Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy

Background: Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Methods: Fifty-five patients who were treated for pancreatic and periampullary carcinoma and 19 patients with chronic pancreatitis were evaluated. Exocrine pancreatic function was evaluated by fecal elastase-1 test, while endocrine pancreatic function was assessed by plasma glucose level. The extent of fibrosis, duct dilation and endocrine tissue loss was examined histopathologically. Results: A strong correlation was found between pancreatic fibrosis and elastase-1 level less than 100 μg/g (p < 0.0001), reflecting severe exocrine pancreatic insufficiency. A strong correlation was found between pancreatic fibrosis and endocrine tissue loss (p < 0.0001). Neither pancreatic fibrosis nor endocrine tissue loss were correlated with the development of postoperative diabetes mellitus. Duct dilation alone was neither correlated with exocrine nor with endocrine function loss. Conclusion: The majority of patients develop severe exocrine pancreatic insufficiency after pancreatoduodenectomy. The extent of exocrine pancreatic insufficiency is strongly correlated with preoperative fibrosis. The loss of endocrine tissue does not correlate with postoperative diabetes mellitus. Preoperative dilation of the pancreatic duct per se does not predict exocrine or endocrine pancreatic insufficiency postoperatively. Copyrigh

Correlates of a good death and the impact of hospice involvement: findings from the national survey of households affected by cancer

Knowing how to improve the dying experience for patients with end-stage cancer is essential for cancer professionals. However, there is little evidence on the relationship between clinically relevant factors and quality of death. Also, while hospice has been linked with improved outcomes, our understanding of factors that contribute to a “good death” when hospice is involved remains limited. This study (1) identified correlates of a good death; and, (2) provided evidence on the impact of hospice on quality of death

Predictors of Preference for Hospice Care Among Diverse Older Adults

The purpose of this study was to identify predictors of preference for hospice care and explore whether the effect of these predictors on preference for hospice care were moderated by race

Alcohol intake and cause-specific mortality: conventional and genetic evidence in a prospective cohort study of 512 000 adults in China

Background Genetic variants that affect alcohol use in East Asian populations could help assess the causal effects of alcohol consumption on cause-specific mortality. We aimed to investigate the associations between alcohol intake and cause-specific mortality using conventional and genetic epidemiological methods among more than 512 000 adults in China. Methods The prospective China Kadoorie Biobank cohort study enrolled 512 724 adults (210 205 men and 302 519 women) aged 30–79 years, during 2004–08. Residents with no major disabilities from ten diverse urban and rural areas of China were invited to participate, and alcohol use was self-reported. During 12 years of follow-up, 56 550 deaths were recorded through linkage to death registries, including 23 457 deaths among 168 050 participants genotyped for ALDH2-rs671 and ADH1B-rs1229984. Adjusted hazard ratios (HRs) for cause-specific mortality by self-reported and genotype-predicted alcohol intake were estimated using Cox regression. Findings 33% of men drank alcohol most weeks. In conventional observational analyses, ex-drinkers, non-drinkers, and heavy drinkers had higher risks of death from most major causes than moderate drinkers. Among current drinkers, each 100 g/week higher alcohol intake was associated with higher mortality risks from cancers (HR 1·18 [95% CI 1·14−1·22]), cardiovascular disease (CVD; HR 1·19 [1·15−1·24]), liver diseases (HR 1·51 [1·27−1·78]), non-medical causes (HR 1·15 [1·08−1·23]), and all causes (HR 1·18 [1·15−1·20]). In men, ALDH2-rs671 and ADH1B-rs1229984 genotypes predicted 60-fold differences in mean alcohol intake (4 g/week in the lowest group vs 255 g/week in the highest). Genotype-predicted alcohol intake was uniformly and positively associated with risks of death from all causes (n=12 939; HR 1·07 [95% CI 1·05−1·10]) and from pre-defined alcohol-related cancers (n=1274; 1·12 [1·04−1·21]), liver diseases (n=110; 1·31 [1·02−1·69]), and CVD (n=6109; 1·15 [1·10−1·19]), chiefly due to stroke (n=3285; 1·18 [1·12–1·24]) rather than ischaemic heart disease (n=2363; 1·06 [0·99–1·14]). Results were largely consistent using a polygenic score to predict alcohol intake, with higher intakes associated with higher risks of death from alcohol-related cancers, CVD, and all causes. Approximately 2% of women were current drinkers, and although power was low to assess observational associations of alcohol with mortality, the genetic evidence suggested that the excess risks in men were due to alcohol, not pleiotropy. Interpretation Higher alcohol intake increased the risks of death overall and from major diseases for men in China. There was no genetic evidence of protection from moderate drinking for all-cause and cause-specific mortality, including CVD. Funding Kadoorie Charitable Foundation, National Natural Science Foundation of China, British Heart Foundation, Cancer Research UK, GlaxoSmithKline, Wellcome Trust, Medical Research Council, and Chinese Ministry of Science and Technology

