Myocardial Ischemia Induced by 5-Fluorouracil: A Prospective Electrocardiographic and Cardiac Biomarker Study

BackgroundCardiotoxicity induced by 5‐fluorouracil (5‐FU) is well known but poorly understood. In this study, we undertook ECG recording (Holter) and analyses of the biomarkers troponin and copeptin in patients receiving 5‐FU to increase our understanding of the cardiotoxicity.Subjects, Materials, and MethodsPatients with colorectal or anal cancer that received first‐time treatment with 5‐FU‐based chemotherapy were prospectively included. Holter recording, clinical evaluation, 12‐lead electrocardiogram, and assessment of plasma concentrations of troponin I and copeptin were performed before (control) and during 5‐FU treatment (intervention).ResultsA total of 108 patients were included, 82 with colorectal and 26 with anal cancer. The proportion of patients with myocardial ischemia on Holter recording was significantly higher during the first 5‐FU infusion (14.1%) than before (3.7%; p = .001). The ischemic burden per day (p = .001), the number of ST depression episodes per day (p = .003), and the total duration of ischemic episodes per day (p = .003) were higher during the first 5‐FU infusion than before, as was plasma copeptin (p < .001), whereas plasma troponin I was similar (p > 0.999). Six patients (5.6%) developed acute coronary syndromes and two (1.8%) developed symptomatic arrhythmias during 5‐FU treatment.Conclusion5‐FU infusion is associated with an increase in the number of patients with myocardial ischemia on Holter recording. According to biomarker analyses, 5‐FU is associated with an increase in copeptin, but rarely with increases in cardiac troponin I. However, 5%–6% of the patients developed acute coronary syndromes during treatment with 5‐FU.Implications for PracticeSymptomatic 5‐fluorouracil (5‐FU) cardiotoxicity occurs in 0.6%–19% of patients treated with this drug, but a small electrocardiographic (Holter) study has revealed silent myocardial ischemia in asymptomatic patients, suggesting a more prevalent subclinical cardiac influence. This study demonstrated a significant increase in the number of patients with myocardial ischemia on Holter recording during 5‐FU treatment and an increase in ischemic burden. Cardiac biomarker analyses suggested that 5‐FU infusion results in endogenous stress (increased copeptin) but rarely induces myocyte injury (no change in troponin). These findings suggest a more prevalent cardiac influence from 5‐FU and that Holter recording is an important tool in the evaluation of patients with suspected cardiotoxicity from 5‐FU.     

Evaluation of methods to assess transmission potential of Venezuelan equine encephalitis virus by mosquitoes and estimation of mosquito saliva titers

Determining the dose of an arbovirus transmitted by a mosquito is important to design transmission and pathogenesis studies simulating natural infection. Several different artificial infection and transmission methods used to assess vector competence and to estimate the dose injected during mosquito feeding have not been fully evaluated to determine whether they accurately reflect natural transmission. Additionally, it is not known whether different mosquito vectors transmit similar amounts of a given virus. Therefore, we compared three traditional artificial transmission methods using Venezuelan equine encephalitis virus (VEEV) and Aedes albopictus and Ochlerotatus taeniorhynchus mosquitoes. Both the mosquito species and the infection route used affected the amount of virus detected in the saliva after a 10-day extrinsic incubation period. Median titers of virus detected in saliva of Ae. albopictus and Oc. taeniorhynchus mosquitoes ranged from 0.2 to 1.1 log(10) (mean 0.7-1.4 log(10)) and 0.2 to 3.2 log(10) (mean 1.0-3.6 log(10)) plaque-forming units, respectively. The results of this study will aid in the design of transmission and pathogenesis studies involving arboviruses.     

