The spread of SARS-CoV-2 in Spain: Hygiene habits, sociodemographic profile, mobility patterns and comorbidities.

COVID-19 constitutes the largest pandemic in the last 100 years. In view of the rapid spread of the virus, it is necessary to study the sociodemographic characteristics, hygiene habits, activity and mobility, and comorbidities of SARS-CoV-2 infection to be able to implement prevention strategies. For this purpose, a survey including the variables of interest was designed to try to understand the exponential spread of the virus despite the implemented severe restrictive mobility measures during the period of maximum confinement in Spain. This study conducted throughout the Spanish territory aims to clarify other routes of transmission of the COVID-19 during confinement, risk factors, and the effectiveness of the recommended hygiene measures to detect critical points of exposure to the virus and thus reduce its spread in this and possible future pandemics that could compromise public health. Our results show that living with a COVID-19 patient increased the risk of contagion by 60 times. Among all the sociodemographic variables analyzed, walking the dog have shown to have the strongest effect by increasing the risk by 78%. The most effective hygiene measure reducing the prevalence of the disease was the disinfection of products purchased from the market upon arrival home (which reduced the risk by 94%), above other hygiene measures, such as wearing masks, gloves, ethanol disinfection, bleaching and others. The mobility variable studied that showed the largest increase in the prevalence of the disease was working on site at the workplace (increased the risk by 76%). A significant higher prevalence of the disease was also detected among respondents who used the modality of acquiring basic commodities using home delivery service compared to those who chose in-store shopping.

Mediation analysis of the alcohol-postmenopausal breast cancer relationship by sex hormones in the EPIC cohort.

Alcohol consumption is associated with higher risk of breast cancer (BC); however, the biological mechanisms underlying this association are not fully elucidated, particularly the extent to which this relationship is mediated by sex hormone levels. Circulating concentrations of estradiol, testosterone, their free fractions and sex-hormone binding globulin (SHBG), were examined in 430 incident BC cases and 645 matched controls among alcohol-consuming postmenopausal women nested within the European Prospective Investigation into Cancer and Nutrition. Mediation analysis was applied to assess whether individual hormone levels mediated the relationship between alcohol intake and BC risk. An alcohol-related hormonal signature, obtained by partial least square (PLS) regression, was evaluated as a potential mediator. Total (TE), natural direct and natural indirect effects (NIE) were estimated. Alcohol intake was positively associated with overall BC risk and specifically with estrogen receptor-positive tumors with respectively TE = 1.17(95%CI: 1.01,1.35) and 1.36(1.08,1.70) for a 1-standard deviation (1-SD) increase of intake. There was no evidence of mediation by sex steroids or SHBG separately except for a weak indirect effect through free estradiol where NIE = 1.03(1.00,1.06). However, an alcohol-related hormonal signature negatively associated with SHBG and positively with estradiol and testosterone was associated with BC risk (odds ratio [OR] = 1.25 [1.07,1.47]) for a 1-SD higher PLS score, and had a statistically significant NIE accounting for a mediated proportion of 24%. There was limited evidence of mediation of the alcohol-BC association by individual sex hormones. However, a hormonal signature, reflecting lower levels of SHBG and higher levels of sex steroids, mediated a substantial proportion of the association.

Disparities in the management of cutaneous malignant melanoma. A population-based high-resolution study.

Population-based cancer registry data from three Spanish areas were used to assess the patterns of care and adherence to guidelines for cutaneous malignant melanoma. We included 934 cases diagnosed in 2009-2013. Completeness of the pathology reports, imaging for detecting distant metastasis and the use of sentinel lymph node biopsy (SLNB) were analysed. The proportion of pathology reports that mentioned the essential pathological features required for T staging was 93%, ranging across geographic areas from 81% to 98% (p < 0.001). The percentage of low-risk patients who underwent no imaging studies, as proposed by guidelines, or only chest imaging ranged among areas from 0.6% to 84% (p < 0.001). Of the patients with clinically node-negative melanoma >1 mm thick and no distant metastases, 68% underwent SLNB, varying by area from 61% to 78% (p = 0.017). This study revealed wide geographic variation in different aspects of melanoma care. The use of a standardised structured pathology report could strengthen the completeness of reporting. Improvement strategies should also include efforts to reduce overuse of imaging in low-risk patients and to increase the adherence to guidelines recommendations on the use of SLNB.

