High-Level Human Herpesvirus-6 Viremia Associated With Onset of Stevens-Johnson Syndrome: Report of Two Cases:

The pathogenesis of Stevens Johnson Syndrome (SJS) remains obscure but it has been associated with various infectious agents, including members of the Herpes virus family. We present the first report of high level human herpesvirus-6 (HHV-6) viremia at the onset of SJS suggesting a possible new association. This finding supports the need for further investigation into the possible relationship between HHV-6 and SJS which may illuminate the pathogenesis of SJS and bring us closer to achieving enhanced prevention and treatment of this rare disease

Safety and Pharmacokinetics of Intravenous Zanamivir Treatment in Hospitalized Adults With Influenza: An Open-label, Multicenter, Single-Arm, Phase II Study

Background. Intravenous zanamivir is a neuraminidase inhibitor suitable for treatment of hospitalized patients with severe influenza

Quality of life and quality-adjusted survival (Q-TWiST) in patients receiving dose-intensive or standard dose chemotherapy for high-risk primary breast cancer

Quality of life (QL) is an important consideration when comparing adjuvant therapies for early breast cancer, especially if they differ substantially in toxicity. We evaluated QL and Q-TWiST among patients randomised to adjuvant dose-intensive epirubicin and cyclophosphamide administered with filgrastim and progenitor cell support (DI-EC) or standard-dose anthracycline-based chemotherapy (SD-CT). We estimated the duration of chemotherapy toxicity (TOX), time without disease symptoms and toxicity (TWiST), and time following relapse (REL). Patients scored QL indicators. Mean durations for the three transition times were weighted with patient reported utilities to obtain mean Q-TWiST. Patients receiving DI-EC reported worse QL during TOX, especially treatment burden (month 3: P<0.01), but a faster recovery 3 months following chemotherapy than patients receiving SD-CT, for example, less coping effort (P<0.01). Average Q-TWiST was 1.8 months longer for patients receiving DI-EC (95% CI, −2.5 to 6.1). Q-TWiST favoured DI-EC for most values of utilities attached to TOX and REL. Despite greater initial toxicity, quality-adjusted survival was similar or better with dose-intensive treatment as compared to standard treatment. Thus, QL considerations should not be prohibitive if future intensive therapies show superior efficacy

Rationale and design of the Exercise Intensity Trial (EXCITE): A randomized trial comparing the effects of moderate versus moderate to high-intensity aerobic training in women with operable breast cancer

<p>Abstract</p> <p>Background</p> <p>The Exercise Intensity Trial (EXcITe) is a randomized trial to compare the efficacy of supervised moderate-intensity aerobic training to moderate to high-intensity aerobic training, relative to attention control, on aerobic capacity, physiologic mechanisms, patient-reported outcomes, and biomarkers in women with operable breast cancer following the completion of definitive adjuvant therapy.</p> <p>Methods/Design</p> <p>Using a single-center, randomized design, 174 postmenopausal women (58 patients/study arm) with histologically confirmed, operable breast cancer presenting to Duke University Medical Center (DUMC) will be enrolled in this trial following completion of primary therapy (including surgery, radiation therapy, and chemotherapy). After baseline assessments, eligible participants will be randomized to one of two supervised aerobic training interventions (moderate-intensity or moderate/high-intensity aerobic training) or an attention-control group (progressive stretching). The aerobic training interventions will include 150 mins.wk^-1of supervised treadmill walking per week at an intensity of 60%-70% (moderate-intensity) or 60% to 100% (moderate to high-intensity) of the individually determined peak oxygen consumption (VO_2peak) between 20-45 minutes/session for 16 weeks. The progressive stretching program will be consistent with the exercise interventions in terms of program length (16 weeks), social interaction (participants will receive one-on-one instruction), and duration (20-45 mins/session). The primary study endpoint is VO_2peak, as measured by an incremental cardiopulmonary exercise test. Secondary endpoints include physiologic determinants that govern VO_2peak, patient-reported outcomes, and biomarkers associated with breast cancer recurrence/mortality. All endpoints will be assessed at baseline and after the intervention (16 weeks).</p> <p>Discussion</p> <p>EXCITE is designed to investigate the intensity of aerobic training required to induce optimal improvements in VO_2peakand other pertinent outcomes in women who have completed definitive adjuvant therapy for operable breast cancer. Overall, this trial will inform and refine exercise guidelines to optimize recovery in breast and other cancer survivors following the completion of primary cytotoxic therapy.</p> <p>Trial Registration</p> <p>NCT01186367</p

