disease that affects mainly the endocardial surface of the heart and cardiac valves (native or prosthetic). The main risk factors for developing infective endocarditis are male sex, older age, intracardiac shunts, prosthetic valves, rheumatic, and congenital heart disease, intracardiac devices, intravenous drugs use, immunosuppression, and hemodialysis. Streptococci and Staphylococci spp. have been the most frequent isolated organisms. On the other hand, the most common fungal organism in infective endocarditis is Candida albicans (24-46%), followed by Aspergillus spp. (25%), and a few cases by Cryptococcus neoformans, which are associated with higher rate of mortality. This case provides an interesting case of Cryptococcus neoformans native valve infective endocarditis in a young woman with stage IV chronic kidney disease and severe malnutrition.

Rheum for Improvement? Delayed Diagnosis of Juvenile Idiopathic Arthritis: A Narrative Review.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood and a disease for which we have safe and effective therapies. Early diagnosis of JIA enables timely initiation of therapy and improves long-term disease outcomes. However, many patients with JIA experience prolonged diagnostic delays and have a turbulent course to diagnosis. In this narrative review, we explore the importance of early diagnosis in JIA, what is known about time to diagnosis and diagnostic trajectory, and factors that contribute to delayed diagnosis. We also discuss next steps to improve time to diagnosis for these vulnerable patients.

Evaluating anchor variables and variation in meaningful score differences for PROMIS® Pediatric measures in children and adolescents living with a rheumatic disease.

Meaningful score differences (MSDs), as defined by recent FDA guidance, can improve the interpretation of outcome measure scores and score changes. Well-accepted methods for estimating MSDs typically rely on external anchor variables, but the applications of these methods are limited in children and adolescents with rheumatic diseases. This project explored multiple candidate anchors for the PROMIS® Pediatric measures of Physical Activity, Fatigue, Pain Interference, and Mobility for children with juvenile idiopathic arthritis (JIA) or systemic lupus erythematosus (SLE). Longitudinal data were extracted from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Candidate anchors included patient-reported domain-specific global impressions of change (GIC) along with other parent- and clinician-reported variables. Prior to MSD estimation, the quality of the anchors was assessed using a priori criteria (correlation ≥0.30, n≥10, <10% missing). Anchors meeting criteria were used to calculate MSDs. Among 289 children with JIA and 47 with SLE, the GIC did not meet criteria inhalf of the scenarios. Other candidate anchors performed slightly better. The calculated MSDs varied by external anchor across measures, diagnoses, and direction of change (better vs worse). Many of the candidate external anchoring variables did not meet pre-specified criteria for calculating MSDs. Even for those that did, the choice of anchoring variable had a strong impact on the estimated MSD value and were different from other published values. As in adults, establishing pediatric MSDs requires selection of high-quality anchors, as changes in the variables used as anchors can impact MSD values and any subsequent score interpretations.

An integrated approach to the treatment of Rheumatic diseases: the role of psychological interventions.

Rheumatic diseases are chronic conditions that often result in significant physical and psychological challenges, reducing patients' quality of life and increasing the economic burden on healthcare systems. This study examines the vital role of psychological interventions in the comprehensive treatment of rheumatic diseases. The findings reveal a high prevalence of psycho-emotional disorders such as depression, anxiety, and stress among these patients, which can worsen disease progression and hinder treatment adherence. The review highlights the bidirectional relationship between the central nervous and immune systems, showing how psychological stress influences the pathophysiology of inflammatory diseases. Various psychological interventions are explored, including mind-body therapies, cognitive behavioral therapy, acceptance and commitment therapy, and mindfulness-based practices such as meditation, yoga, and tai chi. These approaches improve emotional well-being, help reduce pain, and enhance overall quality of life. The article emphasizes a holistic treatment model incorporating pharmacological care, physical rehabilitation, and psychological support. This integrated approach fosters more effective management of rheumatic diseases by addressing their complex nature and promoting better functional outcomes. The study advocates for the seamless incorporation of psychological support into routine clinical practice tailored to the biopsychosocial profile of each patient. Future research should focus on identifying the most effective psychological interventions for different patient groups to enhance the quality of life for individuals with rheumatic diseases.

Secondary Amyloidosis Treated with Tocilizumab as a Complication of Temporal Arteritis.

