Prediagnostic selenium status, selenoprotein gene variants and association with breast cancer risk in a European cohort study.

Selenium (Se) may help prevent breast cancer (BC) development. Owing to limited observational evidence, we investigated whether prediagnostic Se status and/or variants in the selenoprotein genes are associated with BC risk in a large European cohort. Se status was assessed by plasma measures of Se and its major circulating proteins, selenoprotein P (SELENOP) and glutathione peroxidase 3 (GPX3), in matched BC case-control pairs (2208 for SELENOP; 1785 for GPX3 and Se) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Single nucleotide polymorphisms (SNPs, n = 452) in 55 selenoprotein and Se metabolic pathway genes and an additional 18 variants previously associated with Se concentrations were extracted from existing genotyping data within EPIC for 1564 case-control pairs. Multivariable-adjusted logistic regression models were used to calculate the odds ratios (ORs) and 95 % confidence intervals (CIs) of the association between Se status markers, SNP variants and BC risk. Overall, there was no statistically significant association of Se status with BC risk. However, higher GPX3 activity was associated with lower risk of premenopausal BC (4th versus 1st quartile, OR = 0.54, 95 % CI: 0.30-0.98, Ptrend = 0.013). While none of the genetic variant associations (P ≤ 0.05) retained significance after multiple testing correction, rs1004243 in the SELENOM selenoprotein gene and two SNPs in the related antioxidant TXN2 gene (rs4821494 and rs5750261) were associated with respective lower and higher risks of BC at a significance threshold of P ≤ 0.01. Fourteen SNPs in twelve Se pathway genes (P ≤ 0.01) in interaction with Se status were also associated with BC risk. Higher Se status does not appear to be associated with BC risk, although activity of the selenoenzyme GPX3 may be inversely associated with premenopausal BC risk, and SNPs in the Se pathway alone or in combination with suboptimal Se status may influence BC risk.

Duration of the patient interval in breast cancer and factors associated with longer delays in low-and middle-income countries: A systematic review with meta-analysis.

OBJECTIVE: Breast cancer survival is lower in low- and middle-income countries (LMICs) partially due to many women being diagnosed with late-stage disease. The patient interval refers to the time elapsed between the detection of symptoms and the first consultation with a healthcare provider and is considered one of the core indicators for early diagnosis and treatment. The goal of the current research was to conduct a meta-analysis of the duration of the patient interval in LMICs and investigate the socio-demographic and socio-cultural factors related to longer delays in presentation. METHODS: We conducted a systematic review with meta-analysis (pre-registered protocol CRD42020200752). We searched seven information sources (2009-2022) and included 50 articles reporting the duration of patient intervals for 18,014 breast cancer patients residing in LMICs. RESULTS: The longest patient intervals were reported in studies from the Middle East (3-4 months), followed by South-East Asia (2 months), Africa (1-2 months), Latin America (1 month), and Eastern Europe (1 month). Older age, not being married, lower socio-economic status, illiteracy, low knowledge about cancer, disregarding symptoms or not attributing them to cancer, fear, negative beliefs about cancer, and low social support were related to longer delays across most regions. Longer delays were also related to use of alternative medicine in the Middle East, South-East Asia, and Africa and distrust in the healthcare system in Eastern Europe. CONCLUSIONS: There is large variation in the duration of patient intervals across LMICs in different geographical regions. Patient intervals should be reduced and, for this purpose, it is important to explore their determinants taking into account the social, cultural, and economic context.

Vitamin D Deficiency and COVID-19: A Biological Database Study on Pathways and Gene-Disease Associations.

