Evaluation of the frequency of left renal vein variations in computed tomography and its relationship with cancer development

Background: Left renal vein (LRV) variations occur in 0.8–10.2% of the population. The most common LRV variations are retroaortic left renal vein (RLRV) and circumaortic left renal vein (CLRV). The purpose of this study is to determine the frequency of LRV variations in a large series on computed tomography (CT) and to investigate the association between LRV and malignancy development.Materials and methods: Between January 2015 and January 2017, an abdominal CT examination of 12,341 (5505 female, 6836 male) patients was evaluated retrospectively in this study. Patients’ clinical and demographic data were recorded using the Hospital Information System.Results: Left renal vein variations were detected in 314 (2.54%) of the 12,341 patients within the study. Of the 314 cases found to have LRV variations, 227 (1.84%) had RLRV, and 87 (0.70%) had CLRV. There was no statistical difference in total LRV variations (p = 0.083) and CLRV variation (p = 0.96) groups in terms of gender. However, the RLRV variation was found to be 1.32 times higher in males than in females (p = 0.039). Of the 314 patients with LRV variations, 73 (23.2%) had any sort of concomitant malignancy.Conclusions: A high incidence of malignancy was detected in patients with LRV variations. Of the LRV variations, RLRV variation is more common than CLRV variation. The presence of total LRV variations and CLRV variations is not associated with gender; whereas the presence of RLRV variation is more common in males

Isolation, genotyping and antimicrobial susceptibility of pathogenic Escherichia coli serotypes in ready to eat foods

NO ABSTRACT AVAILABLEIn this study, pathogenic Escherichia coli serotypes (E. coli O157:H7, O26, O111) and their molecular proximity and antimicrobial susceptibility were investigated in RTE foods. A total of 240 samples; consist of 105 stuffed mussel, 56 meatless cig kofte, 54 Russian salad, 25 cheese halva, were analyzed. The conventional culture and serotyping methods for determination of the organisms were performed and further confirmation by PCR was carried out. Confirmed E. coli O157 isolates were genotyped by the enterobacterial repetitive intergenic consensus(ERIC)-PCR. Antibacterial susceptibility testing of the isolates was performed by disc diffusion method. E. coli was detected in 7 (2.9 %) of 240 samples, including 3 (5.5%) Russian salad, 3 (2.8%) stuffed mussel, 1 (4 %) cheese halva. Two isolates from Russian salad, 1 from stuffed mussel and 1 from cheese halva were identified as E. coli O157 . In addition, stuffed mussel isolate was found to carry stx1 ve hlyA genes whereas one Russian salad isolate carried the stx1 gene. E. coli isolates were found to be resistant to amoxycillin/clavulonic acid, gentamicin and ciprofloxacin, at the rate of 29%, 14% and 29 %, respectively. Only one (14 %) isolate from stuffed mussel was classified as multidrug resistant to three antimicrobials. Furthermore, the isolates, related to O157 and O157:H7, presented different ribotypes in this study. The results provide useful data for the development of public health policy concerning the potential presence of pathogenic antimicrobial resistant E. coli serotypes in RTE foods. Strict surveillance of RTE foods at retail points for emerging pathogens, their antimicrobial resistance patterns and the potential likelihood of cross-contamination is required

Isolation, genotyping and antimicrobial susceptibility of pathogenic Escherichia coli serotypes in ready to eat foods

NO ABSTRACT AVAILABLEIn this study, pathogenic Escherichia coli serotypes (E. coli O157:H7, O26, O111) and their molecular proximity and antimicrobial susceptibility were investigated in RTE foods. A total of 240 samples; consist of 105 stuffed mussel, 56 meatless cig kofte, 54 Russian salad, 25 cheese halva, were analyzed. The conventional culture and serotyping methods for determination of the organisms were performed and further confirmation by PCR was carried out. Confirmed E. coli O157 isolates were genotyped by the enterobacterial repetitive intergenic consensus(ERIC)-PCR. Antibacterial susceptibility testing of the isolates was performed by disc diffusion method. E. coli was detected in 7 (2.9 %) of 240 samples, including 3 (5.5%) Russian salad, 3 (2.8%) stuffed mussel, 1 (4 %) cheese halva. Two isolates from Russian salad, 1 from stuffed mussel and 1 from cheese halva were identified as E. coli O157 . In addition, stuffed mussel isolate was found to carry stx1 ve hlyA genes whereas one Russian salad isolate carried the stx1 gene. E. coli isolates were found to be resistant to amoxycillin/clavulonic acid, gentamicin and ciprofloxacin, at the rate of 29%, 14% and 29 %, respectively. Only one (14 %) isolate from stuffed mussel was classified as multidrug resistant to three antimicrobials. Furthermore, the isolates, related to O157 and O157:H7, presented different ribotypes in this study. The results provide useful data for the development of public health policy concerning the potential presence of pathogenic antimicrobial resistant E. coli serotypes in RTE foods. Strict surveillance of RTE foods at retail points for emerging pathogens, their antimicrobial resistance patterns and the potential likelihood of cross-contamination is required