Temporal arteritis is a large-vessel vasculitis mostly seen in the elderly. Amyloidosis may be secondary to a chronic inflammation of body organs. Here, we present the second case report of temporal arteritis complicated by amyloidosis that was successfully treated by tocilizumab. A 64-year-old female presented complaining of fatigue, fever, and diarrhea accompanied by abdominal pain. One year before presentation, she was diagnosed with temporal arteritis. She was treated with 15 mg/day oral prednisone for the last 6 months, with partial remission, but persistence of the fatigue and an elevated erythrocyte sedimentation rate (ESR, 56 mm/h). Physical examination showed tenderness of both temporal arteries and a soft abdomen. Colon tissue biopsy showed amyloid depositions in the vessels and stroma that were positive for Congo red staining. Tocilizumab was started with 8 mg/kg intravenous, the diarrhea resolved, and the arthralgia improved within 1 month, with a decrease in the ESR to 8 mm/h, and a C-reactive protein (CRP) level of 0.98 mg/dl. Monthly tocilizumab therapy remains efficacious 12 months later and was stopped due to lack of tocilizumab from the hospital. No side effects of tocilizumab were registered. Chronic inflammation may be complicated by amyloidosis in patients with rheumatic diseases and genetic predisposition. Therefore, it is important to screen for intestinal Amyloid A (AA) amyloidosis in individuals with gastrointestinal disorders complicated by rheumatic disorders. AA amyloidosis may be complicated by temporal arteritis and presented with gastrointestinal symptoms such as diarrhea. Amyloidosis is manifested by the deposition of insoluble protein aggregates in organs.Amyloid A (AA) amyloidosis occurs as a complication of chronic inflammation in patients with a genetic predisposition to rheumatic diseases.Temporal arteritis complicated with AA amyloidosis is extremely rare.

THE ASSOCIATION BETWEEN FACET JOINT TROPISM AND LUMBAR DISC HERNIATION

ABSTRACT Background/Aims: Facet joint tropism is thought to be associated with lumbar disc herniation (LDH), but this relationship has not been fully established. The aim of this study was to investigate the relationship between facet joint tropism and LDH in patients (25-30 years old and body-mass index 28-30 kg/m²) using computed tomography (CT) and lumbar magnetic resonance imaging (MRI). Methods: Facet joint angles were measured on lumbar MRI and CT images of 24 male patients with left-sided LDH; 16 patients with right-sided LDH. Facet joint angle was measured by calculating the angle of the facet joints with the vertebral sagittal line in axial sections parallel to the end plate plane. Patients with trauma, rheumatic and oncologic diseases, additional lumbar or spinal and systemic diseases, patients with far lateral, foraminal and central lumbar disc herniations were excluded. Results: The mean left facet joint angle was 44,56º+/-11,29° and the mean right facet joint angle was 41,2º+/-11,27° in 24 patients with left-sided LDH. In 16 patients with right-sided LDH, the mean right facet joint angle was 45,87º +/-16,41°and the mean left facet joint angle was 42,74º+/-12,54°. Conclusions: In the statistical evaluation, no significant correlation was found between LDH and facet joint angle, but in the numerical analysis, it was observed that the left facet joint angle was larger in patients with left-sided LDH and the right facet joint angle was larger in patients with right-sided LDH.

Development and Validation of a Prediction Model for Dysphagia in Community-Dwelling Older Adults.

Objectives. Dysphagia is a geriatric syndrome, which may lead to complications such as dehydration, malnutrition, aspiration, pneumonia, and a significant reduction in quality of life. The purpose of this study was to construct and validate a prediction model for dysphagia in community-dwelling older adults and provide an assessment tool for the prevention and control of dysphagia. Design. Cross-sectional study. Setting. The community-dwelling Chinese older adults. Participants. 3655 participants aged 65 years and older were involved, who were randomly divided into the training set and the validation set. Methods. Data were collected and analyzed from June 2022 to September 2022. Univariate and multivariate logistic regression analysis were used to identify independent risk factors for dysphagia. We applied R software to develop a nomogram model to predict dysphagia in community-dwelling older adults. The predictive value of the model was assessed by the area under the ROC curve (AUC), the calibration curve was used to evaluate the reliability of the nomogram model for predicting dysphagia in community-dwelling older adults. The model's clinical utility was further evaluated using a Decision Curve Analysis (DCA). Results. The incidence of dysphagia was 11.8% (320/3655). Maximum tongue pressure, number of molars, pneumonia, ADL, sarcopenia, age, neurological diseases, and rheumatic immune diseases were selected as risk predictors for dysphagia. The prediction model demonstrated fair discriminative ability with the AUC was 0.709 (95%CI: 0.679-0.739) in the training set and 0.693 (95%Cl: 0.640-0.747) in the validation set, the calibration is adequate, and the Hosmer and Lemeshow test showed p values of 0.163 and 0.415, respectively. The DCA curve of our model shows a positive clinical net benefit. Conclusions. The prediction model established in this study was of a certain predictive value for the risk of dysphagia in community-dwelling older adults. By estimating the likelihood of future outcomes or the onset of certain diseases, it can assist medical personnel in formulating preventive strategies, lessening the workload of nurses, and also diminishing the financial burden on patients, thereby enhancing their overall quality of life.

