Development of a metabolomics-based data analysis approach for identifying drug metabolites based on high-resolution mass spectrometry.

A metabolomics-based approach to data analysis is required for drug metabolites to be identified quickly. This study developed such an approach based on high-resolution mass spectrometry. Our approach is a two-stage one that combines a time-course experiment with stable isotope tracing. Pioglitazone (PIO) was used to improve glycemic management for type 2 diabetes mellitus. Consequently, PIO was taken as a model drug for identifying metabolites. During Stage I of data analysis, 704 out of 26626 ions exhibited a positive relationship between ion abundance ratio and incubation time in a time-course experiment. During Stage II, 25 isotope pairs were identified among the 704 ions. Among these 25 ions, 18 exhibited a dose-response relationship. Finally, 14 of the 18 ions were verified to be PIO structure-related metabolite ions. Otherwise, orthogonal partial least squares-discriminant analysis (OPLS-DA) was adopted to mine PIO metabolite ions, and 10 PIO structure-related metabolite ions were identified. However, only four ions were identified by both our developed approach and OPLS-DA, indicating that differences in the designs of metabolomics-based approaches to data analysis can result in differences in which metabolites are identified. A total of 20 PIO structure-related metabolites were identified by our developed approach and OPLS-DA, and six metabolites were novel. The results demonstrated that our developed two-stage data analysis approach can be used to effectively mine data on PIO metabolite ions from a relatively complex matrix.

Modified Superior Capsule Reconstruction Using the Long Head of the Biceps Tendon as Reinforcement to Rotator Cuff Repair Lowers Retear Rate in Large to Massive Reparable Rotator Cuff Tears.

PURPOSE: To retrospectively assess the clinical outcomes of the patients with large to massive reparable RCTs treated by arthroscopic rotator cuff repair (ARCR) combined with modified superior capsule reconstruction (mSCR) using the long head of biceps tendon (LHBT) as reinforcement with a minimum of 2 years of follow-up. METHODS: We retrospectively evaluated 40 patients with large to massive reparable RCTs who underwent ARCR and mSCR (group I) between February 2017 and June 2018 (18 patients) or underwent ARCR and tenotomy of LHBT performed at the insertion site (group II) between January 2015 and January 2017 (22 patients). The pain visual analog score (VAS) was assessed preoperatively and 1, 3, 6, 12, 24 months postoperatively. American Shoulder and Elbow Surgeons (ASES) scores, the University of California, Los Angeles (UCLA) shoulder rating scale, and active range of motion (AROM) were assessed before surgery and 6, 12, and 24 months after surgery. The integrity of the rotator cuff and mSCR was evaluated using magnetic resonance images at 12 months postoperatively. RESULTS: After surgery, both groups had significantly improved in VAS, ASES, UCLA and AROM scores in the final follow-up. There were no significant between-group differences in the characteristics of the patients before surgery. Group I had improved pain relief at 1 month (P < .001) and at 3 months (P < .01) after surgery. For the AROM, group I (flexion, external rotation, internal rotation) demonstrated better improvement than group II 6 months after surgery (all P < .05) and better internal rotation 12 and 24 months after surgery (all P < .05). The mSCR survival rate was 94.4% (17/18). The retear rate of repaired rotator cuffs for groups I and II was 16.7% (3/18) and 40.9% (9/22), respectively, and the differences were significant (P < .046). CONCLUSIONS: ARCR combined with mSCR using LHBT as reinforcement may lead to a lower retear rate and earlier functional recovery than conventional ARCR with tenotomy of LHBT for large to massive reparable RCTs. LEVEL OF EVIDENCE: Level III, retrospective therapeutic comparative trial.