HER2 in high-risk rectal cancer patients treated in EXPERT-C, a randomized phase II trial of neoadjuvant capecitabine and oxaliplatin (CAPOX) and chemoradiotherapy (CRT) with or without cetuximab.

BACKGROUND: HER2 is an established therapeutic target in breast and gastric cancers. The role of HER2 in rectal cancer is unclear, as conflicting data on the prevalence of HER2 expression in this disease have been reported. We evaluated the prevalence of HER2 and its impact on the outcome of high-risk rectal cancer patients treated with neoadjuvant CAPOX and CRT±cetuximab in the EXPERT-C trial. PATIENTS AND METHODS: Eligible patients with available tumour tissue for HER2 analysis were included. HER2 expression was determined by immunohistochemistry (IHC) in pre-treatment biopsies and/or surgical specimens (score 0-3+). Immunostaining was scored according to the consensus panel recommendations on HER2 scoring for gastric cancer. Tumours with equivocal IHC result (2+) were tested for HER2 amplification by D-ISH. Tumours with IHC 3+ or D-ISH ratio ≥2.0 were classified as HER2+. The impact of HER2 on primary and secondary end points of the study was analysed. RESULTS: Of 164 eligible study patients, 104 (63%) biopsy and 114 (69%) surgical specimens were available for analysis. Only 3 of 104 (2.9%) and 3 of 114 (2.6%) were HER2+, respectively. In 77 patients with paired specimens, concordance for HER2 status was found in 74 (96%). Overall, 141 patients were assessable for HER2 and 6 out of 141 (4.3%) had HER2 overexpression and/or amplification. The median follow-up was 58.6 months. HER2 was not associated with a difference in the outcome for any of the study end points, including in the subset of 90 KRAS/BRAF wild-type patients treated±cetuximab. CONCLUSIONS: Based on the low prevalence of expression as recorded in the EXPERT-C trial, HER2 does not appear to represent a useful therapeutic target in high-risk rectal cancer. However, the role of HER2 as a potential predictive biomarker of resistance to anti-EGFR-based treatments and a therapeutic target in anti-EGFR refractory metastatic colorectal cancer (CRC) warrants further investigation. TRIAL REGISTRATION: ISRCTN Register: 99828560.

Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C).

PURPOSE: To evaluate the addition of cetuximab to neoadjuvant chemotherapy before chemoradiotherapy in high-risk rectal cancer. PATIENTS AND METHODS: Patients with operable magnetic resonance imaging-defined high-risk rectal cancer received four cycles of capecitabine/oxaliplatin (CAPOX) followed by capecitabine chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen plus weekly cetuximab (CAPOX+C). The primary end point was complete response (CR; pathologic CR or, in patients not undergoing surgery, radiologic CR) in patients with KRAS/BRAF wild-type tumors. Secondary end points were radiologic response (RR), progression-free survival (PFS), overall survival (OS), and safety in the wild-type and overall populations and a molecular biomarker analysis. RESULTS: One hundred sixty-five eligible patients were randomly assigned. Ninety (60%) of 149 assessable tumors were KRAS or BRAF wild type (CAPOX, n = 44; CAPOX+C, n = 46), and in these patients, the addition of cetuximab did not improve the primary end point of CR (9% v 11%, respectively; P = 1.0; odds ratio, 1.22) or PFS (hazard ratio [HR], 0.65; P = .363). Cetuximab significantly improved RR (CAPOX v CAPOX+C: after chemotherapy, 51% v 71%, respectively; P = .038; after chemoradiation, 75% v 93%, respectively; P = .028) and OS (HR, 0.27; P = .034). Skin toxicity and diarrhea were more frequent in the CAPOX+C arm. CONCLUSION: Cetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF wild-type rectal cancer, but the primary end point of improved CR was not met.

Poor communication skills means high risk for aviation safety

Este artigo analisa diferentes tipos de comunicação no ambiente de negócios da aviação civil. Para tanto, utilizou-se uma abordagem qualitativa, delineada por análise documental dos relatórios das agencias governamentais. A comunicação é um sistema complexo que consiste em comunicação verbal, não verbal, escrita, falada e eletrônica. Na aviação, ela é um fator crucial ao enfrentamento de situações de alto risco. Os resultados obtidos indicam que lacunas de comunicação entre os indivíduos que atuam nas operações aeronáuticas e aeroviárias contribuem para a maior parte dos acidentes e incidentes ocorridos. As conclusões pontuam que as habilidades de comunicação são tão importantes quanto às habilidades técnicas e enfatizam a emergência do treinamento em habilidades de comunicação aos profissionais da aviação, possibilitando-os detectar ameaças e comunicar claramente a necessidade de apoio para o enfrentamento de riscos. É imperativo adotar as ações requeridas pela filosofia do Sistema de Gestão de Segurança, visando gerar comportamento seguro.

The Relationship of Diet Quality and Blood Serum Lipid Levels in a Population at High Risk for Diabetes: The Strong Heart Family Study

Thesis (Master's)--University of Washington, 2016-08

Fetal Alcohol Spectrum Disorder Primary Prevention through FASD Diagnosis: Identification of High-Risk Birth Mothers through the Diagnosis of their Children. Follow-up Study

Thesis (Master's)--University of Washington, 2016-08

How new imaging techniques can aid in defining the cardiovascular profile of the high-risk patient

Cardiovascular prevention has been developed in the last eight years producing an ever increasing amount of data requiring frequent updating. Studies using angiography to determine change in coronary obstruction have indicated progression, stabilization, or regression of coronary lesions associated with changes in plasma lipids and lipoproteins. Moreover, the guidelines on arterial hypertension published in 2007 listed the risk factors affecting prognosis but even by 2009 an update modified not only the list of risks, but even the philosophy behind the thought process which introduced as essential element in the prognosis of hypertension the ascertained existence of a damaged organ. Thus, the documentation of atherosclerotic vascular disease (plaques) and the quantification of its extension in the arterial tree became a determinant in the definition of cardiovascular risk. Magnetic Resonance (MRI) and coronary computed tomography (coro CT) applied to the heart and large vessels are the most promising methods.