Efficacy Evaluation of COVID-19 Vaccines in Patients with Autoimmune Rheumatic Diseases in Mashhad, Iran

vaccination. However, since the majority of studies in the related literature are focused on the efficacy of messenger RNA in rheumatic patients, the present study aimed to assess the efficiency of the inactivated whole virus vaccines and viral vector COVID-19 vaccines in rheumatic diseases in Mashhad, Iran. Methods: This prospective cross-sectional study was conducted on ARDs patients who were referred to private clinics and rheumatologic clinics of Ghaem and Imam Reza Hospitals, Mashhad, Iran, during 2021-22. Anti-neutralizing antibodies have been considered to check antibodies of Sinopharm and Barkat vaccines, and an anti-spike antibody was considered to check Sputnik V and AstraZeneca vaccine antibodies. Humoral immunity was investigated using the anti-spike Enzyme-linked immunosorbent assay and anti-neutralizing antibodies. Results: The obtained results showed that humoral immunity after COVID-19 vaccination was observed in 73.9% of the patients with ARDs. However, humoral immunity was lower in ARDs patients who took tacrolimus and higher in patients with a history of COVID-19 infection (χ2=5.84, p=0.01). The infection after the second COVID-19 vaccination was lower in patients with humoral immunity (χ2=5.69, p=0.01). Conclusion: This study demonstrated that a homologous second dose of an inactivated whole viral vector SARS-CoV-2 vaccine was safe and provided a remarkable antibody response in ARDs patients.

Early severe paravalvular leak following mitral valve replacement with a prosthetic mechanical bileaflet valve

Abstract: A middle-aged woman developed severe breathlessness soon after mitral valve replacement for rheumatic heart disease with severe mitral stenosis and moderate mitral regurgitation. Echocardiography (two-dimensional and transesophageal) revealed a severe paravalvular leak into the left atrium between the mechanical bileaflet mitral valve and the aortic annulus. The patient was stabilized with intravenous nitroglycerin and torsemide, and the heart rate was controlled with tablet metoprolol. The patient was successfully treated with a redo surgery using a larger mechanical mitral bileaflet valve (size 29 mm) and interrupted sutures. A 25-mm mechanical bileaflet valve was used during index surgery.

Comparison of mid-to-long term outcomes between mitral valve repair and biological valve replacement in patients over 60 with rheumatic mitral valve disease based on a propensity score matching study