Vitamin D (VD) is a fat-soluble vitamin, and pivotal for maintaining health. Several genetic markers have been related to a deficient VD status; these markers could confer an increased risk to develop osteoporosis and other chronic diseases. A VD deficiency could also be a determinant of a severe COVID-19 disease. This study aimed to interrogate genetic/biological databases on the biological implications of a VD deficiency and its association with diseases, to further explore its link with COVID-19. The genetic variants of both a VD deficiency and COVID-19 were identified in the genome-wide association studies (GWAS) catalog and other sources. We conducted enrichment analyses (considering corrected p-values < 0.05 as statistically significant) of the pathways, and gene-disease associations using tools, such as FUMA, REVIGO, DAVID and DisGeNET, and databases, such as the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). There were 26 and 46 genes associated with a VD deficiency and COVID-19, respectively. However, there were no genes shared between the two. Genes related to a VD deficiency were involved in the metabolism of carbohydrates, retinol, drugs and xenobiotics, and were associated with the metabolic syndrome and related factors (obesity, hypertension and diabetes mellitus), as well as with neoplasms. There were few enriched pathways and disease connections for the COVID-19-related genes, among which some of the aforementioned comorbidities were also present. In conclusion, genetic factors that influence the VD levels in the body are most prominently associated with nutritional and metabolic diseases. A VD deficiency in high-risk populations could be therefore relevant in a severe COVID-19, underlining the need to examine whether a VD supplementation could reduce the severity of this disease.

Intestinal anti-inflammatory and visceral analgesic effects of a Serpylli herba extract in an experimental model of irritable bowel syndrome in rats.

Ethnopharmacological relevance: Serpylli herba extract (SHE), composed of the aerial parts of wild thyme (Thymus serpyllum L.) (Lamiaceae family), is traditionally used in Europe and North Africa to treat diarrhea, gastric ulcers, intestinal parasites and upper respiratory tract infections. Recently, SHE has generated a great interest for irritable bowel syndrome (IBS) management, probably due to its intestinal anti-inflammatory properties shown in experimental colitis and the fact that its active components could preserve the intestinal barrier integrity, which is altered in patients with IBS. Aim of study: We aimed to test the effects of a SHE in a rat experimental model resembling human IBS. Materials and methods: IBS was provoked by deoxycholic acid (DCA). Rats were then treated with SHE (100 mg/kg) or gabapentin (70 mg/kg) and different inflammatory and gut barrier integrity markers were evaluated. Moreover, several gut hypersensitivity and hyperalgesia determinations were performed. Results: SHE improved referred pain and visceral hypersensitivity. Additionally, SHE enhanced immune status by downregulating of the expression of the pro-inflammatory mediators Il-1ß, Il-6, Ifn-γ, Tlr-4, and the inducible enzyme Cox-2, thus inducing visceral analgesia, and promoting the restore of the gut barrier function by upregulating the mucins Muc-2 and Muc-3. These anti-inflammatory effects could be related to its action on mast cells since it significantly inhibited the ß-Hexosaminidase production in RBL-2H3 cells. Lastly, SHE also seems to modulate the serotonin pathway by restoring the altered expression of the 5-HT receptors Htr-3 and Htr-4. Conclusion: SHE could be considered a potential new treatment for IBS, since it ameliorates hypersensitivity, visceral hyperalgesia, and inflammation. These beneficial effects may be due to the inhibition of mast cells degranulation and serotonin pathway.

Protocol proposal for early dental care in infants with cerebral palsy

Introduction: Children with cerebral palsy (CP) are at high risk of developing oral diseases. Objective: To propose an early dental care protocol for infants with CP. Materials and Methods: A computerized systematic search was performed in the PubMed, Scopus and Embase electronic databases for relevant articles. An early dental care protocol was then proposed for infants with cerebral palsy focused on comprehensive care with a multidisciplinary approach and effective health promotion by caregivers. Results: Fifteen published papers were included in the present literature review and protocol proposal. The protocol comprised the following topics: First dental visit, aspects related to the appointment, oral hygiene recommendations, dietary recommendations and recommendations for the prevention and control of harmful oral habits. The first dental visit should occur prior to the eruption of the teeth. As a special group, it is important to determine the affective bond between the patient and caregiver who will receive the oral health care recommendations. During the clinical examination, the correct positioning and stabilization of the infant is important for the control of involuntary movements and the minimization of swallowing difficulties. Counseling with regards to adequate oral hygiene, a healthy diet and the prevention of harmful oral habits is important to the prevention of dental diseases. Children with oral-motor motility problems and feeding difficulties should be referred to therapeutic follow-up. Due to the neuropsychomotor disorders often found in cerebral palsy, affected children are more vulnerable to oral diseases. Thus, oral health care must be performed as early as possible by the parents/caregivers of these children. Conclusion: Individuals with cerebral palsy are at greater risk of developing oral problems. Thus, oral health programs starting in early childhood and targeting the specificities of these individuals is a strategy for minimizing the occurrence of such problems and the associated burden.

