Differential Treatments Based on Drug-induced Gene Expression Signatures and Longitudinal Systemic Lupus Erythematosus Stratification.

Systemic lupus erythematosus (SLE) is a heterogeneous disease with unpredictable patterns of activity. Patients with similar activity levels may have different prognosis and molecular abnormalities. In this study, we aimed to measure the main differences in drug-induced gene expression signatures across SLE patients and to evaluate the potential for clinical data to build a machine learning classifier able to predict the SLE subset for individual patients. SLE transcriptomic data from two cohorts were compared with drug-induced gene signatures from the CLUE database to compute a connectivity score that reflects the capability of a drug to revert the patient signatures. Patient stratification based on drug connectivity scores revealed robust clusters of SLE patients identical to the clusters previously obtained through longitudinal gene expression data, implying that differential treatment depends on the cluster to which patients belongs. The best drug candidates found, mTOR inhibitors or those reducing oxidative stress, showed stronger cluster specificity. We report that drug patterns for reverting disease gene expression follow the cell-specificity of the disease clusters. We used 2 cohorts to train and test a logistic regression model that we employed to classify patients from 3 independent cohorts into the SLE subsets and provide a clinically useful model to predict subset assignment and drug efficacy.

Relationship between Widening and Position of the Tunnels and Clinical Results of Anterior Cruciate Ligament Reconstruction to Knee Osteoarthritis: 30 Patients at a Minimum Follow-Up of 10 Years.

To evaluate the relationship between tunnel position and widening and long-term clinical results in anterior cruciate ligament (ACL) reconstruction, a retrospective cohort of 30 patients undergoing ACL reconstruction with double semitendinous plus double gracilis (SAC technique) with longer than 10-year follow-up was selected. CT scans in the first 3 months and at final follow-up was evaluated. Position, angle, and widening of tunnels including Nebelung criteria were recorded in all CT scans. Physical, KT-1000, and clinical evaluation were performed at final follow-up. Outcomes and knee arthritis severity were evaluated at final follow-up. Mean follow-up was 11.2 ± 1.2. At final follow-up, 85 and 57% of tibial and femoral tunnels, respectively, developed some degree of enlargement. Frontal tibial angle (mean) was 72°, sagittal tibial angle 63°, frontal femoral angle 47°, sagittal femoral angle 20°, and tunnels divergence angle 36°. Preoperatively, KT-1000 30L and Lachman test scores were 5.52 and 5.79 respectively. In the last follow-up, 30L and manual Lachman test scores were 0.97 and 1.13, respectively (p < 0.001). In IKDC scale, pivot shift and Jerk tests showed 83 and 84% grade A results, respectively (p < 0.0001). In Fairbank scale, 23% worsened one grade and 27% worsened more than one grade (p < 0.005). Tibial tunnels widened more than femoral tunnels and further dilatation was found between intermediate and final follow-up. Higher incidence of tibial tunnel widening was observed in patients with tunnel verticalization. Tibial tunnel dilation was associated with long-term degenerative changes but not with final knee instability.