Objective: To compare and discuss the mid-to-long-term outcomes of mitral valve repair (MVP) versus biological mitral valve replacement (bMVR) in patients over 60 years old with rheumatic mitral valve disease. Methods: This is a retrospective cohort study. A total of 765 patients aged 60 years and older, diagnosed with rheumatic mitral valve disease and who underwent MVP or bMVR at Beijing Anzhen Hospital from January 2010 to January 2023, were retrospectively included. Among them, 186 were male and 579 were female, with an age of (66.1±4.5) years (range: 60 to 82 years). Patients were divided into two groups based on the surgical method: the mitral valve repair group (MVP group, n=256) and the bioprosthetic mitral valve replacement group (bMVR group, n=509). A 1∶1 propensity score matching was performed using a caliper value of 0.2 based on preoperative data. Paired sample t-tests, χ² tests, or Fisher's exact tests were used for intergroup comparisons. Kaplan-Meier method was employed to plot survival curves and valve-related reoperation rate curves for both groups before and after matching, and Log-rank tests were used to compare the mid-to long-term survival rates and valve-related reoperation rates between the two groups. Results: A total of 765 patients who completed follow-up were ultimately included, with a follow-up period (M(IQR)) of 5.1(5.0) years (range: 1.0 to 12.9 years). After matching, each group consisted of 256 patients. The incidence of early postoperative atrial fibrillation (39.1% vs. 49.2%, χ2=4.95, P=0.026) and early mortality rates (2.0% vs. 6.2%, χ2=4.97, P=0.026) were lower in the MVP group. Unadjusted Kaplan-Meier analysis showed significantly higher 5-year and 10-year survival rates for the MVP group (92.54% vs. 83.02%, 86.22% vs. 70.19%, Log-rank P=0.001). After adjustment with propensity scores, the Kaplan-Meier analysis still indicated higher 5-year and 10-year survival rates in the MVP group compared to the bMVR group (92.54% vs. 85.89%, 86.22% vs. 74.83%, Log-rank P=0.024). There were no significant differences in the rates of valve-related reoperation between the two groups before and after matching (5-year and 10-year reoperation rates pre-matching: 1.75% vs. 0.57%, 5.39% vs. 7.54%, Log-rank P=0.207; post-matching: 1.75% vs. 0%, 5.39% vs. 9.27%, Log-rank P=0.157). Conclusion: For patients over 60 with rheumatic mitral valve disease, mitral valve repair offers better mid-to-long-term survival compared to biological valve replacement.

Clinical and Serological Profiles in Cryoglobulinemia: Analysis of Isotypes and Etiologies

Objectives: Cryoglobulinemia (CG) is marked by abnormal immunoglobulins (Ig) in serum, precipitating at temperatures below 37 °C. Current classification categorizes CG into three subtypes (types I, II, and III) based on Ig clonality. The features distinguishing patients with CG based on their etiology remain unidentified. Aiming to characterize clinical and serological profiles of CG individuals, we conducted an observational analysis of a large cohort of patients and compared their characteristics based on underlying causes: hepatovirus (HV) infections, rheumatic diseases (RD), hematological disorders, and unidentified etiology (essential CG). Methods: We analyzed 252 cryoglobulin-positive serum samples from 182 patients and classified these into the four etiological groups. A separate sub-analysis was carried out for 10 patients meeting criteria for multiple diseases. We collected demographic, clinical, and laboratory data: CG characterization, complement (C3 and C4) levels, antinuclear antibodies (ANA), and rheumatoid factor (RF). Kruskal–Wallis and Wilcoxon–Mann–Whitney U-tests were used for comparisons. Results: Most patients (93.3%) had mixed cryoglobulinemia (types II + III), with 6.7% having type I. HV infection, predominantly hepatitis C, was the main (52.9%) associated condition within the cohort, followed by rheumatic (27.3%) and hematological (9.8%) disorders. In our cohort, ANA were frequent (45.3%) and often associated with RF positivity (43.6%) and decreased complement levels (C3: 42.4%, C4: 32.5%). Essential CG and CG associated with RD had a higher prevalence of cutaneous manifestations (p &lt; 0.01) and renal involvement (p = 0.017). Hematological disorder-related CG showed higher cryoglobulin and RF concentrations (p &lt; 0.01), despite milder symptoms. Conclusions: Our study underscores a mixed prevalence of CG across disease subgroups, with hepatitis-C virus as the primary factor, followed by rheumatic and hematological disorders. Four clinical and serological profiles of CG were identified based on their etiologies.

Somatic mutations in autoinflammatory and autoimmune disease.

Somatic mutations (also known as acquired mutations) are emerging as common, age-related processes that occur in all cells throughout the body. Somatic mutations are canonically linked to malignant processes but over the past decade have been increasingly causally connected to benign diseases including rheumatic conditions. Here we outline the contribution of somatic mutations to complex and monogenic immunological diseases with a detailed review of unique aspects associated with such causes. Somatic mutations can cause early- or late-onset rheumatic monogenic diseases but also contribute to the pathogenesis of complex inflammatory and immune-mediated diseases, affect disease progression and define new clinical subtypes. Although even variants with a low variant allele fraction can be pathogenic, clonal dynamics could lead to changes over time in the proportion of mutant cells, with possible phenotypic consequences for the individual. Thus, somatic mutagenesis and clonal expansion have relevant implications in genetic testing and counselling. On the basis of both increased recognition of somatic diseases in clinical practice and improved technical and bioinformatic processes, we hypothesize that there will be an ever-expanding list of somatic mutations in various genes leading to inflammatory conditions, particularly in late-onset disease.

