bluuebunny/crossref_metadata_2025_split huggingface dataset:
RADAR – A ra ndomised, multi-centre, prospective study comparing best medical treatment versus best medical treatment plus renal artery stenting in patients with haemod ynamically relevant atherosclerotic renal ar tery stenosis
Authors: Schwarzwälder Uwe , Hauk Michael , Zeller Thomas 
Published: July 2009

Abstract

Background
Prospective, international, multi-centre, randomised (1:1) trial to evaluate the clinical impact of percutaneous transluminal renal artery stenting (PTRAS) on the impaired renal function measured by the estimated glomerular filtration rate (eGFR) in patients with haemodynamically significant atherosclerotic renal artery stenosis.

Methods
Patients will be randomised to receive either PTRAS using the Dynamic Renal Stent system plus best medical treatment or best medical treatment. Renal stenting will be performed under angiographic imaging. For patients randomised to best medical treatment the degree of stenosis measured by renal duplex sonography (RDS) will be confirmed by MR angio or multi-slice CT where possible. Best medical treatment will be initiated at randomisation or post procedure (for PTRAS arm only), and adjusted as needed at all visits. Best medical treatment is defined as optimal drug therapy for control of the major risk factors (blood pressure ≤ 125/80 mmHg, LDL cholesterol ≤ 100 mg/dL, HbA1c ≤ 6.5%). Data recordings include serum creatinine values, eGFR, brain natriuretic peptide, patients' medical history and concomitant medication, clinical events, quality of life questionnaire (SF-12v2™), 24 hour ambulatory blood pressure measurement, renal artery duplex ultrasound and echocardiography. Follow-up intervals are at 2, 6, 12 and 36 months following randomisation.
The primary endpoint is the difference between treatments in change of eGFR over 12 months. Major secondary endpoints are technical success, change of renal function based on the eGFR slope change between pre-treatment and post-treatment (i.e. improvement, stabilisation, failure), clinical events overall such as renal or cardiac death, stroke, myocardial infarction, hospitalisation for congestive heart failure, progressive renal insufficiency (i.e. need for dialysis), need of target vessel revascularisation or target lesion revascularisation, change in average systolic and diastolic blood pressure, change in left ventricular mass index calculated from echocardiography, difference in the size of kidney (pole to pole length) measured by renal duplex sonography, total number, drug name, drug class, daily dose, regimen and Defined Daily Dose (DDD), of anti-hypertensive drugs, and change in New York Heart Association (NYHA) classification. Approximately 30 centres in Europe and South America will enrol patients. Duration of enrolment is expected to be 12 months resulting in study duration of 48 months.

Trial registration

Trial registration number: NCT00640406
Two levels above and one level below pedicle screw fixation for the treatment of unstable thoracolumbar fracture with partial or intact neurology
Authors: Modi Hitesh N , Chung Kook Jin , Seo Il Woo , Yoon Hoi Soo , Hwang Ji Hyo , Kim Hong Kyun , Noh Kyu Cheol , Yoo Jung Han 
Published: July 2009

AbstractBackgroundTreatment of unstable thoracolumbar fractures is controversial regarding short or long segment pedicle screw fixation. Although long level fixation is better, it can decrease one motion segment distally, thus increasing load to lower discs.MethodsWe retrospectively analyzed 31 unstable thoracolumbar fractures with partial or intact neurology. All patients were operated with posterior approach using pedicle screws fixed two levels above and one level below the fracture vertebra. No laminectomy, discectomy or decompression procedure was done. Posterior fusion was achieved in all. Post operative and at final follow-up radiological evaluation was done by measuring the correction and maintenance of kyphotic angle at thoracolumbar junction. Complications were also reported including implant failure.ResultsAverage follow-up was 34 months. All patients had full recovery at final follow-up. Average kyphosis was improved from 26.7° to 4.1° postoperatively and to 6.3° at final follow-up. And mean pain scale was improved from 7.5 to 3.9 postoperatively and to 1.6 at final follow-up, All patients resumed their activity within six months. Only 4 (12%) complications were noted including only one hardware failure.ConclusionTwo levels above and one level below pedicle screw fixation in unstable thoracolumbar burst fracture is useful to prevent progressive kyphosis and preserves one motion segment distally.
Construction of an MUC-1 promoter driven, conditionally replicating adenovirus that expresses the sodium iodide symporter for gene therapy of breast cancer
Authors: Trujillo Miguel A , Oneal Michael J , Davydova Julia , Bergert Elizabeth , Yamamoto Masato , Morris John C 
Published: July 2009

Abstract
Introduction
The sodium iodide symporter (NIS) directs the uptake and concentration of iodide in thyroid cells. This in turn allows radioiodine imaging and therapy for thyroid cancer. To extend the use of NIS-mediated radioiodine therapy to other types of cancer, we successfully transferred and expressed the sodium-iodide symporter (NIS) gene in prostate, colon, and breast cancer cells both in vivo and in vitro by using non-replicating adenoviral vectors.

