Long-term survival for lymphoid neoplasms and national health expenditure (EUROCARE-6): a retrospective, population-based study.

BACKGROUND: Management of lymphoid malignancies requires substantial health system resources. Total national health expenditure might influence population-based lymphoid malignancy survival. We studied the long-term survival of patients with 12 lymphoid malignancy types and examined whether different levels of national health expenditure might explain differences in lymphoid malignancy prognosis between European countries and regions. METHODS: For this observational, retrospective, population-based study, we analysed the EUROCARE-6 dataset of patients aged 15 or older diagnosed between 2001 and 2013 with one of 12 lymphoid malignancies defined according to International Classification of Disease for Oncology (third edition) and WHO classification, and followed up to 2014 (Jan 1, 2001-Dec 31, 2014). Countries were classified according to their mean total national health expenditure quartile in 2001-13. For each lymphoid malignancy, 5-year and 10-year age-standardised relative survival (ASRS) was calculated using the period approach. Generalised linear models indicated the effects of age at diagnosis, gender, and total national health expenditure on the relative excess risk of death (RER). FINDINGS: 82 cancer registries (61 regional and 21 national) from 27 European countries provided data eligible for 10-year survival estimates comprising 890 730 lymphoid malignancy cases diagnosed in 2001-13. Median follow-up time was 13 years (IQR 13-14). Of the 12 lymphoid malignancies, the 10-year ASRS in Europe was highest for hairy cell leukaemia (82·6% [95% CI 78·9-86·5) and Hodgkin lymphoma (79·3% [78·6-79·9]) and lowest for plasma cell neoplasms (29·5% [28·9-30·0]). RER increased with age at diagnosis, particularly from 55-64 years to 75 years or older, for all lymphoid malignancies. Women had higher ASRS than men for all lymphoid malignancies, except for precursor B, T, or natural killer cell, or not-otherwise specified lymphoblastic lymphoma or leukaemia. 10-year ASRS for each lymphoid malignancy was higher (and the RER lower) in countries in the highest national health expenditure quartile than in countries in the lowest quartile, with a decreasing pattern through quartiles for many lymphoid malignancies. 10-year ASRS for non-Hodgkin lymphoma, the most representative class for lymphoid malignancies based on the number of incident cases, was 59·3% (95% CI 58·7-60·0) in the first quartile, 57·6% (55·2-58·7) in the second quartile, 55·4% (54·3-56·5) in the third quartile, and 44·7% (43·6-45·8) in the fourth quartile; with reference to the European mean, the RER was 0·80 (95% CI 0·79-0·82) in the first, 0·91 (0·90-0·93) in the second, 0·94 (0·92-0·96) in the third, and 1·45 (1·42-1·48) in the fourth quartiles. INTERPRETATION: Total national health expenditure is associated with geographical inequalities in lymphoid malignancy prognosis. Policy decisions on allocating economic resources and implementing evidence-based models of care are needed to reduce these differences. FUNDING: Italian Ministry of Health, European Commission, Estonian Research Council.

Pre-diagnostic circulating resistin concentrations and mortality among individuals with colorectal cancer: Results from the European Prospective Investigation into Cancer and Nutrition study.

Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre-diagnostic serum resistin concentrations in relation to CRC-specific and all-cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC-specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause-specific Cox proportional hazards models and further in sensitivity analyses using Fine-Gray proportional subdistribution hazards models. For all-cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow-up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC-specific mortality (HRQ4vsQ1 = 0.95, 95% CI: 0.73-1.23; Ptrend = .97; and HRper doubling of resistin concentration = 1.00; 95% CI: 0.84-1.19; P = .98) or all-cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre-diagnostic circulating resistin concentrations and CRC-specific or all-cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.

Pre-diagnostic plasma advanced glycation end-products and soluble receptor for advanced glycation end-products and mortality in colorectal cancer patients.