Coffee Drinking and Mortality in 10 European Countries: A Multinational Cohort Study.

BACKGROUND: The relationship between coffee consumption and mortality in diverse European populations with variable coffee preparation methods is unclear. OBJECTIVE: To examine whether coffee consumption is associated with all-cause and cause-specific mortality. DESIGN: Prospective cohort study. SETTING: 10 European countries. PARTICIPANTS: 521 330 persons enrolled in EPIC (European Prospective Investigation into Cancer and Nutrition). MEASUREMENTS: Hazard ratios (HRs) and 95% CIs estimated using multivariable Cox proportional hazards models. The association of coffee consumption with serum biomarkers of liver function, inflammation, and metabolic health was evaluated in the EPIC Biomarkers subcohort (n = 14 800). RESULTS: During a mean follow-up of 16.4 years, 41 693 deaths occurred. Compared with nonconsumers, participants in the highest quartile of coffee consumption had statistically significantly lower all-cause mortality (men: HR, 0.88 [95% CI, 0.82 to 0.95]; P for trend < 0.001; women: HR, 0.93 [CI, 0.87 to 0.98]; P for trend = 0.009). Inverse associations were also observed for digestive disease mortality for men (HR, 0.41 [CI, 0.32 to 0.54]; P for trend < 0.001) and women (HR, 0.60 [CI, 0.46 to 0.78]; P for trend < 0.001). Among women, there was a statistically significant inverse association of coffee drinking with circulatory disease mortality (HR, 0.78 [CI, 0.68 to 0.90]; P for trend < 0.001) and cerebrovascular disease mortality (HR, 0.70 [CI, 0.55 to 0.90]; P for trend = 0.002) and a positive association with ovarian cancer mortality (HR, 1.31 [CI, 1.07 to 1.61]; P for trend = 0.015). In the EPIC Biomarkers subcohort, higher coffee consumption was associated with lower serum alkaline phosphatase; alanine aminotransferase; aspartate aminotransferase; γ-glutamyltransferase; and, in women, C-reactive protein, lipoprotein(a), and glycated hemoglobin levels. LIMITATIONS: Reverse causality may have biased the findings; however, results did not differ after exclusion of participants who died within 8 years of baseline. Coffee-drinking habits were assessed only once. CONCLUSION: Coffee drinking was associated with reduced risk for death from various causes. This relationship did not vary by country. PRIMARY FUNDING SOURCE: European Commission Directorate-General for Health and Consumers and International Agency for Research on Cancer.

Malondialdehyde as a Prognostic Factor in Alcoholic Hepatitis.

AIMS: Alcoholic hepatitis is a severe complication of alcoholism, associated with high short-term mortality. Although pathogenesis remains obscure, it is generally accepted that lipopolysaccharide-induced cytokine secretion with further generation of reactive oxygen species (ROS) play outstanding roles. Prognosis is uncertain, and the usually employed prognostic scores do not include variables related to ROS generation. Therefore, this study was performed to assess short-term prognostic value of cytokines, nutritional status, different scores [Maddrey, model for end-stage liver disease (MELD), albumin, bilirubin, INR, creatinine index (ABIC), Lille, Glasgow, MELD-Na, Child-Pugh] and malondialdehyde (MDA, as an indicator of lipid peroxidation) at admission and after 1 week, among patients affected by severe acute alcoholic hepatitis (Maddrey index >32). METHODS: Sixty-two patients affected by severe acute alcoholic hepatitis, for whom we calculated Maddrey, MELD, ABIC, Lille, Glasgow, MELD-Na, Child-Pugh, and determined serum MDA and interleukin (IL)-6, IL-8, IL-4, tumor necrosis factor alpha and interferon gamma levels at admission and after 1 week. RESULTS: Twenty-four patients died during the follow-up period. MDA showed a better prognostic accuracy than the aforementioned scores, both at admission and after 1 week. CONCLUSION: Our study supports the importance of including MDA assessment in the prognostic evaluation of patients with alcoholic hepatitis. SHORT SUMMARY: Alcoholic hepatitis is associated with high short-term mortality. Although not included in prognostic scores, lipid peroxidation plays an outstanding role in its pathogenesis. We found that malondialdehyde levels showed a better prognostic accuracy than the usually employed scores. Therefore, it should be included in the prognostic evaluation of these patients.

