Health-related quality of life parameters as prognostic factors in a nonmetastatic breast cancer population: an international multicenter study.

PURPOSE: The purpose of this research was to evaluate whether baseline health-related quality of life (HRQOL) parameters are prognostic factors for survival in locally advanced breast cancer patients. Although the literature highlights the important role of HRQOL parameters in predicting survival in advanced metastatic disease, little evidence exists for earlier stages. PATIENTS AND METHODS: The overall sample consisted of 448 patients randomly assigned to receive cyclophosphamide, epirubicin, and fluorouracil versus epirubicin, cyclophosphamide, and granulocyte colony-stimulating factor. Patients were enrolled in 12 countries. HRQOL baseline scores were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap resampling technique was used to assess the stability of the outcomes. Bootstrap results were then applied for model averaging purposes as a means to account for the observed model selection uncertainty. RESULTS: The final multivariate model retained inflammatory breast cancer (T4d) as the only factor predicting overall survival (OS) with a hazard ratio of 1.375 (95% CI, 1.027 to 1.840; P =.03). The presence of inflammatory breast cancer lowers the median survival time from 6.6 to 4.2 years (36% reduction). None of the preselected HRQOL variables were prognostic for OS or disease-free survival, in either the univariate or multivariate analysis. CONCLUSION: Our findings suggest that baseline HRQOL parameters have no prognostic value in a nonmetastatic breast cancer population.     

Correlations of selected vaginal cytokine levels with pregnancy-related traits in women with bacterial vaginosis and mycoplasmas

The aim of this study was to examine correlations between vaginal inflammatory cytokines (IL-1alpha, IL-1beta, IL-6 and IL-8) and pregnancy-related traits (gestational age, birth-weight, BMI, weight gain during pregnancy and vaginal pH). Differences in correlation coefficients were examined among bacterial vaginosis (BV) status and the presence or absence of mycoplasmas. A total of 105 women between the 22nd and 34th week of pregnancy were enrolled in this study. There was a strong negative correlation between IL-1alpha and weight gain during pregnancy (r=-0.877, p<0.001) and a strong positive correlation between IL-6 and BMI (r=0.670, p=0.024) in women with normal vaginal flora and mycoplasmas. These correlations were not present in women who had normal flora and no mycoplasmas. In women with BV and no mycoplasmas, there were significant correlations of gestational age with IL-6 (r=0.727, p=0.027) and IL-8 (r=0.689, p=0.040); however, these correlations were not significant in women with mycoplasmas. Our findings support the conclusion that correlations between inflammatory cytokines and pregnancy-related traits are dependent on context, suggesting that expression is labile. In particular, BMI and gestational age correlation differs depending on BV status and the presence or absence of BV-related mycoplasmas such as Mycoplasma hominis and Ureaplasma urealyticum.     

Should There Be Gender Differences in the Guidelines for Colorectal Cancer Screening?

Colorectal cancer screening guidelines are identical for men and women despite reported differences in epidemiology, endoscopy performance, screening preferences, and screening uptake. High-quality research is needed to determine whether gender aspects may in real world increase acceptance and overcome screening barriers, which may lead to better use of limited resources allocated for public health.     

Synergistic effect of low dose Cyclosporine A and human interleukin 10 overexpression on acute rejection in rat lung allotransplantation

Objective: Electroporation mediated transfer of plasmid DNA into peripheral muscle results in high transfection efficiency. The aim of this study was to investigate the effect of gene transfer of human IL-10 (hIL-10) into the tibialis anterior muscle (MTA) in combination with low dose Cyclosporine A (CsA) on acute rejection of lung allografts in the rat. Methods: Lung allotransplantation was performed from male BN donor to male Fisher F344 rats. Gene transfer was achieved by intramuscular injection into the MTA of the recipient followed by electroporation (4×20 ms impulses at 200 V/cm) 24 h prior to the transplantation. Group A (n=5) received CsA (2.5 mg/kg bw ip) for 5 days post-transplant and group B (n=5) 2.5 μg of PCIK hIL-10 (plasmid expression vector containing human CMV immediate early gene promoter and enhancer) and a low dose CsA (2.5 mg/kg bw i.p.). Graft function was assessed by blood gas at day 5 after exclusion of the native lung. Animals were sacrificed and blood was drawn to measure serum hIL-10 levels (ELISA) and tissue was sampled for histological grading of rejection. Results: Local expression of hIL-10 was confirmed at the mRNA level by in situ hybridization. All group A control animals showed severe signs of rejection. At day 5 all grafts in group B showed good gas exchange mean PaO2 233±123 mmHg, vs 44±8 mmHg in group A. Histological examination revealed moderate to severe rejection in all animals in group A (IIIB, ISHLT) in contrast to low moderate rejection in group B (II–IIIA). hIL-10 serum levels on day 5 were 14±7 pg/ml in group B vs. 0 in group A. Conclusions: Electroporation mediated hIL-10 overexpression in a peripheral muscle of the recipient in combination with low dose CsA reduces acute rejection in this model of rat lung allotransplantation.     

