Olfactory ensheathing cells (OECs) are a unique class of glial cells with exceptional translational potential because of their ability to support axon regeneration in the central nervous system. Although OECs are similar in many ways to immature and nonmyelinating Schwann cells, and can myelinate large-diameter axons indistinguishably from myelination by Schwann cells, current dogma holds that OECs arise from the olfactory epithelium. Here, using fatemapping techniques in chicken embryos and genetic lineage tracing in mice, we show that OECs in fact originate from the neural crest and hence share a common developmental heritage with Schwann cells. This explains the similarities between OECs and Schwann cells and overturns the existing dogma on the developmental origin of OECs. Because neural crest stem cells persist in adult tissue, including skin and hair follicles, our results also raise the possibility that patient-derived neural crest stem cells could in the future provide an abundant and accessible source of autologous OECs for cell transplantation therapy for the injured central nervous system. chick embryo | grafting | olfactory placodes | Wnt1-Cre | Sox10

The calibrated spoon was the most accurate producing a mean volume of 5 ml, while the oral syringe had the smallest variance. The increased variability of calibrated or metal spoons may result in under or overdosing especially when administering drugs with a narrow therapeutic window. Health care professionals must make a case-by-case decision regarding which device is preferable depending on the medication in question. Parental education could improve measuring accuracy.

Objectives Patients with alcohol use disorder (AUD) and liver cirrhosis benefit from stopping alcohol intake. Baclofen has been trialled for AUD in cirrhosis and appears to be effective. However, in patients without cirrhosis acamprosate is safer and more efficacious. Acamprosate is rarely used in cirrhosis due to safety concerns: the only published report was for 24 h in a controlled setting. Our centre uses both medications off-label in cirrhotic patients. We performed an audit to pragmatically compare the safety of acamprosate to baclofen in these patients. Methods The electronic records of patients prescribed acamprosate or baclofen between 01/04/17 and 31/03/20 were retrospectively reviewed. Adverse events and abstinence at last follow-up were compared by Student's t-test, Mann-Whitney U or chi-square test. Confounding variables were evaluated by logistic regression. Results In total 48 cirrhotic patients taking acamprosate (median 84 days, range 2-524); 44 baclofen (247 days, 8-910) met inclusion criteria. At baseline, 41% had Childs-Pugh B or C cirrhosis. More patients taking baclofen had an unplanned hospital admission or attendance (23 vs 13; P = 0.013) and the mean number per patient was higher (1.6 vs 0.6; P = 0.032). Subgroup analysis revealed increased admissions in actively drinking patients prescribed baclofen to achieve abstinence (mean 2.4 vs 0.6; P = 0.020); acamprosate use was associated with a reduced chance of admission or attendance (OR, 0.284; 0.095-0.854; P = 0.025) independent of treatment length. No difference in efficacy was observed. Conclusions In patients with cirrhosis, acamprosate was associated with fewer unplanned admissions than baclofen, hence may be safer despite historical concerns.

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Background and Aims Up to 30% of patients with severe alcoholic hepatitis (sAH) die within 3 months of presentation. The degree of ductular reaction, characterized by accumulation of biliary and liver progenitor cells, confers a poor prognosis. Keratin fragments are established serological surrogates of liver injury and keratin 19 (K19) is a histological marker of the ductular reaction. We assessed the relationship between serum K19 levels (viz. CYFRA21‐1), histology and outcome in patients with sAH. Methods Serum CYFRA21‐1 was quantified in pre‐treatment serum samples from 824 patients enrolled in the STOPAH trial. The cohort was randomly divided into two groups to test mortality associations; histological analyses were performed using the 87 cases with suitable samples. Results CYFRA21‐1 levels were elevated in sAH and strongly predicted alcoholic steatohepatitis (ASH) on biopsy (area under the receiver operated characteristic [AUROC] 0.785 [95% Confidence Interval 0.602–0.967]) and 90‐day survival (AUROC 0.684/0.693). The predictive ability of CYFRA21‐1 was comparable with the model of end‐stage liver disease (MELD) score and was independently associated with survival in multivariable analysis. CYFRA21‐1 moderately correlated with hepatocellular injury markers M30/M65 but displayed a more robust predictive ability. A combination of MELD and CYFRA21‐1 conferred a modest improvement in the AUROC value (0.731/0.743). Conclusions In sAH serum, CYFRA21‐1 levels associate with the presence of ASH on biopsy and independently predict 90‐day survival. As a single marker performance is comparable to established scoring systems. Therefore, CYFRA21‐1, which is available in many clinical laboratories, may become a useful component of prognostic models.

Introduction A number of devices including metal teaspoons, calibrated spoons and oral syringes are available to administer medications. The aims of this study were to determine which measuring devices were preferred by caregivers and which were the most accurate. Methods We compared caregivers' accuracy when measuring paracetamol suspension using different devices and the variance of doses achieved using each device. Participants completed a questionnaire detailing demographics, regularity of administering children's medication, preference and perceived accuracy of paediatric medication devices. Caregivers measured 5.0 ml of 120 mg/5 ml paracetamol suspension using a 5.0 ml metal teaspoon, 5.0 ml calibrated spoon and 5.0 ml oral syringe. Samples were weighed then converted into mls (conversion rate=1.09 g/ml, Orbis Pharmaceuticals). Results We recruited 277 caregivers aged 17-68 years attending outpatient clinics. Most (98%) were parents with children less than 18 years of age at home. Most would choose an oral syringe (59%) or calibrated spoon (52%) to dispense medication. The majority (84%) considered the syringe most accurate and easiest to use (70%). Medication was mainly administered by mothers (94%). Accuracy did not vary with caregivers' age, gender, instrument preference, number and age of children. The mean volumes measured with the metal, calibrated spoon and oral syringe were 3.99, 5.00 and 5.13 ml respectively. Volumes administered ranged from 2.49 to 6.52 ml. There were significant differences from the specifi ed 5 ml volume using the metal spoon (single sample t test, t=22.46, p<0.0001), oral syringe (single sample t test, t=0.0087, p<0.0001) and when comparing the volumes measured with each device. The variance of the volumes measured with an oral syringe was signifi cantly smaller than that measured using a calibrated spoon (Pitman's test; ρRho=-0.797, p<0.0001) or metal spoon (Pitman's test; ρ=-0.709, p<0.0001). Conclusions There were significant differences in the volumes of medication measured using commonly available devices. Oral syringes were the most consistently accurate, having the smallest variance. The increased variability with calibrated or metal spoons may result in under or overdosing especially when administering drugs with a narrow therapeutic window. We recommend the oral syringe for measuring children's medication. Accuracy in volume measurements can be further improved by parental education.

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Age-standardised mortality from liver disease in the United Kingdom has risen by 400% since 1970, with three-quarters of deaths from alcohol-related liver disease (ARLD). The 2013 National Confidential Enquiry into Patient Outcome and Death report found that only 47% of the patients dying in hospital from liver disease experienced 'good' care. We discuss common complications in the care of patients with ARLD and the evidence-based best practice that can improve patient outcomes, with a focus on the initial management of patients presenting acutely to the medical take.