Childhood cancer survival in Europe 1999-2007: results of EUROCARE-5--a population-based study.

BACKGROUND: Survival and cure rates for childhood cancers in Europe have greatly improved over the past 40 years and are mostly good, although not in all European countries. The EUROCARE-5 survival study estimates survival of children diagnosed with cancer between 2000 and 2007, assesses whether survival differences among European countries have changed, and investigates changes from 1999 to 2007. METHODS: We analysed survival data for 157,499 children (age 0-14 years) diagnosed between Jan 1, 1978 and Dec 31, 2007. They came from 74 population-based cancer registries in 29 countries. We calculated observed, country-weighted 1-year, 3-year, and 5-year survival for major cancers and all cancers combined. For comparison between countries, we used the corrected group prognosis method to provide survival probabilities adjusted for multiple confounders (sex, age, period of diagnosis, and, for all cancers combined without CNS cancers, casemix). Age-adjusted survival differences by area and calendar period were calculated with period analysis and were given for all cancers combined and the major cancers. FINDINGS: We analysed 59,579 cases. For all cancers combined for children diagnosed in 2000-07, 1-year survival was 90.6% (95% CI 90.2-90.9), 3-year survival was 81.0 % (95% CI 80.5-81.4), and 5-year survival was 77.9% (95% CI 77.4-78.3). For all cancers combined, 5-year survival rose from 76.1% (74.4-77.7) for 1999-2001, to 79.1% (77.3-80.7) for 2005-07 (hazard ratio 0.973, 95% CI 0.965-0.982, p<0.0001). The greatest improvements were in eastern Europe, where 5-year survival rose from 65.2% (95% CI 63.1-67.3) in 1999-2001, to 70.2% (67.9-72.3) in 2005-07. Europe-wide average yearly change in mortality (hazard ratio) was 0.939 (95% CI 0.919-0.960) for acute lymphoid leukaemia, 0.959 (0.933-0.986) for acute myeloid leukaemia, and 0.940 (0.897-0.984) for non-Hodgkin lymphoma. Mortality for all of Europe did not change significantly for Hodgkin's lymphoma, Burkitt's lymphoma, CNS tumours, neuroblastoma, Wilms' tumour, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma. Disparities for 5-year survival persisted between countries and regions, ranging from 70% to 82% (for 2005-07). INTERPRETATION: Several reasons might explain persisting inequalities. The lack of health-care resources is probably most important, especially in some eastern European countries with limited drug supply, lack of specialised centres with multidisciplinary teams, delayed diagnosis and treatment, poor management of treatment, and drug toxicity. In the short term, cross-border care and collaborative programmes could help to narrow the survival gaps in Europe. FUNDING: Italian Ministry of Health, European Commission, Compagnia di San Paolo Foundation.

Value of inflammatory response and oxidative damage in the diagnosis of infections in severe alcoholic hepatitis.

Severe alcoholic hepatitis is the most lethal complication in alcohol dependent patients. The concurrence of infections in these patients is very frequent. Both produce a systemic inflammatory response syndrome (SIRS), secondary to intense release of inflammatory cytokines, which can complicate the diagnosis. In our study, Interleukin (IL)-6 and IL-10 levels are higher in patients with SIRS (p<0.001 and p = 0.033, respectively). IL-4, IL-6, Interferon-gamma (IFNγ), Tumor necrosis factor alpha (TNFα) and IL-17 levels correlate with liver function, as estimated by MELD-Na (p = 0.018, p = 0.008, p = 0.009, p = 0.016 and p = 0.006, respectively). Malondialdehyde (MDA), a product of lipid peroxidation and marker of cell damage, also correlates with liver function (p = 0.002), but not with SIRS or infections. Only elevated IL-6 correlates independently with the presence of infections (RR=1.023 IC 95% 1.000-1.047), so it may be useful for the correct diagnosis in these patients. Values greater than 30 pg/mL have a sensitivity: 86.7% and specificity: 94.7% for the diagnosis of infections.

[Prevention of Neonatal Group B Sreptococcal Infection. Spanish Recommendations. Update 2012. SEIMC/SEGO/SEN/SEQ/SEMFYC Consensus Document]. / Prevención de la infección perinatal por estreptococo del grupo B. Recomendaciones españolas. Actualización 2012. Documento de consenso SEIMC/SEGO/SEN/SEQ/SEMFYC.

