Experimental autoimmune encephalomyelitis (EAE) is an animal model of human multiple sclerosis (MS). EAE, induced by immunisation with myelin-associated autoantigens, is characterised by an inflammatory infiltrate in the central nervous system (CNS) associated with axonal degeneration, demyelination and damage. We have recently shown in an experimental mouse model of autoimmune gastritis that methylprednisolone treatment induces a reversible remission of gastritis with regeneration of the gastric mucosa. Here, we examined the effect of oral methylprednisolone on the mouse EAE model of human MS induced by immunisation with myelin oligodendrocyte glycoprotein peptide (MOG(35-55)). We examined the clinical scores, CNS pathology and lymphocyte reactivity to MOG(35-55) following treatment and withdrawal of the steroid. Methylprednisolone remitted the clinical signs of EAE and the inflammatory infiltrate in the CNS, accompanied by loss of lymphocyte reactivity to MOG(35-55) peptide. Methylprednisolone withdrawal initiated relapse of the clinical features, a return of the CNS inflammatory infiltrate and lymphocyte reactivity to MOG(35-55) peptide. This is the first study to show that methylprednisolone induced a reversible remission in the clinical and pathological features of EAE in mice accompanied by loss of lymphocyte reactivity to the encephalitogen. This model will be useful for studies directed at a better understanding of mechanisms associated with steroid-induced disease remission, relapse and remyelination and also as an essential adjunct to an overall curative strategy.
Background
Bile leak following blunt liver trauma is uncommon. Management is difficult due to complex vasculo‐biliary and liver parenchymal injury and lack of consensus on optimal care compared with bile leak following elective hepatectomy especially in regards to endoscopic retrograde pancreaticocholangiography (ERCP) timing and patient selection.
Methods
This is a retrospective cohort study from a level 1‐trauma centre of patients with bile leak following blunt liver injury between July 2010 and December 2019 identified from the trauma registry. Clinical data retrieved include patient demographics, injury severity score, liver injury grading and its associated complications and treatment. This was supplemented by surgical audit database and patients' electronic medical record.
Results
There were 31 bile leaks amongst 639 patients with blunt liver trauma (4.9%). Bile leak was associated with higher liver injury grade (odds ratio (OR) 36, P = 0.001), hepatic embolization (OR 16, P = 0.003) and need for trauma laparotomy (OR 14, P = 0.024). ERCP was performed in 58.1% (n = 18). This was complicated in 27.7% (n = 5) by mild pancreatitis (n = 1) and intra‐abdominal sepsis (n = 4) requiring surgical drainage of abscess (n = 2) and liver resection (n = 1). Bile leak settled conservatively (including percutaneous drainage) without ERCP in the remaining patients (41.9%). Overall mortality was not increased in those with bile leak (P = 0.998).
Conclusion
Bile leaks resolved conservatively in 41.9% of patients. Complications following ERCP were seen in 27.7%, frequently requiring intervention. Failure of conservative management was more likely in patients with hepatic embolization, in whom early ERCP remains appropriate. ERCP should otherwise be reserved for those who fail conservative management to minimize infective complications.
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