International Journal of Rheumatic Diseases最新文献

Background: Urate transporter 1 (URAT1) is a well-known therapeutic target for reducing urate levels in the treatment of hyperuricemia and gout. However, current pharmacological studies have failed to evaluate the efficacy of URAT1 inhibitors in non-primate animal models. We established a human URAT1 (hURAT1) transgenic knock-in (KI) mouse model to assess uricosuric agents' effectiveness and characterize URAT1-caused pathogenesis.

Methods: We generated hURAT1 transgenic mice using CRISPR/Cas9 KI technique. mUrat1 knockout was achieved by replacing exon 1 coding sequence with a human SLC22A12 coding sequence (CDS)-pA cassette. Based on the above transgenic mice, a hyperuricemia model was further established by hypoxanthine administration.

Results: The hURAT1-KI mice successfully expressed hURAT1 protein to the apical side of the kidney proximal tubule epithelium, where native human URAT1 is localized in human kidney. Upon hypoxanthine challenge, the blood uric acid (UA) level was elevated in hURAT1-KI mice (251 μmol/L), showing an approximately 37% increase compared to wild-type (WT) mice (183.5 μmol/L). The elevated blood UA level could be alleviated by hURAT1 inhibitor benzbromarone treatment in the hURAT1-KI mice (164.2 μmol/L vs. 251 μmol/L, p < 0.05) whereas no response was observed in WT littermates (168.8 μmol/L vs. 183.5 μmol/L).

Conclusion: The hURAT1-KI hyperuricemia mouse model would be valuable for preclinical evaluation of gout treatment with urate-lowering drugs and for studying UA metabolic complexities in humans.

Objective: Various demographic factors, including sex, socioeconomic status, and immigration status, have been linked to disparities in healthcare outcomes. Despite efforts by healthcare providers to address these inequities, interventions are not always effective. The present investigation provides empirical insights from Germany focusing on patients with systemic connective tissue disorders, highlighting the need for evaluated strategies to mitigate healthcare disparities.

Methods: A 10% random sample of 2006-2016 routine data on patients with systemic connective tissue disorders (ICD-10 M30-M36) is used. The sample included information on 1819 patients. The primary outcome assessed was the persistence of impairment following rehabilitation treatment. Logistic regression models were employed to adjust for demographic confounders. Interaction analyses were conducted to explore variations in disparities across different time periods and diagnostic groups.

Results: Non-German nationals were at 87% higher odds of impairment after treatment compared to German nationals (adjusted odds ratio [aOR] = 1.87; 95% confidence interval [CI] = 1.22-2.86). Furthermore, patients employed in semi-skilled or unskilled positions demonstrated a 40% greater chance of poor outcomes compared to those in skilled occupations (aOR = 1.40; 95% CI = 1.03-1.90). Disparities in outcomes did not significantly vary across different years in which services were utilized.

Conclusion: The study demonstrates disparities in healthcare outcomes associated with various diversity characteristics. These disparities are likely due to the different obstacles that some disadvantaged population groups encounter in the healthcare system. To address this heterogeneity, diversity-sensitive healthcare provision strategies need to be implemented.

Aim: This study evaluates the prevalence, risk factors, and quality of life of patients with knee osteoarthritis (OA) in the Indonesian population.

Method: A cross-sectional study of 3597 adults (≥ 18 years old) was conducted in 2023 involving 15 different cities in Indonesia. Knee OA was classified according to the clinical ACR criteria. The COPCORD questionnaire was used for all subjects. The quality of life (QoL) was assessed using the WOMAC score.

