tbuckley/cabot-search huggingface dataset:
Abstract 17910: Patients with Newly Diagnosed Diabetes Have Comparable Long Term Mortality with Known Diabetics After ST Segment Elevation Myocardial Infarction
Authors: Bhuvnesh Aggarwal, Gautam Shah, Mandeep S Randhawa, A M Lincoff, Stephen G Ellis, Venu Menon
Journal: Circulation (2014)

Background: A significant proportion of patients presenting with ST segment elevation myocardial infarction (STEMI) have newly diagnosed diabetes mellitus (DM). Hypothesis: Our aim was to identify patients with previously undiagnosed DM and compare their outcomes to those with known DM and without DM after STEMI. Methods: Consecutive patients undergoing primary PCI for STEMI at our center between Jan 2005 - Dec 2012 were included. Routinely performed admission Glycated hemoglobin (HbA1c) was utilized to identify patients with previously undiagnosed DM (HbA1c ≥ 6.5 and no history of DM or diabetes therapy). Patients were compared for in-hospital and long-term mortality based on follow up data from our institutional PCI registry. Results: 1,734 consecutive patients underwent primary PCI for STEMI and follow up data was available for 1,566 (90%) patients. Mean age was 60 years and 67.3% were males. A quarter of the patients (24.3%, n = 382) had prior history of DM and 8% (n=95) of the remainder had undiagnosed DM. Median follow up was 35 months. Mortality was comparable in patients with known DM and newly diagnosed DM both in hospital (11.2% vs. 12.5%, p=0.87) and at long term follow up (Figure 1, 2). Mortality was significantly worse with both groups when compared with patients with no DM (In-hospital mortality 5.6%; p&lt;0.001 for both groups). Conclusions: One in twelve patients presenting with STEMI have previously undiagnosed DM. Cardiologists have a unique opportunity for identification and initiation of diabetic therapy in this vulnerable population. Patients with newly diagnosed DM have similar short and long-term outcomes when compared with patients with a prior history of DM.
TRAIL synergises with targeted therapeutics to induce cell death in colon carcinoma cells in an oncogene-dependent manner
Authors: Alexander Pintzas, Eftychia Oikonomou, Ladislav Andera, Fotini Psahoulia, Vivian Kosmidou
Journal: Cancer Research (2008)

2374   Most data on the therapeutic potential and expression of TRAIL in colorectal cancer has come from  in vitro  studies using tumour cell lines. To gain a clearer understanding about the susceptibility of patient tumours to TRAIL, we derived primary human cancer epithelial cells (1). Increased apoptosis was observed in both primary PAP60 and MIH55 after treatment with SuperKiller TRAIL. Treating patient tumour xenograft/ SCID mouse models with Killer TRAIL  in vivo  for 5 consecutive days suppressed tumour growth , although less efficiently compared to  in vitro  experiments.The previous  in vivo  finding showed that evading apoptosis induced by anticancer drugs characterizes many types of cancers. This results in the need for combination therapy. We have previously shown that quercetin induces the degradation of Ras oncoproteins (2). We have provided evidence that quercetin enhanced TRAIL induced apoptosis by causing the redistribution of DR4 and DR5 into lipid rafts (3). Based on these results, this study provides a challenging approach to enhance the efficiency of TRAIL-based therapies (4). Oncogene-specific sensitization to TRAIL induced apoptosis has been previously shown by our lab (5) and by others. Here, we will present data by using oncogene specific models, that mutant oncoproteins can sensitise cells to TRAIL induced cell death, in specific synergy with targeted therapeutics.
Use of in vitro dose response effects to select antineoplastics for high-dose or regional administration regimens.
Authors: D D Von Hoff, G M Clark, G R Weiss, M H Marshall, J B Buchok, W A Knight, C F LeMaistre
Journal: Journal of Clinical Oncology (1986)