Methods
To improve virotherapy efficiency, we developed a conditionally replicating adenovirus (CRAd) in which the transcriptional cassette RSV promoter-human NIScDNA-bGH polyA was also inserted at the E3 region. The E1a gene is driven by the tumor-specific promoter MUC-1 in the CRAd Ad5AMUCH_RSV-NIS.

Results
In vitro infection of the MUC-1-positive breast cell line T47D resulted in virus replication, cytolysis, and release of infective viral particles. Conversely, the MUC-1-negative breast cancer cell line MDA-MB-231 was refractory to the viral cytopathic effect and did not support viral replication. The data indicate that Ad5AMUCH_RSV-NIS activity is stringently restricted to MUC-1-positive cancer cells. Radioiodine uptake was readily measurable in T47 cells infected with Ad5AMUCH_RSV-NIS 24 hours after infection, thus confirming NIS expression before viral-induced cell death.

Conclusions
This construct may allow multimodal therapy, combining virotherapy with radioiodine therapy to be developed as a novel treatment for breast and other MUC1-overexpressing cancers.
Translocation of bacterial NOD2 agonist and its link with inflammation
Authors: Kim Oh Yoen , Monsel Antoine , Bertrand Michèle , Cavaillon Jean-Marc , Coriat Pierre , Adib-Conquy Minou 
Published: July 2009

Abstract
Introduction
The gut is often considered as the motor of critical illness through bacterial translocation, which amplifies the inflammatory response and alters the immune status. However, systemic bacterial translocation was rarely proven and endotoxin measurement only reflects translocation of Gram-negative-derived products. The process could be more frequently identified if peptidoglycan, derived from both Gram-negative and Gram-positive bacteria, was measured.

Methods
We developed a new tool to detect circulating peptidoglycan-like structure using a NOD2-transfected cell line. We also measured plasma and cell-associated endotoxin and different plasma markers of inflammation. We studied 21 patients undergoing abdominal aortic surgery (AAS), and 21 patients undergoing carotid artery surgery (CAS) were included as negative controls. Patients were sampled during surgery until two days post-surgery.

Results
In 90.5% of the AAS patients, a NOD2 agonist peak was detected in plasma before aortic clamping, but after gut manipulation by the surgeon, and persisted after blood reperfusion. As expected, no peak was detected in plasma from CAS patients (P = 0.003). Leukocyte-bound endotoxin appeared after blood reperfusion in 71% of the AAS patients, and circulating endotoxin was detected for 57% of them. The levels of interleukin (IL)-6, IL-10 and of inflammatory markers (C-reactive protein, procalcitonin) were maximal at postoperative day 1 or 2 in AAS patients. The levels of circulating NOD2 agonist positively correlated with those of cortisol and IL-10.

Conclusions
The measurement of circulating NOD2 agonist gives a higher informative tool than that of circulating endotoxin for early and sensitive detection of the translocation of bacterial products. The data suggest that circulating NOD2 agonist contributes to further enhance the stress response following surgery.
Comparison of monitoring performance of Bioreactance vs. pulse contour during lung recruitment maneuvers
Authors: Squara Pierre , Rotcajg Dominique , Denjean Dominique , Estagnasie Philippe , Brusset Alain 
Published: July 2009

Abstract
Introduction
This study was designed to test the hypothesis of equivalence in cardiac output (CO) and stroke volume (SV) monitoring capabilities of two devices: non invasive transthoracic bioreactance (NICOM), and a pulse contour analysis (PICCO PC) coupled to transpulmonary thermodilution (PICCO TD).

Methods
We included consecutive patients of a single ICU following cardiac surgery. Continuous minute-by-minute hemodynamic variables obtained from NICOM and PICCO PC were recorded and compared in 20 patients at baseline, during a lung recruitment maneuver (20 cmH2O of PEEP) and following withdrawal of PEEP. PICCO TD measurements were also determined. We evaluated the accuracy of these two technologies at baseline using PICCO TD as reference and we estimated the precision by the fluctuation around the mean value (2SD/mean). Then, we assessed time response, amplitude response and reliability for detecting expected decreases when PEEP was applied. Type I and type II errors were analyzed.