Introdução: Crianças com Paralisia Cerebral (PC) apresentam um alto risco para o desenvolvimento de doenças bucais. Objetivo: Propor um protocolo de atendimento odontológico precoce para lactentes com PC. Materiais e Métodos: Foi realizada uma busca computadorizada sistemática nas bases de dados eletrônicas PubMed, Scopus e Embase. Também foi desenvolvida uma proposta de protocolo de atendimento a bebês com Paralisia Cerebral com foco no cuidado integral, abordagem transdisciplinar e promoção efetiva da saúde pelos cuidadores. Resultados: Foram incluídos 15 artigos publicados na literatura científica. O protocolo desenvolvido é composto pelos seguintes tópicos: Primeira consulta odontológica, tempo ideal da consulta, recomendações de higiene bucal, recomendações sobre dieta e recomendações sobre prevenção e controle dos hábitos bucais. A primeira visita ao dentista deve ser feita antes da erupção do primeiro dente. Como um grupo especial, é importante determinar o vínculo afetivo entre o paciente e o cuidador que receberá as recomendações de cuidados com a saúde bucal. Durante o exame clínico, a correta posição e estabilização do bebê na cadeira odontológica é importante para controlar os movimentos involuntários e reduzir a dificuldade de deglutição. Recomendações quanto à higiene bucal adequada, alimentação saudável e prevenção de hábitos bucais deletérios são importantes para prevenir o desenvolvimento de doenças bucais. Crianças com problemas de motilidade oral-motora e dificuldades de alimentação devem ser encaminhadas para acompanhamento terapêutico. Devido à presença de distúrbios neuropsicomotores normalmente presentes na Paralisia Cerebral, as crianças afetadas são mais vulneráveis às doenças bucais. Assim, os cuidados com a saúde bucal devem ser realizados o quanto antes pelos pais/responsáveis. Conclusão: Indivíduos com PC apresentam maior risco de desenvolver doenças bucais e programas de saúde bucal iniciados na primeira infância e direcionados às suas especificidades podem ser uma estratégia para minimizar as consequências que possam vir a acontecer.

Evaluation of Physical Therapy Interventions for Improving Musculoskeletal Pain and Quality of Life in Older Adults.

Background: The ageing process may lead to functional limitations, musculoskeletal pain, and worsened quality of life. The aim of this paper is to evaluate two physical therapy interventions for reducing musculoskeletal pain and improving quality of life in older adults. Methods: A cohort study was carried out with older people (60−75 years old). The Geriatric Physical Therapy group (n = 70) received massage therapy, therapeutic exercise, and therapeutic education program for 5 weeks; the Standardized Therapeutic Exercise group (n = 140) received a standardized therapeutic exercise and therapeutic education program for 3 weeks. Health-related quality of life (SF-36v2) and musculoskeletal pain intensity (VAS) were collected at baseline (A0), post-intervention (A1), and 12 weeks after baseline (A2). Results: There was pain intensity reduction in both groups (p < 0.05) and health-related quality of life improvement, except for Emotional Role (p = 0.34); Physical Function (p = 0.07), Bodily Pain (p = 0.02), and General Health (p = 0.09). At A2 there was a difference (p < 0.05) for neck pain in favor of the Geriatric Physical Therapy Group. Conclusions: Within the limitations of the study, it was possible to conclude that both physical therapy interventions showed a positive effect for reducing non-specific neck pain and low back pain in older adults, which may contribute to health-related quality of life improvement.

Manual Lymph Drainage With Progressive Arm Exercises for Axillary Web Syndrome After Breast Cancer Surgery: A Randomized Controlled Trial.

