High-grade serous carcinoma (HGSC) is the most prevalent and aggressive subtype of ovarian cancer. The large degree of clinical heterogeneity within HGSC has justified deviations from the traditional one-size-fits-all clinical management approach. However, the majority of HGSC patients still relapse with chemo-resistant cancer and eventually succumb to their disease, evidence that further work is needed to improve patient outcomes. Advancements in high-throughput technologies have enabled novel insights into biological complexity, offering a large potential for informing precision medicine efforts. Here, we review the current landscape of clinical management for HGSC and highlight applications of high-throughput biological approaches for molecular subtyping and the discovery of putative blood-based biomarkers and novel therapeutic targets. Additionally, we present recent improvements in model systems and discuss how their intersection with high-throughput platforms and technological advancements is positioned to accelerate the realization of precision medicine in HGSC.

Urine is a complex biofluid that reflects both overall physiologic state and the state of the genitourinary tissues through which it passes. It contains both secreted proteins and proteins encapsulated in tissue-derived extracellular vesicles (EVs). To understand the population variability and clinical utility of urine, we quantified the secreted and EV proteomes from 190 men, including a subset with prostate cancer. We demonstrate that a simple protocol enriches prostatic proteins in urine. Secreted and EV proteins arise from different subcellular compartments. Urinary EVs are faithful surrogates of tissue proteomes, but secreted proteins in urine or cell line EVs are not. The urinary proteome is longitudinally stable over several years. It can accurately and non-invasively distinguish malignant from benign prostatic lesions, and can risk-stratify prostate tumors. This resource quantifies the complexity of the urinary proteome, and reveals the synergistic value of secreted and EV proteomes for translational and biomarker studies.

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Despite inaccuracies due to artifact and variations in patient positioning, anteroposterior (AP) radiographs remain the clinical standard for post-operative evaluation of component placement following total hip arthroplasty (THA). However, cup position, specifically anteversion, can be significantly affected by variations in patient positioning on an X-ray. A major cause of such artifact is unaccounted for pelvic tilt. Several methods for correcting the effects of pelvic tilt on radiographic anteversion have been proposed, with varying degrees of accuracy. The purpose of this study was to evaluate the accuracy and reliability of a commonly referenced method for correcting acetabular cup anteversion in a cohort undergoing total hip arthroplasty and determine its appropriateness for use in this population of patients. Radiographs from patients who underwent primary or revision hip arthroplasty between February 2016 and February 2017 were retrospectively reviewed. Corrected anteversion was calculated by measuring the vertical distance between the symphysis pubis and the sacrococcygeal joint, per the method outlined by Tannast et al. This symphococcygeal distance was then applied to Tannast’s nomograms to calculate the magnitude of pelvic tilt. Corrected and uncorrected anteversion values were compared to anteversion values collected intraoperatively using an imageless computer-assisted navigation device. A total of 71 cases were initially eligible for inclusion in the study. The correction method could not be applied in 44% (31/71) of the cases, chiefly due to difficulties in visualizing the required landmarks. In cases where it could be applied, corrected values correlated very poorly with navigation measurements (r = -0.07). Mean corrected anteversion (36.9°, SD: 7.4°) differed from uncorrected anteversion (25.2°, SD: 7.6°) by an average of 13.5° (p<0.001). Mean navigated anteversion (27.4°, SD: 5.7°) differed from corrected values by an average of 10.8° (p=0.16). The evaluated correction method could not be consistently applied to radiographs and did not reliably correct anteversion due to pelvic tilt in this population of patients undergoing hip arthroplasty. This correction method does not appear to be appropriate for use in this patient population.

Background: Changes in acetabular or hip center of rotation (HCOR) commonly occur during acetabular component preparation during total hip arthroplasty (THA). HCOR displacement in mediolateral or superoinferior directions is known to influence offset and leg length, but the incidence and range of HCOR change in the anteroposterior direction is less understood as the sagittal plane cannot be measured on standard anteroposterior radiographs. This study assessed the 3-dimensional displacement of HCOR after cup implantation and evaluated for potential factors associated with increased acetabular component translations. Methods: A total of 894 THAs were performed using a posterior, lateral, or direct anterior approach. Only intraoperative data from the navigation device were included in the analysis. All THAs performed between September 2015 and October 2017 were included. Paired t-tests were used to compare native HCOR and new HCOR values. Results: The mean HCOR displacement in 3 directions was 4.97mm medially (P < .001), 0.83mm superiorly (P < .001), and 0.64mm posteriorly (P < .001). Subgroup analysis revealed greater posterior HCOR displacement with the anterior approach than the lateral/posterior approach (2.32mm vs 0.44mm; P < .001). Increasing medial HCOR displacement also resulted in increased superior and posterior HCOR displacement across surgical cases (P < .001). Conclusions: HCOR displacement is commonly observed in medial, superior, and posterior directions. HCOR changes are influenced by surgical approach, potentially secondary to patient positioning, with greater posterior HCOR displacement observed in anterior cases. Surgeons should be aware of these factors, particularly in cases with deficient or reduced posterior column bone stock.