Intracerebral hemorrhage (ICH) is a devastating type of stroke characterized by bleeding into the brain parenchyma and secondary brain injury resulting from strong neuroinflammatory responses to blood components. Production of prostaglandin E2 (PGE2) is significantly upregulated following ICH and contributes to this inflammatory response in part through its E prostanoid receptor subtype 2 (EP2). Signaling through the EP2 receptor has been shown to affect outcomes of many acute and chronic neurological disorders; although, not yet explored in the context of ICH. Wildtype (WT) and EP2 receptor knockout (EP2−/−) mice were subjected to ICH, and various anatomical and functional outcomes were assessed by histology and neurobehavioral testing, respectively. When compared with age-matched WT controls, EP2−/− mice had 41.9 ± 4.7% smaller ICH-induced brain lesions and displayed significantly less ipsilateral hemispheric enlargement and incidence of intraventricular hemorrhage. Anatomical outcomes correlated with improved functional recovery as identified by neurological deficit scoring. Histological staining was performed to begin investigating the mechanisms involved in EP2-mediated neurotoxicity after ICH. EP2−/− mice exhibited 45.5 ± 5.8% and 41.4 ± 8.1% less blood and ferric iron accumulation, respectively. Furthermore, significantly less striatal and cortical microgliosis, striatal and cortical astrogliosis, blood–brain barrier breakdown, and peripheral neutrophil infiltration were seen in EP2−/− mice. This study is the first to suggest a deleterious role for the PGE2-EP2 signaling axis in modulating brain injury, inflammation, and functional recovery following ICH. Targeting the EP2 G protein-coupled receptor may represent a new therapeutic avenue for the treatment of hemorrhagic stroke.

Professional society guidelines recommend semiannual screening for hepatocellular carcinoma (HCC) in patients with cirrhosis; however, studies suggest underuse of screening in clinical practice. Our study's aim was to characterize reasons for HCC screening underuse among patients with cirrhosis. We conducted a retrospective cohort study of patients with cirrhosis diagnosed with HCC in two large health systems from 2011 to 2019. We classified screening receipt as consistent, inconsistent, or no screening in the year before HCC diagnosis. We categorized reasons for screening underuse as a potential failure at each of the following steps required for HCC screening: receipt of regular outpatient care, recognition of liver disease, recognition of cirrhosis, screening orders in patients with cirrhosis, and adherence to screening ultrasound appointments. Among 1,014 patients with cirrhosis with HCC, only 377 (37.2%) had regular outpatient care in the year before HCC presentation. Consistent screening was observed in 93 (24.7%) patients under regular outpatient care, whereas 161 (42.7%) had inconsistent screening and 123 (32.6%) no screening. We found screening underuse related to failures at each step in the screening process, although nearly half (49.6%) were due to lack of screening orders in patients with known cirrhosis. Conclusion: The most common reasons for HCC screening underuse in patients with cirrhosis are lack of regular outpatient care and lack of screening orders in those with known cirrhosis, highlighting the need for interventions targeted at these steps to increase HCC screening use. (Hepatology Communications 2021;0:1-9).

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Inflammation after intracerebral hemorrhage (ICH) is a key component to secondary brain injury, a major cause of morbidity and disability after ICH. Prostaglandin E2 (PGE 2 ) plays an important role in modulating inflammatory responses and in many neurologic disorders. PGE 2 binds with high affinity to the G-protein-coupled receptors EP1, EP2, EP3, and EP4, which collectively mediate its neuroimmunomodulatory effects. We and others have documented that the EP2 receptor mediates the neuroprotective properties of PGE 2 in neuronal cultures and in the middle cerebral artery occlusion model of ischemia/reperfusion-induced brain injury. The present study aimed to investigate the role of EP2 receptor signaling on anatomical and functional outcomes after ICH. The collagenase model was used to induce an ICH in wildtype (WT) and EP2 -/- mice (n=8-11/group). After 72h, mice were sacrificed and brains collected for Cresyl Violet staining and lesion volume quantification. The EP2 -/- displayed significantly reduced lesion volumes when compared to WT controls (p<0.005). The EP2 -/- also showed reduced cortical and striatal microglial activation (p<0.05), and less cortical astrocyte activation (p<0.05). Collectively, these results suggest that PGE 2 -EP2 receptor signaling aggravates ICH-induced brain injury in vivo, which is in contrast to previous reports in stroke models, highlighting the dynamic role of the EP2 receptor in modulating inflammatory responses following brain damage. Further investigations are necessary in order to identify the mechanism of EP2-mediated hematoma resolution. Additional studies using a selective EP2 receptor antagonist could lead to the development of improved drugs that minimize the side effects often associated with anti-inflammatory medications in order to help prevent or improve neurologic recovery following ICH.