Several preclinical and clinical studies have documented that dose or dose intensity of chemotherapeutic agents are important factors for response of patients' tumors. This finding has prompted empiric trials of certain chemotherapeutic agents in high-dose or regional administration treatment regimens. The present study was performed to identify agents that would be particularly good candidates for high-dose or regional administration regimens against particular types of tumors. Using a human tumor cloning technique, we constructed dose in vitro response lines for ten different chemotherapeutic agents against seven different histologic types of malignancies. Slopes of the lines indicated the agents with the greatest increases of in vitro response per increment in dose of the agent. Tumors against which the agents gave the steepest dose response lines included lymphoma, head and neck cancer, ovarian cancer, and small-cell lung cancer, while the dose response lines for non-small-cell lung cancer, breast cancer, and colon cancer were quite flat. Suggestions for clinical trials based on these findings include the use of high-dose melphalan for patients with lymphoma, head and neck, and ovarian cancer; the use of mitoxantrone in high-dose regimens for patients with breast cancer; high-dose cisplatin regimens for patients with small-cell lung cancer; high-dose bleomycin regimens for patients with non-small-cell lung and head and neck cancer; and regional perfusion of liver metastases from colorectal cancer with cisplatin. Prospective testing of high-dose or regional administration regimens suggested by this new model should indicate its use for prediction of the best agent to use in high-dose regimens against a particular tumor type.
Junior doctors are set to take industrial action, says BMA
Authors: Abi Rimmer
Journal: BMJ (2016)

Junior doctors are set to take three days of industrial action, after negotiations between the association and the government over the terms of the junior doctor contract broke down on Monday 4 January, the BMA has said.

As The BMJ went to press the association announced that the action would take place in January and February, after the government failed to meet junior doctors’ concerns over changes to the contract. It said that the government did not recognise the need …
Retrospective analysis investigating the correlation between ki-67 expression, the EGFR mutational status and histotype in a Non Small Cell Lung Cancer patient cohort
Authors: J. Menis, M. Macerelli, A. Follador, G. De Maglio, F. Valent, S. Bolzonello, E. De Carlo, L. Pagani, S. Ciani, M.C. Barducci, S. Pizzolitto, G. Fasola
Journal: Annals of Oncology (2015)
Phase II study of xyotax (PPX) for androgen independent prostate cancer (AIPC)
Authors: M. Khan, S. Sharef, R. J. Amato
Journal: Journal of Clinical Oncology (2006)

14624 Background: PPX is a polymer conjugate of paclitaxel. In preclinical studies, PPX has an improved therapeutic profile relative to paclitaxel, in addition demonstrated activity in paclitaxel-resistant tumor models. This study investigates whether single agent PPX can induce PSA responses and increase time to progression in AIPC. Methods: Eligibility included: progressive disease based on at least one of the following: a) 3 consecutive rising PSA levels or b) new or progressive measurable disease, or c) new or progressive metastatic lesions on bone scan. Castrate levels of serum testosterone (≤ 50 ug/l), anti-androgen withdrawal, no more than 1 prior chemotherapy regimen, Zubrod performance status of ≤ 2, neuropathy ≤ grade 1, and adequate organ/marrow function. PPX is administered intravenously over 10–20 minutes without routine premedications, at a dose of 150 mg/m 2 every 28 days. Dose modifications are based on nature and grade of toxicity observed. Patients (pts) are restaged every 8 weeks until progression or a maximum of 12 months of therapy. Results: 12 patients (pts) (11 previously treated/1 untreated) have been enrolled to date. 7 of the previously treated pts received prior taxanes. 3 pts continue on treatment. 9 pts have completed a range of 6–28 weeks of therapy. Based on a reduction in PSA of at least 50% and maintained for at least 8 weeks, 2 previously treated pts (1 prior taxotere) responded to treatment. 3 pts demonstrated a delay in their PSA velocity. Adverse events were assessed and included: 1 pt who developed a hypersensitivity reaction, 5 pts with grade 2/3 neuropathy, 5 pts with grade 2/3 leukopenia, 2 pts with grade 3/4 neutropenia and 1 pt with grade 4 thrombocytopenia. Other common reversible grade 1/2 toxic effects have been: nausea, fatigue, elevated LFTs and anemia. 6 pts have required dose reduction. Conclusion: PPX is well tolerated and demonstrates promising activity in patients with AIPC. Efficacy assessments are measured by: absolute PSA response, PSA velocity changes, and toxicity data will be presented. [Table: see text]
Yttrium-90 ibritumomab tiuxetan combined with high-dose BEAM chemotherapy and autologous stem cell transplantation for relapsed/refractory B-cell non-Hodgkin’s lymphoma
Authors: A. Shimabukuro-Vornhagen, A. Josting, K. Hübel, C. Scheid, M. Dietlein, A. Engert, R. Schnell
Journal: Journal of Clinical Oncology (2008)