Advanced glycation end-products (AGEs), formed endogenously or obtained exogenously from diet, may contribute to chronic inflammation, intracellular signaling alterations, and pathogenesis of several chronic diseases including colorectal cancer (CRC). However, the role of AGEs in CRC survival is less known. The associations of pre-diagnostic circulating AGEs and their soluble receptor (sRAGE) with CRC-specific and overall mortality were estimated using multivariable-adjusted Cox proportional hazards regression among 1369 CRC cases in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Concentrations of major plasma AGEs, Nε-[carboxy-methyl]lysine (CML), Nε-[carboxy-ethyl]lysine (CEL) and Nδ-[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), were measured using ultra-performance liquid chromatography mass-spectrometry. sRAGE was assessed by enzyme-linked immunosorbent assay. Over a mean follow-up period of 96 months, 693 deaths occurred of which 541 were due to CRC. Individual and combined AGEs were not statistically significantly associated with CRC-specific or overall mortality. However, there was a possible interaction by sex for CEL (Pinteraction = .05). Participants with higher sRAGE had a higher risk of dying from CRC (HRQ5vs.Q1 = 1.67, 95% CI: 1.21-2.30, Ptrend = .02) or any cause (HRQ5vs.Q1 = 1.38, 95% CI: 1.05-1.83, Ptrend = .09). These associations tended to be stronger among cases with diabetes (Pinteraction = .03) and pre-diabetes (Pinteraction <.01) before CRC diagnosis. Pre-diagnostic AGEs were not associated with CRC-specific and overall mortality in individuals with CRC. However, a positive association was observed for sRAGE. Our findings may stimulate further research on the role of AGEs and sRAGE in survival among cancer patients with special emphasis on potential effect modifications by sex and diabetes.

Healthy lifestyle change and all-cause and cancer mortality in the European Prospective Investigation into Cancer and Nutrition cohort.

BACKGROUND: Healthy lifestyles are inversely associated with the risk of noncommunicable diseases, which are leading causes of death. However, few studies have used longitudinal data to assess the impact of changing lifestyle behaviours on all-cause and cancer mortality. METHODS: Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, lifestyle profiles of 308,497 cancer-free adults (71% female) aged 35-70 years at recruitment across nine countries were assessed with baseline and follow-up questionnaires administered on average of 7 years apart. A healthy lifestyle index (HLI), assessed at two time points, combined information on smoking status, alcohol intake, body mass index, and physical activity, and ranged from 0 to 16 units. A change score was calculated as the difference between HLI at baseline and follow-up. Associations between HLI change and all-cause and cancer mortality were modelled with Cox regression, and the impact of changing HLI on accelerating mortality rate was estimated by rate advancement periods (RAP, in years). RESULTS: After the follow-up questionnaire, participants were followed for an average of 9.9 years, with 21,696 deaths (8407 cancer deaths) documented. Compared to participants whose HLIs remained stable (within one unit), improving HLI by more than one unit was inversely associated with all-cause and cancer mortality (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.81, 0.88; and HR: 0.87; 95% CI: 0.82, 0.92; respectively), while worsening HLI by more than one unit was associated with an increase in mortality (all-cause mortality HR: 1.26; 95% CI: 1.20, 1.33; cancer mortality HR: 1.19; 95% CI: 1.09, 1.29). Participants who worsened HLI by more than one advanced their risk of death by 1.62 (1.44, 1.96) years, while participants who improved HLI by the same amount delayed their risk of death by 1.19 (0.65, 2.32) years, compared to those with stable HLI. CONCLUSIONS: Making healthier lifestyle changes during adulthood was inversely associated with all-cause and cancer mortality and delayed risk of death. Conversely, making unhealthier lifestyle changes was positively associated with mortality and an accelerated risk of death.

Circulating free insulin-like growth factor-I and prostate cancer: a case-control study nested in the European prospective investigation into cancer and nutrition.

BACKGROUND: Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk. METHODS: We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics. RESULTS: Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade. CONCLUSIONS: Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk.

Inflammation and Gut Barrier Function-Related Genes and Colorectal Cancer Risk in Western European Populations.

Gut barrier dysfunction and related inflammation are known to be associated with the development and progression of colorectal cancer (CRC). We investigated associations of 292 single-nucleotide polymorphisms (SNPs) from 27 genes related to endotoxins/lipopolysaccharide (LPS) sensing and tolerance, mucin synthesis, inflammation, and Crohn's disease with colon and rectal cancer risks. Incident CRC cases (N=1,374; colon=871, rectum=503) were matched 1:1 to controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. Previously measured serum concentrations of gut barrier function and inflammation biomarkers (flagellin/LPS-specific immunoglobulins and C-reactive protein [CRP]) were available for a sub-set of participants (Ncases=1,001; Ncontrols=667). Forty-two unique SNPs from 19 different genes were associated with serum biomarkers at Punadjusted≤0.05 among controls. Among SNPs associated with a gut permeability score, 24 SNPs were in genes related to LPS sensing and mucin synthesis. Nine out of 12 SNPs associated with CRP were in genes related to inflammation or Crohn's disease. TLR4 was associated with colon cancer at the SNP level (nine SNPs, all Punadjusted≤0.04) and at the gene level (Punadjusted≤0.01). TLR4 rs10759934 was associated with rectal cancer but not colon cancer. Similarly, IL10 was associated with rectal cancer risk at a SNP and gene level (both Punadjusted ≤ 0.01), but not colon cancer. Genes and SNPs were selected a priori therefore we present unadjusted P-values. However, no association was statistically significant after multiple testing correction. This large and comprehensive study has identified gut barrier function and inflammation-related genes possibly contributing to CRC risk in European populations and is consistent with potential etiological links between host genetic background, gut barrier permeability, microbial endotoxemia and CRC development.

