Pipeline for fluorescent imaging and volumetric analysis of neurons in cleared mouse spinal cords.

Precisely measuring the number and somatic volume of neurons in the central nervous system at single-cell resolution is technically challenging. Here, we combine multiple techniques to address this challenge in optically cleared mouse spinal cords. We describe in vivo neuron labeling approaches, tissue-clearing technology, light sheet fluorescence microscopy, and machine learning-guided imaging analysis. This combination provides a precise determination of the cell number and somatic volume of any neuron population in the spinal cords.

Geographical Variation in Traumatic Brain Injury Mortality by Proximity to the Nearest Neurosurgeon.

BACKGROUND: Trauma mortality disproportionately affects populations farther from potentially lifesaving trauma care, and traumatic brain injury (TBI) is no exception. Previous examinations have examined proximity to trauma centers as an explanation for trauma mortality, but little is known about the relationship between proximity to neurosurgeons specifically in TBI mortality. MATERIALS AND METHODS: In this cross-sectional study, county-level TBI mortality rates from 2008 to 2014 were examined in relation to the distance to the nearest neurosurgeon and trauma facility. The locations of practicing neurosurgeons and trauma facilities in the United States were determined by geocoding data from the 2017 Medicare Physician and Other Supplier and Provider of Services files (respectively). The association between TBI mortality and the distance from the population-weighted centroid of the county to a closest neurosurgeon and trauma facility was examined using multivariate negative binomial regression. RESULTS: A total of 761 of the 3108 counties (24.5%) in the continental United States were excluded from the analysis because they had 20 or fewer TBI deaths during this time, producing unstable estimates. Excluded counties accounted for 1.67% of the US population. Multivariate analysis revealed a county's mortality increased 10% for every 25 miles from the nearest neurosurgeon (adjusted incident rate ratio: 1.10 [95% confidence interval: 1.08-1.12]; P < 0.001). The distance to the nearest trauma facility was not found to be significantly associated with mortality (adjusted incident rate ratio: 1.01 [95% confidence interval: 0.99-1.03]; P = 0.36). CONCLUSIONS: These findings suggest that proximity to neurosurgeons may influence county-level TBI mortality. Further research into this topic with more granular data may help to allocate scarce public health resources.

Usefulness of nivolumab plus ipilimumab immunotherapy for metastatic uveal melanoma.

A 53-year-old woman with known localized uveal melanoma presented with pain from a large destructive lesion of the left iliac bone. Biopsy confirmed metastatic melanoma, and positron emission tomography scan showed extensive osseous destruction. Because her uveal melanoma was successfully treated with brachytherapy 15 years earlier, next-generation sequencing was performed, and a GNAQ mutation proved the lesion to be of uveal origin. Uveal melanoma has a worse prognosis than cutaneous melanoma. We initiated treatment with the combination of nivolumab and ipilimumab, and after four cycles of treatment a positron emission tomography scan showed resolution of all prior lesions. The patient was then placed on maintenance therapy.