Is TIMP-1 immunoreactivity alone or in combination with other markers a predictor of benefit from anthracyclines in the BR9601 adjuvant breast cancer chemotherapy trial?

Introduction

Predictive cancer biomarkers to guide the right treatment to the right patient at the right time are strongly needed. The purpose of the present study was to validate prior results that tissue inhibitor of metalloproteinase 1 (TIMP-1) alone or in combination with either HER2 or TOP2A copy number can be used to predict benefit from epirubicin (E) containing chemotherapy compared with cyclophosphamide, methotrexate and fluorouracil (CMF) treatment.

Methods

For the purpose of this study, formalin fixed paraffin embedded tumor tissue from women recruited into the BR9601 clinical trial, which randomized patients to E-CMF versus CMF, were analyzed for TIMP-1 immunoreactivity. Using previously collected data for HER2 amplification and TOP2A gene aberrations, we defined patients as "anthracycline non-responsive", that is, 2T (TIMP-1 immunoreactive and TOP2A normal) and HT (TIMP-1 immunoreactive and HER2 negative) and anthracycline responsive (all other cases).

Results

In total, 288 tumors were available for TIMP-1 analysis with (183/274) 66.8%, and (181/274) 66.0% being classed as 2T and HT responsive, respectively. TIMP-1 was neither associated with patient prognosis (relapse free survival or overall survival) nor with a differential effect of E-CMF and CMF. Also, TIMP-1 did not add to the predictive value of HER2, TOP2A gene aberrations, or to Ki67 immunoreactivity.

Conclusion

This study could not confirm the predictive value of TIMP-1 immunoreactivity in patients randomized to receive E-CMF versus CMF as adjuvant treatment for primary breast cancer.     

What is a virtual multidisciplinary team (vMDT)?

Background:

Multidisciplinary team meetings (MDTs), also known as tumour boards or multidisciplinary case conferences, are an integral component of contemporary cancer care. There are logistical problems with setting up and maintaining participation in these meetings. An ill-defined concept, the virtual MDT (vMDT), has arisen in response to these difficulties. We have, in order to provide clarity and to generate discussion, attempted to define the concept of the vMDT, outline its advantages and disadvantages, and consider some of the practical aspects involved in setting up a virtual MDT.

Methods:

This is an unstructured review of published evidence and personal experience relating to virtual teams in general, and to MDTs in particular.

Results:

We have devised a simple taxonomy for MDTs, discussed some of the practicalities involved in setting up a vMDT, and described some of the potential advantages and disadvantages associated with vMDTs.

Conclusion:

The vMDT may be useful for discussions concerning rare or unusual tumours, or for helping guide the assessment and management of patients with uncommon complications related to treatment. However, the vMDT is a niche concept and is currently unlikely to replace the more traditional face-to-face MDT in the management of common tumours at specific sites.     

High live birth rate in the subsequent IVF cycle after first-cycle poor response among women with mean age 35 and normal FSH

Poor ovarian response in IVF cycles is associated with diminished ovarian reserve and poor pregnancy outcome. Little is known about pregnancy outcome after a poor response in women with a normal ovarian reserve. This retrospective study studied women undergoing IVF/intracytoplasmic sperm injection between January 2003 to December 2008 in the FertilityPLUS Clinic in Auckland, New Zealand. All women with a poor response in the first cycle were selected. Primary outcome was live birth after the second cycle. Secondary outcomes were poor response in the second cycle and the predictive values of female age and basal FSH at first cycle and IVF outcome at second cycle. Of the 2487 women starting IVF, 142 women (5.7%) with a poor response in the first cycle were selected, of which 66 (46.5%) women had a repeated poor response in the second cycle. There were 31 live births in the second cycle (21.8%). Female age was the only significant predictor for repeated poor response (AUC 0.69, 95% CI 0.61–0.78) and clinical pregnancy (AUC 0.66, 95% CI 0.57–0.75), but the predictive value was low. Therefore poor response in women with a normal ovarian reserve should not be a reason to discontinue further IVF treatment.Poor ovarian response in IVF cycles is associated with diminished ovarian reserve and poor pregnancy outcome. Little is known about pregnancy outcome after a poor response in women with a normal ovarian reserve. In this retrospective study, we studied women undergoing IVF/intracytoplasmic sperm injection (ICSI) between January 2003 to December 2008 in the FertilityPLUS Clinic in Auckland, New Zealand. All women with a poor response in the first cycle were selected. Primary outcome was live birth after the second cycle. Secondary outcomes were poor response in the second cycle and the predictive value of female age and basal FSH at first cycle and IVF outcome at the second cycle. Of the 2487 women starting wit IVF, a total of 142 women (5.7%) with a poor response in the first cycle were selected, of which 66 (46.5%) women had a repeated poor response in the second cycle. There were 31 live births in the second cycle (22%). Female age was the only significant predictor for repeated poor response and clinical pregnancy, but the predictive value was low. Therefore poor response in women with a normal ovarian reserve should not be a reason to discontinue further IVF treatment.     

