Neuropsychological effects of deep brain stimulation in subjects with early stage Parkinson's disease in a randomized clinical trial.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for patients with advanced Parkinson's disease (PD) and motor symptom complications. Recently, attention has been focused on whether offering DBS earlier in the course of PD is beneficial. OBJECTIVE: The purpose of this study was to determine the effects of DBS on neuropsychological functioning in subjects with early stage PD. METHODS: Thirty subjects with early PD (Hoehn & Yahr Stage II off medication) were randomized to optimal drug therapy (ODT) (n = 15) or bilateral subthalamic nucleus (STN) DBS+ODT (n = 15) after completing an expanded informed consent process specially designed for the study and administered by a medical ethicist and the study team. Comprehensive neuropsychological testing was completed in the treatment-withdrawn state at baseline and at 12 month and 24 month follow-ups. RESULTS: Two serious adverse events occurred in the DBS+ODT group. One subject experienced a stroke and another developed infected hardware that contributed to specific declines in cognitive functioning. However, compared to the ODT group, the remaining subjects in the DBS+ODT group exhibited modest reductions on a few measures of attention, executive function, and word fluency at 12 months. These differences were largely diminished at 24 months, especially when those with the adverse events were excluded. CONCLUSIONS: The results of this trial provide novel data regarding the effects of DBS on cognitive function in early PD. We believe that the findings and insights from this trial can help guide the safety analysis and risk-benefit evaluations in future discussions of DBS in early stage PD.

Metabolome-Wide Association Study of Primary Open Angle Glaucoma.

PURPOSE: To determine if primary open-angle glaucoma (POAG) patients can be differentiated from controls based on metabolic characteristics. METHODS: We used ultra-high resolution mass spectrometry with C18 liquid chromatography for metabolomic analysis on frozen plasma samples from 72 POAG patients and 72 controls. Metabolome-wide Spearman correlation was performed to select differentially expressed metabolites (DEM) correlated with POAG. We corrected P values for multiple testing using Benjamini and Hochberg false discovery rate (FDR). Hierarchical cluster analysis (HCA) was used to depict the relationship between participants and DEM. Differentially expressed metabolites were matched to the METLIN metabolomics database; both DEM and metabolites significantly correlating with DEM were analyzed using MetaboAnalyst to identify metabolic pathways altered in POAG. RESULTS: Of the 2440 m/z (mass/charge) features recovered after filtering, 41 differed between POAG cases and controls at FDR = 0.05. Hierarchical cluster analysis revealed these DEM to associate into eight clusters; three of these clusters contained the majority of the DEM and included palmitoylcarnitine, hydroxyergocalciferol, and high-resolution METLIN matches to sphingolipids, other vitamin D-related metabolites, and terpenes. MetaboAnalyst also indicated likely alteration in steroid biosynthesis pathways. CONCLUSIONS: Global ultrahigh resolution metabolomics emphasized the importance of altered lipid metabolism in POAG. The results suggest specific metabolic processes, such as those involving palmitoylcarnitine, sphingolipids, vitamin D-related compounds, and steroid precursors, may contribute to POAG status and merit more detailed study with targeted methods.

Biochemical recurrence-free survival after robotic-assisted laparoscopic vs open radical prostatectomy for intermediate- and high-risk prostate cancer.

OBJECTIVE: To compare biochemical recurrence (BCR)-free survival and predictors of BCR in intermediate-risk (IR) and high-risk (HR) patients undergoing robotic-assisted laparoscopic prostatectomy (RALP) vs open radical prostatectomy (ORP). MATERIALS AND METHODS: We conducted a retrospective study on 1336 men with D'Amico IR or HR prostate cancer who underwent RALP or ORP between 2003 and 2009. Exclusion criteria were use of neoadjuvant therapy, <6 months of follow-up, and insufficient clinicopathologic data. We compared demographic, clinical, and pathologic variables between groups. Kaplan-Meier analysis was performed to compare the 5-year BCR-free survival between groups. Multivariate models were developed to determine whether surgical approach influences BCR. RESULTS: A total of 979 IR and HR patients (237 ORP and 742 RALP patients) met inclusion criteria. Median follow-up was shorter for RALP (43 vs 63 months; P<.001). ORP patients had a higher median prostate-specific antigen level (7.9 vs 6.7 ng/mL; P<.002), significantly more Gleason sum 8-10 tumors, and more adverse pathologic features overall. There was no difference in positive surgical margins between groups. Pathologic features including extraprostatic extension, seminal vesicle involvement, lymph node involvement, pathologic Gleason sum, and positive surgical margin were significant independent predictors of BCR in multivariate analysis. Surgical approach (RALP vs ORP) did not predict BCR when controlling for other known predictors of BCR. CONCLUSION: Among IR and HR prostate cancer patients, the oncologic outcomes are similar between RALP and ORP. Not surprisingly, adverse pathologic features are harbingers of BCR.