Chemotherapy for Uterine Carcinosarcoma with Carboplatin, Ifosfamide and Mesna.

BACKGROUND/AIM: Uterine carcinosarcomas (UCSs) are highly aggressive, rare, biphasic tumors composed of epithelial and mesenchymal elements. Surgery remains the mainstay of treatment in early-stage disease. Adjuvant pelvic radiotherapy improves locoregional control without proven overall survival (OS) benefit. Although adjuvant ifosfamide-based combination chemotherapy with cisplatin or paclitaxel has shown superiority to radiotherapy or single-agent chemotherapy in randomized controlled trials, there is no consensus on a standard regimen due to toxicities. The aim of this retrospective study was to assess the efficacy and toxicity of a novel combination chemotherapy using carboplatin, ifosfamide and mesna (CIM) and compare with other regimens for patients with UCSs in both the adjuvant and palliative setting. PATIENTS AND METHODS: Between 1997 and 2010, 60 patients with UCS, 70% of whom with international federation of gynecology and obstetrics (FIGO) stage III/IV disease, were treated with adjuvant or palliative chemotherapy. Two groups were identified: Group1 (n=22) included patients receiving CIM chemotherapy; and group 2 (n=38) receiving other regimens (carboplatin/paclitaxel/cisplatin/doxorubicin/epirubicin). RESULTS: After a median follow-up of 60 months, disease in seven patients in group 1 (CIM) and 20 patients in group 2 had progressed/relapsed. Out of these, six patients in group 1 and 13 patients in group 2 had died. The progression-free survival (PFS) and OS for patients treated with adjuvant or palliative CIM was 35 months [95% confidence interval (CI) =0.26-0.43] and 47 months (95% CI=0.38-0.56; log-rank, p=0.001) respectively, whereas for group 2 patients treated with other regimens, PFS was 27.48 months (95% CI=0.20-0.33) and OS was 30 months (95% CI=0.21-0.38; log-rank, p=0.001). While none of the patients in group 1 experienced neurotoxicity or other grade 3 or 4 toxicities, 3/38 patients in group 2 experienced grade 3 neutropenia, 4/38 had peripheral sensory neuropathy, 6/38 patients had treatment deferred due to toxicities or allergic reaction to paclitaxel. CONCLUSION: In the phase III randomized controlled trial combination of ifosfamide and taxanes has shown PFS and OS benefit when compared to single-agent ifosfamide at the expense of significant toxicities. Results from our study show that the combination of CIM is an effective and safe alternative regimen for patients with advanced UCSs. In addition to improved OS and PFS, the main advantage of this regimen over taxane-based regimens includes minimal neuropathy, less use of steroids, and low risk of allergic reaction. CIM should be considered in future prospective studies looking at the treatment of UCS.

Use of SimpliRED D-dimer assay and computerised tomography in the diagnosis of acute pulmonary embolism.

BACKGROUND: The utility of D-dimer in the diagnostic workup of pulmonary embolism has been established. Several D-dimer tests are available with different sensitivities and specificities. SimpliRED D-dimer is a rapid qualitative whole blood D-dimer assay suitable for bedside use. OBJECTIVE: To assess the utility of the SimpliRED D-dimer test in patients with suspected acute pulmonary embolism in the absence of formal 'risk scoring'. DESIGN: A prospective study measuring SimpliRED D-dimer in unselected patients undergoing computed tomographic pulmonary angiography (CTPA) examination for suspected acute pulmonary embolism. MAIN OUTCOME MEASURES: D-dimer and CTPA results were compared. Sensitivity, specificity, and positive and negative predictive values of SimpliRED D-dimer were calculated for the unselected patient group. RESULTS: Forty-seven patients underwent D-dimer testing and CTPA. SimpliRED D-dimer was positive in 23 and negative in 24 patients. D-dimer was positive in only 6 (50%) of the 12 patients with positive CTPA. Of the 35 with negative CTPA, 17 had positive D-dimer. The positive predictive value of the D-dimer was 26.1 % and the negative predictive value 75.0%. CONCLUSION: SimpliRED D-dimer should not be used in the diagnosis of pulmonary embolism in the absence of risk scoring.

Pre-spliceosomal binding of U1 small nuclear ribonucleoprotein (RNP) and heterogenous nuclear RNP E1 is associated with suppression of a growth hormone receptor pseudoexon.

Pseudoexons occur frequently in the human genome. This paper characterizes a pseudoexon in the GH receptor gene. Inappropriate activation of this pseudoexon causes Laron syndrome. Using in vitro splicing assays, pseudoexon silencing was shown to require a combination of a weak 5' pseudosplice-site and splicing silencing elements within the pseudoexon. Immunoprecipitation experiments showed that specific binding of heterogenous nuclear ribonucleoprotein E1 (hnRNP E1) and U1 small nuclear ribonucleoprotein (snRNP) in the pre-spliceosomal complex was associated with silencing of pseudoexon splicing. The possible role of hnRNP E1 was further supported by RNA interference experiments in cultured cells. Immunoprecipitation experiments with three other pseudoexons suggested that pre-spliceosomal binding of U1 snRNP is a potential general mechanism of suppression of pseudoexons.

Primary prevention of fatal ventricular arrhythmias with implantable cardioverter-defibrillator therapy--an analysis of implications based on MADIT II criteria.

AIMS: The primary aim of this retrospective study was to determine the proportion of patients with myocardial infarction (MI) who fulfil the criteria of the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II and the implications of MADIT II criteria in practice. METHODS: We performed a retrospective analysis of three hundred and ninety four admissions to the Coronary Care Unit (CCU) of the Royal Infirmary of Edinburgh. We selected those with myocardial infarction (MI) and attempted to retrieve electronic copies of their echocardiogram reports. When available, these were used to assess requirement for primary-prevention Implantable Cardioverter Defibrillator (ICD) therapy based on reported left ventricular function. RESULTS: One hundred and ninety patients were admitted to the CCU with a diagnosis of MI. Of these, 100 patients (51.5%) had an echocardiogram. Requirement for ICD therapy was unlikely in 87 (87%), probable in 6 (6%) and necessary in 7 (7%). Since a significant number of patients in the probable category were also likely to meet MADIT II criteria, we concluded that the proportion of patients requiring primary-prevention ICD therapy would be no less than 7% and more likely to be 13%. CONCLUSION: In the context of a busy teaching hospital, a figure of 13% for the requirement of ICD therapy in MI patients represents annual implantation activity of at least 100 per million. This is likely to have very significant resource implications.