Early proactive monitoring of DNA-thioguanine in patients with Crohn's disease predicts thiopurine-induced late leucopenia in NUDT15/TPMT normal metabolizers.

BACKGROUND: Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines. Dose optimization guided by nudix hydrolase 15 (NUDT15) has significantly reduced the early leucopenia rate, but there are no definitive biomarkers for late risk leucopenia prediction. AIM: To determine the predictive value of early monitoring of DNA-thioguanine (DNATG) or 6-thioguanine nucleotides (6TGN) for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn's disease (CD). METHODS: Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations. Late leucopenia was defined as a leukocyte count < 3.5 × 109/L over two months. RESULTS: Of 148 patients studied, late leucopenia was observed in 15.6% (17/109) of NUDT15/thiopurine methyltransferase (TPMT) normal and 64.1% (25/39) of intermediate metabolizers. In patients suffering late leucopenia, early DNATG levels were significantly higher than in those who did not develop late leucopenia (P = 4.9 × 10-13). The DNATG threshold of 319.43 fmol/µg DNA could predict late leucopenia in the entire sample with an area under the curve (AUC) of 0.855 (sensitivity 83%, specificity 81%), and in NUDT15/TPMT normal metabolizers, the predictive performance of a threshold of 315.72 fmol/µg DNA was much more remarkable with an AUC of 0.902 (sensitivity 88%, specificity 85%). 6TGN had a relatively poor correlation with late leucopenia whether in the entire sample (P = 0.021) or NUDT15/TPMT normal or intermediate metabolizers (P = 0.018, P = 0.55, respectively). CONCLUSION: Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD, especially the former.

Cross-Cultural Adaptation and Validation of the Hong Kong Version of the Knee Injury and Osteoarthritis Outcome Score (HK-KOOS) for Patients with Knee Osteoarthritis.

INTRODUCTION: This study aimed to validate the Hong Kong version of the Knee Injury and Osteoarthritis Outcome Score (HK-KOOS) for patients with knee osteoarthritis. METHODS: Content validity was assessed using the Item and Scale Content Validity Index (I-CVI and S-CVI). Test-retest reliability and internal consistency were assessed by the Intraclass Correlation Coefficient (ICC) and Cronbach's alpha. Dimensionality was assessed by performing exploratory factor analysis (EFA). Convergent and Divergent Validity was performed by examining the correlation between the HK-KOOS and the Chinese version of the Short Form 12 (SF-12) Health Survey, the Chinese Modified Barthel Index (C-MBI), and the Visual Analogue Scale for Pain (VAS-Pain). Ceiling and floor effects were also examined. RESULTS: A total of 125 participants were recruited in this study. In general, all instructions, items, and response options were considered as understandable, indicating a satisfactory cross-cultural adaptation. The I-CVI and S-CVI scores were 0.80-1 and 0.90-1, respectively, indicating excellent content validity in terms of relevance, representativeness, and understandability. The test-retest reliability of all HK-KOOS subscales was satisfactory with ICC exceeding 0.70 for all domains. Cronbach's alpha exceeded 0.80 for all subscales, indicating satisfactory internal consistency. Medium to strong correlations were found between the HK-KOOS and the VAS-Pain, SF-12, and C-MBI. However, factor analysis indicated a seven-factor structure, rather than the original five-factor structure. Items on pain and activities of daily living were loaded in the same factors. A floor effect was present in the sports and recreation subscale. DISCUSSION AND CONCLUSIONS: Future studies should further examine the dimensionality of the KOOS. The HK-KOOS is a culturally adapted, reliable, and valid outcome measure instrument to be used in Hong Kong patients with primary knee osteoarthritis.