tbuckley/cabot-search huggingface dataset:
Comparison of Aortic Root Dimensions and Geometries Pre- and Post-Transcatheter Aortic Valve Implantation by 2-and 3-Dimensional Transesophageal Echocardiography and Multislice Computed Tomography
Authors: Arnold C. Ng, Victoria Delgado, Frank van der Kley, Rutger J. van Bommel, Miriam Shanks, Arend de Weger, Giuseppe Tavilla, Nico R. van de Veire, Matteo Bertini, Gaetano Nucifora, Dominic Y. Leung, Joanne Schuijf, Martin J. Schalij, Jeroen J. Bax
Journal: Circulation (2009)
Ethnic variations in morbidity and mortality from lower respiratory tract infections: a retrospective cohort study
Authors: Colin R Simpson, Markus FC Steiner, Genevieve Cezard, Narinder Bansal, Colin Fischbacher, Anne Douglas, Raj Bhopal, Aziz Sheikh
Journal: Journal of the Royal Society of Medicine (2015)

Objective There is evidence of substantial ethnic variations in asthma morbidity and the risk of hospitalisation, but the picture in relation to lower respiratory tract infections is unclear. We carried out an observational study to identify ethnic group differences for lower respiratory tract infections. Design A retrospective, cohort study. Setting Scotland. Participants 4.65 million people on whom information was available from the 2001 census, followed from May 2001 to April 2010. Main outcome measures Hospitalisations and deaths (any time following first hospitalisation) from lower respiratory tract infections, adjusted risk ratios and hazard ratios by ethnicity and sex were calculated. We multiplied ratios and confidence intervals by 100, so the reference Scottish White population’s risk ratio and hazard ratio was 100. Results Among men, adjusted risk ratios for lower respiratory tract infection hospitalisation were lower in Other White British (80, 95% confidence interval 73–86) and Chinese (69, 95% confidence interval 56–84) populations and higher in Pakistani groups (152, 95% confidence interval 136–169). In women, results were mostly similar to those in men (e.g. Chinese 68, 95% confidence interval 56–82), although higher adjusted risk ratios were found among women of the Other South Asians group (145, 95% confidence interval 120–175). Survival (adjusted hazard ratio) following lower respiratory tract infection for Pakistani men (54, 95% confidence interval 39–74) and women (31, 95% confidence interval 18–53) was better than the reference population. Conclusions Substantial differences in the rates of lower respiratory tract infections amongst different ethnic groups in Scotland were found. Pakistani men and women had particularly high rates of lower respiratory tract infection hospitalisation. The reasons behind the high rates of lower respiratory tract infection in the Pakistani community are now required.
Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial
Authors: E. Van Cutsem, M. Nowacki, I. Lang, S. Cascinu, I. Shchepotin, J. Maurel, P. Rougier, D. Cunningham, J. Nippgen, C. Köhne
Journal: Journal of Clinical Oncology (2007)

4000 Background: Cetuximab in combination with irinotecan-based regimens has proven activity in previously-treated patients (pts) with mCRC. The present trial investigated the effectiveness of cetuximab in combination with standard FOLFIRI compared with FOLFIRI alone in the first-line treatment of pts with epidermal growth factor receptor (EGFR)-expressing mCRC. Methods: Pts were randomized 1:1 to receive either cetuximab (400 mg/m 2 initial dose then 250 mg/m 2 /week [w]) plus FOLFIRI q 2 w (irinotecan 180 mg/m 2 , FA 400 mg/m 2 , 5-FU bolus 400 mg/m 2 , 5-FU infusion 2,400 mg/m 2 over 46 hours) (Group A) or FOLFIRI alone (Group B). The primary endpoint was progression-free survival (PFS), with secondary endpoints of overall survival (OS), response rate (RR), disease control rate and safety. 633 events were required to statistically differentiate PFS between groups with 80% power. Results: Between August 2004 and October 2005, 1,217 pts were randomized, 608 to Group A and 609 to Group B (60% male, median age 61 [19–84], ECOG performance status: 0=54%; 1=43.5%; 2=3.5%). Median PFS was significantly longer for Group A compared to Group B (8,9 months [8 - 9,5] for Group A vs. 8 months [7.6 - 9] for Group B, p=0.036). Response Rate was also significantly increased by cetuximab (46.9% vs. 38.7%, p=0.005). Treatment was generally well tolerated with neutropenia (26.7% Group A, 23.3% Group B), diarrhea (15.2% and 10.5% respectively) and skin reactions (18.7% and 0.2% respectively) being the most common grade 3/4 adverse events. Conclusions: Cetuximab in combination with FOLFIRI significantly increases response rate and significantly prolongs PFS in the first-line treatment of pts with mCRC, reducing the relative risk of progression by approximately 15%. Treatment-related side effects of cetuximab in combination with FOLFIRI were as expected, with diarrhea being moderately and skin reactions significantly more frequent as compared to FOLFIRI alone. [Table: see text]
A phase III trial comparing mFOLFOX6 to mFOLFOX6 plus bevacizumab in stage II or III carcinoma of the colon: Results of NSABP Protocol C-08
Authors: N. Wolmark, G. Yothers, M. J. O'Connell, S. Sharif, J. N. Atkins, T. E. Seay, L. Feherenbacher, S. O'Reilly, C. J. Allegra
Journal: Journal of Clinical Oncology (2009)

LBA4 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. No significant financial relationships to disclose.
Identification of tumor suppressor genes by large-scale profiling of cytosine-methylation in glioblastoma cell lines
Authors: Mathias Ehrich, Wolf Muller, David Louis, Dirk van den Boom
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

260 

Glioblastoma, the most aggressive and least treatable form of malignant glioma, is the most common human brain tumor. Although many regions of allelic loss occur in glioblastomas, relatively few tumor suppressor genes have been found mutated at such loci.

