Mortality data in patients with adrenal insufficiency are inconsistent, possibly due to temporal and geographical differences between patients and their reference populations.

To compare mortality risk and causes of death in adrenal insufficiency with an individually matched reference population.

A retrospective cohort study was done using a UK general practitioner database (CPRD). A total of 6821 patients with adrenal insufficiency (primary, 2052; secondary, 3948) were compared with 67564 individually-matched controls (primary, 20366; secondary, 39134). Main outcomes were all-cause and cause-specific mortality, and hospital admission from adrenal crisis.

With follow-up of 40 799 and 406 899 person-years for patients and controls respectively, the hazard ratio (HR [95% CI]) for all-cause mortality was 1.68 [1.58-1.77]. HRs were greater in primary (1.83 [1.66-2.02]) than in secondary (1.52 [1.40-1.64]) disease; primary versus secondary disease (1.16 [1.03-1.30]). The leading cause of death was cardiovar. Early education for prompt treatment of infections and avoidance of adrenal crisis hold potential to reduce mortality.

Mutations in IL10 or the IL10 receptor lead to very early onset [VEO] inflammatory bowel disease [IBD], a life-threatening disease which is often unresponsive to conventional medication. Recent studies have demonstrated that defective IL-10 receptor signalling in innate immune cells is a key driver of severe intestinal inflammation in VEO-IBD. Specifically, IL10 unresponsiveness of macrophages, which govern the tight balance between pro- and anti-inflammatory responses in the intestinal system, plays a central role in the events leading to excessive inflammatory responses and the development of IBD.

We here evaluated haematopoietic stem cell gene therapy in a VEO-IBD mouse model and demonstrated that the therapeutic response closely correlates with gene correction of the IL10 signalling pathway in intestinal macrophages. This finding prompted us to evaluate the therapeutic efficacy of macrophage transplantation in the Il10rb-/- VEO-IBD mouse model. A 6-week regimen employing a combination of depletion of endogenous hyperinflammatory macrophages followed by intraperitoneal administration of wild-type [WT] macrophages significantly reduced colitis symptoms.

In summary, we show that the correction of the IL10 receptor defect in macrophages, either by genetic therapy or transfer of WT macrophages to the peritoneum, can ameliorate disease-related symptoms and potentially represent novel treatment approaches for VEO-IBD patients.

In summary, we show that the correction of the IL10 receptor defect in macrophages, either by genetic therapy or transfer of WT macrophages to the peritoneum, can ameliorate disease-related symptoms and potentially represent novel treatment approaches for VEO-IBD patients.

Ulcerative colitis [UC] is a chronic inflammatory disease of the colon with an intractable course. Although the goal of UC therapy is to achieve mucosal healing, the pathogenesis of mucosal injury caused by chronic inflammation remains unknown. We therefore aim to elucidate molecular mechanisms of mucosal injury by establishing in vitro and in vivo humanised UC-mimicking models.

An in vitro model using human colon organoids was established by 60 weeks of inflammatory stimulation. The key gene for mucosal injury caused by long-term inflammation was identified by microarray analysis. An in vivo model was established by xenotransplantation of organoids into mouse colonic mucosa.

An in vitro model demonstrated that long-term inflammation induced irrecoverable changes in organoids inflammatory response and apoptosis with oxidative stress and suppression of cell viability. This model also mimicked organoids derived from patients with UC at the gene expression and phenotype levels. Homoharringtonine cell line Microarray analysis revealed Schlafen11 [SLFN11] was irreversibly induced by long-term inflammation. Consistently, SLFN11 was highly expressed in UC mucosa but absent in normal mucosa. The knockdown of SLFN11 [SLFN11-KD] suppressed apoptosis of intestinal epithelial cells [IECs] induced by inflammation. Moreover, SLFN11-KD improved the take rates of xenotransplantation and induced the regenerative changes of crypts observed in patients with UC in remission.

In vitro and in vivo UC-mimicking models were uniquely established using human colonic organoids. They revealed that SLFN11 is significant for mucosal injury in UC, and demonstrated its potential as a novel target for mucosal regeneration.

In vitro and in vivo UC-mimicking models were uniquely established using human colonic organoids. They revealed that SLFN11 is significant for mucosal injury in UC, and demonstrated its potential as a novel target for mucosal regeneration.

Quality improvement collaboratives (QICs) bring together multidisciplinary teams in a structured process to improve care quality. How QICs can be used to support healthcare improvement in care homes is not fully understood.

A realist evaluation to develop and test a programme theory of how QICs work to improve healthcare in care homes. A multiple case study design considered implementation across 4 sites and 29 care homes. Observations, interviews and focus groups captured contexts and mechanisms operating within QICs. Data analysis classified emerging themes using context-mechanism-outcome configurations to explain how NHS and care home staff work together to design and implement improvement.

QICs will be able to implement and iterate improvements in care homes where they have a broad and easily understandable remit; recruit staff with established partnership working between the NHS and care homes; use strategies to build relationships and minimise hierarchy; protect and pay for staff time; enable staff to implement improvements aligned with existing work; help members develop plans in manageable chunks through QI coaching; encourage QIC members to recruit multidisciplinary support through existing networks; facilitate meetings in care homes and use shared learning events to build multidisciplinary interventions stepwise. Teams did not use measurement for change, citing difficulties integrating this into pre-existing and QI-related workload.

These findings outline what needs to be in place for health and social care staff to work together to effect change. Further research needs to consider ways to work alongside staff to incorporate measurement for change into QI.

These findings outline what needs to be in place for health and social care staff to work together to effect change. Further research needs to consider ways to work alongside staff to incorporate measurement for change into QI.