Results
CO values (PICCO TD) ranged from 1.6 to 8.0 L.min-1. At baseline, CO values were comparable for NICOM, PICCO PC and PICCO TD: 5.0 ± 1.2, 4.7 ± 1.4 and 4.6 ± 1.3 L.min.-1, respectively (NS). Limits of agreements with PICCO TD were 1.52 L.min.-1 for NICOM and 1.77 L.min.-1 for PICCO PC, NS. The 95% statistical power gives an equivalence with a threshold of 0.52 L.min.-1 for NICOM vs. PICCO PC. The CO precision was 6 ± 3% and 6 ± 5% for NICOM and PICCO PC, respectively, NS. When PEEP was applied, CO was reduced by 33 ± 12%, 31 ± 14% and 32 ± 13%, for NICOM, PICCO PC and PICCO TD, respectively (NS). Time response was 3.2 ± 0.7 minute for NICOM vs. 2 ± 0.5 minute for PICCO PC (NS). SV results were comparable to those for CO.

Conclusions
Although limited to 20 patients, this study has enough power to show comparable CO and SV monitoring capabilities of Bioreactance and pulse contour analysis calibrated by transpulmonary thermodilution.
Late Pelvic Toxicity After Bladder-Sparing Therapy in Patients With Invasive Bladder Cancer: RTOG 89-03, 95-06, 97-06, 99-06
Authors: Efstathiou Jason A. , Bae Kyounghwa , Shipley William U. , Kaufman Donald S. , Hagan Michael P. , Heney Niall M. , Sandler Howard M. 
Published: July 2009

Purpose In selected patients with muscle-invasive bladder cancer, combined-modality therapy (transurethral resection bladder tumor [TURBT], radiation therapy, chemotherapy) with salvage cystectomy, if necessary, can achieve survival rates similar to radical cystectomy. We investigated late pelvic toxicity after chemoradiotherapy for patients treated on prospective protocols. Patients and Methods Between 1990 and 2002, 285 eligible patients enrolled on four prospective protocols (Radiation Therapy Oncology Group [RTOG] 8903, 9506, 9706, 9906) and 157 underwent combined-modality therapy, surviving ≥ 2 years from start of treatment with their bladder intact. Rates of late genitourinary (GU) and GI toxicity were assessed using the RTOG Late Radiation Morbidity Schema, with worst toxicity grade (scale 0 to 5) occurring ≥ 180 days after start of consolidation therapy reported for each patient. Persistence of toxicity was defined as grade 3+ toxicity not decreasing by at least one grade. Logistic and Cox regression analyses were performed to evaluate relationship between clinical characteristics, frequency, and time to late grade 3+ pelvic toxicity. Covariates included age, sex, stage, presence of carcinoma in situ, completeness of TURBT, and protocol. Results Median follow-up was 5.4 years (range, 2.0 to 13.2 years). Seven percent of patients experienced late grade 3+ pelvic toxicity: 5.7% GU and 1.9% GI. In only one of nine patients did a grade 3+ GU toxicity persist. Notably there were no late grade 4 toxicities and no treatment-related deaths. None of the clinical variables studied predicted for late grade 3+ pelvic toxicity. Conclusion Rates of significant late pelvic toxicity for patients completing combined-modality therapy for invasive bladder cancer and retaining their native bladder are low.
Model-Based Prediction of Phase III Overall Survival in Colorectal Cancer on the Basis of Phase II Tumor Dynamics
Authors: Claret Laurent , Girard Pascal , Hoff Paulo M. , Van Cutsem Eric , Zuideveld Klaas P. , Jorga Karin , Fagerberg Jan , Bruno René 
Published: July 2009

Purpose We developed a drug-disease simulation model to predict antitumor response and overall survival in phase III studies from longitudinal tumor size data in phase II trials. Methods We developed a longitudinal exposure-response tumor-growth inhibition (TGI) model of drug effect (and resistance) using phase II data of capecitabine (n = 34) and historical phase III data of fluorouracil (FU; n = 252) in colorectal cancer (CRC); and we developed a parametric survival model that related change in tumor size and patient characteristics to survival time using historical phase III data (n = 245). The models were validated in simulation of antitumor response and survival in an independent phase III study (n = 1,000 replicates) of capecitabine versus FU in CRC. Results The TGI model provided a good fit of longitudinal tumor size data. A lognormal distribution best described the survival time, and baseline tumor size and change in tumor size from baseline at week 7 were predictors (P < .00001). Predicted change of tumor size and survival time distributions in the phase III study for both capecitabine and FU were consistent with observed values, for example, 431 days (90% prediction interval, 362 to 514 days) versus 401 days observed for survival in the capecitabine arm. A modest survival improvement of 39 days (90% prediction interval, −21 to 110 days) versus 35 days observed was predicted for capecitabine. Conclusion The modeling framework successfully predicted survival in a phase III trial on the basis of capecitabine phase II data in CRC. It is a useful tool to support end-of-phase II decisions and design of phase III studies.
Final Results of Sequential Doxorubicin Plus Gemcitabine and Ifosfamide, Paclitaxel, and Cisplatin Chemotherapy in Patients With Metastatic or Locally Advanced Transitional Cell Carcinoma of the Urothelium
Authors: Milowsky Matthew I. , Nanus David M. , Maluf Fernando C. , Mironov Svetlana , Shi Weiji , Iasonos Alexia , Riches Jamie , Regazzi Ashley , Bajorin Dean F. 
Published: July 2009