Discrimination of capsular stage brain abscesses from necrotic or cystic neoplasms using diffusion-weighted magnetic resonance imaging

OBJECT: The authors' aim was to assess the ability of apparent diffusion coefficient (ADC) ratios in distinguishing brain abscesses from cystic or necrotic neoplasms. METHODS: Fifty-three patients with rim-enhancing masses in the brain observed on T1-weighted MR images were included: 26 had abscesses (14 bacterial, six nonbacterial, and six of unknown origin), 11 had glioblastoma multiforme, and 16 had rim-enhancing metastasis. The ADC values, derived from diffusion-weighted imaging, were measured in the most homogeneous portion of the cystic component of the mass. The ADC ratios were calculated by dividing the ADC values from the nonenhancing cystic portion of the mass by the ADC values from contralateral normal-appearing white matter. Lesions were further differentiated based on presence, absence, or incompleteness of a T2 hypointensity rim. The mean (+/- standard deviation) ADC ratios were significantly higher in neoplasms than in abscesses (2.45 +/- 0.91 compared with 1.12 +/- 0:53, p < 0.01). The accuracy of ADC ratios in discriminating abscesses from neoplasms, determined by the area under the receiver operating characteristic curve (Az), was high: 0.91 +/- 0.04 (mean +/- standard error of the mean [SEM]). The threshold of 1.7 was associated with highest efficiency (87%) in discriminating abscesses from neoplasms. If only bacterial abscesses were analyzed compared with neoplasms, the Az increased to 0.96 +/- 0.03 (SEM). Using ADC ratios and T1 rim characteristics, 50 of 53 lesions were correctly classified (efficiency 94.3%). CONCLUSIONS: The accuracy of ADC ratios in discriminating brain abscesses from cystic or necrotic neoplasms is very high and can be further improved using T2 rim characteristics.     

Human cytomegalovirus persists in myeloid progenitors and is passed to the myeloid progeny in a latent form

CD34+ progenitor cells can harbour latent human cytomegalovirus (HCMV); however, the mechanisms of HCMV latency remain unclear. We have investigated the effects of the haematopoietic lineage restriction on the establishment and spread of the latent HCMV to progeny cells. In vitro-infected and latently-infected haematopoietic progenitor cells derived from HCMV seropositive donors were studied. The presence of HCMV DNA in bone marrow progenitor (BMP) cells was determined by single colony polymerase chain reaction and fluorescent in situ hybridization (FISH). The presence of CMV DNA was found to be restricted to myeloid progenitors and the percentage of HCMV-infected cells was lower in naturally-infected cells than in in vitro-infected cells. Erythroid differentiation resulted in an abortive infection with persistence of the viral nucleic acids in red cell precursors. In BMP cells from HCMV seronegative donors, HCMV DNA was localized in the nucleus. Bone marrow progenitors in the presence of granulocyte-macrophage colony stimulating factor (GMCSF) maintained HCMV DNA for extended periods of time. No viral production could be detected throughout the culture but the comparison of the numbers of latently-infected cells prior to and after the culture suggests that proliferation of haematopoietic progenitor cells may lead to the expansion of latently-infected cells.     

Multivariate analysis of risk factors for development of duodenal ulcer in Helicobacter pylori-infected patients

BACKGROUND: Although Helicobacter pylori is a significant etiologic factor of peptic ulcer disease, it remains unknown why ulcers develop only in the minority of infected individuals. AIM: The aim of this cross-sectional study was to evaluate the association between the presence of duodenal ulcer in H. pylori-infected patients and different risk factors. METHODS: A total of 122 H. pylori-infected patients were enrolled; 79 had duodenal ulcer and 43 gastritis. Univariate analysis was conducted using either Fisher's exact test or exact Cochrane-Armitage trend test. In multivariate analysis the logistic model was used. RESULTS: Univariate analysis indicated six factors (male sex, smoking, antral H. pylori density, CAGA presence in antrum, and VACA s1a presence in antrum and corpus). Four factors (sex, smoking-alcohol index, H. pylori density index, and CAGA index) were found to be significant in multivariate analysis. The best model predicting duodenal ulcer included male sex, smoking, presence of H. PYLORI on histopathology in antrum and CAGA presence in corpus. CONCLUSION: Although several risk factors were significantly associated with duodenal ulcer, we failed in the identification of either a single risk factor or a set of factors that can unequivocally differentiate patients with ulcer from those with gastritis.