Purpose We determined whether a novel combination of field defect DNA methylation markers could predict the presence of prostate cancer using histologically normal transrectal ultrasound guided biopsy cores. Materials and Methods Methylation was assessed using quantitative Pyrosequencing® in a training set consisting of 65 nontumor and tumor associated prostate tissues from University of Wisconsin. A multiplex model was generated using multivariate logistic regression and externally validated in blinded fashion in a set of 47 nontumor and tumor associated biopsy specimens from University of Washington. Results We observed robust methylation differences in all genes at all CpGs assayed (p <0.0001). Regression models incorporating individual genes (EVX1, CAV1 and FGF1) and a gene combination (EVX1 and FGF1) discriminated nontumor from tumor associated tissues in the original training set (AUC 0.796-0.898, p <0.001). On external validation uniplex models incorporating EVX1, CAV1 or FGF1 discriminated tumor from nontumor associated biopsy negative specimens (AUC 0.702, 0.696 and 0.658, respectively, p <0.05). A multiplex model (EVX1 and FGF1) identified patients with prostate cancer (AUC 0.774, p = 0.001) and had a negative predictive value of 0.909. Comparison between 2 separate cores in patients in this validation set revealed similar methylation defects, indicating detection of a widespread field defect. Conclusions A widespread epigenetic field defect can be used to detect prostate cancer in patients with histologically negative biopsies. To our knowledge this assay is unique, in that it detects alterations in nontumor cells. With further validation this marker combination (EVX1 and FGF1) has the potential to decrease the need for repeat prostate biopsies, a procedure associated with cost and complications.

Introduction and Objective Active surveillance (AS) is an option for the management of favorable risk prostate cancer (CaP) in the PSA era. Published studies have reported variable inclusion criteria for cohort selection. Accurate assessment of individual patient risk in AS is dependent not only upon rigorous selection criteria, but also reliability of diagnosis at tissue biopsy. To date, the impact of immediate transrectal ultrasound (TRUS) rebiopsy in confirming candidates for AS has been incompletely defined. Methods From a total of over 567 men, 67 met criteria for AS (Gleason <7, PSA <10, PSAD <0.15, <3 cores with <50% involvement of any 1 core). Fifty-two men agreed to a 12-core TRUS rebiopsy within 6 months of first diagnosis performed in clinic. Statistical analysis was performed using Wilcoxon signed rank test and logistic regression to determine predictors of rebiopsy characteristics, histopathologic outcomes, and impact on treatment choice. Results Mean cohort age was 63.9 years (range 56–72 years), PSA 5.9 ng/ml (4.1–10), and PSA density 0.12 ng/ml/cc at initial biopsy. Tumor involved 1.1 cores and 3.2% (range 1%–5%) of the total tissue. Average time to rebiopsy was 2.7 months. Notably, 29 of 52 men (56%) demonstrated no evidence of CaP on repeat biopsy; 14 of 23 men with a positive repeat biopsy showed either an increase in cancer volume (2.8% mean increase) and 9 (18%) were upgraded to Gleason pattern 3+4 = 7. Rebiopsy demonstrated 9 (17%) patients exceeded AS criteria. Nine patients chose curative surgical intervention (radical prostatectomy) based on increased cancer volume or grade (4) or an elective desire for treatment (5). All had organ confined disease with negative margins on final pathologic analysis. Statistical review revealed that initial Gleason score, PSA density, and number of positive cores at first biopsy were not predictive of men with higher volume/grade on re-biopsy. Conclusions Immediate TRUS repeat biopsy after diagnosis frequently fails to redemonstrate prostate cancer confirming the favorable-risk nature of disease burden in this group being considered for AS. A subset of patients are upgraded (17%) leading to reconsideration of AS. We conclude this clinic-based approach provides valuable additional information to discriminate appropriate AS candidates.