OBJECTIVE: This study aimed to determine the effectiveness of a physical therapist-designed program tailored to axillary web syndrome (AWS) in women after breast cancer surgery. METHODS: A prospective, single-center, assessor-blinded, randomized controlled trial was conducted at the Physiotherapy in Women's Health Research Unit of the Alcalá University (Madrid, Spain). Ninety-six women with AWS were assigned to the physical therapy group (manual lymph drainage [MLD] using resorption strokes and arm exercises as if performing median nerve neurodynamic glide exercises with no neural loading; n = 48) or the control group (standard arm exercises; n = 48), with both groups receiving treatment 3 times a week for 3 weeks. Both interventions included an educational component. RESULTS: Compared with the control group, the physical therapy group showed significant and clinically relevant improvements in the primary outcome (self-reported pain intensity) at the primary and 3-month follow-ups. Significant and clinically relevant differences between groups were also found in the secondary outcomes (shoulder active range of motion, shoulder disability, and physical and functional aspects of health-related quality of life) at the primary follow-up and in the secondary outcomes as well as the trial outcome index at the 3-month follow-up. No significant differences were found at the 6-month follow-up in either primary or secondary outcomes. CONCLUSION: The physical therapy program tailored to AWS was found to be effective for AWS symptoms in women after breast cancer surgery, both immediately after the program and after 3 months. IMPACT: To our knowledge, this is the first appropriately designed study to demonstrate the effectiveness of MLD with progressive arm exercises for AWS. Clinicians and health service providers should consider how to provide survivors of breast cancer with AWS the opportunity to participate in physical therapy programs, including MLD with progressive arm exercises. LAY SUMMARY: For axillary web syndrome following breast cancer surgery, a physical therapist can design a treatment program including manual lymph drainage and progressive arm exercises, which has been shown to result in reduced pain and improved motion compared with standard arm exercises.

Prediagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma.

Bile acids (BAs) play different roles in cancer development. Some are carcinogenic and BA signaling is also involved in various metabolic, inflammatory and immune-related processes. The liver is the primary site of BA synthesis. Liver dysfunction and microbiome compositional changes, such as during hepatocellular carcinoma (HCC) development, may modulate BA metabolism increasing concentration of carcinogenic BAs. Observations from prospective cohorts are sparse. We conducted a study (233 HCC case-control pairs) nested within a large observational prospective cohort with blood samples taken at recruitment when healthy with follow-up over time for later cancer development. A targeted metabolomics method was used to quantify 17 BAs (primary/secondary/tertiary; conjugated/unconjugated) in prediagnostic plasma. Odd ratios (OR) for HCC risk associations were calculated by multivariable conditional logistic regression models. Positive HCC risk associations were observed for the molar sum of all BAs (ORdoubling  = 2.30, 95% confidence intervals [CI]: 1.76-3.00), and choline- and taurine-conjugated BAs. Relative concentrations of BAs showed positive HCC risk associations for glycoholic acid and most taurine-conjugated BAs. We observe an association between increased HCC risk and higher levels of major circulating BAs, from several years prior to tumor diagnosis and after multivariable adjustment for confounders and liver functionality. Increase in BA concentration is accompanied by a shift in BA profile toward higher proportions of taurine-conjugated BAs, indicating early alterations of BA metabolism with HCC development. Future studies are needed to assess BA profiles for improved stratification of patients at high HCC risk and to determine whether supplementation with certain BAs may ameliorate liver dysfunction.

Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations.

OBJECTIVE: Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants. RESULTS: We identified 11 genomic regions associated with plasma vitamin C (P < 5 × 10-8), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10). CONCLUSIONS: These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.

Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome-negative adult lymphoblastic leukemia.

The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph- adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.1% after induction and <0.01% after early consolidation were assigned to receive delayed consolidation and maintenance therapy up to 2 years in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD <0.1% after induction in 220/289 patients (76%). By intention-to-treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (±95% confidence interval) cumulative incidence of relapse (CIR), overall survival (OS), and event-free survival probabilities for the whole series were 43% ± 7%, 49% ± 7%, and 40% ± 6%, respectively, with CIR and OS rates of 45% ± 8% and 59% ± 9% for patients assigned to chemotherapy and of 40% ± 12% and 38% ± 11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph- adult ALL patients up to 60 years with adequate MRD response after induction and consolidation. Better postremission alternative therapies are especially needed for patients with poor MRD clearance. This trial was registered at www.clinicaltrials.gov as # NCT01540812.

