T2-Weighted magnetic resonance imaging measurements of optic nerve sheath diameter in dogs with and without presumed intracranial hypertension

Intracranial hypertension is a cause of cerebral ischemia and neurologic deficits in dogs. Goals of this retrospective study were to test interobserver agreement for MRI measurements of optic nerve sheath diameter and associations between optic nerve sheath diameter, signalment data, and presumed intracranial hypertension status in a cohort of dogs. A veterinary radiologist interpreted scans of 100 dogs and dogs were assigned to groups based on presence or absence of at least two MRI characteristics of presumed intracranial hypertension. Two observers who were unaware of group status independently measured optic nerve diameter from transverse T2-weighted sequences. Mean optic nerve sheath diameter for all dogs was 3 mm (1-4 mm). The mean difference between observers was 0.3 mm (limits of agreement, -0.4 and 1.0 mm). There was no correlation between optic nerve sheath diameter and age for either observer (r = -0.06 to 0.00) but a moderate positive correlation was observed between optic nerve sheath diameter and body weight for both observers (r = 0.70-0.76). The 22 dogs with presumed intracranial hypertension weighed less than the 78 dogs without (P = 0.02) and were more often female (P = 0.04). Dogs with presumed intracranial hypertension had a larger ratio of optic nerve sheath diameter to body weight for each observer-side pair (P = 0.01-0.04) than dogs without. Findings indicated that the ratio of MRI optic nerve sheath diameter relative to body weight may be a repeatable predictor of intracranial hypertension in dogs

Genetic factors associated with prostate cancer conversion from active surveillance to treatment

Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for PC, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9 × 10−7 and GAB2, p = 2.0 × 10−6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% confidence interval [CI] = 0.94–1.36); whereas decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04–1.50). These results suggest that germline genetics may help inform and individualize the decision of AS—or the intensity of monitoring on AS—versus treatment for the initial management of patients with low-risk PC