Group B streptococci (GBS) remain the most common cause of early onset neonatal sepsis. In 2003 the Spanish Societies of Obstetrics and Gynaecology, Neonatology, Infectious Diseases and Clinical Microbiology, Chemotherapy, and Family and Community Medicine published updated recommendations for the prevention of early onset neonatal GBS infection. It was recommended to study all pregnant women at 35-37 weeks gestation to determine whether they were colonised by GBS, and to administer intrapartum antibiotic prophylaxis (IAP) to all colonised women. There has been a significant reduction in neonatal GBS infection in Spain following the widespread application of IAP. Today most cases of early onset GBS neonatal infection are due to false negative results in detecting GBS, to the lack of communication between laboratories and obstetric units, and to failures in implementing the prevention protocol. In 2010, new recommendations were published by the CDC, and this fact, together with the new knowledge and experience available, has led to the publishing of these new recommendations. The main changes in these revised recommendations include: microbiological methods to identify pregnant GBS carriers and for testing GBS antibiotic sensitivity, and the antibiotics used for IAP are updated; The significance of the presence of GBS in urine, including criteria for the diagnosis of UTI and asymptomatic bacteriuria in pregnancy are clarified; IAP in preterm labour and premature rupture of membranes, and the management of the newborn in relation to GBS carrier status of the mother are also revised. These recommendations are only addressed to the prevention of GBS early neonatal infection, are not effective against late neonatal infection.

Cerebral Abscess Due to Nocardia beijingensis Associated With HIV: Case Report and Mini Review.

Brain abscesses are severe focal infections of the central nervous system. We report the case of a 37-year-old patient with a recent diagnosis of HIV, who presented with weakness in the left arm that progressed to left hemiplegia, ipsilateral paresthesia, holo cranial headache, fever accompanied by chills, and left tonic-clonic movements. A craniectomy and lesion resection were performed along with antimicrobial treatment. Subsequently, the patient persisted with left hemiplegia, which significantly improved after the procedure and gradually through physical physiotherapy. During the investigation, we complete medical history, physical examination, Image tests, laboratory tests, and cultures. After the finalization of the approach, the final diagnosis was a brain abscess due to Nocardia beijingensis associated with HIV. The patient was managed with anticonvulsants: levetiracetam, antimicrobials: ceftriaxone, trimethoprim/sulfamethoxazole, metronidazole, and vancomycin, Craniotomy plus resection of two brain abscesses, Steroidal anti-inflammatory: dexamethasone and antiretroviral therapy. With this, the patient was discharged successfully from the hospital.

Sclerostin, vascular risk factors, and brain atrophy in excessive drinkers.

Objective: Heavy alcohol consumption causes several organic complications, including vessel wall calcification. Vascular damage may be involved in the development of brain atrophy and cognitive impairment. Recently, sclerostin (whose levels may be altered in alcoholics) has emerged as a major vascular risk factor. The objective of the present study is to analyze the prevalence of vascular calcifications in alcoholics, and the relationships of these lesions with brain atrophy, as well as the role of sclerostin on these alterations. Patients and methods: A total of 299 heavy drinkers and 32 controls were included. Patients underwent cranial computed tomography, and several indices related to brain atrophy were calculated. In addition, patients and controls underwent plain radiography and were evaluated for the presence or absence of vascular calcium deposits, cardiovascular risk factors, liver function, alcohol intake, serum sclerostin, and routine laboratory variables. Results: A total of 145 (48.47%) patients showed vascular calcium deposits, a proportion significantly higher than that observed in controls (χ2 = 16.31; p < 0.001). Vascular calcium deposits were associated with age (t = 6.57; p < 0.001), hypertension (t = 5.49; p < 0.001), daily ethanol ingestion (Z = 2.18; p = 0.029), duration of alcohol consumption (Z = 3.03; p = 0.002), obesity (χ2 = 4.65; p = 0.031), total cholesterol (Z = 2.04; p = 0.041), triglycerides (Z = 2.05; p = 0.04), and sclerostin levels (Z = 2.64; p = 0.008). Calcium deposits were significantly related to Bifrontal index (Z = 2.20; p = 0.028) and Evans index (Z = 2.25; p = 0.025). Serum sclerostin levels were related to subcortical brain atrophy, assessed by cella media index (Z = 2.43; p = 0.015) and Huckmann index (ρ = 0.204; p = 0.024). Logistic regression analyses disclosed that sclerostin was the only variable independently related to brain atrophy assessed by altered cella media index. Sclerostin was also related to the presence of vascular calcifications, although this relationship was displaced by age if this variable was also included. Conclusion: Prevalence of vascular calcification in alcoholics is very high. Vascular calcium deposits are related to brain atrophy. Serum sclerostin is strongly related to brain shrinkage and also shows a significant relationship with vascular calcifications, only displaced by advanced age.