Lifestyle changes in middle age and risk of cancer: evidence from the European Prospective Investigation into Cancer and Nutrition.

In this study, we aimed to provide novel evidence on the impact of changing lifestyle habits on cancer risk. In the EPIC cohort, 295,865 middle-aged participants returned a lifestyle questionnaire at baseline and during follow-up. At both timepoints, we calculated a healthy lifestyle index (HLI) score based on cigarette smoking, alcohol consumption, body mass index and physical activity. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI change and risk of lifestyle-related cancers-including cancer of the breast, lung, colorectum, stomach, liver, cervix, oesophagus, bladder, and others-using Cox regression models. We reported hazard ratios (HR) with 95% confidence intervals (CI). Median time between the two questionnaires was 5.7 years, median age at follow-up questionnaire was 59 years. After the follow-up questionnaire, we observed 14,933 lifestyle-related cancers over a median follow-up of 7.8 years. Each unit increase in the HLI score was associated with 4% lower risk of lifestyle-related cancers (HR 0.96; 95%CI 0.95-0.97). Among participants in the top HLI third at baseline (HLI > 11), those in the bottom third at follow-up (HLI ≤ 9) had 21% higher risk of lifestyle-related cancers (HR 1.21; 95%CI 1.07-1.37) than those remaining in the top third. Among participants in the bottom HLI third at baseline, those in the top third at follow-up had 25% lower risk of lifestyle-related cancers (HR 0.75; 95%CI 0.65-0.86) than those remaining in the bottom third. These results indicate that lifestyle changes in middle age may have a significant impact on cancer risk.

Sexuality and self-concept of morbidly obese women who are sexually attracted to men after bariatric surgery: a phenomenological study.

BACKGROUND: Morbid Obesity (MO) is a public health problem that affects a person's physical, psychological and sexual well-being. Women with MO are affected by their body image and self-concept, and obesity stigma may affect women in social and sexual relationships. OBJECTIVE: To describe and understand the experiences of morbidly obese heterosexual women (who are sexually attracted to men) in relation to their body image and sexuality after bariatric surgery. METHODOLOGY: Qualitative study using Merleau-Ponty's hermeneutic phenomenology as a philosophical framework. Data collection took place between 2020 and 2021 in a southern Spanish province. A total of 22 in-depth interviews were conducted using open-ended questions until data saturation was reached. RESULTS: Two main themes were identified: (1) "Escaping from a cruel environment": weight loss to increase self-esteem; with the sub-themes: 'I love myself now', and 'Body image and social relationships; a vicious circle; (2) "Now, I am truly me": accepting my body to reclaim my sexuality, with the sub-themes: 'The body as the focal point of sexuality', and 'When regaining your sex drive reignites your sex life and relationship'. CONCLUSION: Weight loss and body acceptance radically change morbidly obese women's sex lives after bariatric surgery. They rediscover their bodies, have increased self-esteem, and see improvements in their social relationships and sexuality. These women feel seen, loved and desired, and now value their body image and femininity. As they go through continuous improvements following bariatric surgery, they gradually regain self-esteem, acceptance of their bodies and control over their sex life. Even though the women's partners benefit from these improvements, they seem to be afraid of being left.

Obesity is a problem that affects women's physical, psychological and sexual well-being, as well as their social relationships. It is important to explore and understand the experiences of heterosexual women regarding their body and sexuality. After other treatments, women undergo surgery to reduce their obesity. After bariatric surgery women feel happier about themselves, experience less stigma and progressively recover their social and sex lives.

