Penetrating gluteal injuries in North West London: a retrospective cohort study and initial management guideline.

BACKGROUND: Penetrating gluteal injuries (PGIs) are an increasingly common presentation to major trauma centers (MTCs) in the UK and especially in London. PGIs can be associated with mortality and significant morbidity. There is a paucity of consistent guidance on how best to investigate and manage these patients. METHODS: A retrospective cohort study was performed by interrogating prospectively collected patient records for PGI presenting to a level 1 MTC in London between 2017 and 2019. RESULTS: There were 125 presentations with PGI, accounting for 6.86% of all penetrating injuries. Of these, 95.2% (119) were male, with a median age of 21 (IQR 18-29), and 20.80% (26) were under 18. Compared with the 3 years prior to this study, the number of PGI increased by 87%. The absolute risk (AR) of injury to a significant structure was 27.20%; the most frequently injured structure was a blood vessel (17.60%), followed by the rectum (4.80%) and the urethra (1.60%). The AR by anatomic quadrant of injury was highest in the lower inner quadrant (56%) and lowest in the upper outer quadrant (14%). CT scanning had an overall sensitivity of 50% and specificity of 92.38% in identifying rectal injury. DISCUSSION: The anatomic quadrant of injury can be helpful in stratifying risk of rectal and urethral injuries when assessing a patient in the emergency department. Given the low sensitivity in identifying rectal injury on initial CT, this data supports assesing any patients considered at high risk of rectal injury with an examination under general anesthetic with or without rigid sigmoidoscopy. The pathway has created a clear tool that optimizes investigation and treatment, minimizing the likelihood of missed injury or unnecessary use of resources. It therefore represents a potential pathway other centers receiving a similar trauma burden could consider adopting. LEVEL OF EVIDENCE: 2b.

Persistent mTORC1 signaling in cell senescence results from defects in amino acid and growth factor sensing.

Mammalian target of rapamycin complex 1 (mTORC1) and cell senescence are intimately linked to each other and to organismal aging. Inhibition of mTORC1 is the best-known intervention to extend lifespan, and recent evidence suggests that clearance of senescent cells can also improve health and lifespan. Enhanced mTORC1 activity drives characteristic phenotypes of senescence, although the underlying mechanisms responsible for increased activity are not well understood. We have identified that in human fibroblasts rendered senescent by stress, replicative exhaustion, or oncogene activation, mTORC1 is constitutively active and resistant to serum and amino acid starvation. This is driven in part by depolarization of senescent cell plasma membrane, which leads to primary cilia defects and a resultant failure to inhibit growth factor signaling. Further, increased autophagy and high levels of intracellular amino acids may act to support mTORC1 activity in starvation conditions. Interventions to correct these phenotypes restore sensitivity to the mTORC1 signaling pathway and cause death, indicating that persistent signaling supports senescent cell survival.