The cost-effectiveness of a uniform versus age-based threshold for one-off screening for prevention of cardiovascular disease.

The objective of this article was to assess the cost-effectiveness of screening strategies for cardiovascular diseases (CVD). A decision analytic model was constructed to estimate the costs and benefits of one-off screening strategies differentiated by screening age, sex and the threshold for initiating statin therapy ("uniform" or "age-adjusted") from the Spanish NHS perspective. The age-adjusted thresholds were configured so that the same number of people at high risk would be treated as under the uniform threshold. Health benefit was measured in quality-adjusted life years (QALY). Transition rates were estimated from the European Prospective Investigation into Cancer and Nutrition (EPIC-CVD), a large multicentre nested case-cohort study with 12 years of follow-up. Unit costs of primary care, hospitalizations and CVD care were taken from the Spanish health system. Univariate and probabilistic sensitivity analyses were employed. The comparator was no systematic screening program. The base case model showed that the most efficient one-off strategy is to screen both men and women at 40 years old using a uniform risk threshold for initiating statin treatment (Incremental Cost-Effectiveness Ratio of €3,274/QALY and €6,085/QALY for men and women, respectively). Re-allocating statin treatment towards younger individuals at high risk for their age and sex would not offset the benefit obtained using those same resources to treat older individuals. Results are sensitive to assumptions about CVD incidence rates. To conclude, one-off screening for CVD using a uniform risk threshold appears cost-effective compared with no systematic screening. These results should be evaluated in clinical studies.

Educational level and risk of colorectal cancer in EPIC with specific reference to tumor location.

Existing evidence is inconclusive on whether socioeconomic status (SES) and educational inequalities influence colorectal cancer (CRC) risk, and whether low or high SES/educational level is associated with developing CRC. The aim of our study was to investigate the relationship between educational level and CRC. We studied data from 400,510 participants in the EPIC (European Prospective Investigation into Cancer and Nutrition) study, of whom 2,447 developed CRC (colon: 1,551, rectum: 896, mean follow-up 8.3 years). Cox proportional hazard regression analysis stratified by age, gender and center, and adjusted for potential confounders were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI). Relative indices of inequality (RII) for education were estimated using Cox regression models. We conducted separate analyses for tumor location, gender and geographical region. Compared with participants with college/university education, participants with vocational secondary education or less had a nonsignificantly lower risk of developing CRC. When further stratified for tumor location, adjusted risk estimates for the proximal colon were statistically significant for primary education or less (HR 0.73, 95%CI 0.57-0.94) and for vocational secondary education (HR 0.76, 95%CI 0.58-0.98). The inverse association between low education and CRC risk was particularly found in women and Southern Europe. These associations were statistically significant for CRC, for colon cancer and for proximal colon cancer. In conclusion, CRC risk, especially in the proximal colon, is lower in subjects with a lower educational level compared to those with a higher educational level. This association is most pronounced in women and Southern Europe.

Association of Sentinel Node Biopsy and Pathological Report Completeness with Survival Benefit for Cutaneous Melanoma and Factors Influencing Their Different Uses in European Populations.

