Citations

The NCCN Guidelines for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer and other urinary tract cancers (upper tract tumors, urothelial carcinoma of the prostate, primary carcinoma of the urethra). These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines regarding the treatment of non–muscle-invasive bladder cancer, including how to treat in the event of a bacillus Calmette-Guérin (BCG) shortage; new roles for immune checkpoint inhibitors in non–muscle invasive, muscle-invasive, and metastatic bladder cancer; and the addition of antibody–drug conjugates for metastatic bladder cancer.

AbstractPurposeAccurate prediction of outcome following hip arthroscopy is challenging and machine learning has the potential to improve our predictive capability. The purpose of this study was to determine if machine learning analysis of the Danish Hip Arthroscopy Registry (DHAR) can develop a clinically meaningful calculator for predicting the probability of a patient undergoing subsequent revision surgery following primary hip arthroscopy.MethodsMachine learning analysis was performed on the DHAR. The primary outcome for the models was probability of revision hip arthroscopy within 1, 2, and/or 5 years after primary hip arthroscopy. Data were split randomly into training (75%) and test (25%) sets. Four models intended for these types of data were tested: Cox elastic net, random survival forest, gradient boosted regression (GBM), and super learner. These four models represent a range of approaches to statistical details like variable selection and model complexity. Model performance was assessed by calculating calibration and area under the curve (AUC). Analysis was performed using only variables available in the pre‐operative clinical setting and then repeated to compare model performance using all variables available in the registry.ResultsIn total, 5581 patients were included for analysis. Average follow‐up time or time‐to‐revision was 4.25 years (± 2.51) years and overall revision rate was 11%. All four models were generally well calibrated and demonstrated concordance in the moderate range when restricted to only pre‐operative variables (0.62–0.67), and when considering all variables available in the registry (0.63–0.66). The 95% confidence intervals for model concordance were wide for both analyses, ranging from a low of 0.53 to a high of 0.75, indicating uncertainty about the true accuracy of the models.ConclusionThe association between pre‐surgical factors and outcome following hip arthroscopy is complex. Machine learning analysis of the DHAR produced a model capable of predicting revision surgery risk following primary hip arthroscopy that demonstrated moderate accuracy but likely limited clinical usefulness. Prediction accuracy would benefit from enhanced data quality within the registry and this preliminary study holds promise for future model generation as the DHAR matures. Ongoing collection of high‐quality data by the DHAR should enable improved patient‐specific outcome prediction that is generalisable across the population.Level of evidenceLevel III.

➢ Pathologic meniscal extrusion can compromise meniscal function, leading to increased contact forces in the tibiofemoral compartment and the acceleration of osteoarthritic changes. ➢ Extrusion is typically defined as radial displacement of ≥3 mm outside the tibial border and is best diagnosed via magnetic resonance imaging, although ultrasonography has also demonstrated encouraging diagnostic utility. ➢ Surgical management of meniscal extrusion is based on the underlying etiology, the patient’s symptom profile, the preexisting health of the articular surface, and the risk of future chondral injury and osteoarthritis.

Understanding the mechanisms promoting chromosomal translocations of the rearranging receptor loci in leukemia and lymphoma remains incomplete. Here we show that leukemias induced by aberrant activation of β-catenin in thymocytes, which bear recurrent Tcra/Myc-Pvt1 translocations, depend on Tcf-1. The DNA double strand breaks (DSBs) in the Tcra site of the translocation are Rag-generated, whereas the Myc-Pvt1 DSBs are not. Aberrantly activated β-catenin redirects Tcf-1 binding to novel DNA sites to alter chromatin accessibility and down-regulate genome-stability pathways. Impaired homologous recombination (HR) DNA repair and replication checkpoints lead to retention of DSBs that promote translocations and transformation of double-positive (DP) thymocytes. The resulting lymphomas, which resemble human T cell acute lymphoblastic leukemia (T-ALL), are sensitive to PARP inhibitors (PARPis). Our findings indicate that aberrant β-catenin signaling contributes to translocations in thymocytes by guiding Tcf-1 to promote the generation and retention of replication-induced DSBs allowing their coexistence with Rag-generated DSBs. Thus, PARPis could offer therapeutic options in hematologic malignancies with active Wnt/β-catenin signaling.

Objectives: To evaluate mechanical treatment failure in a large patient cohort sustaining a distal femur fracture treated with a distal femoral locking plate (DFLP). Design: This retrospective case–control series evaluated mechanical treatment failures of DFLPs. Setting: The study was conducted at 8 Level I trauma centers from 2010 to 2017. Patients and Participants: One hundred one patients sustaining OTA/AO 33-A and C distal femur fractures were treated with DFLPs that experienced mechanical failure. Intervention: The intervention included the treatment of a distal femur fracture with a DFLP, affected by mechanical failure (implant failure by loosening or breakage). Main Outcome Measure: The main outcome measures included injury and DFLP details; modes and timing of failure were studied. Results: One hundred forty-six nonunions were found overall (13.4%) including 101 mechanical failures (9.3%). Failures occurred in different manners, locations, and times depending on the DFLPs. For example, 33 of 101 stainless steel (SS) plates (33%) failed by bending or breaking in the working length, whereas no Ti plates failed here ( P < 0.05). Eleven of 12 failures with titanium-Less Invasive Stabilization System (92%) occurred by lost shaft fixation, mostly by the loosening of unicortical screws (91%). Sixteen of 44 variable –angled–LCP failures (36%) occurred at the distal plate–screw junction, whereas only 5 of 61 other DFLPs (8%) failed this way ( P < 0.05). Distal failures occurred on average at 23.7 weeks compared with others that occurred at 38.4 weeks ( P < 0.05). Variable –angled–LCP distal screw–plate junction failures occurred earlier (mean 21.4 weeks). Conclusion: Nonunion and mechanical failure occurred in 14% and 9% of patients, respectively, in this large series of distal femur fracture treated with a DFLP. The mode, location, presence of a prosthesis, and timing of failure varied depending on the characteristics of DFLP. This information should be used to optimize implant usage and design to prolong the period of stable fixation before potential implant failures occur in patients with a prolonged time to union. Level of Evidence: Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.