Molecular Mechanisms Linking Genes and Vitamins of the Complex B Related to One-Carbon Metabolism in Breast Cancer: An In Silico Functional Database Study.

Carcinogenesis is closely related to the expression, maintenance, and stability of DNA. These processes are regulated by one-carbon metabolism (1CM), which involves several vitamins of the complex B (folate, B2, B6, and B12), whereas alcohol disrupts the cycle due to the inhibition of folate activity. The relationship between nutrients related to 1CM (all aforementioned vitamins and alcohol) in breast cancer has been reviewed. The interplay of genes related to 1CM was also analyzed. Single nucleotide polymorphisms located in those genes were selected by considering the minor allele frequency in the Caucasian population and the linkage disequilibrium. These genes were used to perform several in silico functional analyses (considering corrected p-values < 0.05 as statistically significant) using various tools (FUMA, ShinyGO, and REVIGO) and databases such as the Kyoto Encyclopedia of Genes and Genomes (KEGG) and GeneOntology (GO). The results of this study showed that intake of 1CM-related B-complex vitamins is key to preventing breast cancer development and survival. Also, the genes involved in 1CM are overexpressed in mammary breast tissue and participate in a wide variety of biological phenomena related to cancer. Moreover, these genes are involved in alterations that give rise to several types of neoplasms, including breast cancer. Thus, this study supports the role of one-carbon metabolism B-complex vitamins and genes in breast cancer; the interaction between both should be addressed in future studies.

Open clinical trial evaluating the efficacy of a novel eyelash growth enhancer with peptides and glycosaminoglycans.

BACKGROUND: Eyelashes play a crucial role in self-image and ocular protection. Enhancements to their structure are of both cosmetic and clinical interest. AIMS: To assess the efficacy of a peptide and glycosaminoglycan-based eyelash enhancer serum in improving eyelash structure. PATIENTS/METHODS: This open-label clinical trial involved 30 females aged 25-65. Eyelashes were assessed at baseline (D0), 4 weeks (D28), and 12 weeks (D84) using specialized software and high-resolution imagery. Measurements included lash number, width, length, volume, arc, and angle. RESULTS: At 12 weeks, significant increases were observed in lash length (+8.3%), number (+5%), width (+10.1%), volume (+14.1%), arc (+13.4%), and angle (+28.3%) compared to baseline. Global Eyelash Assessment (GEA) scores significantly improved, and patient treatment satisfaction increased from 73.34% at D28 to 84.33% at D84. No adverse effects were reported. CONCLUSIONS: The eyelash growth enhancer serum demonstrated significant efficacy in improving eyelash structure by Week 12, with early signs of improvement evident by Week 4. The high patient satisfaction levels underscore the perceived effectiveness of the product.

High adherence to Western dietary pattern increases breast cancer risk (an EPIC-Spain study).

OBJECTIVE: To explore the association between three previously identified and validated dietary patterns (Western, Prudent and Mediterranean) and breast cancer risk by tumour subtype and menopausal status. METHODS: Data from the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition study provided epidemiological information (including diet and cancer incidence) from 24,892 women (639 breast cancer cases) recruited between 1992 and 1996. The associations between adherence to the three dietary patterns and breast cancer risk (overall and by tumour subtype) were explored by fitting multivariate Cox proportional hazards regression models stratified by region, among other variables. A possible interaction with menopausal status (changing over time) was explored. RESULTS: No clear association of the Prudent and Mediterranean dietary patterns with breast cancer risk was found. When compared with women with a level of adherence to the Western diet in the first quartile, women with a level of adherence in the third (hazard ratio (95 % confidence interval) (HR(95%CI)):1.37 (1.07;1.77)) and fourth quartiles (1.37 (1.03;1.83)); p for curvature of splines = 0.016) showed a non-linear increased risk, especially postmenopausal women (HR (95 % CI) 1.30 (0.98;1.72) in the third and 1.42 (1.04;1.94) in the fourth quartiles; p for curvature of splines = 0.081) and for estrogen or progesterone receptor positive with human epidermal growth factor receptor 2 negative tumours (HR (95 % CI) 1.62 (1.10;2.38) and 1.71 (1.11;2.63) for the third and fourth quartiles respectively; p for curvature of splines = 0.013). CONCLUSIONS: Intake of foods such as high-fat dairy products, red and processed meats, refined grains, sweets, caloric drinks, convenience food and sauces might be associated with a higher risk of breast cancer.

In Situ Use of Mining Substrates for Wetland Construction: Results of a Pilot Experiment.