Ongoing under-reporting of clinically relevant safety data in phase II studies of tyrosine kinase inhibitors

status: publishe

Higher Absolute Lymphocyte Counts Predict Lower Mortality from Early-Stage Triple-Negative Breast Cancer

Purpose: Tumor-infiltrating lymphocytes (TIL) in pretreatment biopsies are associated with improved survival in triple-negative breast cancer (TNBC). We investigated whether higher peripheral lymphocyte counts are associated with lower breast cancer–specific mortality (BCM) and overall mortality (OM) in TNBC. Experimental Design: Data on treatments and diagnostic tests from electronic medical records of two health care systems were linked with demographic, clinical, pathologic, and mortality data from the California Cancer Registry. Multivariable regression models adjusted for age, race/ethnicity, socioeconomic status, cancer stage, grade, neoadjuvant/adjuvant chemotherapy use, radiotherapy use, and germline BRCA1/2 mutations were used to evaluate associations between absolute lymphocyte count (ALC), BCM, and OM. For a subgroup with TIL data available, we explored the relationship between TILs and peripheral lymphocyte counts. Results: A total of 1,463 stage I–III TNBC patients were diagnosed from 2000 to 2014; 1,113 (76%) received neoadjuvant/adjuvant chemotherapy within 1 year of diagnosis. Of 759 patients with available ALC data, 481 (63.4%) were ever lymphopenic (minimum ALC <1.0 K/μL). On multivariable analysis, higher minimum ALC, but not absolute neutrophil count, predicted lower OM [HR = 0.23; 95% confidence interval (CI), 0.16–0.35] and BCM (HR = 0.19; CI, 0.11–0.34). Five-year probability of BCM was 15% for patients who were ever lymphopenic versus 4% for those who were not. An exploratory analysis (n = 70) showed a significant association between TILs and higher peripheral lymphocyte counts during neoadjuvant chemotherapy. Conclusions: Higher peripheral lymphocyte counts predicted lower mortality from early-stage, potentially curable TNBC, suggesting that immune function may enhance the effectiveness of early TNBC treatment

Single Cell Profiling of Circulating Tumor Cells: Transcriptional Heterogeneity and Diversity from Breast Cancer Cell Lines

BACKGROUND: To improve cancer therapy, it is critical to target metastasizing cells. Circulating tumor cells (CTCs) are rare cells found in the blood of patients with solid tumors and may play a key role in cancer dissemination. Uncovering CTC phenotypes offers a potential avenue to inform treatment. However, CTC transcriptional profiling is limited by leukocyte contamination; an approach to surmount this problem is single cell analysis. Here we demonstrate feasibility of performing high dimensional single CTC profiling, providing early insight into CTC heterogeneity and allowing comparisons to breast cancer cell lines widely used for drug discovery. METHODOLOGY/PRINCIPAL FINDINGS: We purified CTCs using the MagSweeper, an immunomagnetic enrichment device that isolates live tumor cells from unfractionated blood. CTCs that met stringent criteria for further analysis were obtained from 70% (14/20) of primary and 70% (21/30) of metastatic breast cancer patients; none were captured from patients with non-epithelial cancer (n = 20) or healthy subjects (n = 25). Microfluidic-based single cell transcriptional profiling of 87 cancer-associated and reference genes showed heterogeneity among individual CTCs, separating them into two major subgroups, based on 31 highly expressed genes. In contrast, single cells from seven breast cancer cell lines were tightly clustered together by sample ID and ER status. CTC profiles were distinct from those of cancer cell lines, questioning the suitability of such lines for drug discovery efforts for late stage cancer therapy. CONCLUSIONS/SIGNIFICANCE: For the first time, we directly measured high dimensional gene expression in individual CTCs without the common practice of pooling such cells. Elevated transcript levels of genes associated with metastasis NPTN, S100A4, S100A9, and with epithelial mesenchymal transition: VIM, TGFß1, ZEB2, FOXC1, CXCR4, were striking compared to cell lines. Our findings demonstrate that profiling CTCs on a cell-by-cell basis is possible and may facilitate the application of 'liquid biopsies' to better model drug discovery

Ethanol production from xylose by pichia stipitis NRRL Y-7124 in a stirred tank bioreactor

