Are work-related stressors associated with diagnosis of more advanced stages of incident breast cancers?

Objective To assess the relation between work-related stressors and breast cancer incidence and prognostic characteristics (estrogen receptor status, grade, lymph node status, size, stage) at the time of diagnosis. Methods The 18,932 women included in the Danish Nurse Cohort reported work-related stressors in 1993 and again in 1999 and were followed until the end of 2003 in national registries. Prognostic characteristics were obtained from a clinical database and fewer than 0.1% were lost to follow up. Results During follow-up, 455 women were diagnosed with breast cancer. Neither women with high work pressure (HR = 1.17; 95% CI: 0.79, 1.73) nor women with self-reported low influence on work organization (0.98; 0.69, 1.39) or long working hours (0.93; 0.54, 1.58) were at higher risk of breast cancer than women with no such stressors. Women with high work tempo had a slightly higher risk of breast cancer (1.25; 1.02, 1.54) than women with a suitable work tempo, but there was no dose-response effect. There were no clear differences in the prognostic characteristics of breast tumors diagnosed in women with and without work-related stressors. Conclusions Work-related stressors do not affect breast cancer risk or the prognostic characteristics of incident breast cancers at the time of diagnosis. These results may be a comfort to working women and can hopefully prevent self-blaming among women who develop breast cancer.     

The prevalence and prognostic value of concomitant eosinophilia in chronic graft-versus-host disease after allogeneic stem cell transplantation

The prognostic significance of eosinophilia after myeloablative allogeneic stem cell transplantation (ASCT) remains to be established. Patients, whom developed chronic graft-versus-host disease (cGVHD) after ASCT, were included (n = 142). Eosinophil count was analyzed at cGVHD onset. We observed no significant association between EO and the grade of cGVHD, thrombocytopenia, nor extensive skin involvement. Importantly, we observed no significant association between cGVHD with concomitant eosinophilia and long-term clinical outcomes, and subgroup analyses revealed a considerable confounding effect of ongoing steroid treatment. In conclusion, we advocate that prognostic conclusions regarding cGVHD with concomitant eosinophilia after ASCT should be interpreted with caution.     

Impact of surgical aortic valve replacement on global and regional longitudinal strain across four flow gradient patterns of severe aortic stenosis

The International Journal of Cardiovascular Imaging - To evaluate the impact of surgical aortic valve replacement (SAVR) on global (GLS) and regional longitudinal strain (RLS) across four...     

The accuracy of quantitative parameters in 99mTc‐MAG3 dynamic renography: a national audit based on virtual image data

Assessment of image analysis methods and computer software used in ^99mTc‐MAG3 dynamic renography is important to ensure reliable study results and ultimately the best possible care for patients. In this work, we present a national multicentre study of the quantification accuracy in ^99mTc‐MAG3 renography, utilizing virtual dynamic scintigraphic data obtained by Monte Carlo‐simulated scintillation camera imaging of digital phantoms with time‐varying activity distributions. Three digital phantom studies were distributed to the participating departments, and quantitative evaluation was performed with standard clinical software according to local routines. The differential renal function (DRF) and time to maximum renal activity (T_max) were reported by 21 of the 28 Swedish departments performing ^99mTc‐MAG3 studies as of 2012. The reported DRF estimates showed a significantly lower precision for the phantom with impaired renal uptake than for the phantom with normal uptake. The T_max estimates showed a similar trend, but the difference was only significant for the right kidney. There was a significant bias in the measured DRF for all phantoms caused by different positions of the left and right kidney in the anterior–posterior direction. In conclusion, this study shows that virtual scintigraphic studies are applicable for quality assurance and that there is a considerable uncertainty associated with standard quantitative parameters in dynamic ^99mTc‐MAG3 renography, especially for patients with impaired renal function.     

Assessment of quality in psychiatric nursing documentation – a clinical audit

Background

Quality in nursing documentation facilitates continuity of care and patient safety. Lack of communication between healthcare providers is associated with errors and adverse events. Shortcomings are identified in nursing documentation in several clinical specialties, but very little is known about the quality of how nurses document in the field of psychiatry. Therefore, the aim of this study was to assess the quality of the written nursing documentation in a psychiatric hospital.

Method

A cross-sectional, retrospective patient record review was conducted using the N-Catch audit instrument. In 2011 the nursing documentation from 21 persons admitted to a psychiatric department from September to December 2010 was assessed. The N-Catch instrument was used to audit the record structure, admission notes, nursing care plans, progress and outcome reports, discharge notes and information about the patients’ personal details. The items of N-Catch were scored for quantity and/or quality (0–3 points).

Results

The item ‘quantity of progress and evaluation notes’ had the lowest score: in 86% of the records progress and outcome were evaluated only sporadically. The items ‘the patients’ personal details’ and ‘quantity of record structure’ had the highest scores: respectively 100% and 71% of the records achieved the highest score of these items.

Conclusions

Deficiencies in nursing documentation identified in other clinical specialties also apply to the clinical field of psychiatry. The quality of electronic written nursing documentation in psychiatric nursing needs improvements to ensure continuity and patient safety. This study shows the importance of the existence of a validated tool, readily available to assess local levels of nursing documentation quality.

