A single-cell atlas deconstructs heterogeneity across multiple models in murine traumatic brain injury and identifies novel cell-specific targets.

Traumatic brain injury (TBI) heterogeneity remains a critical barrier to translating therapies. Identifying final common pathways/molecular signatures that integrate this heterogeneity informs biomarker and therapeutic-target development. We present the first large-scale murine single-cell atlas of the transcriptomic response to TBI (334,376 cells) across clinically relevant models, sex, brain region, and time as a foundational step in molecularly deconstructing TBI heterogeneity. Results were unique to cell populations, injury models, sex, brain regions, and time, highlighting the importance of cell-level resolution. We identify cell-specific targets and previously unrecognized roles for microglial and ependymal subtypes. Ependymal-4 was a hub of neuroinflammatory signaling. A distinct microglial lineage shared features with disease-associated microglia at 24 h, with persistent gene-expression changes in microglia-4 even 6 months after contusional TBI, contrasting all other cell types that mostly returned to naive levels. Regional and sexual dimorphism were noted. CEREBRI, our searchable atlas (https://shiny.crc.pitt.edu/cerebri/), identifies previously unrecognized cell subtypes/molecular targets and is a leverageable platform for future efforts in TBI and other diseases with overlapping pathophysiology.

General surgery involvement with ventriculoperitoneal shunt insertions reduces revision rates.

BACKGROUND: Ventriculoperitoneal shunts (VPS) are placed for a variety of etiologies. It is common for general surgery to assist with insertion of the distal portion in the peritoneum. OBJECTIVE: To determine if there is a difference in revision rates in patients undergoing VPS placement with general surgery as well as those undergoing laparoscopic insertion. METHODS: A retrospective review of all consecutive patients undergoing VPS placements was performed in a three-year period (2017-2019). Those that underwent placement with general surgery were compared to those without general surgery. Additionally, patients undergoing distal placement via mini-laparotomy versus laparoscopy were compared. Multivariable logistic regression was used to examine risk factors for distal VPS failure. RESULTS: 331 patients were included. 202 (61.0 %) underwent VPS placement with general surgery. 121 (36.6 %) patients underwent insertion via laparoscopic technique. General surgery involvement reduced operative times, decreased length of stay, and lowered overall revision rates with distal revision rates being most significant (1.5 % vs 8.5 %; p = 0.0034). Patients undergoing VPS placement via laparoscopic technique had decreased operative time, length of stay, in-hospital complications and revision rates, with significant decrease in shunt infection (1.7 % vs 7.1 %; p = 0.0366). A history of prior shunt or abdominal surgery (OR 3.826; p = 0.0282) and lack of general surgery involvement (OR 20.98; p = 0.0314) are independent risk factors for distal shunt revision in our cohort. CONCLUSION: The use of general surgeons in VPS insertion can be of benefit by decreasing operative time, length of stay, total revisions, and distal revision rates. Further prospective studies are warranted to determine true benefit.