Aims A significant percentage of patients remain dissatisfied after total knee arthroplasty (TKA). The aim of this study was to determine whether the sequential addition of accelerometer-based navigation for femoral component preparation and sensor-guided ligament balancing improved complication rates, radiological alignment, or patient-reported outcomes (PROMs) compared with a historical control group using conventional instrumentation. Methods This retrospective cohort study included 371 TKAs performed by a single surgeon sequentially. A historical control group, with the use of intramedullary guides for distal femoral resection and surgeon-guided ligament balancing, was compared with a group using accelerometer-based navigation for distal femoral resection and surgeon-guided balancing (group 1), and one using navigated femoral resection and sensor-guided balancing (group 2). Primary outcome measures were Patient-Reported Outcomes Measurement Information System (PROMIS) and Knee injury and Osteoarthritis Outcome (KOOS) scores measured preoperatively and at six weeks and 12 months postoperatively. The position of the components and the mechanical axis of the limb were measured postoperatively. The postoperative range of motion (ROM), haematocrit change, and complications were also recorded. Results There were 194 patients in the control group, 103 in group 1, and 74 in group 2. There were no significant differences in baseline demographics between the groups. Patients in group 2 had significantly higher baseline mental health subscores than control and group 1 patients (53.2 vs 50.2 vs 50.2, p = 0.041). There were no significant differences in any PROMs at six weeks or 12 months postoperatively (p > 0.05). There was no difference in the rate of manipulation under anaesthesia (MUA), complication rates, postoperative ROM, or blood loss. There were fewer mechanical axis outliers in groups 1 and 2 (25.2%, 14.9% respectively) versus control (28.4%), but this was not statistically significant (p = 0.10). Conclusion The sequential addition of navigation of the distal femoral cut and sensor-guided ligament balancing did not improve short-term PROMs, radiological outcomes, or complication rates compared with conventional techniques. The costs of these added technologies may not be justified. Cite this article: Bone Joint J 2020;102-B(6 Supple A):24–30.

Purpose Unstable supracondylar humerus (SCH) fractures may have different outcomes as a result of direction of displacement and pin configuration. This study evaluates the impact of fracture displacement, pin configuration and fellowship training on clinical and radiographic outcomes in unstable fractures. Methods A total of 99 patients with completely displaced type III fractures were identified at an academic centre and a local community hospital. Patient characteristics and the fellowship training of the treating surgeon were recorded, and injury films documented the direction of displacement. Pin configuration, coronal and sagittal alignment were recorded from postoperative radiographs and at healing. Radiographic outcomes including coronal, sagittal and rotational malunion as well as clinical complications were analyzed. Results Fractures with direct posterior displacement had a lower composite malunion rate compared with those with posterolateral (PL) or posteromedial (PM) displacement (6.9%, 36.4%, 29.2% respectively; p = 0.019). PM displacement had a higher rate of coronal malunion compared with PL (18.2% versus 0%; post hoc p = 0.024). All-lateral constructs resulted in more rotational malunions (20.9% versus 1.8%; p = 0.002) compared with crossed pinning. PL fractures treated with all-lateral fixation showed a trend toward increased rotational instability or malunion (23.8% versus 1.3%; p = 0.073). Higher composite complication rates were noted in patients treated by surgeons with non-paediatric, non-trauma fellowship training. Conclusion For displaced SCH fractures, all-lateral fixation is associated with higher rates of rotational instability and malunion. Posteromedially and posterolaterally displaced fractures have higher rates of malunion compared with fractures with straight posterior displacement. Fellowship training other than paediatric or trauma was associated with increased complications. Level of Evidence Level III

Glycation of horse heart metmyoglobin with D-ribose 5-phosphate (R5P), D-2-deoxyribose 5-phosphate (dR5P), and D-ribose with inorganic phosphate at 37 °C generates an altered protein (Myo-X) with increased SDS PAGE mobility. The novel protein product has been observed only for reactions with the protein myoglobin and it is not evident with other common sugars reacted over a one week period. Myo-X is first observed at 1-2 days at 37 °C along with a second form that is consistent in mass with that of myoglobin attached to several sugars. MALDI mass spectrometry and other techniques show no evidence of the cleavage of a peptide from the myoglobin chain. Apomyoglobin in reaction with R5P also exhibited this protein form suggesting its occurrence was not heme-related. While significant amounts of O2− and H2O2 are generated during the R5P glycation reaction, they do not appear to play roles in the formation of the new form. The modification is likely due to an internal cross-link formed during a glycation reaction involving the N-terminus and an internal amine group; most likely the neighboring Lys133. The study shows the unique nature of these common pentose sugars in spontaneous glycation reactions with proteins.