Innate and adaptive T cells in asthmatic patients: relationship to severity and disease mechanisms

BackgroundAsthma is a chronic inflammatory disease involving diverse cells and mediators whose interconnectivity and relationships to asthma severity are unclear.ObjectiveWe performed a comprehensive assessment of TH17 cells, regulatory T cells, mucosal-associated invariant T (MAIT) cells, other T-cell subsets, and granulocyte mediators in asthmatic patients.MethodsSixty patients with mild-to-severe asthma and 24 control subjects underwent detailed clinical assessment and provided induced sputum, endobronchial biopsy, bronchoalveolar lavage, and blood samples. Adaptive and invariant T-cell subsets, cytokines, mast cells, and basophil mediators were analyzed.ResultsSignificant heterogeneity of T-cell phenotypes was observed, with levels of IL-13–secreting T cells and type 2 cytokines increased at some, but not all, asthma severities. TH17 cells and ??-17 cells, proposed drivers of neutrophilic inflammation, were not strongly associated with asthma, even in severe neutrophilic forms. MAIT cell frequencies were strikingly reduced in both blood and lung tissue in relation to corticosteroid therapy and vitamin D levels, especially in patients with severe asthma in whom bronchoalveolar lavage regulatory T-cell numbers were also reduced. Bayesian network analysis identified complex relationships between pathobiologic and clinical parameters. Topological data analysis identified 6 novel clusters that are associated with diverse underlying disease mechanisms, with increased mast cell mediator levels in patients with severe asthma both in its atopic (type 2 cytokine–high) and nonatopic forms.ConclusionThe evidence for a role for TH17 cells in patients with severe asthma is limited. Severe asthma is associated with a striking deficiency of MAIT cells and high mast cell mediator levels. This study provides proof of concept for disease mechanistic networks in asthmatic patients with clusters that could inform the development of new therapies

Associations of alcohol intake with subclinical carotid atherosclerosis in 22,000 Chinese adults

Background and aims We investigated the causal relevance of alcohol intake with measures of carotid artery thickness and atherosclerosis in Chinese adults. Methods The study included 22,384 adults from the China Kadoorie Biobank, with self-reported alcohol use at baseline and resurvey, carotid artery ultrasound measurements, and genotyping data for ALDH2-rs671 and ADH1B-rs1229984. Associations of carotid intima media thickness (cIMT), any carotid plaque, and total plaque burden (derived from plaque number and size) with self-reported (conventional analyses) and genotype-predicted mean alcohol intake (Mendelian randomisation) were assessed using linear and logistic regression models. Results Overall 34.2% men and 2.1% women drank alcohol regularly at baseline. Mean cIMT was 0.70 mm in men and 0.64 mm in women, with 39.1% and 26.5% having carotid plaque, respectively. Among men, cIMT was not associated with self-reported or genotype-predicted mean alcohol intake. The risk of plaque increased significantly with self-reported intake among current drinkers (odds ratio 1.42 [95% CI 1.14–1.76] per 280 g/week), with directionally consistent findings with genotype-predicted mean intake (1.21 [0.99–1.49]). Higher alcohol intake was significantly associated with higher carotid plaque burden in both conventional (0.19 [0.10–0.28] mm higher per 280 g/week) and genetic analyses (0.09 [0.02–0.17]). Genetic findings in women suggested the association of genotype-predicted alcohol with carotid plaque burden in men was likely to due to alcohol itself, rather than pleiotropic genotypic effects. Conclusion Higher alcohol intake was associated with a higher carotid plaque burden, but not with cIMT, providing support for a potential causal association of alcohol intake with carotid atherosclerosis