Oral streptococcal bacteremia in hospitalized patients: taxonomic identification and clinical characterization

Oral streptococci have been associated with systemic diseases, including infective endocarditis and neutropenic bacteremia. We analyzed 58 recent oral streptococcal bloodstream isolates, and we obtained clinical and demographic data for source patients. The sodA gene was found to be a better target than the 16S-23S rRNA internal transcribed spacer for DNA sequence-based species identification. Together, Streptococcus mitis and Streptococcus oralis were significantly more likely than the 12 combined remaining species to be isolated from neutropenic patients.     

Ventilator-associated Pneumonia: The Potential Critical Role of Emergency Medicine in Prevention

Background

Delivery of critical care within a certain window of opportunity is paramount in many disease states, and providing the right care to these patients at the right time in the Emergency Department (ED) can significantly reduce mortality. However, aggressive treatment of these patients often requires endotracheal intubation and mechanical ventilation either in the pre-hospital or ED phase of care. Care of mechanically ventilated patients in the ED is not trivial or without potential complications, including ventilator-associated pneumonia (VAP).

Objective/Discussion

This article summarizes the epidemiology, pathophysiology, and specific risk factors associated with VAP and provides evidence-based recommendations for its prevention. We emphasize practices that are particularly important in the early stages of care of intubated, mechanically ventilated patients; thus, they should be instituted in the ED.

Conclusion

Specifically, we recommend continuous backrest elevation of 30–45°, chlorhexidine application to the oral cavity after intubation and every 12 h thereafter, orotracheal intubation with a tube that enables continuous subglottic suctioning, and cuff pressure assessments after intubation and every 4 h thereafter to maintain pressure between 20 and 30 cm H₂O.     

Case mix in paediatric rheumatology: implications for training in Australia

Background: Despite a move towards the provision of specialist training in Australia in settings that extend beyond the public hospital system, formal comparisons of case mix between public and private specialty clinics have rarely been performed. It is therefore unclear for many specialties how well training in one setting prepares trainees for practice in the other. Aims: This study aims to compare the case mix of paediatric rheumatology patients seen in public and private settings and the referral sources of patients in each. Methods: An audit of all new patients seen in the public and private paediatric rheumatology clinics on campus at Royal Children's Hospital between June 2009 and January 2011. Data related to demographics, primary diagnosis, referral source and location seen were abstracted and compared. Results: Eight hundred and seventy‐six new patients were seen during the period of interest. Of these, 429 patients (48.9%) were seen in private clinics. The commonest diagnostic categories for both type of clinics were non‐inflammatory musculoskeletal pain/orthopaedic conditions (public 39.4%, private 33.6%) followed by juvenile idiopathic arthritis (public 16.6%, %, private 18.6%), other skin/soft tissue disorders (public 8.7%, private 9.6%) and pain syndromes (public 4.9%, private 11.4%). Patients with haematological and vasculitic disorders were predominantly seen in public clinics. The commonest source of referrals to both clinics was general practitioners (public 40.6%, private 53.1%). Conclusion: The case mix in private paediatric rheumatology clinics closely mirrors that of public clinics at our centre. Training in either setting would provide sufficient case‐mix exposure to prepare trainees for practice in the other.