Search

Aim: To evaluate whether seasonal changes influence fluctuations in serum Krebs von den Lungen‐6 (KL‐6) levels in systemic sclerosis‐related interstitial lung disease (SSc‐ILD). Methods: Summer was defined as the period between July and September, and winter as between December and February. The study was conducted between 2015 and 2016, with a focus on these two seasons. A diagnosis of ILD and ILD progression overtime were evaluated using chest computed tomography. Among patients with SSc‐ILD, those with data on serum KL‐6 and lactate dehydrogenase (LDH) levels in the 2015 winter, 2015 summer, and 2016 winter seasons were included. Patients with comorbidities that could affect serum KL‐6 levels were excluded. Results: Of 60 patients with SSc‐ILD, 52 (86.7%) had stable ILD, 5 (8.3%) had worsened ILD, and 3 (5.0%) had improved ILD. Serum KL‐6 levels were significantly higher during the winter than those during the summer (2015 winter vs. 2015 summer: 649 U/mL vs. 585 U/mL, p <.0001; 2016 winter vs. 2015 summer: 690 U/mL vs. 585 U/mL, p <.0001). No significant differences were observed between the winters of 2015 and 2016 (649 U/mL vs. 690 U/mL, p =.78). However, serum LDH levels did not exhibit seasonal fluctuations (2015 winter vs. 2015 summer: 203 U/L vs. 199 U/L, p =.3; 2016 winter vs. 2015 summer: 201 U/L vs. 199 U/L, p =.6; 2015 winter vs. 2016 winter: 203 U/L vs. 201 U/L, p =.24). Conclusion: Seasonal fluctuations in serum KL‐6 levels were observed in patients with SSc‐ILD. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the Ministry of Health, Labour and Welfare (MHLW) diagnostic criteria for antineutrophil cytoplasmic antibody–associated vasculitis compared to the new American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria. Methods: Two nationwide cohort studies were used, and participants were categorised as having eosinophilic granulomatosis with polyangiitis, granulomatosis with polyangiitis (GPA), or microscopic polyangiitis (MPA) according to the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 and MHLW criteria. Results: Of the entire patient population, only 10 (2.1%) were unclassifiable according to the MHLW probable criteria, while a significant number of patients (71.3%) met at least two criteria. The MHLW probable criteria for MPA had some challenges in differentiating between MPA and eosinophilic granulomatosis with polyangiitis, and the same was true for MHLW probable criteria for GPA in differentiating MPA from GPA. Nevertheless, improved classification results were obtained when the MHLW probable criteria were applied in the order of eosinophilic granulomatosis with polyangiitis, MPA, and GPA. Conclusions: The application of MHLW criteria could categorise a substantial number of patients with antineutrophil cytoplasmic antibody–associated vasculitis into one of the three antineutrophil cytoplasmic antibody–associated vasculitis diseases. The classification was in accordance with the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria when considering the order of application. [ABSTRACT FROM AUTHOR]

Aim: To assess the usefulness of carbohydrate antigen 19‐9 (CA19‐9) as a biomarker for systemic sclerosis‐associated interstitial lung disease (SSc‐ILD), using serum samples and clinical parameters of patients with SSc. Methods: Patients with SSc admitted to Tokyo Women's Medical University Hospital between 2010 and 2021 and those who underwent chest computed tomography (CT) were included. Patients were diagnosed with ILD based on chest CT findings, and SSc‐ILD was categorized as either a limited or extensive disease based on chest CT and pulmonary function test findings. Serum CA19‐9 levels were measured in 56 patients with SSc and in 32 healthy individuals. Additionally, we evaluated the difference in serum CA19‐9 levels between the groups, the correlation with ILD area and pulmonary function, and discriminative performance to diagnose extensive ILD. Results: Of the 56 patients with SSc, 40 (71.4%) had ILD, and 17 (30.4%) were classified as having extensive disease. Serum CA19‐9 levels were significantly elevated in patients with extensive disease compared to those with limited disease (median [interquartile range]: 25.7 U/mL [10.1–50.8] vs. 8.8 U/mL [4.5–17.6], p =.02) and correlated with ILD area (r =.30, p =.02). There was no significant correlation between serum CA19‐9 level and pulmonary function. The cutoff of CA19‐9 for the diagnosis of the extensive disease was determined to be 19.8 U/mL, with a sensitivity of 64% and specificity of 82% and an area under the curve of 0.74 (95% confidence interval 0.58–0.90). Conclusion: The serum CA19‐9 level may be a useful marker for identifying patients with SSc‐ILD with extensive disease. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to compare the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria with the previous classification algorithm for anti-neutrophil cytoplasmic antibody–associated vasculitis. Methods: We used data from two nationwide, prospective, inception cohort studies. The enrolled patients were classified as having eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA), or microscopic polyangiitis (MPA) according to the new criteria; these criteria were compared with Watts' algorithm. Results: Among 477 patients, 10.7%, 9.9%, and 75.6% were classified as having EGPA, GPA, and MPA, respectively; 6.1% were unclassifiable. Three patients met both the EGPA and MPA criteria, and eight patients met both the GPA and MPA criteria. Of 78 patients with GPA classified using Watts' algorithm, 27 (34.6%) patients were reclassified as having MPA. Ear, nose, and throat involvement was significantly less frequent in patients reclassified as having MPA than in those reclassified as having GPA. Of 73 patients unclassifiable using Watts' algorithm, 62 were reclassified as having MPA. All patients reclassified as having MPA were myeloperoxidase-anti-neutrophil cytoplasmic antibody positive, and 46 had interstitial lung disease. Conclusion: Although the American College of Rheumatology/European Alliance of Associations for Rheumatology 2022 criteria cause overlapping multiple criteria fulfilments in some patients, those items contribute to classifying unclassifiable patients using Watts' algorithm into MPA. [ABSTRACT FROM AUTHOR]

The absorption, distribution, metabolism, and excretion of fasiglifam were investigated in rats, dogs, and humans. The absolute oral bioavailability of fasiglifam was high in all species (>76.0%). After oral administration of [14C]fasiglifam, the administered radioactivity was quantitatively recovered and the major route of excretion of radioactivity was via feces in all species. Fasiglifam was a major component in the plasma and feces in all species. Its oxidative metabolite (M-I) was observed as a minor metabolite in rat and human plasma (<10% of plasma radioactivity). In human plasma, hydroxylated fasiglifam (T-1676427), the glucuronide of fasiglifam (fasiglifam-G), and the glucuronide of M-I were detected as additional minor metabolites (<2% of plasma radioactivity). None of these metabolites were specific to humans. Fasiglifam-G was the major component in the rat and dog bile. In vitro cytochrome P450 (CYP) and uridine diphosphate glucuronosyltransferase (UGT) reaction phenotyping indicated that oxidation (to form M-I and T-1676427) and glucuronidation of fasiglifam are mainly mediated by CYP3A4/5 and UGT1A3, respectively. Fasiglifam and fasiglifam-G are substrates of BCRP and Mrp2/MRP2, respectively. Glucuronidation of fasiglifam-G was found to be the predominant elimination pathway of fasiglifam in all species tested, including humans. [ABSTRACT FROM AUTHOR]