Plasma miR-200b in ovarian carcinoma patients: distinct pattern of pre/post-treatment variation compared to CA-125 and potential for prediction of progression-free survival

Ovarian carcinomas (OvCa) are highly heterogeneous malignancies. We investigated four circulating plasma microRNAs (miR-21, miR-34a, miR-200b and miR-205) as candidate biomarkers. Using qPCR, we assessed the plasma concentration of these markers in 101 women, including 51 previously untreated OvCa patients, 25 healthy women and 25 patients bearing benign pelvic lesions. For a subset of 33 OvCa patients, the assay was repeated at the end of the primary treatment. The pattern of variations (post- minus pre-treatment) of concentration was compared to that of CA-125. A Cox regression model was used to study the association between variations and the progression-free survival (PFS). Plasma miR-200b proved to have a greater average concentration in OvCa samples (median 2^−ΔΔCt = 15.18) than in samples linked to non-malignant lesions (median 2^−ΔΔCt = 1.26, p-value = 0.0004). Its concentration was highly heterogeneous among OvCa patients, without any correlations with the FIGO stage and the pre-treatment CA-125 level. The decrease in CA-125 concentration was constant and often dramatic, while the variations of miR-200b concentration were much more diverse. The variation of miR-200b was marginally associated with the PFS (hazard ratio=2.95 95%CI=[0.94; 9.28], p=0.06) while miR-200b as a continuous time-dependent variable was significantly associated (HR=1.06 [1.02; 1.10], p=0.003). This study is the first direct empirical evidence that miR-200b can provide additional information, independent of CA-125 in OvCa patients.     

Pregnancy-associated breast cancers: Do they differ from other breast cancers in young women?

The impact of pregnancy in the physiopathology of pregnancy-associated breast cancer (PABC) is still unclear. We compared the characteristics of PABCs and breast cancers not associated with pregnancy (non-PABCs) in terms of their loco-regional invasion and histological phenotype. We conducted a retrospective chart review on women less than 43 years of age treated for breast cancer from January 1, 2004 to December 31, 2010. We compared age at diagnosis, loco-regional invasion and histological data. We recorded 282 breast cancers in 276 patients. Forty-one tumors (14.5%) were PABCs. PABC patients were significantly younger than non-PABC patients. Compared with the non-PABCs, PABCs were twice more frequent advanced tumors (T3-4) and have twice more frequent HER2 over-expression and hormone negative status. The more aggressive histological profile observed in the PABCs, especially in post-partum tumors and women older than 35 years of age, seems to be a direct consequence of the association with pregnancy.     

Translation and Cultural Validation of the WERF EPHect Endometriosis Patient Questionnaire into Canadian French

ObjectiveTo produce a culturally validated Canadian French version of the Standard EPHect Endometriosis Patient Questionnaire (EPQ-S) from the World Endometriosis Research Foundation (WERF).MethodsWe studied 17 premenopausal women who were seen for pelvic pain symptoms or suspicion of endometriosis at the gynaecology clinic of the CHU de Québec – Université Laval (Québec City, Canada). Participants completed the French language version of the questionnaire at their first visit, and the validation took place about 1 week later.ResultsAll 22 of the invited women agreed to participate, of whom 17 were reached for the validation. The mean age of participants was 38.9 years, and 15 (88%) had a confirmed diagnosis of endometriosis. Fourteen participants (82%) found the questionnaire clear and relevant. The average length of time to complete the questionnaire was 36.25 ± 10.8 minutes. The validation process resulted in the addition of lines at the end of each section to allow space for specific comments and some clarifications with respect to timelines.ConclusionThis study validated a Canadian French version of the EPHect questionnaire. With such validation studies, differences in language and culture will no longer be a barrier to large national and international studies on endometriosis, leading to high-quality research and breakthroughs for millions of individuals living with this disease.     

Idiopathic gastric perforation in the newborn. Report of 2 cases

We report two cases of spontaneous neonatal gastric perforation in neonates born at term. The first neonate experienced on the second day of life a shock related to gastric perforation and he died 24 hours postoperatively from multisystemic failure. In the second case, gastric perforation occurred in a twin on the third day of life. Total gastrectomy was performed and the baby was well at the age of 13 months. Among the different causes of neonatal gastric perforation reported in the literature, none was found in our two cases. To our knowledge, our second case is the fourth case of survival after total gastrectomy for spontaneous neonatal gastric perforation described in the literature.     

Clinical insights into a tertiary care center cohort of patients with bicuspid aortic valve

The International Journal of Cardiovascular Imaging - Although bicuspid aortic valve (BAV) is one of the most common congenital heart diseases, clinical data associated with valve dysfunction are...