Crohn's disease and ulcerative colitis, collectively known as IBD, are chronic inflammatory disorders of the gastrointestinal tract. Although the aetiopathogenesis of IBD is largely unknown, it is ...widely thought that diet has a crucial role in the development and progression of IBD. Indeed, epidemiological and genetic association studies have identified a number of promising dietary and genetic risk factors for IBD. These preliminary studies have led to major interest in investigating the complex interaction between diet, host genetics, the gut microbiota and immune function in the pathogenesis of IBD. In this Review, we discuss the recent epidemiological, gene-environment interaction, microbiome and animal studies that have explored the relationship between diet and the risk of IBD. In addition, we highlight the limitations of these prior studies, in part by explaining their contradictory findings, and review future directions.
To examine the relationship between Mediterranean diet and risk of later-onset Crohn's disease (CD) or ulcerative colitis (UC).
We conducted a prospective cohort study of 83 147 participants (age ...range: 45-79 years) enrolled in the Cohort of Swedish Men and Swedish Mammography Cohort. A validated food frequency questionnaire was used to calculate an adherence score to a modified Mediterranean diet (mMED) at baseline in 1997. Incident diagnoses of CD and UC were ascertained from the Swedish Patient Register. We used Cox proportional hazards modelling to calculate HRs and 95% CI.
Through December of 2017, we confirmed 164 incident cases of CD and 395 incident cases of UC with an average follow-up of 17 years. Higher mMED score was associated with a lower risk of CD (P
=0.03) but not UC (P
=0.61). Compared with participants in the lowest category of mMED score (0-2), there was a statistically significant lower risk of CD (HR=0.42, 95% CI 0.22 to 0.80) but not UC (HR=1.08, 95% CI 0.74 to 1.58). These associations were not modified by age, sex, education level, body mass index or smoking (all P
>0.30). The prevalence of poor adherence to a Mediterranean diet (mMED score=0-2) was 27% in our cohorts, conferring a population attributable risk of 12% for later-onset CD.
In two prospective studies, greater adherence to a Mediterranean diet was associated with a significantly lower risk of later-onset CD.
Summary Background Colorectal cancer is the third most common cancer worldwide and has a high mortality rate. We tested the hypothesis that only one flexible sigmoidoscopy screening between 55 and 64 ...years of age can substantially reduce colorectal cancer incidence and mortality. Methods This randomised controlled trial was undertaken in 14 UK centres. 170 432 eligible men and women, who had indicated on a previous questionnaire that they would accept an invitation for screening, were randomly allocated to the intervention group (offered flexible sigmoidoscopy screening) or the control group (not contacted). Randomisation by sequential number generation was done centrally in blocks of 12, with stratification by trial centre, general practice, and household type. The primary outcomes were the incidence of colorectal cancer, including prevalent cases detected at screening, and mortality from colorectal cancer. Analyses were intention to treat and per protocol. The trial is registered, number ISRCTN28352761. Findings 113 195 people were assigned to the control group and 57 237 to the intervention group, of whom 112 939 and 57 099, respectively, were included in the final analyses. 40 674 (71%) people underwent flexible sigmoidoscopy. During screening and median follow-up of 11·2 years (IQR 10·7–11·9), 2524 participants were diagnosed with colorectal cancer (1818 in control group vs 706 in intervention group) and 20 543 died (13 768 vs 6775; 727 certified from colorectal cancer 538 vs 189). In intention-to-treat analyses, colorectal cancer incidence in the intervention group was reduced by 23% (hazard ratio 0·77, 95% CI 0·70–0·84) and mortality by 31% (0·69, 0·59–0·82). In per-protocol analyses, adjusting for self-selection bias in the intervention group, incidence of colorectal cancer in people attending screening was reduced by 33% (0·67, 0·60–0·76) and mortality by 43% (0·57, 0·45–0·72). Incidence of distal colorectal cancer (rectum and sigmoid colon) was reduced by 50% (0·50, 0·42–0·59; secondary outcome). The numbers needed to be screened to prevent one colorectal cancer diagnosis or death, by the end of the study period, were 191 (95% CI 145–277) and 489 (343–852), respectively. Interpretation Flexible sigmoidoscopy is a safe and practical test and, when offered only once between ages 55 and 64 years, confers a substantial and longlasting benefit. Funding Medical Research Council, National Health Service R&D, Cancer Research UK, KeyMed.
Pain affects approximately 80% of patients with pancreatic cancer, with half requiring strong opioid analgesia, namely: morphine-based drugs on step three of the WHO analgesic ladder (as opposed to ...the weak opioids: codeine and tramadol). The presence of pain is associated with reduced survival. This article reviews the literature regarding pain: prevalence, mechanisms, pharmacological, and endoscopic treatments and identifies areas for research to develop individualized patient pain management pathways. The online literature review was conducted through: PubMed, Clinical Key, Uptodate, and NICE Evidence. There are two principal mechanisms for pain: pancreatic duct obstruction and pancreatic neuropathy which, respectively, activate mechanical and chemical nociceptors. In pancreatic neuropathy, several histological, molecular, and immunological changes occur which correlate with pain including: transient receptor potential cation channel activation and mast cell infiltration. Current pain management is empirical rather etiology-based and is informed by the WHO analgesic ladder for first-line therapies, and then endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in patients with resistant pain. For EUS-CPN, there is only one clinical trial reporting a benefit, which has limited generalizability. Case series report pancreatic duct stenting gives effective analgesia, but there are no clinical trials. Progress in understanding the mechanisms for pain and when this occurs in the natural history, together with assessing new therapies both pharmacological and endoscopic, will enable individualized care and may improve patients’ quality of life and survival.
Microbiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and risk patterns is lacking.