8615 Background: High-dose chemotherapy followed by autologous stem cell transplantation is an established treatment option for patients with relapsed or refractory non-Hodgkin’s lymphoma (NHL). Recently, radioimmunotherapy has emerged as a new treatment modality for B-cell NHL with the combined benefits of immunotherapy and radiotherapy. The incorporation of Yttrium-90 ibritumomab tiuxetan into a high-dose chemotherapy conditioning regimen promises to improve the outcome after autologous stem cell transplantation for relapsed or refractory NHL. Methods: A phase II trial to evaluate the safety and efficacy of combining Yttrium-90 ibritumomab tiuxetan with high-dose carmustine, cytarabine, etoposide, and melphalan (BEAM) conditioning chemotherapy and autologous stem- cell transplantation in patients with relapsed or refractory NHL. Patients with either relapsed, refractory or transformed follicular lymphoma (FL) or relapsed, refractory diffuse large B cell lymphoma (DLBCL) were eligible. All patients received a sequential high-dose regimen including rituximab as salvage chemotherapy. Results for the first 10 out of a planned 20 patients are reported. Results: The median age was 57 years. 7 patients had DLBCL, 2 had FL, and 1 patient had a transformed FL. The median number of relapses was 1 (range 1–3). After a median time of follow up of 11 months (range 1 to 26 months) 2 patients relapsed. Interestingly, both patients had central nervous system relapse. One of these patients died. Adverse events were similar to those seen historically with high-dose BEAM alone. There were no treatment-related deaths or secondary malignancies. Conclusions: Theses preliminary results suggest that the combination of Yittrium-90 ibritumomab tiuxetan and BEAM followed by autologous stem cell transplantation is safe and effective for the treatment of patients with relapsed or refractory NHL. No significant financial relationships to disclose.
Comparison of open and closed techniques of delivery of hyperthermic chemotherapy following cytoreductive surgery in patients with peritoneal carcinomatosis
Authors: A. Sardi, V. Thillainathan, C. Nieroda, B. Merriman, P. N. Kostuik
Journal: Journal of Clinical Oncology (2006)

14067 Background: Intraperitoneal hyperthermic chemotherapy (IPHC) combined with Cytoreductive surgery (CRS) is an effective approach in the management of peritoneal carcinomatosis. A controversy exists concerning the use of an open or closed technique of delivery of the hyperthermic chemotherapy. A retrospective study of a prospective data base was performed to compare these two techniques with respect to overall survival, disease-free survival, length of hospital stay (LOS), and incidence of complications. Methods: From 1998 to 2005, 64 patients underwent CRS and IPHC. Nineteen patients underwent open technique and forty-five underwent closed technique. The pathological diagnoses included appendiceal carcinoma (35), pseudomyxoma peritonei (10), ovarian carcinoma (7), colon carcinoma (6), mesothelioma (5), and sarcoma (1). Cox Proportional-Hazards Regression analysis was performed. Results: Overall 5- year survival and disease free survival was 46% and 22%, respectively. No significant difference in overall survival (p=0.58), disease-free survival (p=0.37), or incidence of complications (p=0.66) was found between the groups. Open technique patients had a significantly shorter LOS than closed with a mean of 8.7 vs. 11.4 days [p=0.01] and a median of 8 vs.11 days [p=0.002] (Kruskal-Wallis Rank Sum Test). Conclusions: The improved survival seen in patients undergoing CRS and IPHC is not dependent on the choice of technique of delivery of the hyperthermic chemotherapy No significant financial relationships to disclose.
Detection of mTOR/Raptor activity using a 96 well ELISA based assay
Authors: Kevin Harvey, Trevor Kimbler, Lothar Goretzki, Mo Saedi
Journal: Cancer Research (2007)