     

Activation of ErbB3, EGFR and Erk is essential for growth of human breast cancer cell lines with acquired resistance to fulvestrant

Seven fulvestrant resistant cell lines derived from the estrogen receptor α positive MCF-7 human breast cancer cell line were used to investigate the importance of epidermal growth factor receptor (ErbB1-4) signaling. We found an increase in mRNA expression of EGFR and the ErbB3/ErbB4 ligand heregulin2 (hrg2) and a decrease of ErbB4 in all resistant cell lines. Western analyses confirmed the upregulation of EGFR and hrg2 and the downregulation of ErbB4. Elevated activation of EGFR and ErbB3 was seen in all resistant cell lines and the ErbB3 activation occurred by an autocrine mechanism. ErbB4 activation was observed only in the parental MCF-7 cells. The downstream kinases pAkt and pErk were increased in five of seven and in all seven resistant cell lines, respectively. Treatment with the EGFR inhibitor gefitinib preferentially inhibited growth and reduced the S phase fraction in the resistant cell lines concomitant with inhibition of Erk and unaltered Akt activation. In concert, inhibition of Erk with U0126 preferentially reduced growth of resistant cell lines. Treatment with ErbB3 neutralizing antibodies inhibited ErbB3 activation and resulted in a modest but statistically significant growth inhibition of two resistant cell lines. These data indicate that ligand activated ErbB3 and EGFR, and Erk signaling play important roles in fulvestrant resistant cell growth. Furthermore, the decreased level of ErbB4 in resistant cells may facilitate heterodimerization of ErbB3 with EGFR and ErbB2. Our data support that a concerted action against EGFR, ErbB2 and ErbB3 may be required to obtain complete growth suppression of fulvestrant resistant cells.     

Presence of Insulin-Like Growth Factor Binding Proteins Correlates With Tumor-Promoting Effects of Matrix Metalloproteinase 9 in Breast Cancer

The stroma of breast cancer can promote the disease’s progression, but whether its composition and functions are shared among different subtypes is poorly explored. We compared stromal components of a luminal [mouse mammary tumor virus (MMTV)–Neu] and a triple-negative/basal-like [C3(1)–Simian virus 40 large T antigen (Tag)] genetically engineered breast cancer mouse model. The types of cytokines and their expression levels were very different in the two models, as was the extent of innate immune cell infiltration; however, both models showed infiltration of innate immune cells that expressed matrix metalloproteinase 9 (MMP9), an extracellular protease linked to the progression of many types of cancer. By intercrossing with Mmp9 null mice, we found that the absence of MMP9 delayed tumor onset in the C3(1)-Tag model but had no effect on tumor onset in the MMTV-Neu model. We discovered that protein levels of insulin-like growth factor binding protein-1 (IGFBP-1), an MMP9 substrate, were increased in C3(1)-Tag;Mmp9^−/− compared to C3(1)-Tag;Mmp9^+/+ tumors. In contrast, IGFBP-1 protein expression was low in MMTV-Neu tumors regardless of Mmp9 status. IGFBP-1 binds and antagonizes IGFs, preventing them from activating their receptors to promote cell proliferation and survival. Tumors from C3(1)-Tag;Mmp9^−/− mice had reduced IGF-1 receptor phosphorylation, consistent with slower tumor onset. Finally, gene expression analysis of human breast tumors showed that high expression of IGFBP mRNA was strongly correlated with good prognosis but not when MMP9 mRNA was also highly expressed. In conclusion, MMP9 has different effects on breast cancer progression depending on whether IGFBPs are expressed.Abbreviations: αSMA, α smooth muscle actin, C3(1)-Tag, transgene mouse expressing Simian virus 40 large T antigen under a C3(1) promoter, HER2, human epidermal growth factor receptor 2, IGF, insulin-like growth factor, IGFBP, insulin-like growth factor binding protein, IL, interleukin, MMP, matrix metalloproteinase, MMTV, mouse mammary tumor virus, NF-κB, nuclear factor κB, PyMT, polyoma middle T antigen     

Independent and tissue-specific prognostic impact of miR-126 in nonsmall cell lung cancer: coexpression with vascular endothelial growth factor-A predicts poor survival

BACKGROUND:

Angiogenesis is pivotal in tumor development. Vascular endothelial growth factor‐A (VEGF‐A) is considered one of the most important angiogenic factors, but lately several microRNAs (miRs) have been associated with vascular development. miR‐126 has been related to tumor angiogenesis and in the regulation of VEGF‐A. The authors aimed to investigate the prognostic impact of miR‐126 and its co‐expression with VEGF‐A in nonsmall cell lung cancer (NSCLC) patients.

METHODS:

Tumor tissue samples from 335 resected stage I to IIIA NSCLC patients were obtained and tissue microarrays (TMAs) were constructed with 4 cores from each tumor specimen. VEGF‐A expression was evaluated by immunohistochemistry, and in situ hybridization was used to evaluate the expression of miR‐126.

RESULTS:

In the total material, miR‐126 was a significant negative prognostic factor in both univariate (P = .005) and multivariate analyses (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.2‐2.8, P = .01). Stratified by histology, miR‐126 was only significant in squamous cell carcinomas (univariate: P < .001; multivariate: HR 3.1, CI 95% 1.7‐5.6, P<.001). Stratified by lymph node status, miR‐126 was significant only in the lymph node‐positive subgroup (univariate: P<.001; multivariate: HR 4.1, CI 95% 2.0‐8.4, P < .001). High miR‐126 expression correlated significantly with high VEGF‐A expression (P = .037). The co‐expression of miR‐126 and VEGF‐A had a significant prognostic impact (P = .002), with 5‐year survival rates of 68%, 51%, and 42% for low/low (n = 150), mixed combinations (n = 129), and high/high (n = 35) expression, respectively.

CONCLUSIONS:

miR‐126 is a strong and independent negative prognostic factor in NSCLC, and its prognostic impact appears related primarily to histology and nodal status. Cancer 2011. © 2011 American Cancer Society.