Burden of rheumatic diseases among people with diabetes: A systematic review and meta-analysis

Diabetes mellitus type 2 (DM2) is a prevalent metabolic condition affecting over 500 million people globally and associated with serious comorbidities, including various rheumatologic conditions. Some studies have reported a significant association between rheumatological conditions and DM2. However, the global burden of rheumatological conditions among people with DM2 remains unknown. The aim of this study was to assess the cumulative prevalence of rheumatological conditions in DM2 patients. An extensive electronic search was conducted utilizing multiple databases of studies published until January 2024. The quality of the studies included in the review was evaluated using a modified version of the Newcastle-Ottawa Scale (NOS). The overall quality of the studies included was rated as moderate. The review included a total of 13 studies, with 830,649 DM2 patients reported to have rheumatological conditions. Eleven studies were used to determine the individual results of rheumatoid arthritis (RA), gout, and osteoarthritis (OA). The pooled prevalence of OA was 26% (95%CI: 19–32%) and the prediction interval ranged from 6% to 51%. The pooled prevalence of gout disease was 1% (95%CI: 0.0–5.0%), and the prediction interval ranged from 0% to 99%. For RA, the combined prevalence was 0.3% (95%CI: 0.2–0.5%) and the prediction interval ranged from 0% to 5%. In conclusion, this review suggests a considerable prevalence of OA among DM2 patients, while the prevalence of RA and gout was minimal. Early diagnosis and management of certain rheumatologic conditions in individuals with DM2 may help improve health outcomes and prevent premature mortality. Further research is warranted to explore and understand the mechanisms underlying the association between DM2 and rheumatological conditions.

Development and validation of an image-based questionnaire ARTROVIS to identify risk factors for the articular syndrome and related conditions

Background: The importance of timely diagnosis of rheumatic diseases is beyond any doubt. However, in the real practice the time from manifestation of the first symptoms to the assessment by a rheumatologist and treatment administration often exceeds the window of opportunity for disease control. At the moment, there has been no Russian-language questionnaire that would allow a primary care physician to suspect a rheumatic disease manifesting with an articular syndrome. Aim: To develop, validate and test a questionnaire to identify risk factors for joint disorders and related conditions. Methods: From November 2022 to April 2024, we performed the study on the image-based questionnaire on identification of the risk factors for joint syndromes and associated conditions (ARTROVIS), which we have developed for early detection of both joint syndromes, as well as comorbid conditions associated with elevated serum uric acid levels (hyperuricemia). The initial test version of the questionnaire was tested in a focus group of respondents (n = 20) who came for regular medical examination. Based on the results of this face validity assessment, we corrected the wording of 10 questionnaire items. At the second study step, we assessed the primary validity and reliability of the questionnaire in a group of 41 rheumatology patients. The third study step involved 828 respondents (408 men and 420 women, median age 19 [18,0; 20,0] years; 21% with joint syndromes), who came for routine medical examination. The reliability of the questionnaire, its face and discriminant validity, as well as sensitivity and specificity (the ROC analysis) were assessed from 827 questionnaires included in the final processing (one was excluded due to questionnaire completion defects). Results: The self-report questionnaire for patients (ARTROVIS) has 24 items aimed at collecting social and demographic data, identifying risk factors for non-communicable diseases, assessing genetic aspects, identifying complaints from various organ systems, providing information on medical treatments taken by the patient (non-steroid anti-inflammatory agents, diuretics, antihypertensives, glucocorticosteroids, chemotherapy and radiation therapy), as well as an additional question for women on current pregnancy pathology. The questionnaire contains visual aids (colored photos) that facilitate the detection of clinical signs of autoimmune (psoriatic arthritis, Reynolds’s syndrome) and inflammatory rheumatic disease (gout), as well as the differential diagnosis of the joint syndrome. The assessment of face validity of the questionnaire showed the total number of missed answers of 3.42%; 62.85% of the respondents gave their full answers to all items. Good discriminant validity was demonstrated. The ROC analysis showed high correlation between the questionnaire score and the presence of a joint syndrome: the area under the curve was 0.884. The Cronbach’s alfa was 0.798, which is sufficient for a medical questionnaire. Conclusion: We have performed the approbation and standardization of the questionnaire to identify risk factors for the joint syndrome and related comorbidities by assessing its validity and reliability. The ARTROVIS as a self-report questionnaire can be used in primary care as a tool enabling general practitioners and internists to decide on further patient routing to corresponding specialists.

