Empirical assessment of biases in cerebrospinal fluid biomarkers of Alzheimer's disease: an umbrella review and re-analysis of data from meta-analyses.

OBJECTIVE: Alzheimer's disease (AD) is a leading cause of years lived with disability in older age, and several cerebrospinal fluid (CSF) markers have been proposed in individual meta-analyses to be associated with AD but field-wide evaluation and scrutiny of the literature is not available. MATERIALS AND METHODS: We performed an umbrella review for the reported associations between CSF biomarkers and AD. Data from available meta-analyses were reanalyzed using both random and fixed effects models. We also estimated between-study heterogeneity, small-study effects, excess significance, and prediction interval. RESULTS: A total of 38 meta-analyses on CSF markers from 11 eligible articles were identified and reanalyzed. In 14 (36%) of the meta-analyses, the summary estimate and the results of the largest study showed non-concordant results in terms of statistical significance. Large heterogeneity (I2≥75%) was observed in 73% and small-study effects under Egger's test were shown in 28% of CSF biomarkers. CONCLUSIONS: Our results suggest that there is an excess of statistically significant results and significant biases in the literature of CSF biomarkers for AD. Therefore, the results of CSF biomarkers should be interpreted with caution.

Site-specific positive margins at radical prostatectomy: assessing cancer-control benefits of wide excision of the neurovascular bundle on a side with cancer on biopsy.

OBJECTIVE: To determine the potential risk of biopsy-selected nerve-sparing surgery based on the findings of site-specific extracapsular extension (ECE) and positive surgical margins (PSMs) in the area of the neurovascular bundle in radical prostatectomy specimens. PATIENTS AND METHODS: Controlling for surgical technique and pathological interpretation, 221 consecutive patients had their neurovascular bundles removed on the side with a positive biopsy. The surgical specimens were reviewed for ECE and PSM status, specifically in the area of the neurovascular bundle, from apex to base. RESULTS: Of the 221 patients, 38% had ECE and 43 (20%) had a PSM in the area of the neurovascular bundle. This equates to a ratio of 51% for PSM/ECE. An additional 42 men (18%) had ECE with negative margins, but would have been at potential risk for PSMs if the neurovascular bundle had been preserved. CONCLUSION: Preserving the neurovascular bundle on the side with a positive biopsy could result in a significantly greater incidence of PSM than with wide excision. Optimizing cancer control may require excision of the neurovascular bundle on a side known to have cancer on biopsy. In future site-specific analyses, the PSM/ECE ratio could be used as a marker comparing cancer-control outcomes from studies with differing technical approaches and indications for nerve-sparing surgery.