Interaction Between GAD65 Antibodies and Dietary Fish Intake or Plasma Phospholipid n-3 Polyunsaturated Fatty Acids on Incident Adult-Onset Diabetes: The EPIC-InterAct Study.

OBJECTIVE: Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes. RESEARCH DESIGN AND METHODS: We used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction [AP]) and multiplicative interactions between GAD65 antibody positivity (≥65 units/mL) and low fish/n-3 PUFA were assessed. RESULTS: The hazard of diabetes in antibody-positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52 [95% CI 1.76-3.63] and 2.48 [1.79-3.45]) compared with people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44 [95% CI 0.16-0.72] and 0.48 [0.24-0.72]) and multiplicative (P = 0.0465 and 0.0103) interactions. Individuals with high GAD65 antibody levels (≥167.5 units/mL) and low total plasma phospholipid n-3 PUFAs had a more than fourfold higher hazard of diabetes (HR 4.26 [2.70-6.72]) and an AP of 0.46 (0.12-0.80) compared with antibody-negative individuals with high n-3 PUFAs. CONCLUSIONS: High fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.

Fried-Food Consumption Does Not Increase the Risk of Stroke in the Spanish Cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) Study.

BACKGROUND: The nutritional determinants of stroke and, more specifically, the association of frying with the risk of incident stroke have rarely been studied. OBJECTIVES: Our aim was to evaluate prospectively the association between the consumption of fried food and the risk of incident stroke in the European Prospective Investigation into Cancer and Nutrition study using the Spanish cohort. METHODS: Participants included 40,328 healthy adults (62% women) aged 29-69 y at study entry who were enrolled between 1992 and 1996. Participants were followed up until 31 December, 2017, at which time incident stroke (the main outcome) was measured. The main exposure measure was the percentage of energy obtained from fried-food consumption. Sex-specific quintiles were calculated. RESULTS: During a follow-up period of 23.5 y, 975 cases of stroke occurred (750 ischemic, 185 hemorrhagic, and 40 undetermined). Compared with those in the first (lowest) quintile of fried-food consumption, the multivariate HRs (95% CIs) of incident stroke in the consecutive quintiles were 1.05 (0.86, 1.30), 1.11 (0.90, 1.36), 1.05 (0.84, 1.31), and 0.91 (0.72, 1.15; P-trend = 0.45). There were no differences identified when subtypes of stroke were considered. CONCLUSIONS: In this Spanish cohort, whose participants mainly used olive oil or sunflower oil when frying, the consumption of fried food was not associated with an increased risk of incident stroke.

Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort.

BACKGROUND & AIMS: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. RESULTS: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). CONCLUSIONS: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case-control sets from EPIC.

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR1SD ) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR1SD = 0.77, 95% confidence interval 0.66-0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR1SD = 0.72, 0.57-0.90), or lysophosphatidylcholines (OR1SD = 0.81, 0.69-0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR1SD = 0.77, 0.61-0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.

Coffee and tea consumption and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition.

The epidemiological evidence regarding the association of coffee and tea consumption with prostate cancer risk is inconclusive, and few cohort studies have assessed these associations by disease stage and grade. We examined the associations of coffee (total, caffeinated and decaffeinated) and tea intake with prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 142,196 men, 7,036 incident prostate cancer cases were diagnosed over 14 years of follow-up. Data on coffee and tea consumption were collected through validated country-specific food questionnaires at baseline. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (CI). Models were stratified by center and age, and adjusted for anthropometric, lifestyle and dietary factors. Median coffee and tea intake were 375 and 106 mL/day, respectively, but large variations existed by country. Comparing the highest (median of 855 mL/day) versus lowest (median of 103 mL/day) consumers of coffee and tea (450 vs. 12 mL/day) the HRs were 1.02 (95% CI, 0.94-1.09) and 0.98 (95% CI, 0.90-1.07) for risk of total prostate cancer and 0.97 (95% CI, 0.79-1.21) and 0.89 (95% CI, 0.70-1.13) for risk of fatal disease, respectively. No evidence of association was seen for consumption of total, caffeinated or decaffeinated coffee or tea and risk of total prostate cancer or cancer by stage, grade or fatality in this large cohort. Further investigations are needed to clarify whether an association exists by different preparations or by concentrations and constituents of these beverages.