Results: The prevalence of knee OA was 15.0%. Banda Aceh has the highest prevalence of knee OA at 70.79%, whereas Bandung has the lowest (4.18%)-the odds of having knee OA increased with age. The adjusted odds ratio (aOR) were 5.01 (95% CI 2.47-10.15, p < 0.001) for participants aged 40-49 years and 72.19 (95% CI 36.32-143.51, p < 0.001) for participants aged 70 years or over, compared to participants under 40 years. Knee OA was higher among female participants (aOR = 1.91; 95% CI 1.53-2.39, p < 0.001). Married and divorced participants had higher odds of having knee OA compared to those who never married (aORs 2.56 (95% CI 1.37-4.77, p = 0.003) and 2.40 (95% CI 1.23-4.68, p < 0.010), respectively). Knee OA is less likely found among participants with elementary school education background (aOR 0.37; 95% CI 0.22-0.64, p < 0.001) and those with senior high school (aOR 0.49; 95% CI 0.29-0.83, p = 0.007). The total WOMAC score was 25.9 ± 18.7 from all participants, indicating moderate impairment in QoL.

Conclusion: The prevalence of knee OA in several urban districts in Indonesia was 15.0%, with most patients having moderate impairment in QoL. Several sociodemographic factors were associated with the odds of having knee OA.

Objective: Osteoarthritis is a common joint disease caused by a variety of risk factors, and it has been found that many biochemical markers are abnormal in peripheral blood and urine of patients with OA. The aim of this study was to elucidate the causal relationship between biomarkers associated with these processes and OA using Mendelian randomization (MR) analysis.

Method: The inverse variance weighted (IVW) approach to MR was primarily used to explore causal associations between exposures and outcomes using publicly available genetic variants from large genome-wide association studies (GWAS). That is, single nucleotide polymorphisms (SNPs) associated with 35 human blood and urine markers (363 228 healthy participants) were used as exposure, and osteoarthritis, hip osteoarthritis, and knee osteoarthritis were used as outcome variables, with the aim of exploring the causal relationship between 35 human blood and urine markers and osteoarthritis. MR-Egger, weighted median (WM), and simple and weighted models were used as complementary methods to IVW to assess the reliability of causality. Steiger's test was used to confirm whether the causal relationship between exposure and outcome was biased by reverse causality. Sensitivity analyses used Cochran's Q statistic and funnel plots to detect heterogeneity, and the MR-Egger intercept test and leave-one-out to assess horizontal multidimensionality.

Results: Our MR analysis study identified the protective effects of CA, TP, ALB, SHBG, and VITD on OA and the pathogenic effects of TES, ALP, GGT, CRP, and CHOL on OA. It suggests that the above 10 hematological and urinary markers have the potential to be important indicators for the clinical diagnosis of OA as well as for the assessment of therapeutic efficacy and disease progression.

Conclusion: This MR analysis reinforces the importance of biomarkers in the diagnosis and prediction of OA. Future studies should further investigate the mechanisms of these biomarkers and their potential as therapeutic targets for OA.

Aim: Uncontrolled chronic inflammatory diseases (CIDs) before, during, and after pregnancy, as well as some CID medications, can increase the risk of impaired fertility in addition to adverse maternal/pregnancy outcomes in women of childbearing age. We report pregnancy outcomes from prospectively reported pregnancies in Japanese women treated with certolizumab pegol (CZP).

Methods: Data from July 2001 to November 2020 on CZP-exposed pregnancies from the CZP Pharmacovigilance safety database were reviewed. Pregnancy outcomes analyzed included live birth, ectopic pregnancy, abortion (miscarriage or medically indicated/elective), and stillbirth. Congenital anomalies (major and minor), preterm delivery, and low birth weight were also examined.

Results: Among 149 prospective pregnancies with maternal CZP exposure and known outcomes identified in Japanese women, 111/149 (74.5%) involved at least first-trimester exposure and 53/149 (35.6%) were exposed in all trimesters; 135/149 (90.6%) live births, 12/149 (8.1%) abortions (11 miscarriages, one elective termination), 2/149 (1.3%) stillbirths, no ectopic pregnancies reported. One (0.7%) infant, whose mother had first-trimester exposure, manifested a minor congenital anomaly (accessory auricle). There were no major congenital anomalies. Among live births, 3/135 (2.2%) were preterm and 10/135 (7.4%) had low birth weight.

Conclusion: The safety profile of CZP in pregnant Japanese women was consistent with published global data.