Upregulation of PSMA Expression by Enzalutamide in Patients with Advanced mCRPC.

In this study, we investigated upregulation of prostate-specific membrane antigen (PSMA) by enzalutamide in a cohort (n = 30) of patients with advanced metastatic castration-resistant prostate cancer (mCRPC). Patients were examined by [68Ga]Ga-PSMA-11 PET/CT pre- and post-enzalutamide medication (mean 13 ± 7 days). Imaging results were compared based on quantification of whole-body PSMA tumor burden: total lesion PSMA (TLP) and normalized TLP values to liver (TLP-LR) and to parotid gland (TLP-PR). In addition, lesion-based analyses were performed. The median (mean) increases in TLP, TLP-LR and TLP-PR after enzalutamide medication were 10.1% (20.2%), 29.5% (34.8%) and 27.6% (24.4%), respectively. These increases were statistically significant (p = 0.002, p < 0.001, and p < 0.001), while prostate-specific antigen (PSA) serum values did not change significantly (p = 0.483). The increase was independent of prior patient exposure to enzalutamide. SUVmax increased substantially (>10%) in 49.6% of target lesions. The relative change was significantly higher in the subgroup of lesions with SUVmax < 10 (p < 0.001). In conclusion, short-term enzalutamide medication significantly increases PSMA expression in patients with mCRPC, irrespective of prior enzalutamide exposure. The relative PSMA upregulation effect seems to be more pronounced in lesions with only moderate baseline PSMA expression. Enzalutamide may provide a potential enhancer medication for PSMA-targeted radioligand therapy.

Using Patient Demographics and Statistical Modeling to Predict Knee Tibia Component Sizing in Total Knee Arthroplasty.

BACKGROUND: Preoperative planning is important to achieve successful implantation in primary total knee arthroplasty (TKA). However, traditional TKA templating techniques are not accurate enough to predict the component size to a very close range. METHODS: With the goal of developing a general predictive statistical model using patient demographic information, ordinal logistic regression was applied to build a proportional odds model to predict the tibia component size. The study retrospectively collected the data of 1992 primary Persona Knee System TKA procedures. Of them, 199 procedures were randomly selected as testing data and the rest of the data were randomly partitioned between model training data and model evaluation data with a ratio of 7:3. Different models were trained and evaluated on the training and validation data sets after data exploration. RESULTS: The final model had patient gender, age, weight, and height as independent variables and predicted the tibia size within 1 size difference 96% of the time on the validation data, 94% of the time on the testing data, and 92% on a prospective cadaver data set. CONCLUSION: The study results indicated the statistical model built by ordinal logistic regression can increase the accuracy of tibia sizing information for Persona Knee preoperative templating. This research shows statistical modeling may be used with radiographs to dramatically enhance the templating accuracy, efficiency, and quality. In general, this methodology can be applied to other TKA products when the data are applicable.

Sagittal tibiotalar translation and clinical outcomes in mobile and fixed-bearing total ankle replacement.

BACKGROUND: Sagittal implant malalignment after total ankle replacement (TAR) has been considered to be a possible cause for premature implant failure. In a prior study, the change over time of the tibiotalar ratio (T-T ratio), which is the ratio between the posterior longitudinal talar length and the full longitudinal talar length, was assessed in 66 TARs where an unconstrained, mobile-bearing implant was implanted. The analysis documented an increase in the T-T ratio between 2 and 6 months post-surgery (on average from 34.6% to 37.2%). We hypothesized that this change might have been related to the presence of a mobile-bearing insert. In order to test our hypothesis, we designed a study to compare the translation of the talus in TARs performed with an unconstrained, mobile-bearing implant (designated the "Mobile ankle") and those performed with a semi-constrained, fixed-bearing implant (designated the "Fixed ankle"). METHODS: The study included 71 consecutive patients (71 ankles) who underwent TAR with the Mobile ankle and 24 consecutive patients (24 ankles) who received the Fixed ankle from May 2011 to December 2014. Patients were assessed clinically and radiologically preoperatively (T0), at 6 months (T2) and 12 months (T3) post-surgery. There was also a radiological assessment at 2 months post-surgery (T1). RESULTS: The comparison of the T-T ratio between the two implant groups and over time indicated an interaction between time and group, therefore the changes of the T-T ratio over time were affected by the implant type factor (P<0.001). The changes of the postoperative T-T ratio over time were not significant in the Fixed ankle group (35.7±6.7% at T1, T2, and T3; P=1.0 for each pairwise comparison). In the Mobile ankle group, the T-T ratio at 2 months (34.4±5.5%) was significantly different to the T-T ratio at 6 months (37.0±5.8%; P<0.001; i.e. there was a significant posterior translation of the talus). The AOFAS score increased from preop to 12 months post-surgery in both the Mobile ankle (72.7±12.8 at 12 months; P<0.001) and the Fixed ankle (85.0±9.7 at 12 months; P<0.001). CONCLUSION: The significant posterior translation of the talus from 2 to 6 months documented only in the Mobile ankle group may have been associated with the presence of the mobile bearing interface.