Explore the vast range of titles available.

PurposeThe Danish Pathology Life Course (PATHOLIFE) cohort was established to facilitate epidemiological research relating histological and cytological features extracted from patient tissue specimens to the rich life course histories, including both prior and future register data, of the entire Danish population. Research results may increase quality of diagnosis, prognosis and stratification of patient subtypes, possibly identifying novel routes of treatment.ParticipantsAll Danish residents from 1 January 1986 to 31 December 2019, totalling 8 593 421 individuals.Findings to dateWe provide an overview of the subpopulation of Danish residents who have had a tissue specimen investigated within the Danish healthcare system, including both the primary sector and hospitals. We demonstrate heterogeneity in sociodemographic and prognostic factors between the general Danish population and the above mentioned subpopulation, and also between the general Danish population and subpopulations of patients with tissue specimens from selected anatomical sites. Results demonstrate the potential of the PATHOLIFE cohort for integrating many different factors into identification and selection of the most valuable tissue blocks for studies of specific diseases and their progression. Broadly, we find that living with a partner, having higher education and income associates with having a biopsy overall. However, this association varies across different tissue and patient types, which also display differences in time-to-death and causes of death.Future plansThe PATHOLIFE cohort may be used to study specified patient groups and link health related events from several national health registries, and to sample patient groups, for which stored tissue specimens are available for further research investigations. The PATHOLIFE cohort thereby provides a unique opportunity to prospectively follow people that were characterised and sampled in the past.

Aims/hypotheses Glucagon and glucagon-like peptide-1 (GLP-1) are derived from the same precursor; proglucagon, and dual agonists of their receptors are currently being explored for the treatment of obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Elevated levels of endogenous glucagon (hyperglucagonaemia) have been linked with hyperglycaemia in individuals with type 2 diabetes but are also observed in individuals with obesity and MASLD. GLP-1 levels have been reported to be largely unaffected or even reduced in similar conditions. We investigated potential determinants of plasma proglucagon and associations of glucagon receptor signalling with metabolic diseases based on data from the UK Biobank. Methods We used exome sequencing data from the UK Biobank for ~410,000 white participants to identify glucagon receptor variants and grouped them based on their known or predicted signalling. Data on plasma levels of proglucagon estimated using Olink technology were available for a subset of the cohort (~40,000). We determined associations of glucagon receptor variants and proglucagon with BMI, type 2 diabetes and liver fat (quantified by liver MRI) and performed survival analyses to investigate if elevated proglucagon predicts type 2 diabetes development. Results Obesity, MASLD and type 2 diabetes were associated with elevated plasma levels of proglucagon independently of each other. Baseline proglucagon levels were associated with the risk of type 2 diabetes development over a 14 year follow-up period (HR 1.13; 95% CI 1.09, 1.17; n =1562; p =1.3×10 −12 ). This association was of the same magnitude across strata of BMI. Carriers of glucagon receptor variants with reduced cAMP signalling had elevated levels of proglucagon (β 0.847; 95% CI 0.04, 1.66; n =17; p =0.04), and carriers of variants with a predicted frameshift mutation had higher levels of liver fat compared with the wild-type reference group (β 0.504; 95% CI 0.03, 0.98; n =11; p =0.04). Conclusions/interpretation Our findings support the suggestion that glucagon receptor signalling is involved in MASLD, that plasma levels of proglucagon are linked to the risk of type 2 diabetes development, and that proglucagon levels are influenced by genetic variation in the glucagon receptor, obesity, type 2 diabetes and MASLD. Determining the molecular signalling pathways downstream of glucagon receptor activation may guide the development of biased GLP-1/glucagon co-agonist with improved metabolic benefits. Data availability All coding is available through https://github.com/nicwin98/UK-Biobank-GCG Graphical Abstract

Background Chronic Pancreatitis (CP) causes morphological changes in the pancreatic tissue, leading to complications and pain, which may require endoscopic interventions. Objective Our aim was to determine the frequency of endoscopic procedures (EP) in CP patients and to analyse pain and quality of life (QoL) in these patients after their EP. Methods This study included 1327 CP patients from the Scandinavian Baltic Pancreatic Club (SBPC) database including four countries and eight centres. We analysed patients undergoing EPs and gathered information on the EP, pancreatic function, pain, disease and duration. The EORTC C‐30 QoL questionnaire was gathered prospectively and multivariable analysis was conducted on independent parameters between the groups. The reference population had no interventions (n = 870). Results 260 CP patients (22%) underwent EPs, median one year (range 0–39 years) after CP diagnosis. 68% were males. The median age was 59 (20–90) years. Most common aetiological factors were alcohol in 65% and smoking in 71%. Extracorporeal shock wave lithotripsy (ESWL) was used in 6% of the CP population and in 21% of the EP group. Biliary duct stenting was performed on 37% and pancreatic stenting was performed on 56% of the patients. There was no difference in pain patterns between patients who had pancreatic stenting and the reference population. The EP group had slightly better QoL (p = 0.047), functioning and fewer symptoms than the reference population, in the multivariable analysis there was no interaction effect analysis between the groups. The pancreatic stent group had better QoL and the same amount of pain than the reference group. The patients who needed later surgery (23%) had more pain (p = 0.043) and fatigue (p = 0.021). Conclusions One in five of the CP patients underwent EP. These patients scored higher on QoL responses and had better symptom scores. CP patients who had pancreatic stenting performed had the same pain patterns as the reference population. Randomised prospective trials are needed to determine the effect of endoscopy procedures on CP patients.

This study investigated the prevalence of disordered eating cognitions and behaviours across mid-adolescence in a large European sample, and explored the extent to which prevalence ratings were affected by informant (parent/adolescent), or the sex or age of the adolescent. The Development and Well-Being Assessment was completed by parent–adolescent dyads at age 14 ( n  = 2225) and again at age 16 ( n  = 1607) to explore the prevalence of 7 eating disorder symptoms (binge eating, purging, fear of weight gain, distress over shape/weight, avoidance of fattening foods, food restriction, and exercise for weight loss). Informant agreement was assessed using kappa coefficients. Generalised estimating equations were performed to explore the impact of age, sex and informant on symptom prevalence. Slight to fair agreement was observed between parent and adolescent reports (kappa estimates between 0.045 and 0.318); however, this was largely driven by agreement on the absence of behaviours. Disordered eating behaviours were more consistently endorsed amongst girls compared to boys (odds ratios: 2.96–5.90) and by adolescents compared to their parents (odds ratios: 2.71–9.05). Our data are consistent with previous findings in epidemiological studies. The findings suggest that sex-related differences in the prevalence of disordered eating behaviour are established by mid-adolescence. The greater prevalence rates obtained from adolescent compared to parent reports may be due to the secretive nature of the behaviours and/or lack of awareness by parents. If adolescent reports are overlooked, the disordered behaviour may have a greater opportunity to become more entrenched.