This paper evaluates an experimental wetland as part of a pilot soil reclamation project in a mining area. The wetland was constructed using materials of mining origin from the area; most reactive materials of acid pH were stabilised using limestone filler. The study selected macrophytes that are tolerant to potentially toxic elements (PTEs) and resistant to salinity, namely Phragmites australis, Juncus effusus, and Iris pseudacorus. These macrophytes were then placed in pots containing substrates composed of different mixtures of topsoil, peat, and mining waste (black or yellow sand). A thorough analysis of the physicochemical and mineralogical characteristics of the materials included studies of PTE mobilisation. This study emphasises the significance of the rhizosphere in directing the transfer of PTEs to the plant and the correlation between the substrate and the development of plant defence mechanisms, such as the formation of Fe-plates. Scanning electron microscopy was used to highlight these aspects and validate the results of the analytical determinations. These wetlands can be proposed as a phytoremediation strategy for areas affected by mining and maritime influence. They are easy to construct and remain stable, providing important ecosystem services such as the natural attenuation of acid mine drainage, support for vegetation development and fauna, and a clean ecosystem.

Toxinological profile and histopathological alterations induced by Bothrocophias campbelli venom from Colombia.

Snakebite envenomings most frequently reported in Colombia are caused by snakes of the genera Bothrops, Bothriechis, Bothrocophias, and Porthidium. Their venoms induce local and systemic pathophysiological effects, sometimes leading to permanent sequelae such as reduced mobility of the limbs, amputations, besides the risk of death. The genus Bothrocophias includes nine species, among which B. campbelli has a distribution restricted to the department of Nariño in Colombia. In this work we determined the toxinological profile its venom, by performing assays for the lethal, hemorrhagic, edematogenic, and myotoxic activities in mouse models, as well as for in vitro coagulant activity on human plasma. The lethal toxicity of the venom was 142.7 µg venom/mouse (111.4-179.8 µg/mouse; 6.6-10.6 µg/g body weight) by intraperitoneal route. Its hemorrhagic activity (minimum hemorrhagic dose: 12.7 ± 2.3 µg) is generally weaker compared to other South American vipers, but edematogenic (minimum edematogenic dose 1.0 ± 0.3 µg), and myotoxic (minimum myotoxic dose 3.9 ± 2.5 µg) activities are very potent. Histopathological examination of the injected mouse gastrocnemius muscle showed prominent disorganization of the myofibrils, myonecrosis, and an intense inflammatory leukocyte infiltrate. In vitro, the minimal coagulant dose was 12.3 ± 0.5 µg. Overall, this toxinological profile would predict that the clinical picture of envenomings by B. campbelli might be characterized by moderate disturbances in the coagulation cascade, mild local hemorrhage, and, conversely, severe myonecrosis and edema, which could potentially lead to compartment syndrome and gangrene.

Nitrosyl-Heme and Heme Iron Intake from Processed Meats in Subjects from the EPIC-Spain Cohort.

BACKGROUND: The consumption of processed meats (PMs) and red meats are linked to the likelihood of developing colorectal cancer. Various theories have been proposed to explain this connection, focusing on nitrosyl-heme and heme iron intake. We hypothesized that differences in nitrosyl-heme and heme iron intakes will be associated with various sociodemographic and lifestyle factors. METHODS: The study included 38,471 healthy volunteers (62% females) from five Spanish regions within the EPIC-Spain cohort. High-Performance Liquid Chromatography (HPLC) determined nitrosyl-heme and heme iron levels in the 39 most consumed PMs. Food intake was assessed using validated questionnaires in interviews. Nitrosyl-heme and heme iron intakes, adjusted for sex, age, body mass index (BMI), center, and energy intake, were expressed as geometric means due to their skewed distribution. Variance analysis identified foods explaining the variability of nitrosyl-heme and heme iron intakes. RESULTS: The estimated intakes were 528.6 µg/day for nitrosyl-heme and 1676.2 µg/day for heme iron. Significant differences in nitrosyl-heme intake were found by sex, center, energy, and education level. Heme iron intake varied significantly by sex, center, energy, and smoking status. "Jamón serrano" and "jamón cocido/jamón de York" had the highest intake values, while "morcilla asturiana" and "sangrecilla" were key sources of nitrosyl-heme and heme iron. CONCLUSIONS: This is the first study to estimate levels of nitrosyl-heme intake directly in PMs for a large sample, revealing variations based on sex, BMI, smoking, and activity. Its data aids future exposure estimations in diverse populations.