The ethanol production by Pichia stipitis was evaluated in a stirred tank bioreactor using semidefined medium containing xylose (90.0 g/l) as the main carbon source. Experimental assays were performed according to a 22 full factorial design to evaluate the influence of aeration (0.25 to 0.75 vvm) and agitation (150 to 250 rpm) conditions on ethanol production. In the studied range of values, the agitation increase and aeration decrease favored ethanol production, which was maximum (26.7 g/l) using 250 rpm and 0.25 vvm, conditions that gave a volumetric oxygen transfer coefficient (kLa value) of 4.9 h-1. Under these conditions, the ethanol yield factor, ethanol productivity, and the process efficiency were 0.32 g/g, 0.32 g/l.h, and 63%, respectively. These results are promising and contribute to the development of a suitable process for ethanol production from xylose by Pichia stipitis.The authors gratefully acknowledge Santander, Fapesp, Capes, and CNPq (Brazil)

Rationale and design of the Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research Trial (MANTICORE 101 - Breast): a randomized, placebo-controlled trial to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer using cardiac MRI

<p>Abstract</p> <p>Background</p> <p>MANTICORE 101 - Breast (Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research) is a randomized trial to determine if conventional heart failure pharmacotherapy (angiotensin converting enzyme inhibitor or beta-blocker) can prevent trastuzumab-mediated left ventricular remodeling, measured with cardiac MRI, among patients with HER2+ early breast cancer.</p> <p>Methods/Design</p> <p>One hundred and fifty-nine patients with histologically confirmed HER2+ breast cancer will be enrolled in a parallel 3-arm, randomized, placebo controlled, double-blind design. After baseline assessments, participants will be randomized in a 1:1:1 ratio to an angiotensin-converting enzyme inhibitor (perindopril), beta-blocker (bisoprolol), or placebo. Participants will receive drug or placebo for 1 year beginning 7 days before trastuzumab therapy. Dosages for all groups will be systematically up-titrated, as tolerated, at 1 week intervals for a total of 3 weeks. The primary objective of this randomized clinical trial is to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer, as measured by 12 month change in left ventricular end-diastolic volume using cardiac MRI. Secondary objectives include 1) determine the evolution of left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer, 2) understand the mechanism of trastuzumab mediated cardiac toxicity by assessing for the presence of myocardial injury and apoptosis on serum biomarkers and cardiac MRI, and 3) correlate cardiac biomarkers of myocyte injury and extra-cellular matrix remodeling with left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer.</p> <p>Discussion</p> <p>Cardiac toxicity as a result of cancer therapies is now recognized as a significant health problem of increasing prevalence. To our knowledge, MANTICORE will be the first randomized trial testing proven heart failure pharmacotherapy in the prevention of trastuzumab-mediated cardiotoxicity. We expect the findings of this trial to provide important evidence in the development of guidelines for preventive therapy.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01016886">NCT01016886</a></p

A phase I open-label study evaluating the cardiovascular safety of sorafenib in patients with advanced cancer

Purpose: To characterize the cardiovascular profile of sorafenib, a multitargeted kinase inhibitor, in patients with advanced cancer. Methods: Fifty-three patients with advanced cancer received oral sorafenib 400 mg bid in continuous 28-day cycles in this open-label study. Left ventricular ejection fraction (LVEF) was evaluated using multigated acquisition scanning at baseline and after 2 and 4 cycles of sorafenib. QT/QTc interval on the electrocardiograph (ECG) was measured in triplicate with a Holter 12-lead ECG at baseline and after 1 cycle of sorafenib. Heart rate (HR) and blood pressure (BP) were obtained in duplicate at baseline and after 1 and 4 cycles of sorafenib. Plasma pharmacokinetic data were obtained for sorafenib and its 3 main metabolites after 1 and 4 cycles of sorafenib. Results: LVEF (SD) mean change from baseline was -0.8 ($\pm$8.6) LVEF(%) after 2 cycles (n=31) and -1.2 $\pm$7.8) LVEF(%) after 4 cycles of sorafenib (n=24). The QT/QTc mean changes from baseline observed at maximum sorafenib concentrations ($t_{max}$) after 1 cycle (n=31) were small (QTcB: 4.2 ms; QTcF: 9.0 ms). Mean changes observed after 1 cycle in BP (n=31) and HR (n=30) at maximum sorafenib concentrations ($t_{max}$) were moderate (up to 11.7 mm Hg and -6.6 bpm, respectively). No correlation was found between the AUC and ($C_{max}$) of sorafenib and its main metabolites and any cardiovascular parameters. Conclusions: The effects of sorafenib on changes in QT/QTc interval on the ECG, LVEF, BP, and HR were modest and unlikely to be of clinical significance in the setting of advanced cancer treatment