Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption.

Osteoclasts are large multinucleated bone-resorbing cells formed by the fusion of monocyte/macrophage-derived precursors that are thought to undergo apoptosis once resorption is complete. Here, by intravital imaging, we reveal that RANKL-stimulated osteoclasts have an alternative cell fate in which they fission into daughter cells called osteomorphs. Inhibiting RANKL blocked this cellular recycling and resulted in osteomorph accumulation. Single-cell RNA sequencing showed that osteomorphs are transcriptionally distinct from osteoclasts and macrophages and express a number of non-canonical osteoclast genes that are associated with structural and functional bone phenotypes when deleted in mice. Furthermore, genetic variation in human orthologs of osteomorph genes causes monogenic skeletal disorders and associates with bone mineral density, a polygenetic skeletal trait. Thus, osteoclasts recycle via osteomorphs, a cell type involved in the regulation of bone resorption that may be targeted for the treatment of skeletal diseases.

The management of low-risk primary upper gastrointestinal haemorrhage in the community: a 5-year observational study.

BACKGROUND: Acute upper gastrointestinal haemorrhage is a common medical emergency, initially managed with inpatient care. Bleeding stops spontaneously in over 80% of cases, indicating that patients with low-risk upper gastrointestinal haemorrhage may be more optimally managed in the community, without the need for admission to hospital. AIM: To assess the safety of managing patients with low-risk upper gastrointestinal haemorrhage without admission to hospital. METHODS: Prospective/retrospective study of all patients presenting to a UK teaching hospital with low-risk upper gastrointestinal haemorrhage who were managed without admission to hospital over 5 years. Low risk was defined as Glasgow Blatchford Score of 2 or less, age below 70 years, no other active medical problems, not taking warfarin and suspected nonvariceal bleed. Outcome measures were the need for intervention (blood transfusion, endoscopic therapy or surgery) and death. RESULTS: One hundred and forty-two patients fulfilled the inclusion criteria, and were managed without admission to hospital. No patients required endoscopic intervention, blood transfusion or surgery. The 28-day mortality was nil. Forty-one patients had normal endoscopic examination and 11 had significant endoscopic findings (peptic ulceration=10, oozing Mallory-Weiss tear=1) but did not require intervention. CONCLUSION: Patients presenting with a primary upper gastrointestinal haemorrhage aged below 70 years with a Glasgow Blatchford Score of 2 or less are at a low risk, and can be safely managed in the community.

Host risk factors and autochthonous hepatitis E infection.

INTRODUCTION: In developed countries autochthonous hepatitis E infection is caused by hepatitis E virus (HEV) genotype 3 or 4 and mainly affects middle aged/elderly men. Host factors might explain why older men develop clinically overt disease. METHODS: Retrospective review of 53 patients with symptomatic autochthonous hepatitis E infection to determine putative host risk factors. Patients were compared with 564 controls with adjustment for age and sex. Anti-HEV seroprevalence was determined in controls and 189 patients with chronic liver disease. RESULTS: Mean age of the patients was 62.4 years, 73.6% were men. Compared with controls, patients with hepatitis E were more likely to drink at least 22 U alcohol/week (OR=9.4; 95% confidence interval=3.8-25.0; P<0.001). The seroprevalence of anti-HEV IgG in controls increased with age (P<0.001) but was similar in men and women. There was no association between alcohol consumption and anti-HEV IgG seroprevalence in the control group. There was no difference in the anti-HEV IgG seroprevalence between the controls and patients with chronic liver disease of all aetiologies, but seroprevalence was higher in controls (13.8%) than patients with alcoholic liver disease (4.8%, P=0.04). CONCLUSION: Clinically apparent hepatitis E infection is more common in individuals who consume at least 22 U alcohol/week. Patients with established chronic alcoholic liver disease have a low seroprevalence compared with controls. The reason for this observation is uncertain, but patients with alcoholic liver disease have clinically severe disease with a high mortality when exposed to HEV. The low seroprevalence in this group may represent a 'culled' population.

Management of minor upper gastrointestinal haemorrhage in the community using the Glasgow Blatchford Score.

BACKGROUND: The Glasgow Blatchford Score (GBS) is a validated risk assessment tool in primary upper gastrointestinal haemorrhage, which accurately predicts the need for intervention (endoscopic therapy, blood transfusion or surgery) or death. AIMS: To identify the GBS that predicts lack of intervention or death and to apply this to clinical practice by managing low-risk patients in the community. METHODS: GBSs prospectively calculated on 232 patients with upper gastrointestinal haemorrhage to identify low-risk score. Patients with low-risk of requiring intervention (GBS