Real-World Evidence of Clinical Outcomes of the Use of the Adalimumab Biosimilar SB5 in Rheumatic and Gastrointestinal Immune-Mediated Inflammatory Diseases: 12-Month Data from the PERFUSE Study.

There is a need for published data on real-world use of SB5, an adalimumab (ADL) biosimilar approved in Europe in 2017, on the basis of evidence from pre-clinical and analytic data as well as phase I and III clinical studies demonstrating equivalent efficacy and comparable pharmacokinetics, safety and immunogenicity profiles as the reference ADL. The purpose of this study was to estimate patient persistence on SB5 at 12 months post-initiation using clinical and healthcare claims data from the French Système National des Données de Santé (national healthcare claims database, SNDS) in addressing data gaps. PERFUSE is a 12-month, observational, multi-centre cohort study of patients with rheumatic or gastrointestinal immune-mediated inflammatory diseases (IMIDs) who initiated routine SB5 treatment between October 2018 and October 2020, either as their first ADL (naïve) or transitioning from another ADL (switched). Clinical data, including disease activity scores, C-reactive protein levels, and dosing information, were collected as available from patient records captured during routine visits to specialist physicians. Persistence data were supplemented with data from the French national healthcare claims database (SNDS). Analyses of clinical data were descriptive, while persistence was assessed using a Kaplan-Meier survival analysis. Overall, 911 patients were included: 507 from rheumatology centres [116 with rheumatoid arthritis (RA), 78 psoriatic arthritis (PsA), and 313 ankylosing spondylitis (AS)] and 404 from gastroenterology centres [316 with Crohn's disease (CD) and 88 ulcerative colitis (UC)]. Among naïve patients, 12-month remission/low activity rates were 58% for RA, 66% for PsA, 59% for AS, 94% for CD, and 85% for UC, increasing significantly from baseline for all indications (p < 0.05). Switched patients' remission rates remained stable between baseline and month 12 (M12) for all indications (p > 0.05). Persistence (95% CI) at M12 among naïve patients was 59% (46.5, 68.8) for RA, 65% (49.7, 77.1) for PsA, 56% (48.3, 62.6) for AS, 70% (63.0, 75.7) for CD, and 42% (30.7, 53.1) for UC, compared to 60% (42.7, 73.7) for RA, 57% (37.3, 72.1) for PsA, 55% (45.8, 64.0) for AS, 63% (53.4, 71.7) for CD, and 56% (27.2, 77.6) for UC among switched patients. No significant differences were observed between naïve and switched patients (p > 0.05). SNDS pairing provided information on 68 of the 132 patients (52%) who were lost to follow-up in the clinical database, of whom 57 (84%) were confirmed persistent at M12 and 11 (16%) non-persistent. Primary treatment failure (naïve patients) and patient decision (switched patients) were the most common reasons stated for treatment discontinuation. SB5 provides clinically effective treatment of both gastrointestinal and rheumatic IMIDs for naïve and switched patients, with no loss of control observed when switching. Persistence was comparable between naïve and switched populations, though the reasons for non-persistence differed. Trial registration number: Clinical Trials identifier NCT03662919. Trial registration date: 10 September 2018.

Development of a prediction model for the incidence of type 2 diabetic kidney disease and its application based on a regional health data platform

Objective: To construct a risk prediction model for diabetes kidney disease (DKD). Methods: Patients newly diagnosed with type 2 diabetes mellitus (T2DM) between January 1, 2015, and December 31, 2022, were selected as study subjects from the Yinzhou Regional Health Information Platform in Ningbo City. The Lasso method was used to screen the risk factors, and the DKD risk prediction model was established using Cox proportional hazard regression models. Bootstrap 500 resampling was applied for internal validation. Results: The study included 49 706 subjects, with an median (Q1, Q3) age of 60.00 (50.00, 68.00) years old, and 55% were male. A total of 4 405 subjects eventually developed DKD. Age at first diagnosis of T2DM, BMI, education level, fasting plasma glucose, glycated hemoglobin A1c, urinary albumin, past medical history (hyperuricemia, rheumatic diseases), triglycerides, and estimated glomerular filtration rate were included in the final model. The final model's C-index was 0.653, with an average of 0.654 after Bootstrap correction. The final model's area under the receiver operating characteristic curve for predicting 4-year, 5-year, and 6-year was 0.657, 0.659, and 0.664, respectively. The calibration curve was closely aligned with the ideal curve. Conclusions: This study constructed a DKD risk prediction model for newly diagnosed T2DM patients based on real-world data that is simple, easy to use, and highly practical. It provides a reliable basis for screening high-risk groups for DKD.