Hepatitis B and C prevalence in Portugal: disparity between the general population and high-risk groups

Background and aims: The prevalence of anti-HCV and HBsAg in Portugal has been shown to be elevated in high-risk groups, such as intravenous drug-users and incarcerated individuals. However, in the general population, prevalence remains largely unknown. The aims of this study were to estimate the prevalence of anti-HCV and HBsAg in the general Portuguese population and identify associated risk factors. Materials and methods: We carried out a nationwide, population-based cross-sectional study of adults resident in mainland Portugal. Serology for HBsAg, anti-HBc, anti-HBs, and anti-HCV was performed. Anti-HCV-positive individuals were tested for HCV RNA by PCR. Results: Of 1685 participants, 50.6% were men, mean age 50.2±18.3 years. In terms of hepatitis C, the prevalence of anti-HCV was 0.54% [95% confidence interval (CI): 0.2–0.9] and 0.12% (95% CI: 0.0–0.3) were viremic, with peak prevalence among individuals 35–64 years of age (0.8%), men (0.8%), and individuals from Lisbon and Tagus Valley region (1.9%). In terms of hepatitis B, the estimated prevalence of HBsAg was 1.45% (95% CI: 0.9–2.0). A higher prevalence was found in individuals who were 35–64 years old (2.2%), in men (2.5%), and in the Northern region (2.6%). The presence of positive serological markers of hepatitis C virus and hepatitis B virus infection did not correlate with elevated aminotransferases, race, place of birth, and alcohol consumption. Conclusion: These results suggest a low endemicity for both hepatitis B and hepatitis C in the general population, in contrast to a very high prevalence in risk groups, thus suggesting that targeted screening to high-risk groups may be more cost-effective than general population screening.

Chromium supplementation in patients with type 2 diabetes and high risk of type 2 diabetes: a meta-analysis of randomized controlled trials

Introduction: Chromium is an essential trace mineral for carbohydrate and lipid metabolism, which is currently prescribed to control diabetes mellitus. Results of previous systematic reviews and meta-analyses of chromium supplementation and metabolic profiles in diabetes have been inconsistent. Aim: The objective of this meta-analysis was to assess the effects on metabolic profiles and safety of chromium supplementation in type 2 diabetes mellitus and cholesterol. Methods: Literature searches in PubMed, Scopus and Web of Science were made by use of related terms-keywords and randomized clinical trials during the period of 2000-2014. Results: Thirteen trials fulfilled the inclusion criteria and were included in this systematic review. Total doses of Cr supplementation and brewer's yeast ranged from 42 to 1,000 µg/day, and duration of supplementation ranged from 30 to 120 days. The analysis indicated that there was a significant effect of chromium supplementation in diabetics on fasting plasma glucose with a weighted average effect size of -29.26 mg/dL, p = 0.01, CI 95% = -52.4 to -6.09; and on total cholesterol with a weighted average effect size of -6.7 mg/dL, p = 0.01, CI 95% = -11.88 to -1.53. Conclusions: The available evidence suggests favourable effects of chromium supplementation on glycaemic control in patients with diabetes. Chromium supplementation may additionally improve total cholesterol levels.

Awareness and prevalence of metabolic syndrome among high-risk individuals attending internal medicine clinics across Jordan

Purpose: To examine the prevalence and awareness of metabolic syndrome (MetS) in high-risk individuals attending 30 internal medicine clinics in Amman, Jordan, and also to evaluate the various factors associated with increased risk of MetS among them. Methods: This retrospective cross-sectional study was carried out across Amman, Jordan from October to December 2014. During the study period, 900 high-risk individuals (with hypertension, diabetes, central obesity and/or dyslipidemia) were recruited from thirty internal medicine clinics in Amman, Jordan. Data collection forms were filled based on patient interview and medical case file. Results: The prevalence of MetS among high-risk individuals was around 40 % (361/900), with around 79 % (284/361) of MetS patients unaware of their condition. Older age, lower income and family history of premature cardiovascular diseases were associated with a higher prevalence of MetS. Conclusion: Although MetS was found to be highly prevalent among high-risk individuals in this study, the awareness of the condition in this group is very poor. These findings support the need for educational programs that involve both health care providers and patients. These programs should especially target those at risk of MetS, in order to improve awareness of the concept of MetS.

Antibiotic-resistant Klebsiella pneumoniae and Escherichia coli high-risk clones and an IncFII(k) mosaic plasmid hosting Tn1 (blaTEM-4) in isolates from 1990 to 2004

We describe the genetic background of bla(TEM-4) and the complete sequence of pRYC11::bla(TEM-4), a mosaic plasmid that is highly similar to pKpQIL-like variants, predominant among TEM-4 producers in a Spanish hospital (1990 to 2004), which belong to Klebsiella pneumoniae and Escherichia coli high-risk clones responsible for the current spread of different antibiotic resistance genes. Predominant populations of plasmids and host adapted clonal lineages seem to have greatly contributed to the spread of resistance to extended-spectrum cephalosporins.