Objectives: Standard care for cutaneous melanoma includes an accurate pathology report (PR) and sentinel lymph node biopsy (SLNB) for staging clinically node-negative >1 mm melanomas. We aimed to investigate the frequency of these indicators across European countries, also assessing consequences for survival. Methods: We analyzed 4245 melanoma cases diagnosed in six European countries in 2009−2013. Multivariable logistic regression was used to estimate the Odds Ratio (OR) of receiving complete PR with eight items or SLNB and model-based survival to estimate the five-year relative excess risks of death (RER). Results: Overall, 12% patients received a complete PR (range 2.3%, Estonia­20.1%, Italy); SLNB was performed for 68.8% of those with cN0cM0 stage (range 54.4%, Spain­81.7%, Portugal). The adjusted OR of receiving a complete PR was lower than the mean in Estonia (OR 0.11 (0.06−0.18)) and higher in Italy (OR 6.39 (4.90−8.34)) and Portugal (OR 1.39 (1.02−1.89)); it was higher for patients operated on in specialized than general hospitals (OR 1.42 (1.08−1.42)). In the multivariate models adjusted for age, sex, country and clinical-pathological characteristics, the RER resulted in being higher than the reference for patients not receiving a complete PR with eight items (RER 1.72 (1.08−2.72)), or for those not undergoing SLNB (RER 1.76 (1.26−2.47)) Patients with non-metastatic node-negative thickness >1 mm melanoma who did not undergo SLNB had a higher risk of death (RER (RER 1.69 (1.02−2.80)) than those who did. Conclusions: Accurate pathology profiling and SLNB carried survival benefit. Narrowing down between-countries differences in adhesion to guidelines might achieve better outcomes.

Differences in the management and survival of metastatic colorectal cancer in Europe. A population-based study.

BACKGROUND: The management regarding metastatic colorectal cancer throughout Europe is not well known. AIMS: To draw a European comparison of the management and prognosis of metastatic colorectal cancers. METHODS: Factors associated with chemotherapy administration were identified through logistic regressions. Net survival was estimated and crude probabilities of death related to cancer and other causes using a flexible cumulative hazard model. RESULTS: Among the 13 227 patients with colorectal cancer diagnosed between 2010 and 2013 in cancer registries from 10 European countries, 3140 were metastatic. 62% of metastatic patients received chemotherapy. Compared to Spain, the related adjusted odds ratios ranged from 0.7 to 4.0 (P<0.001) according to country. The 3-year net survival by country ranged between 16% and 37%. The survival gap between countries diminished from 21% to 10% when adjusting for chemotherapy, age and sex. Geographical differences in the crude probability of death related to cancer were large for patients <70 or ≥80 years at diagnosis. CONCLUSION: Heterogeneity in the application of European guidelines partly explain these differences. General health between populations, accessibility to a reference centre, or provision of health care could also be involved. Further population-based studies are warranted to disentangle between these possible explanations.

Kaposi sarcoma incidence, survival and trends: Data from the information network on rare cancers in Europe (RARECAREnet).

BACKGROUND: This study provides updated information on Kaposi sarcoma (KS) in Europe during 1995-2007 from the RARECARENet project. METHODS: Data comes from 59 population-based cancer registries in 22 countries. KS was defined as ICD-O-3 morphology code 9140 combined with any topography code. Crude and age-adjusted incidence rates and relative survival for years of diagnosis 2000-2007 and with trends during 1995-2007 were calculated overall, by age and by country. RESULTS: The crude annual incidence rate was 0.28 per 100,000 and age-adjusted incidence was 0.23 per 100,000; incidence increased with age, from 0.18/100,000 at age 0-44 to 0.25/100,000 at age 45-64 and 0.69/100,000 at age 65 and over. Age-adjusted incidence in males was more than four times that in females. Portugal, which had the highest incidence of AIDS in Europe, had by far the highest incidence of KS at age 0-44, 1.44/100,000, more than four times the rate in any other country. Incidence among males in Europe aged 0-44 fell significantly between 1995-1998 and 1999-2002, followed by a significant increase in 2003-2007. Younger patients, with predominantly AIDS-related KS, formerly had a worse prognosis, but since 1999-2001 5-year relative survival increased for patients aged under 65, and by 2005-2007 was 83-86 % for all three age groups 0-44, 45-64, and 65 and over. CONCLUSION: Survival and quality of life for the increasing number of people in Europe affected by KS should improve further following the development of evidence-based guidelines for its management. Population-based cancer registries will continue to play a vital role in monitoring the burden of KS and improvements in its outcome.

Association of Pre-diagnostic Antibody Responses to Escherichia coli and Bacteroides fragilis Toxin Proteins with Colorectal Cancer in a European Cohort.