Purpose Sequential chemotherapy with doxorubicin and gemcitabine (AG) followed by ifosfamide, paclitaxel, and cisplatin (ITP) was previously demonstrated to be well tolerated in patients with advanced transitional cell carcinoma (TCC). This study sought to evaluate the efficacy and to additionally define toxicity. Patients and Methods Sixty patients with advanced TCC received AG every 2 weeks for five or six cycles followed by ITP every 21 days for four cycles. Granulocyte colony-stimulating factor was given between cycles. Results Myelosuppression was seen with 68% of patients who experienced grades 3 to 4 neutropenia and with 25% who experienced febrile neutropenia. Grade 3 or greater nonhematologic toxicities were infrequent. Forty (73%) of 55 evaluable patients (95% CI, 59% to 84%) demonstrated a major response (complete, n = 19; partial, n = 21) and had a median response duration of 11.3 months (range, 1.7 to ≥ 105.6 months). Twenty-seven (79%) of 34 patients with locally advanced disease (ie, T4, N0, M0) or with regional lymph node involvement (ie, T3-4, N1, M0) and 10 (56%) of 18 patients with distant metastases achieved a major response. The median progression-free survival was 12.1 months (95% CI, 9.0 to 14.8 months), and the median overall survival was 16.4 months (95% CI, 14.0 to 22.5 months). At a median follow-up of 76.4 months, seven (11.7%) patients remain alive, and all were disease free. Conclusion AG plus ITP is an active regimen in previously untreated patients with advanced TCC; however, it is associated with toxicity and does not clearly offer a benefit compared with other nonsequential, cisplatin-based regimens.
Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Recombinant Human Intestinal Trefoil Factor Oral Spray for Prevention of Oral Mucositis in Patients With Colorectal Cancer Who Are Receiving Fluorouracil-Based Chemotherapy
Authors: Peterson Douglas E. , Barker Nicholas P. , Akhmadullina Lilia I. , Rodionova Irina , Sherman Nailya Z. , Davidenko Irina S. , Rakovskaya Galina N. , Gotovkin Eugeny A. , Shinkarev Sergey A. , Kopp Mikhail V. , Kulikov Eugeny P. , Moiseyenko Vladimir M. , Gertner Joseph M. , Firsov Igor , Tuleneva Tamara , Yarosh Alexander , Woon Chee-Wai 
Published: July 2009

Purpose This study evaluated the safety and efficacy of recombinant human intestinal trefoil factor (rhITF) administered as topical oral spray for prevention and treatment of chemotherapy-induced oral mucositis (OM). Patients and Methods Ninety-nine patients with colorectal cancer who had moderate to severe OM (WHO grade ≥ 2) in the first cycle of chemotherapy were randomly assigned to receive either placebo, rhITF 10 mg/mL (ie, low dose), or rhITF 80 mg/mL (ie, high dose) by oral spray (300 μL, eight times each day) for 14 consecutive days in the second chemotherapy cycle. Patients were assessed on days 1, 3, 5, 7, 10, 12, 14, and 21 (± 2 days for the last assessment) for safety and for OM incidence and severity. Results Treatment of patients at high risk for developing OM with low- or high-dose rhITF significantly reduced the amount of incidence (75% to 81%; low-dose rhITF P < .001; high-dose rhITF P = .002). Frequencies of WHO grade ≥ 2 OM in the placebo, low-dose rhITF, and high-dose rhITF groups were 48.5%, 9.1%, and 12.1%, respectively. Assessment of the area under the curve revealed statistically significant reductions in OM severity in the rhITF-treated groups versus placebo. Only a minority of patients (6.1%) reported treatment-emergent adverse events (TEAEs), all of which were mild to moderate in intensity and resolved without sequelae. The incidence of TEAEs was not significantly different among treatment groups. Conclusion rhITF oral spray formulation was safe and effective when used for the reduction of chemotherapy-associated OM in patients with colorectal cancer. Patients exhibited high compliance in dosing administration. Future clinical study is planned to develop this drug for use in OM management in patients with cancer.
Phase II Study of High-Dose [131I]Metaiodobenzylguanidine Therapy for Patients With Metastatic Pheochromocytoma and Paraganglioma
Authors: Gonias Sara , Goldsby Robert , Matthay Katherine K. , Hawkins Randall , Price David , Huberty John , Damon Lloyd , Linker Charles , Sznewajs Aimee , Shiboski Steve , Fitzgerald Paul 
Published: July 2009