Dietary intake of total polyphenol and polyphenol classes and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Polyphenols may play a chemopreventive role in colorectal cancer (CRC); however, epidemiological evidence supporting a role for intake of individual polyphenol classes, other than flavonoids is insufficient. We evaluated the association between dietary intakes of total and individual classes and subclasses of polyphenols and CRC risk and its main subsites, colon and rectum, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The cohort included 476,160 men and women from 10 European countries. During a mean follow-up of 14 years, there were 5991 incident CRC cases, of which 3897 were in the colon and 2094 were in the rectum. Polyphenol intake was estimated using validated centre/country specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, a doubling in total dietary polyphenol intake was not associated with CRC risk in women (HRlog2 = 1.06, 95% CI 0.99-1.14) or in men (HRlog2 = 0.97, 95% CI 0.90-1.05), respectively. Phenolic acid intake, highly correlated with coffee consumption, was inversely associated with colon cancer in men (HRlog2 = 0.91, 95% CI 0.85-0.97) and positively associated with rectal cancer in women (HRlog2 = 1.10, 95% CI 1.02-1.19); although associations did not exceed the Bonferroni threshold for significance. Intake of other polyphenol classes was not related to colorectal, colon or rectal cancer risks. Our study suggests a possible inverse association between phenolic acid intake and colon cancer risk in men and positive with rectal cancer risk in women.

[Tetany secondary to phosphate enema toxicity, case report]. / Tetania severa por uso de enemas fosfatados, reporte de caso.

Phosphate enemas are frequently used in the treatment of constipation. Errors in dosage and administration can lead to severe complications. OBJECTIVE: To report a case of severe toxicity of phosphate enemas in a child with no risk factors. CASE: 2 years old female, with functional constipation, was brought to emergency department because abdominal pain. She was diagnosed with fecal impaction and received half a bottle of Fleet Adult® (Laboratorio Synthon, Chile) two times, with no clinical resolution, deciding to start proctoclisis in pediatric ward. Soon after admission, she presented painful tetany, but alert and oriented. Patient was transferred to PICU where severe hyperphosphatemia and secondary hypocalcemia were confirmed. Her treatment included electrolyte correction; removal of residual phosphate enema and hyperhydration. Tetany resolved over 2 hours after admission and no other complications. Proctoclisis was performed and patient was discharged three days after admission with pharmacological management of constipation. CONCLUSION: Phosphate enemas may cause serious complications in children with no risk factors. Errors in dosage, administration and removal of the enema are causes of toxicity in this group. Pediatricians and health personnel must be aware of risks and signs of toxicity of phosphate enema.

Tetania severa por uso de enemas fosfatados, reporte de caso / Tetany secondary to phosphate enema toxicity, case report

Los enemas fosfatados son utilizados frecuentemente en el tratamiento de la constipación. Errores en la posología pueden producir complicaciones graves. Objetivo: Reportar un caso de toxicidad grave por enema fosfatado en un pre escolar sin factores de riesgo. Caso clínico: Paciente de 2 años con constipación funcional, evaluada en servicio de urgencia por dolor abdominal a quién se le diagnosticó un fecaloma impactado. Recibió 2 dosis de enema de fosfato, “medio frasco” de Fleet® adulto (Synthon, Chile) por vez, sin resolución de su fecaloma, decidiéndose hospitalización para proctoclisis. Posterior al ingreso presentó un cuadro clínico de tetania. Ingresó a la Unidad de Paciente Crítico donde se confirmó una hiperfosfemia e hipocalcemia secundaria. Se realizó corrección electrolítica progresiva, retiro de enema fosfatado residual del recto e hiperhidratación forzando diuresis. La tetania cedió 2 horas después del ingreso sin otras complicaciones. Se realizó proctoclisis y fue dada de alta a los 3 días. Conclusión: Los enemas fosfatados pueden presentar complicaciones graves en niños sin factores de riesgo. Errores en la posología son la causa más frecuente de toxicidad en este grupo, pero esta puede estar favorecida también por una administración y eliminación inadecuadas. Pediatras y personal de salud que atiende a niños deben conocer factores de riesgo, signos y síntomas de intoxicación por enemas fosfatados.

