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Background/Objective: Patients with intracranial hemorrhage (ICH) have a 30-day mortality rate up to 52%, and the risk of mortality is increased in patients with disease-induced coagulopathy such as cirrhosis. The objective of this study was to evaluate whether 4F-PCC administration mitigates hematoma expansion in ICH patients with cirrhosis not currently receiving anticoagulation therapy compared to standard of care therapies. Methods: This was a single-center, retrospective study comparing adult patients with ICH and history of cirrhosis who received 4F-PCC versus standard of care therapies. The primary outcome was rate of ICH expansion within 24 hours after admission. Results: A total of 58 patients were included with 21 who received 4FPCC vs 37 who received standard of care therapies. The 4F-PCC group had a significantly higher number of patients with Child Pugh Class C cirrhosis (85.7% vs. 48.6%, P = 0.006), higher baseline INR (1.7 vs. 1.4, P = 0.001) and more patients with a spontaneous cause of hemorrhage (61.9% vs. 29.7%, P = 0.01). Stable follow-up head CT was achieved in 68.4% of patients who received 4F-PCC versus 72.7% of patients treated with standard of care therapies ( P = 0.11). Patients who received 4F-PCC had a significantly greater change in INR within 24 hours (-0.2 vs. 0, P = 0.02) and higher rate of mortality (61.9% vs. 18.9%, P = 0.001). Baseline INR > 2 and surgical evacuation for ICH were associated with decreased odds of stable follow-up head CT in the multivariate logistic regression model. Conclusions: A single dose of 4F-PCC did not significantly improve the rate of stable head CT at 24 hours in patients with ICH and cirrhosis. Randomized clinical trials with larger patient populations are warranted to fully determine the role of 4F-PCC in this unique population.

Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease mainly affecting retinal ganglion cells (RGCs). The pathogenesis of LHON remains ill-characterized due to a historic lack of effective disease models. Promising models have recently begun to emerge; however, less effective models remain popular. Many such models represent LHON using non-neuronal cells or assume that mutant mtDNA alone is sufficient to model the disease. This is problematic because context-specific factors play a significant role in LHON pathogenesis, as the mtDNA mutation itself is necessary but not sufficient to cause LHON. Effective models of LHON should be capable of demonstrating processes that distinguish healthy carrier cells from diseased cells. In light of these considerations, we review the pathophysiology of LHON as it relates to old, new and future models. We further discuss treatments for LHON and unanswered questions that might be explored using these new model systems.

Background: Transient Ischaemic Attacks (TIA) should be treated as a medical emergency. While high-risk TIAs have higher stroke risks than low-risk patients, there is an inherent limitation to this risk stratification, as some low-risk patients may have undiagnosed high-risk conditions. Inequity of care for TIA patients was observed, such that high-risk patients received urgent assessment through acute admission, while low-risk patients faced long waits for clinical consultation. A redesign of the TIA service was planned to offer timely assessment for all patients and avoid acute admission for high-risk patients. Methods: Service reconfiguration was undertaken to set up a daily weekday rapid access TIA clinic where patients would be assessed, investigated, and treated. Results: A re-audit of clinic performance showed a significant increase in the number of patients seen in the ages of 18 to 52. The median time from referral to clinical consultation improved from 10 days to 1. There were similar significant improvements seen in median time to brain imaging (from 10.5 days to 1), and carotid ultrasound (from 10 days to all scans being performed on the same day). Conclusions: The redesigned service achieved the objective of offering urgent assessment and investigations for all TIA patients, including low-risk patients, while avoiding the acute admission for high-risk patients. We share our experience of establishing a successful rapid access ambulatory service without any additional resources.