287  We have developed a convenient and sensitive assay for the measurement of mTOR activity. A GST fusion of the classical mTOR substrate p70S6K is pre-bound to a microtiter plate coated with glutathione. mTOR-containing sample is then added to the sample well in the presence of ATP and manganese containing assay buffer. Active mTOR phosphorylates p70S6K at Thr389. The phosphorylated substrate is detected with a phosphospecific anti-p70S6K(T389) antibody, followed by detection with HRP-antibody conjugate and relative activity is determined by reading absorbance. Using the assay we are able to measure kinase activity of a partially purified mTOR standard generated from an enriched rat brain fraction. The enriched mTOR standard contains both mTOR/Raptor and mTOR/Rictor complexes. The detected mTOR activity is inhibited by the general PI-3K inhibitor wortmannin as well as rapamycin/FKBP12 (IC50 of 8 nM), a specific inhibitor of the mTOR/Raptor complex. The assay was miniaturized to a well volume of 20ul using a 384 well plate format and a fluorescent HRP substrate to improve sensitivity and dynamics. Additionally we detect mTOR activity associated with various mTOR complexes immunoprecipitated from crude 293 cell lysates. Unlike the mTOR /Rictor complex, immunoprecipitation of active mTOR/Raptor requires the use of a CHAPS containing lysis buffer to ensure capture of the intact complex. Phosphorylation of Ser473 on Akt was used to analyze the kinase activity associated with the mTOR/Rictor complex. The described non-radioactive assays are useful for in vitro mTOR inhibitor screening and for assessing the regulation of mTOR in cell signaling.
Elevated troponin and abnormalities of cardiac structure and function in AL cardiac amyloidosis
Authors: T. Apridonidze, R. Steingart, R. L. Comenzo, J. E. Hoffman, Y. Goldsmith, J. Liu
Journal: Journal of Clinical Oncology (2009)

e19524 Background: Patients with systemic amyloidosis involving the heart have generally a poor prognosis. Elevated cardiac troponin (cTn) has been shown to predict poor survival in patients with AL cardiac amyloidosis (CA). However, cardiac structure and function associated with an elevated cTn in patients with CA remains uncertain. Methods: Eighty patients with CA who had an echocardiogram and cTnI measured at the time of diagnosis between March 1997 May 2008 were included in the study. The patients were divided into 2 groups: normal cTnI ( &lt;0.06 ng/ml, n = 28) or elevated cTnI (≥0.06 ng/ml; n = 52). Results: The elevated cTnI group was slightly older with higher brain natriuretic peptide (BNP) level and creatinine clearance than the normal cTnI group. There was a trend towards higher prevalence of congestive heart failure (CHF) in the elevated cTnI group than the normal group at time of diagnosis. The elevated cTnIgroup had thicker interventricular septum and higher left atrial (LA) volume than the normal group. LV ejection fraction, left atrial systolic force (LASF) and stroke volume were lower in the elevated cTnI group than the normal group. Mean survival was significantly shorter in the elevated cTnI group than the normal group (10 vs. 47 months). Conclusions: Elevated troponin in patients with AL cardiac amyloidosis is associated with worse left atrial and ventricular structure and function. The raised troponin level reflects myocardial injury due to the amyloid deposition and correlates with more abnormal alteration of cardiac structure and function. Routine measurement of troponin is useful in identifying high risk patients with CA. [Table: see text] No significant financial relationships to disclose.
Abstract 11418: Ablation of Ventricular Tachycardias in Adults with Congenital Heart Disease: Acute and Long Term Results
Authors: G.F. Kapel, T Reichlin, A.P. Wijnmaalen, S.R. Piers, M.J. Schalij, W.G. Stevenson, K. Zeppenfeld
Journal: Circulation (2012)