Relationship between exposure to parabens and benzophenones and prostate cancer risk in the EPIC-Spain cohort.

The etiology of prostate cancer is not fully elucidated. Among environmental risk factors, endocrine-disrupting chemicals (EDCs) deserve special mention, as they alter metabolic pathways involved in hormone-dependent cancers. Epidemiological evidence assessing the carcinogenicity of EDCs is scarce. The aim of this study was to analyze the relationship between exposure to parabens and benzophenones and prostate cancer risk. We conducted a case-cohort study nested within the EPIC-Spain prospective multi-center cohort. Study population comprised 1,838 sub-cohort participants and 467 non-sub-cohort prostate cancer cases. Serum concentrations of four parabens and two benzophenones were assessed at recruitment. Covariates included age, physical activity, tobacco smoking, alcohol consumption, body mass index, educational level and diabetes. Borgan II weighted Cox proportional hazard models stratified by study center were applied. Median follow-up time was 18.6 years (range = 1.0-21.7 years). Most sub-cohort participants reached primary education at most (65.5%), were overweight (57.7%) and had a low level of physical activity (51.3%). Detection percentages varied widely, being lowest for butyl-paraben (11.3%) and highest for methyl-paraben (80.7%), which also showed the highest geometric mean (0.95 ng/ml). Cases showed significantly higher concentrations of methyl-paraben (p = 0.041) and propyl-paraben (p < 0.001). In the multivariable analysis, methyl-paraben - log-transformed (HR = 1.07; 95%CI = 1.01-1.12) and categorized into tertiles (HR = 1.60 for T3; 95%CI = 1.16-2.20) -, butyl-paraben - linear (HR = 1.19; 95%CI = 1.14-1.23) and log-transformed (HR = 1.17; 95%CI = 1.01-1.35) - and total parabens - log-transformed (HR = 1.09; 95%CI = 1.02-1.17) and categorized into tertiles (HR = 1.62 for T3; 95%CI = 1.10-2.40) - were associated with an increased prostate cancer risk. In this study, higher concentrations of methyl-, butyl-, and total parabens were positively associated with prostate cancer risk. Further research is warranted to confirm these findings.

Nitrosyl-heme and Heme Iron Intake from Processed Meats and Risk of Colorectal Cancer in the EPIC-Spain Cohort.

BACKGROUND: The International Agency for Research on Cancer classified processed meats (PM) as "carcinogenic" and red meat as "probably carcinogenic" for humans. The possible relationship between colorectal cancer risk and the mechanisms involved in the carcinogenesis of PMs have not been established yet. Nitrosyl-heme and heme iron have been proposed as potential-related compounds. The aim of this study was to determine the association between nitrosyl-heme and heme iron intake and colorectal cancer risk among participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain study. METHODS: This prospective study included 38,262 men and women from the EPIC-Spain study. Food consumption was assessed using diet history and food composition tables. Heme iron and nitrosyl-heme intake were determined by estimating the intake of PM items and conducting laboratory analyses. HR estimates were obtained by proportional hazard models, stratified by age at recruitment and study center and adjusted for sex, total energy intake, education, smoking, body mass index, waist size, physical activity, lifetime alcohol, fibre, calcium, and familiar colorectal cancer history. RESULTS: During a mean follow-up of 16.7 years, 577 participants were diagnosed with colorectal cancer. We found no overall association between nitrosyl-heme [HRT3vsT1, 0.98; 95% confidence interval (CI), 0.79-1.21] or heme iron intakes (HRT3vsT1, 0.88; 95% CI, 0.70-1.10) with colorectal cancer risk, nor according to tumor subtypes. CONCLUSIONS: Our study found no evidence supporting a link between nitrosyl-heme or heme iron intake and colorectal cancer risk in Spanish subjects. IMPACT: As research on nitrosyl-heme is preliminary, more heterogeneous studies are necessary to provide more convincing evidence on their role in colorectal cancer carcinogenesis.

Dietary index based on the Food Standards Agency nutrient profiling system and risk of Crohn's disease and ulcerative colitis.