To assess the association between oral antibiotic ...use and CRC risk.
A matched case-control study (incident CRC cases and up to five matched controls) was performed using the Clinical Practice Research Datalink from 1989 to 2012.
28 980 CRC cases and 137 077 controls were identified. Oral antibiotic use was associated with CRC risk, but effects differed by anatomical location. Antibiotic use increased the risk of colon cancer in a dose-dependent fashion (p
<0.001). The risk was observed after minimal use, and was greatest in the proximal colon and with antibiotics with anti-anaerobic activity. In contrast, an inverse association was detected between antibiotic use and rectal cancers (p
=0.003), particularly with length of antibiotic exposure >60 days (adjusted OR (aOR), 0.85, 95% CI 0.79 to 0.93) as compared with no antibiotic exposure. Penicillins, particularly ampicillin/amoxicillin increased the risk of colon cancer (aOR=1.09 (1.05 to 1.13)), whereas tetracyclines reduced the risk of rectal cancer (aOR=0.90 (0.84 to 0.97)). Significant interactions were detected between antibiotic use and tumour location (colon vs rectum, p
<0.001; proximal colon versus distal colon, p
=0.019). The antibiotic-cancer association was found for antibiotic exposure occurring >10 years before diagnosis (aOR=1.17 (1.06 to 1.31)).
Oral antibiotic use is associated with an increased risk of colon cancer but a reduced risk of rectal cancer. This effect heterogeneity may suggest differences in gut microbiota and carcinogenesis mechanisms along the lower intestinal tract.
Inhibitors of alpha(v)beta(3) and alpha(v)beta(5) integrin have entered clinical trials as antiangiogenic agents for cancer treatment but generally have been unsuccessful. Here we present in vivo ...evidence that low (nanomolar) concentrations of RGD-mimetic alpha(v)beta(3) and alpha(v)beta(5) inhibitors can paradoxically stimulate tumor growth and tumor angiogenesis. We show that low concentrations of these inhibitors promote VEGF-mediated angiogenesis by altering alpha(v)beta(3) integrin and vascular endothelial growth factor receptor-2 trafficking, thereby promoting endothelial cell migration to VEGF. The proangiogenic effects of low concentrations of RGD-mimetic integrin inhibitors could compromise their efficacy as anticancer agents and have major implications for the use of RGD-mimetic compounds in humans.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In this study, a consortium of intensive care units (ICUs) in Australia and New Zealand reported their experience with admissions associated with infection with the 2009 H1N1 virus. The overall rate ...of ICU admission was estimated to be 28.7 per million persons, approximately 15 times that in previous years. During the period of peak transmission in communities, the ICU bed-occupancy rate ranged from 8.9 to 19.0%.
A consortium of ICUs in Australia and New Zealand report their experience with admissions associated with infection with the 2009 H1N1 virus.
Infection with the 2009 pandemic influenza A (H1N1) virus emerged in Mexico toward the end of the 2008–2009 influenza season in the Northern Hemisphere. As of September 6, 2009, the World Health Organization had reported over 277,607 laboratory-confirmed cases of 2009 H1N1 influenza, with at least 3205 deaths.
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From June through August 2009, Australia and New Zealand experienced the combined effect of the pandemic and winter in the Southern Hemisphere. The reported incidence of infection with the 2009 H1N1 virus during winter in Australia and New Zealand was 8 times that reported for the same period in the United States. . . .
Multimorbidity rates are both increasing in prevalence across age ranges, and also increasing in diagnostic importance within and outside the family medicine clinic. Here we aim to describe the ...course of multimorbidity across the lifespan.
This was a retrospective cohort study across 211,953 patients from a large northeastern health care system. Past medical histories were collected in the form of ICD-10 diagnostic codes. Rates of multimorbidity were calculated from comorbid diagnoses defined from the ICD10 codes identified in the past medical histories.
We identify 4 main age groups of diagnosis and multimorbidity. Ages 0 to 10 contain diagnoses which are infectious or respiratory, whereas ages 10 to 40 are related to mental health. From ages 40 to 70 there is an emergence of alcohol use disorders and cardiometabolic disorders. And ages 70 to 90 are predominantly long-term sequelae of the most common cardiometabolic disorders. The mortality of the whole population over the study period was 5.7%, whereas the multimorbidity with the highest mortality across the study period was Circulatory Disorders-Circulatory Disorders at 23.1%.
The results from this study provide a comparison for the presence of multimorbidity within age cohorts longitudinally across the population. These patterns of comorbidity can assist in the allocation to practice resources that will best support the common conditions that patients need assistance with, especially as the patients transition between pediatric, adult, and geriatric care. Future work examining and comparing multimorbidity indices is warranted.
Pancreatic cancer kills more than 250,000 people each year worldwide and has a poor prognosis. The aim of this article is to critically review the epidemiologic evidence for exposures that may either ...increase or decrease the risk. A Medline search was performed for epidemiologic studies and reviews published up to April 2007. Consistent evidence of a positive association was found for family history and cigarette smoking. Many studies documented a positive association with diabetes mellitus and chronic pancreatitis, although the etiologic mechanisms are unclear. Other associations were detected, but the results were either inconsistent or from few studies. These included positive associations with red meat, sugar, fat, body mass index, gallstones, and Helicobacter pylori , and protective effects of increasing parity, dietary folate, aspirin, and statins. There was no evidence linking alcohol or coffee consumption with an increased risk of pancreatic cancer. The associations with many exposures need to be clarified from further epidemiologic work in which there is both precise measurement of risk factors, adjustment for potential confounders, and, for dietary studies, information recorded on the method of food preparation and pattern of consumption. Such work is important to reduce the incidence of this fatal disease.
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