INTRODUCTION  Ventricular tachycardia (VT) is an important cause of late morbidity and mortality in the increasing population with surgically corrected congenital heart disease (CHD). Radiofrequency catheter ablation (RFCA) of VT may prevent VT recurrence.  METHODS  Thirty-one patients (49±13 years, 71% male) referred for RFCA of VT after repair of CHD (25 Tetralogy of Fallot (TOF), 2 Ventricular Septal Defect (VSD), 2 D-Transposition of the Great Arteries (D-TGA), 1 Atrioventricular Septal Defect (AVSD), 1 Congenital Pulmonary Stenosis (cPS); age of repair 13±10 years) in two centres were included. Ventricular function was evaluated by echocardiography and/or magnetic resonance imaging. Ablation targeted anatomical isthmuses for VT re-entry circuits identified by 3D substrate, pace- and/or entrainment mapping. Acute success was defined as non-inducibility of any VT, partial success as elimination of clinical VT, failure as inducibility of clinical VT. Patients (pts) were followed for 43±28 months.  RESULTS  Before RFCA, 7 (23%) pts had ≥moderate impairment of RV and/or LV function. Pts were inducible for 2.0±1.4 VTs, cycle length 297±74ms. Complete procedural success was achieved in 22 (71%) pts (18 TOF, 2 D-TGA, 1 VSD and 1 AVSD), partial success in 3 pts (2 TOF and 1 VSD) and in 2 pts (1 TOF and 1 cPS) VT induction was not repeated after RFCA (undetermined outcome). Ablation failed in 4 TOF pts (13%) because the targeted anatomical isthmus could not be transected (hypertrophic myocardium in 2, interposed pulmonary homograft in 2). Twenty-four pts (77%) were discharged with an ICD. During follow-up VT recurred in 4 pts (13%); partial success 1 (VSD), failure 1 (TOF), undetermined 2 pts. One pt (complete success, TOF) with progressive heart failure received one ICD shock for VF. Nineteen pts with complete procedure success and preserved RV and LV function (13/19 with ICDs) had no VT recurrence, however 6/13 ICD pts (46%) received inappropriate therapy. Two pts died during follow-up (heart failure 1, acute leukaemia 1).  Conclusion  RFCA of VT in adults with CHD is highly effective with a low recurrence rate during long term follow up. In patients with complete procedure success and preserved cardiac function disadvantages of ICD may outweigh benefits.
A strategy to increase and assess vaccine coverage in the north of Portugal
Authors: G Gonçalves, M A Frutuoso, M C Ferreira, M G Freitas
Journal: Eurosurveillance (2005)

In the Northern Health Region of Portugal, vaccine coverage is measured by checking and studying individual vaccination records in health centres. Each year from 2001-2004, birth cohorts completing 2, 6 and 14 years of age were selected for assessment. Data collection occurred on January the following year and meetings with district immunisation coordinators took place every March. For all vaccines and birth cohorts considered, vaccine coverage values observed in the north of Portugal were excellent. In this paper, we make comparisons with published international data on vaccine coverage and discuss validity issues; we believe that no serious biases have affected the validity of our vaccine coverage data but comparisons with international data must be addressed with caution; the methods we used have been useful in increasing vaccination coverage.
Immunomagnetic Purging of Ewing’s Sarcoma From Blood and Bone Marrow: Quantitation by Real-Time Polymerase Chain Reaction
Authors: Margret E. Merino, Fariba Navid, Barbara L. Christensen, Jeffrey A. Toretsky, Lee J. Helman, Nai-Kong V. Cheung, Crystal L. Mackall
Journal: Journal of Clinical Oncology (2001)

PURPOSE: A propensity for hematogenous spread with resulting contamination of autologous cell products complicates cellular therapies for Ewing’s sarcoma. We used a new approach to purge artificially contaminated cellular specimens of Ewing’s sarcoma and show the capacity for real-time polymerase chain reaction (PCR) to quantify the contamination level of Ewing’s sarcoma in such specimens. PATIENTS AND METHODS: Binding of monoclonal antibody (MoAb) 8H9 to Ewing’s sarcoma cell lines and normal hematopoietic cells was studied using flow cytometry. Using real-time PCR–based amplification of t(11;22), levels of Ewing’s contamination of experimental and clinical cellular products were monitored. Purging was accomplished using immunomagnetic-based depletion. Monitoring of the function of residual hematopoietic progenitors and T cells was performed using functional assays. RESULTS: MoAb 8H9 shows binding to Ewing’s sarcoma but spares normal hematopoietic tissues. Nested real-time PCR is capable of detecting contaminating Ewing’s sarcoma cells with a sensitivity of one cell in 10 6 normal cells. After 8H9-based purging, a 2- to 3-log reduction in contaminating Ewing’s sarcoma was shown by real-time PCR, with purging to PCR negativity at levels of contamination of 1:10 6 . Levels of contamination in clinical samples ranged from 1:10 5 to 10 6 . Therefore, 8H9-based purging of clinical samples is predicted to reduce tumor cell contamination to a level below the limit of detection of PCR. CONCLUSION: These results demonstrate a new approach for purging contaminated cellular products of Ewing’s sarcoma and demonstrate the capacity of real-time PCR to provide accurate quantitative estimates of circulating tumor burden in this disease.