Impact of COVID-19 on a Neurosurgical Service: Lessons from the University of California San Diego.

BACKGROUND: The institution-wide response of the University of California San Diego Health system to the 2019 novel coronavirus disease (COVID-19) pandemic was founded on rapid development of in-house testing capacity, optimization of personal protective equipment usage, expansion of intensive care unit capacity, development of analytic dashboards for monitoring of institutional status, and implementation of an operating room (OR) triage plan that postponed nonessential/elective procedures. We analyzed the impact of this triage plan on the only academic neurosurgery center in San Diego County, California, USA. METHODS: We conducted a de-identified retrospective review of all operative cases and procedures performed by the Department of Neurosurgery from November 24, 2019, through July 6, 2020, a 226-day period. Statistical analysis involved 2-sample z tests assessing daily case totals over the 113-day periods before and after implementation of the OR triage plan on March 16, 2020. RESULTS: The neurosurgical service performed 1429 surgical and interventional radiologic procedures over the study period. There was no statistically significant difference in mean number of daily total cases in the pre-versus post-OR triage plan periods (6.9 vs. 5.8 mean daily cases; 1-tail P = 0.050, 2-tail P = 0.101), a trend reflected by nearly every category of neurosurgical cases. CONCLUSIONS: During the COVID-19 pandemic, the University of California San Diego Department of Neurosurgery maintained an operative volume that was only modestly diminished and continued to meet the essential neurosurgical needs of a large population. Lessons from our experience can guide other departments as they triage neurosurgical cases to meet community needs.

Two-Element Transcriptional Regulation in the Canonical Wnt Pathway.

The canonical Wnt pathway regulates numerous fundamental processes throughout development and adult physiology and is often disrupted in diseases [1-4]. Signal in the pathway is transduced by ß-catenin, which in complex with Tcf/Lef regulates transcription. Despite the many processes that the Wnt pathway governs, ß-catenin acts primarily on a single cis element in the DNA, the Wnt-responsive element (WRE), at times potentiated by a nearby Helper site. In this study, working with Xenopus, mouse, and human systems, we identified a cis element, distinct from WRE, upon which ß-catenin and Tcf act. The element is 11 bp long, hundreds of bases apart from the WRE, and exhibits a suppressive effect. In Xenopus patterning, loss of the 11-bp negative regulatory elements (11-bp NREs) broadened dorsal expression of siamois. In mouse embryonic stem cells, genomic deletion of the 11-bp NREs in the promoter elevated Brachyury expression. This reveals a previously unappreciated mechanism within the Wnt pathway, where gene response is not only driven by WREs but also tuned by 11-bp NREs. Using electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP), we found evidence for the NREs binding to ß-catenin and Tcf-suggesting a dual action by ß-catenin as a signal and a feedforward sensor. Analyzing ß-catenin ChIP sequencing in human cells, we found the 11-bp NREs co-localizing with the WRE in 45%-71% of the peaks, suggesting a widespread role for the mechanism. This study presents an example of a more complex cis regulation by a signaling pathway, where a signal is processed through two distinct cis elements in a gene circuitry.

Traumatic brain injury induces macrophage subsets in the brain.

Traumatic brain injury (TBI) elicits innate inflammatory responses that can lead to secondary brain injury. To better understand the mechanisms involved in TBI-induced inflammation, we examined the nature of macrophages responding to TBI in mice. In this model, brain macrophages were increased >20-fold the day after injury and >77-fold 4 days after injury in the ipsilateral hemisphere compared with sham controls. TBI macrophage subsets were identified by using a reporter mouse strain (YARG) that expresses eYFP from an internal ribosome entry site (IRES) inserted at the 3' end of the gene for arginase-1 (Arg1), a hallmark of alternatively activated (M2) macrophages. One day after TBI, 21 ± 1.5% of ipsilateral brain macrophages expressed relatively high levels of Arg1 as detected by yellow fluorescent protein, and this subpopulation declined thereafter. Arg1(+) cells localized with macrophages near the TBI lesion. Gene expression analysis of sorted Arg1(+) and Arg1(-) brain macrophages revealed that both populations had profiles that included features of conventional M2 macrophages and classically activated (M1) macrophages. The Arg1(+) cells differed from Arg1(-) cells in multiple aspects, most notably in their chemokine repertoires. Thus, the macrophage response to TBI initially involves heterogeneous polarization toward at least two major subsets.