BACKGROUND: Nutri-score is now widely available in food packages in Europe. AIM: To study the overall nutritional quality of the diet in relation to risks of Crohn's disease (CD) and ulcerative colitis (UC), in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort METHODS: We collected dietary data at baseline from validated food frequency questionnaires. We used a dietary index based on the UK Food Standards Agency modified nutrient profiling system (FSAm-NPS-DI) underlying the Nutri-Score label, to measure the nutritional quality of the diet. We estimated the association between FSAm-NPS-DI score, and CD and UC risks using Cox models stratified by centre, sex and age; and adjusted for smoking status, BMI, physical activity, energy intake, educational level and alcohol intake. RESULTS: We included 394,255 participants (68.1% women; mean age at recruitment 52.1 years). After a mean follow-up of 13.6 years, there were 184 incident cases of CD and 459 incident cases of UC. Risk of CD was higher in those with a lower nutritional quality, that is higher FSAm-NPS-DI Score (fourth vs. first quartile: aHR: 2.04, 95% CI: 1.24-3.36; p-trend: <0.01). Among items of the FSAm-NPS-DI Score, low intakes of dietary fibre and fruits/vegetables/legumes/nuts were associated with higher risk of CD. Nutritional quality was not associated with risk of UC (fourth vs. first quartile of the FSAm-NPS-DI Score: aHR: 0.91, 95% CI: 0.69-1.21; p-trend: 0.76). CONCLUSIONS: A diet with low nutritional quality as measured by the FSAm-NPS-DI Score is associated with a higher risk of CD but not UC.

Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk: a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND: Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain. METHODS: In a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk. FINDINGS: Of the 97 assayed lipids, 24 were inversely associated (nominally p < 0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (ORper doubling 0.60, 95% CI 0.47-0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (ORper doubling 0.71, 95% CI 0.59-0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding the first 5 years of follow-up after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30 phosphatidylcholines, were weakly inversely associated with colorectal cancer. INTERPRETATION: Elevated pre-diagnostic circulating levels of SM (OH) C22:2 and PC ae C34:3 and lipid patterns including phosphatidylcholines and sphingolipids were associated with lower colorectal cancer risk. This study may provide insight into potential links between specific lipids and colorectal cancer development. Additional prospective studies are needed to validate the observed associations. FUNDING: World Cancer Research Fund (reference: 2013/1002); European Commission (FP7: BBMRI-LPC; reference: 313010).

Exploring Definitions and Predictors of Response to Biologics for Severe Asthma.

BACKGROUND: Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging. OBJECTIVE: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response. METHODS: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in four asthma outcome domains were assessed in the 1-year period before and after biologic initiation in patients with a predefined level of prebiologic impairment. Responder cutoffs were 50% or greater reduction in exacerbation rate, 50% or greater reduction in long-term oral corticosteroid daily dose, improvement in one or more category in asthma control, and 100 mL or greater improvement in FEV1. Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis. RESULTS: A total of 2,210 patients were included. Responder rate ranged from 80.7% (n = 566 of 701) for exacerbation response to 10.6% (n = 9 of 85) for a four-domain response. Many responders still exhibited significant impairment after biologic initiation: 46.7% (n = 206 of 441) of asthma control responders with uncontrolled asthma before the biologic still had incompletely controlled disease postbiologic initiation. Predictors of response were outcome-dependent. Lung function responders were more likely to have higher prebiologic FeNO (odds ratio = 1.20 for every 25-parts per billion increase), and shorter asthma duration (odds ratio = 0.81 for every 10-year increase in duration). Higher blood eosinophil count and the presence of type 2-related comorbidities were positively associated with higher odds of meeting long-term oral corticosteroid, control, and lung function responder criteria. CONCLUSIONS: Our findings underscore the multimodal nature of response, showing that many responders experience residual symptoms after biologic initiation and that predictors of response vary according to the outcome assessed.

Feasibility of Using the International Classification of Functioning, Disability and Health for Children and Youth (ICF-CY) as a Framework for Aquatic Activities: A Scoping Review.

(1) Background: In recent years, reviewing studies of aquatic activities for children with developmental delays has been a complex task due to the multitude of indices and professional languages. (2) Aim: To determine if the ICF-CY framework can be used as the unifying language in AA studies of children with DD. (3) Methods: Part One-A systematic review of selected studies focusing on goals that were found to be positive. These goals were linked to the ICF-CY categories. Part Two-Review of all studies using the ICF-CY's functioning components. (4) Results: Most of the positive goals were properly linked to ICF-CY and made it possible to review the 71 articles in a uniform language. (5) Conclusions: It is feasible to use the ICF framework as a universal structure and language.