Purpose To evaluate the safety and efficacy of high-dose [131I]metaiodobenzylguanidine ([131I]MIBG) in the treatment of malignant pheochromocytoma (PHEO) and paraganglioma (PGL). Methods Fifty patients with metastatic PHEO or PGL, age 10 to 64 years, were treated with [131I]MIBG doses ranging from 492 to 1,160 mCi (median, 12 mCi/kg). Cumulative [131I]MIBG administered ranged from 492 to 3,191 mCi. Autologous hematopoietic stem cells were collected and cryopreserved before treatment with [131I]MIBG greater than 12 mCi/kg or with a total dose greater than 500 mCi. Sixty-nine [131I]MIBG infusions were given, which included infusions to 35 patients treated once and infusions to 15 patients who received two or three treatments. Response was evaluated by [123I]MIBG scans, computed tomography/magnetic resonance imaging, urinary catecholamines/metanephrines, and chromogranin A. Results The overall complete response (CR) plus partial response (PR) rate in 49 evaluable patients was 22%. Additionally, 35% of patients achieved a CR or PR in at least one measure of response without progressive disease, and 8% of patients maintained stable disease for greater than 12 months. Thirty-five percent of patients experienced progressive disease within 1 year after therapy. The estimated 5-year overall survival rate was 64%. Toxicities included grades 3 to 4 neutropenia (87%) and thrombocytopenia (83%). Grades 3 to 4 nonhematologic toxicity included acute respiratory distress syndrome (n = 2), bronchiolitis obliterans organizing pneumonia (n = 2), pulmonary embolism (n = 1), fever with neutropenia (n = 7), acute hypertension (n = 10), infection (n = 2), myelodysplastic syndrome (n = 2), and hypogonadism (n = 4). Conclusion Although serious toxicity may occur, the survival and response rates achieved with high-dose [131I]MIBG suggest its utility in the management of selected patients with metastatic PHEO and PGL.
Isocitrate Dehydrogenase 1 Codon 132 Mutation Is an Important Prognostic Biomarker in Gliomas
Authors: Sanson Marc , Marie Yannick , Paris Sophie , Idbaih Ahmed , Laffaire Julien , Ducray François , El Hallani Soufiane , Boisselier Blandine , Mokhtari Karima , Hoang-Xuan Khe , Delattre Jean-Yves 
Published: July 2009

Purpose Unexpected mutations affecting the isocitrate dehydrogenase (IDH1) gene at codon 132 have been found in 12% of glioblastomas. Patients and Methods IDH1 codon 132 sequencing was performed in a series of 404 patients with glioma (100 grade 2, 121 grade 3, and 183 grade 4 gliomas) and correlated with histology, genomic profile, methylguanyl methyltransferase (MGMT) promoter methylation status, and outcome. Results A total of 155 codon 132 mutations were found, of which 131 were Arg132His (88.5%). The IDH1 mutation was inversely correlated with grade, affecting 77% of grade 2, 55% of grade 3, and 6% of grade 4 gliomas (P < 10−15). The IDH1 mutation was tightly associated with a 1p19q codeleted genotype (P < 10−14) and an MGMT methylated status (P < .001) but mutually exclusive with EGFR amplification (P < 10−15) and loss of chromosome 10 (P < 10−15). The presence (v absence) of IDH1 mutation was associated with a better outcome in grade 2 (150.9 v 60.1 months, respectively; P = .01), grade 3 (81.1 v 19.4 months, respectively; P < .001), and grade 4 gliomas (27.4 v 14 months, respectively; P < .01). After adjustment for grade, age, MGMT status, genomic profile, and treatment, multivariate analysis confirmed that IDH1 mutation was an independent favorable prognostic marker (hazard ratio = 0.297; 95% CI, 0.157 to 0.564, P = .00021). Conclusion This study indicates that IDH1 codon 132 mutation is closely linked to the genomic profile of the tumor and constitutes an important prognostic marker in grade 2 to 4 gliomas.