Experimental evidence has implicated genotoxic Escherichia coli (E. coli) and enterotoxigenic Bacteroides fragilis (ETBF) in the development of colorectal cancer (CRC). However, evidence from epidemiological studies is sparse. We therefore assessed the association of serological markers of E. coli and ETBF exposure with odds of developing CRC in the European Prospective Investigation into Nutrition and Cancer (EPIC) study.Serum samples of incident CRC cases and matched controls (n = 442 pairs) were analyzed for immunoglobulin (Ig) A and G antibody responses to seven E. coli proteins and two isoforms of the ETBF toxin via multiplex serology. Multivariable-adjusted conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of sero-positivity to E. coli and ETBF with CRC.The IgA-positivity of any of the tested E. coli antigens was associated with higher odds of developing CRC (OR: 1.42; 95% CI: 1.05-1.91). Dual-positivity for both IgA and IgG to E. coli and ETBF was associated with >1.7-fold higher odds of developing CRC, with a significant association only for IgG (OR: 1.75; 95% CI: 1.04, 2.94). This association was more pronounced when restricted to the proximal colon cancers (OR: 2.62; 95% CI: 1.09, 6.29) compared to those of the distal colon (OR: 1.24; 95% CI: 0.51, 3.00) (pheterogeneity = 0.095). Sero-positivity to E. coli and ETBF was associated with CRC development, suggesting that co-infection of these bacterial species may contribute to colorectal carcinogenesis. These findings warrant further exploration in larger prospective studies and within different population groups.

Co-benefits from sustainable dietary shifts for population and environmental health: an assessment from a large European cohort study.

BACKGROUND: Unhealthy diets, the rise of non-communicable diseases, and the declining health of the planet are highly intertwined, where food production and consumption are major drivers of increases in greenhouse gas emissions, substantial land use, and adverse health such as cancer and mortality. To assess the potential co-benefits from shifting to more sustainable diets, we aimed to investigate the associations of dietary greenhouse gas emissions and land use with all-cause and cause-specific mortality and cancer incidence rates. METHODS: Using data from 443 991 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a multicentre prospective cohort, we estimated associations between dietary contributions to greenhouse gas emissions and land use and all-cause and cause-specific mortality and incident cancers using Cox proportional hazards regression models. The main exposures were modelled as quartiles. Co-benefits, encompassing the potential effects of alternative diets on all-cause mortality and cancer and potential reductions in greenhouse gas emissions and land use, were estimated with counterfactual attributable fraction intervention models, simulating potential effects of dietary shifts based on the EAT-Lancet reference diet. FINDINGS: In the pooled analysis, there was an association between levels of dietary greenhouse gas emissions and all-cause mortality (adjusted hazard ratio [HR] 1·13 [95% CI 1·10-1·16]) and between land use and all-cause mortality (1·18 [1·15-1·21]) when comparing the fourth quartile to the first quartile. Similar associations were observed for cause-specific mortality. Associations were also observed between all-cause cancer incidence rates and greenhouse gas emissions, when comparing the fourth quartile to the first quartile (adjusted HR 1·11 [95% CI 1·09-1·14]) and between all-cause cancer incidence rates and land use (1·13 [1·10-1·15]); however, estimates differed by cancer type. Through counterfactual attributable fraction modelling of shifts in levels of adherence to the EAT-Lancet diet, we estimated that up to 19-63% of deaths and up to 10-39% of cancers could be prevented, in a 20-year risk period, by different levels of adherence to the EAT-Lancet reference diet. Additionally, switching from lower adherence to the EAT-Lancet reference diet to higher adherence could potentially reduce food-associated greenhouse gas emissions up to 50% and land use up to 62%. INTERPRETATION: Our results indicate that shifts towards universally sustainable diets could lead to co-benefits, such as minimising diet-related greenhouse gas emissions and land use, reducing the environmental footprint, aiding in climate change mitigation, and improving population health. FUNDING: European Commission (DG-SANCO), the International Agency for Research on Cancer (IARC), MRC Early Career Fellowship (MR/M501669/1).

Prognostic Value of Serum Iron, Ferritin, and Transferrin in Chronic Alcoholic Liver Disease.