Aqueous Extracts of Rhus trilobata Inhibit the Lipopolysaccharide-Induced Inflammatory Response In Vitro and In Vivo.

Chronic noncommunicable diseases (NCDs) are responsible for approximately 74% of deaths globally. Medicinal plants have traditionally been used to treat NCDs, including diabetes, cancer, and rheumatic diseases, and are a source of anti-inflammatory compounds. This study aimed to evaluate the anti-inflammatory effects of Rhus trilobata (Rt) extracts and fractions in lipopolysaccharide (LPS)-induced inflammation models in vitro and in vivo. The aqueous extract (RtAE) and five fractions (F2 to F6) were obtained via C18 solid-phase separation and tested in murine LPS-induced J774.1 macrophages. Key inflammatory markers, such as IL-1β, IL-6, TNF-α, and COX-2 gene expression were measured using RT-qPCR, and PGE2 production was assessed via HPLC-DAD. The in vivo effects were tested in an LPS-induced paw edema model in Wistar rats. Results showed that RtAE at 15 μg/mL significantly decreased IL-1β and IL-6 gene expression in vitro. Fraction F6 further reduced IL-1β, TNF-α, and IL-6 gene expression, COX-2 expression, and PGE2 production. In vivo, F6 significantly reduced LPS-induced paw edema, inflammatory infiltration, and IL-1β and COX-2 protein expression. Chemical characterization of F6 by UPLC/MS-QTOF revealed at least eight compounds with anti-inflammatory activity. These findings support the anti-inflammatory potential of RtAE and F6, reinforcing the medicinal use of Rt.

Bioactivity of Talisia esculenta extracts: Antioxidant and anti-inflammatory action on RAW 264.7 macrophages and protective potential on the Zebrafish exposed to oxidative stress inducers

Ethnopharmacological relevanceTalisia esculenta is a fruit tree commonly found in various regions of Brazil. Its fruit is consumed by the local population, and the leaves are used in infusions within traditional Brazilian medicine. These infusions are employed to alleviate pathological conditions such as rheumatic diseases and hypertension, both of which are strongly linked to oxidative stress and chronic inflammation. The investigation of plant extracts represents a promising field of research, as bioactive compounds abundant in plants exhibit pharmacological effects against a variety of pathological conditions. Aim of the studyTo investigate the antioxidant, anti-inflammatory activities, and toxicity of the infusion and hydroethanolic extracts of T. esculenta leaves (IF and HF) and fruit peels (IC and HC). Materials and methodsInitially, the cytotoxicity and the effects of the extracts on oxidative stress in RAW264.7 macrophages were assessed through exposure to H₂O₂, as well as their impact on NO production in RAW264.7 macrophages exposed to LPS. Additionally, the toxicity and ROS production in zebrafish larvae were evaluated using two oxidative stress inducers: H₂O₂ and CuSO₄ combined with ascorbate. ResultsThe MTT assay indicated that the extracts exhibited low cytotoxicity, with HF and IF demonstrating protective effects against H₂O₂ exposure. HC reduced NO production in macrophages by 30%. The zebrafish analysis showed that all four T. esculenta extracts (100 μg/mL) were non-toxic, as they did not affect the survival, heart rate, or body size of the animals. Furthermore, all extracts were capable of reducing ROS levels in zebrafish larvae exposed to the H₂O₂ stressor. Notably, ROS reduction by HF, IF, and HC extracts exceeded 50% compared to the positive control (H₂O₂ alone). T. esculenta extracts also demonstrated a significant ability to reduce ROS levels in zebrafish larvae exposed to CuSO₄, with a 70% reduction observed for leaf extracts and over 30% for fruit peel extracts. ConclusionThis study demonstrated that T. esculenta extracts exhibit significant activity against oxidative damage and contain components with anti-inflammatory properties. Among the extracts, those obtained from leaves were the most effective in providing oxidative protection, supporting the traditional use of leaf infusions.