Lack of evidence for KRAS oncogenic mutations in triple-negative breast cancer

<p>Abstract</p> <p>Background</p> <p>Mutational analysis of the <it>KRAS </it>gene has recently been established as a complementary <it>in vitro </it>diagnostic tool for the identification of patients with colorectal cancer who will not benefit from anti-epidermal growth factor receptor (EGFR) therapies. Assessment of the mutation status of <it>KRAS </it>might also be of potential relevance in other EGFR-overexpressing tumors, such as those occurring in breast cancer. Although <it>KRAS </it>is mutated in only a minor fraction of breast tumors (5%), about 60% of the basal-like subtype express EGFR and, therefore could be targeted by EGFR inhibitors. We aimed to study the mutation frequency of <it>KRAS </it>in that subtype of breast tumors to provide a molecular basis for the evaluation of anti-EGFR therapies.</p> <p>Methods</p> <p>Total, genomic DNA was obtained from a group of 35 formalin-fixed paraffin-embedded, triple-negative breast tumor samples. Among these, 77.1% (27/35) were defined as basal-like by immunostaining specific for the established surrogate markers cytokeratin (CK) 5/6 and/or EGFR. <it>KRAS </it>mutational status was determined in the purified DNA samples by Real Time (RT)-PCR using primers specific for the detection of wild-type <it>KRAS </it>or the following seven oncogenic somatic mutations: Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13Asp.</p> <p>Results</p> <p>We found no evidence of <it>KRAS </it>oncogenic mutations in all analyzed tumors.</p> <p>Conclusions</p> <p>This study indicates that <it>KRAS </it>mutations are very infrequent in triple-negative breast tumors and that EGFR inhibitors may be of potential benefit in the treatment of basal-like breast tumors, which overexpress EGFR in about 60% of all cases.</p

Mirror, mirror on the wall: which microbiomes will help heal them all?

BACKGROUND: Clinicians have known for centuries that there is substantial variability between patients in their response to medications—some individuals exhibit a miraculous recovery while others fail to respond at all. Still others experience dangerous side effects. The hunt for the factors responsible for this variation has been aided by the ability to sequence the human genome, but this just provides part of the picture. Here, we discuss the emerging field of study focused on the human microbiome and how it may help to better predict drug response and improve the treatment of human disease. DISCUSSION: Various clinical disciplines characterize drug response using either continuous or categorical descriptors that are then correlated to environmental and genetic risk factors. However, these approaches typically ignore the microbiome, which can directly metabolize drugs into downstream metabolites with altered activity, clearance, and/or toxicity. Variations in the ability of each individual’s microbiome to metabolize drugs may be an underappreciated source of differences in clinical response. Complementary studies in humans and animal models are necessary to elucidate the mechanisms responsible and to test the feasibility of identifying microbiome-based biomarkers of treatment outcomes. SUMMARY: We propose that the predictive power of genetic testing could be improved by taking a more comprehensive view of human genetics that encompasses our human and microbial genomes. Furthermore, unlike the human genome, the microbiome is rapidly altered by diet, pharmaceuticals, and other interventions, providing the potential to improve patient care by re-shaping our associated microbial communities

Breast cancer prognostic classification in the molecular era: the role of histological grade

Breast cancer is a heterogeneous disease with varied morphological appearances, molecular features, behavior, and response to therapy. Current routine clinical management of breast cancer relies on the availability of robust clinical and pathological prognostic and predictive factors to support clinical and patient decision making in which potentially suitable treatment options are increasingly available. One of the best-established prognostic factors in breast cancer is histological grade, which represents the morphological assessment of tumor biological characteristics and has been shown to be able to generate important information related to the clinical behavior of breast cancers. Genome-wide microarray-based expression profiling studies have unraveled several characteristics of breast cancer biology and have provided further evidence that the biological features captured by histological grade are important in determining tumor behavior. Also, expression profiling studies have generated clinically useful data that have significantly improved our understanding of the biology of breast cancer, and these studies are undergoing evaluation as improved prognostic and predictive tools in clinical practice. Clinical acceptance of these molecular assays will require them to be more than expensive surrogates of established traditional factors such as histological grade. It is essential that they provide additional prognostic or predictive information above and beyond that offered by current parameters. Here, we present an analysis of the validity of histological grade as a prognostic factor and a consensus view on the significance of histological grade and its role in breast cancer classification and staging systems in this era of emerging clinical use of molecular classifiers. © 2010 BioMed Central Lt