Ethanol increases iron absorption. Therefore, increased amount of iron reaches the liver, and exerts pro-oxidant effects and stimulates ferritin synthesis and hepatic stellate cell activation, promoting fibrosis and inflammation. These mechanisms would theoretically support a role of ferritin as a marker of the transition to liver cirrhosis, and, consequently, as a prognostic factor, but there is controversy regarding its behavior in alcoholics. We analyzed among 238 severe alcoholics the prognostic value of iron, ferritin, transferrin, transferrin saturation index (TSI) and total iron binding capacity (TIBC), and the relationships of these variables with liver function, proinflammatory markers (C-reactive protein (CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor α), and the presence of cirrhosis. Patients showed higher serum ferritin (Z = 2.50, p = 0.031) but lower transferrin (t(264) = 4.81, p < 0.001), TIBC (t(262) = 4.44, p < 0.001), and iron (Z = 3.19, p = 0.001) values compared with 32 age- and sex-matched controls. Ferritin was related to inflammatory cytokines such as IL-8 (ρ = 0.18, p = 0.012) and to IL-6 (ρ = 0.16, p = 0.016), but not to liver function. On the contrary, cirrhotics showed lower transferrin (t(234) = 4.77, p < 0.001) and TIBC (t(232) = 4.67, p < 0.001), but higher TSI (Z = 3.35, p < 0.001) than non-cirrhotics. Transferrin, TSI, and TIBC were related to liver function impairment (marked differences among the Child's groups regarding transferrin (KW (2) = 22.83, p < 0.001), TSI (KW (2) = 15.81, p < 0.001), and TIBC (KW (2) = 21.38, p < 0.001) but only weakly to inflammation (inverse relationships between IL-6 and total iron (ρ = - 0.16, p = 0.017), TIBC (ρ = - 0.20, p = 0.002), and transferrin (ρ = - 0.20, p = 0.003). In accordance, albumin, IL-6, alcohol quitting, and TSI, in this order, were independently related to mortality, but not ferritin or iron.

Prostate cancer treatment in Europe at the end of 1990s.

BACKGROUND: There is wide variation in prostate cancer incidence and survival across Europe. In many countries incidence is rising sharply in relation to the introduction of prostate-specific antigen assay, and there is concern that patients may not be treated appropriately. We therefore aimed to characterize treatment for prostate cancer across Europe. METHODS: We performed a high resolution population-based study, collecting information on the treatment of 3 486 prostate cancer cases diagnosed in 1995-1999 in 11 cancer registries from six European countries. RESULTS: Overall, about one in three patients received radical treatment (prostatectomy 23% or radiotherapy 14%); about 60% of younger patients (<70 years) received radical treatment, while a similar proportion of older patients (> or =70 years) received palliation (transurethral prostatectomy or hormone treatment only). A considerable proportion (61%) of patients with apparently high-risk disease were treated radically within a year of diagnosis, with large variation between regions: >70% in Calvados, Haut-Rhin, Tarn and Eindhoven and <50% in Slovakia and Cracow. Overall 34% of patients with apparently low-risk disease received radical treatment, varying from 17% and 22% in Bas-Rhin and Granada, to 52% and 56% in Calvados and Eindhoven. CONCLUSIONS: Our data indicate wide variation in the treatment for prostate cancer even among patients with apparently similar disease, and further suggest a non-negligible proportion may be receiving inappropriate radical treatment for apparently low-risk disease. Current guidelines indicate active surveillance should become the main means of managing low-risk disease.

Prognostic value of serum selenium levels in alcoholics.

In alcoholics, exposure of Kupffer cells to intestinal-borne Gram-negative bacteria increases free radical release, which may, in turn, enhance cytokine secretion, creating a positive feedback loop, which contributes to liver inflammation. Impaired antioxidant mechanisms further aggravates this scenario. Some trace elements, such as selenium, are main cofactors of antioxidant enzymes. Some authors have found low Se levels in alcoholics in relation either with undernutrition, liver dysfunction, or intensity of alcoholism, but in general, Se supplementation has no effect on survival. In this study we measured serum Se in 16 controls and 76 alcoholics, 34 of them cirrhotics, 68 of whom were followed up for a median period of 38 months; 17 died during this period. Se levels were lower in patients than in controls and were related to prothrombin activity and nutritional status, more closely to this last parameter (stepwise logistic regression analysis). Patients who died showed lower Se values than those who survived. Se values over the median were associated with better survival, assessed by Kaplan-Meier curves and log-rank test. However, in multivariate analysis (Cox regression model), prothrombin activity displaced serum Se as a prognostic factor. We conclude that serum Se levels are low in alcoholics; these low values depend more heavily on impaired nutrition but also on liver dysfunction; although low Se levels were associated with a higher mortality, prothrombin activity displaced serum Se when survival was assessed using Cox's regression model.