Phosphate enemas are frequently used in the treatment of constipation. Errors in dosage and administration can lead to severe complications. Objective: To report a case of severe toxicity of phosphate enemas in a child with no risk factors. Case: 2 years old female, with functional constipation, was brought to emergency department because abdominal pain. She was diagnosed with fecal impaction and received half a bottle of Fleet Adult® (Laboratorio Synthon, Chile) two times, with no clinical resolution, deciding to start proctoclisis in pediatric ward. Soon after admission, she presented painful tetany, but alert and oriented. Patient was transferred to PICU where severe hyperphosphatemia and secondary hypocalcemia were confirmed. Her treatment included electrolyte correction; removal of residual phosphate enema and hyperhydration. Tetany resolved over 2 hours after admission and no other complications. Proctoclisis was performed and patient was discharged three days after admission with pharmacological management of constipation. Conclusion: Phosphate enemas may cause serious complications in children with no risk factors. Errors in dosage, administration and removal of the enema are causes of toxicity in this group. Pediatricians and health personnel must be aware of risks and signs of toxicity of phosphate enema.

Dietary flavonoid intake and colorectal cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort.

Flavonoids have been shown to inhibit colon cancer cell proliferation in vitro and protect against colorectal carcinogenesis in animal models. However, epidemiological evidence on the potential role of flavonoid intake in colorectal cancer (CRC) development remains sparse and inconsistent. We evaluated the association between dietary intakes of total flavonoids and their subclasses and risk of development of CRC, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A cohort of 477,312 adult men and women were recruited in 10 European countries. At baseline, dietary intakes of total flavonoids and individual subclasses were estimated using centre-specific validated dietary questionnaires and composition data from the Phenol-Explorer database. During an average of 11 years of follow-up, 4,517 new cases of primary CRC were identified, of which 2,869 were colon (proximal = 1,298 and distal = 1,266) and 1,648 rectal tumours. No association was found between total flavonoid intake and the risk of overall CRC (HR for comparison of extreme quintiles 1.05, 95% CI 0.93-1.18; p-trend = 0.58) or any CRC subtype. No association was also observed with any intake of individual flavonoid subclasses. Similar results were observed for flavonoid intake expressed as glycosides or aglycone equivalents. Intake of total flavonoids and flavonoid subclasses, as estimated from dietary questionnaires, did not show any association with risk of CRC development.

Influence of waterborne arsenic on nutritive and potentially harmful elements in gilthead seabream (Sparus aurata).

Fish are an important source of nutrients in human nutrition. Although arsenic (As) is considered potentially carcinogenic for human being, very little is known about its toxicity in fish biology. To increase our knowledge of the effect of exposure to waterborne As on fish, gilthead seabream (Sparus aurata) were exposed to 5 µM As2O3 and the bioaccumulation of macronutrients (Ca, K, Mg, Na, P), micronutrients (Fe, Mn, Zn) and Potentially Harmful Elements (As, Cd) was determined using spectrometric techniques. All elements were determined in the muscle and liver of non-exposed fish and those exposed to As for 2, 10 or 30 days. The concentrations of K, Na, Mg, Mn and Zn (in muscle) and Fe and Mn (in liver) of control (non-exposed) fish were higher than those determined in exposed fish. Furthermore, neither As nor Cd accumulated in the edible part (muscle) of seabream and were only evident in liver after 30 days of continuous exposure to As, but both concentrations remained below legally established limits.