Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with prognosis of estrogen receptor-negative breast cancer after chemotherapy

Introduction: Tumor lymphocyte infiltration is associated with clinical response to chemotherapy in estrogen receptor (ER) negative breast cancer. To identify variants in immunosuppressive pathway genes associated with prognosis after adjuvant chemotherapy for ER-negative patients, we studied stage I-III invasive breast cancer patients of European ancestry, including 9,334 ER-positive (3,151 treated with chemotherapy) and 2,334 ER-negative patients (1,499 treated with chemotherapy). Methods: We pooled data from sixteen studies from the Breast Cancer Association Consortium (BCAC), and employed two independent studies for replications. Overall 3,610 single nucleotide polymorphisms (SNPs) in 133 genes were genotyped as part of the Collaborative Oncological Gene-environment Study, in which phenotype and clinical data were collected and harmonized. Multivariable Cox proportional hazard regression was used to assess genetic associations with overall survival (OS) and breast

An Evaluation of the COVID-19 Pandemic and Perceived Social Distancing Policies in Relation to Planning, Selecting, and Preparing Healthy Meals: An Observational Study in 38 Countries Worldwide

Objectives: To examine changes in planning, selecting, and preparing healthy foods in relation to personal factors (time, money, stress) and social distancing policies during the COVID-19 crisis. Methods: Using cross-sectional online surveys collected in 38 countries worldwide in April-June 2020 (N = 37,207, Mage 36.7 SD 14.8, 77% women), we compared changes in food literacy behaviors to changes in personal factors and social distancing policies, using hierarchical multiple regression analyses controlling for sociodemographic variables. Results: Increases in planning (4.7 SD 1.3, 4.9 SD 1.3), selecting (3.6 SD 1.7, 3.7 SD 1.7), and preparing (4.6 SD 1.2, 4.7 SD 1.3) healthy foods were found for women and men, and positively related to perceived time availability and stay-at-home policies. Psychological distress was a barrier for women, and an enabler for men. Financial stress was a barrier and enabler depending on various sociodemographic variables (all p < 0.01). Conclusion: Stay-at-home policies and feelings of having more time during COVID-19 seem to have improved food literacy. Stress and other social distancing policies relate to food literacy in more complex ways, highlighting the necessity of a health equity lens. Copyright 2021 De Backer, Teunissen, Cuykx, Decorte, Pabian, Gerritsen, Matthys, Al Sabbah, Van Royen and the Corona Cooking Survey Study Group.This research was funded by the Research Foundation Flanders (G047518N) and Flanders Innovation and Entrepreneurship (HBC.2018.0397). These funding sources had no role in the design of the study, the analysis and interpretation of the data or the writing of, nor the decision to publish the manuscript.Scopu

Management practices for postdural puncture headache in obstetrics: a prospective, international, cohort study

Background: Accidental dural puncture is an uncommon complication of epidural analgesia and can cause postdural puncture headache (PDPH). We aimed to describe management practices and outcomes after PDPH treated by epidural blood patch (EBP) or no EBP. Methods: Following ethics committee approval, patients who developed PDPH after accidental dural puncture were recruited from participating countries and divided into two groups, those receiving EBP or no EBP. Data registered included patient and procedure characteristics, headache symptoms and intensity, management practices, and complications. Follow-up was at 3 months. Results: A total of 1001 patients from 24 countries were included, of which 647 (64.6%) received an EBP and 354 (35.4%) did not receive an EBP (no-EBP). Higher initial headache intensity was associated with greater use of EBP, odds ratio 1.29 (95% confidence interval 1.19–1.41) per pain intensity unit increase. Headache intensity declined sharply at 4 h after EBP and 127 (19.3%) patients received a second EBP. On average, no or mild headache (numeric rating score≤3) was observed 7 days after diagnosis. Intracranial bleeding was diagnosed in three patients (0.46%), and backache, headache, and analgesic use were more common at 3 months in the EBP group. Conclusions: Management practices vary between countries, but EBP was more often used in patients with greater initial headache intensity. EBP reduced headache intensity quickly, but about 20% of patients needed a second EBP. After 7 days, most patients had no or mild headache. Backache, headache, and analgesic use were more common at 3 months in patients receiving an EBP. © 2020 British Journal of Anaesthesi

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10-43) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology