Relatives of Crohn's disease patients and breast cancer: An overlooked condition

AbstractRecent data suggest that patients suffering from Crohn’s disease (CD) may be at higher risk of developing extra-intestinal malignancies. This is attributed to inflammation and immunodepression due to medications. However, a genetic predisposition cannot ruled out. In the present study we investigated the prevalence of breast cancer in first-degree female relatives of CD patients compared with relatives of patients without evidence of gastrointestinal diseases. A total of 1302 female first-degree relatives of CD patients and 1294 relatives of controls were included. We found that CD was an independent risk factor for breast cancer development (OR = 2.76, 95% CI = 1.2–6.2; p = 0.017), and this is particularly evident in mothers (3.6% vs 1%, p = 0.009 − OR = 3.7, 95% CI 1.4–10). Among CD group, smoking habit of CD patients was associated with increased risk of cancer compared with relatives of non-smokers (7.7% vs 2.9%, p = 0.01 – OR = 2.8 95% CI 1.2–6.6). Intriguingly, stage at diagnosis was significantly higher in CD relatives (p = 0.04). Our findings suggest that first-degree female relatives of CD patients are at higher risk of developing breast cancer but receive diagnosis at more advanced stages, therefore advocating the need of more active screening protocol in this population

Local adaptation shapes functional traits and resource allocation in black spruce

Climate change is rapidly altering weather patterns, resulting in shifts in climatic zones. The survival of trees in specific locations depends on their functional traits. Local populations exhibit trait adaptations that ensure their survival and accomplishment of growth and reproduction processes during the growing season. Studying these traits offers valuable insights into species responses to present and future environmental conditions, aiding the implementation of measures to ensure forest resilience and productivity. This study investigates the variability in functional traits among five black spruce ( Picea mariana (Mill.) B.S.P.) provenances originating from a latitudinal gradient along the boreal forest, and planted in a common garden in Quebec, Canada. We examined differences in bud phenology, growth performance, lifetime first reproduction, and the impact of a late-frost event on tree growth and phenological adjustments. The findings revealed that trees from northern sites exhibit earlier budbreak, lower growth increments, and reach reproductive maturity earlier than those from southern sites. Late-frost damage affected growth performance, but no phenological adjustment was observed in the successive year. Local adaptation in the functional traits may lead to maladaptation of black spruce under future climate conditions or serve as a potent evolutionary force promoting rapid adaptation under changing environmental conditions

Effects of Oestrogen on MicroRNA Expression in Hormone-Responsive Breast Cancer Cells

Oestrogen receptor alpha (ERα) is a ligand-dependent transcription factor that mediates oestrogen effects in hormone-responsive cells. Following oestrogenic activation, ERα directly regulates the transcription of target genes via DNA binding. MicroRNAs (miRNAs) represent a class of small noncoding RNAs that function as negative regulators of protein-coding gene expression. They are found aberrantly expressed or mutated in cancer, suggesting their crucial role as either oncogenes or tumour suppressor genes. Here, we analysed changes in miRNA expression in response to oestrogen in hormone-responsive breast cancer MCF-7 and ZR-75.1 cells by microarray-mediated expression profiling. This led to the identification of 172 miRNAs up- or down-regulated by ERα in response to 17β-oestradiol, of which 52 are similarly regulated by the hormone in the two cell models investigated. To identify mechanisms by which ERα exerts its effects on oestrogen-responsive miRNA genes, the oestrogen-dependent miRNA expression profiles were integrated with global in vivo ERα binding site mapping in the genome by ChIP-Seq. In addition, data from miRNA and messenger RNA (mRNA) expression profiles obtained under identical experimental conditions were compared to identify relevant miRNA target transcripts. Results show that miRNAs modulated by ERα represent a novel genomic pathway to impact oestrogen-dependent processes that affect hormone-responsive breast cancer cell behaviour. MiRNome analysis in tumour tissues from breast cancer patients confirmed a strong association between expression of these small RNAs and clinical outcome of the disease, although this appears to involve only marginally the oestrogen-regulated miRNAs identified in this study

Survival analysis of a multicentre, randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in patients with metastatic colorectal cancer (mCRC)

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A política de habitação rural e o desenvolvimento da agricultura familiar.

Este artigo analisa a contribuição do Programa Nacional de Habitação Rural (PNHR) para o desenvolvimento de territórios predominantemente rurais. A partir do estudo de sua implementação na região Oeste Catarinense, ponder sobre os avanços e as restrições desta política social. Para as análises realizadas procedeu-se a uma revisão de literatura, à busca de documentação sobre a política e sua implementação na região estudada, bem como a entrevistas com lideranças e agricultores demandantes e beneficiados por uma casa nova ou reforma. Verificou-se que o PNHR cria uma oportunidade para as famílias rurais descapitalizadas construírem ou reformarem sua casa, apesar de ser ainda restrita a sua abrangência para o conjunto dessas famílias. A reformulação do programa, reduzindo exigências financeiras e para operação dos créditos, pode oportunizar que maior número de famílias dele se beneficie, com impacto social positivo no desenvolvimento regional

Toward an international consensus-Integrating lipoprotein apheresis and new lipid-lowering drugs

Background: Despite advances in pharmacotherapy of lipid disorders, many dyslipidemic patients do not attain sufficient lipid lowering to mitigate risk of atherosclerotic cardiovascular disease. Several classes of novel lipid-lowering agents are being evaluated to reduce atherosclerotic cardiovascular disease risk. Lipoprotein apheresis (LA) is effective in acutely lowering the plasma concentrations of atherogenic lipoproteins including low-density lipoprotein cholesterol and lipoprotein(a), and novel lipid-lowering drugs may dampen the lipid rebound effect of LA, with the possibility that LA frequency may be decreased, in some cases even be discontinued. Sources of material: This document builds on current American Society for Apheresis guidelines and, for the first time, makes recommendations from summarized data of the emerging lipid-lowering drug classes (inhibitors of proprotein convertase subtilisin/kexin type 9 or microsomal triglyceride transfer protein, high-density lipoprotein mimetic), including the available evidence on combination therapy with LA with respect to the management of patients with dyslipidemia. Abstract of findings: Recommendations for different indications are given based on the latest evidence. However, except for lomitapide in homozygous familial hypercholesterolemia and alirocumab/evolocumab in heterozygous familial hypercholesterolemia subjects, limited data are available on the effectiveness and safety of combination therapy. More studies on combining LA with novel lipid-lowering drugs are needed. Conclusion: Novel lipid-lowering agents have potential to improve the performance of LA, but more evidence is needed. The Multidisciplinary International Group for Hemapheresis TherapY and Metabolic DIsturbances Contrast scientific society aims to establish an international registry of clinical experience on LA combination therapy to expand the evidence on this treatment in individuals at high cardiovascular disease risk

Effect of High-Titer Convalescent Plasma on Progression to Severe Respiratory Failure or Death in Hospitalized Patients with COVID-19 Pneumonia: A Randomized Clinical Trial

Importance: Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia. Objective: To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia. Design, Setting, and Participants: This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg were eligible. Interventions: Patients in the experimental group received intravenous high-titer CP (≥1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations. Main Outcomes and Measures: The primary outcome was a composite of worsening respiratory failure (Pao2/Fio2ratio <150 mm Hg) or death within 30 days from randomization. Results: Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P =.54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P =.04). Conclusions and Relevance: In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04716556

Toward an international consensus-Integrating lipoprotein apheresis and new lipid-lowering drugs

Background: Despite advances in pharmacotherapy of lipid disorders, many dyslipidemic patients do not attain sufficient lipid lowering to mitigate risk of atherosclerotic cardiovascular disease. Several classes of novel lipid-lowering agents are being evaluated to reduce atherosclerotic cardiovascular disease risk. Lipoprotein apheresis (LA) is effective in acutely lowering the plasma concentrations of atherogenic lipoproteins including low-density lipoprotein cholesterol and lipoprotein(a), and novel lipid-lowering drugs may dampen the lipid rebound effect of LA, with the possibility that LA frequency may be decreased, in some cases even be discontinued. Sources of material: This document builds on current American Society for Apheresis guidelines and, for the first time, makes recommendations from summarized data of the emerging lipid-lowering drug classes (inhibitors of proprotein convertase subtilisin/kexin type 9 or microsomal triglyceride transfer protein, high-density lipoprotein mimetic), including the available evidence on combination therapy with LA with respect to the management of patients with dyslipidemia. Abstract of findings: Recommendations for different indications are given based on the latest evidence. However, except for lomitapide in homozygous familial hypercholesterolemia and alirocumab/evolocumab in heterozygous familial hypercholesterolemia subjects, limited data are available on the effectiveness and safety of combination therapy. More studies on combining LA with novel lipid-lowering drugs are needed. Conclusion: Novel lipid-lowering agents have potential to improve the performance of LA, but more evidence is needed. The Multidisciplinary International Group for Hemapheresis TherapY and Metabolic DIsturbances Contrast scientific society aims to establish an international registry of clinical experience on LA combination therapy to expand the evidence on this treatment in individuals at high cardiovascular disease risk

Patterns of recurrence in the randomised PORTEC-3 trial of chemoradiotherapy for endometrial cancer

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