The methylation status of MGMT has previously been shown to be closely linked to treatment outcome in brain tumors indicating an epigenetic involvement in the pathology of these tumors. We recently published a study in which we exposed triplicates of three short-term cultured glioblastomas to 5μM 5-aza-dC for 96 hours followed by cRNA hybridization to an oligonucleotide microarray (Affymetrix U133A). The results identified RUNX and TES as two genes with altered methylation patterns in glioblastoma.

Here we present quantitative methylation data for a set of 16 additional genes. We used a novel method based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to perform large-scale quantitative methylation profiling. We found 4 genes to have identical methylation patterns between normal and tumor cell lines, 13 showed hypermethylation in glioblastoma cell lines and 1 gene showed hypomethylation. We also show a correlation between differential methylation and gene expression changes.

The results shown here indicate a strong bias towards hypermethylation in glioblastoma cell lines. This bias should initiate further validation of non-cell line samples, validating epigenetic disregulation as an essential biological process in malignant glioma progression.
Cetuximab and irinotecan-based chemotherapy as an active and safe treatment option for elderly patients with extensively pre-treated metastatic colorectal cancer
Authors: M. Bouchahda, T. Macarulla, J. P. Spano, J. B. Bachet, G. Liedo, T. Andre, B. Landi, J. Tabernero, F. Levi, P. Rougier
Journal: Journal of Clinical Oncology (2007)

14528 Background: Cetuximab ( C ) has demonstrated activity both as a single agent and in combination with irinotecan (CPT11) in patients (pts) with metastatic colorectal cancer (mCRC) expressing epidermal growth factor receptor (EGFR) refractory to CPT 11 and oxaliplatin based chemotherapy. This European retrospective study explored the tolerability and activity of C combined with CPT 11 in an unselected population of elderly pts with CPT11- refractory mCRC Methods: 67 pts with mCRC aged = 70 yrs were treated with C (400 mg/m 2 loading dose over 2 hours, then 250 mg/m 2 over 1 hour weekly). C was given alone (2 pts), combined with CPT11 (56 pts) or CPT11 + 5FU-LV as conventional (4 pts) or chronomodulated delivery (5 pts). Treatment was administered as 2 nd to 6 th line. Primary endpoint was time to tumor progression (TTP). Secondary endpoints were toxicity, objective response rate (RR) (with RECIST Criteria) and overall survival (OS). Results: Median age was 77 yrs (70–84); M/F: 44/23; WHO performance status 0/1/2/unknown: 12/40/11/4; EGFR expression: + in 55 pts, - in 2 pts and unknown in 10 pts; colon/rectum/unknown: 49/14 /4. More frequent toxicities included acneiform skin rash, which occurred in 33 pts (Grade (G) 2: 24 pts, 35%; G3: 9 pts, 13%), diarrhea (G3, 11 pts, 16%; G4, 2 pts, 3%) and neutropenia (G3: 4 pts, 6%; G4: 5 pts, 7%). RR was 23% including 1 complete and 14 partial responses. Disease control rate (RR + stable disease) was 53%. No correlation was found between skin rash and response. Median TTP (intent-to treat) was 4.5 months [95% CI: 3.2 - 5.7]. Median OS was 15 months [12.0–17.9]. Conclusions: The combination of C with CPT11-based chemotherapy resulted in good activity and acceptable tolerability in elderly patients with heavily pre-treated mCRC, comparable to that of the younger patients. This treatment option can be reasonably proposed to the elderly population. No significant financial relationships to disclose.
Atherogenic Lipoprotein Subfractions Determined by Ion Mobility and First Cardiovascular Events After Random Allocation to High-Intensity Statin or Placebo
Authors: Samia Mora, Michael P. Caulfield, Jay Wohlgemuth, Zhihong Chen, H. Robert Superko, Charles M. Rowland, Robert J. Glynn, Paul M Ridker, Ronald M. Krauss
Journal: Circulation (2015)

Cardiovascular disease (CVD) can occur in individuals with low low-density lipoprotein (LDL) cholesterol (LDL-C). We investigated whether detailed measures of LDL subfractions and other lipoproteins can be used to assess CVD risk in a population with both low LDL-C and high C-reactive protein who were randomized to high-intensity statin or placebo.In 11 186 Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) participants, we tested whether lipids, apolipoproteins, and ion mobility-measured particle concentrations at baseline and after random allocation to rosuvastatin 20 mg/d or placebo were associated with first CVD events (n=307) or CVD/all-cause death (n=522). In placebo-allocated participants, baseline LDL-C was not associated with CVD (adjusted hazard ratio [HR] per SD, 1.03; 95% confidence interval [CI], 0.88-1.21). In contrast, associations with CVD events were observed for baseline non-high-density lipoprotein (HDL) cholesterol (HR, 1.18; 95% CI, 1.01-1.38), apolipoprotein B (HR, 1.28; 95% CI, 1.11-1.48), and ion mobility-measured non-HDL particles (HR, 1.19; 95% CI, 1.05-1.35) and LDL particles (HR, 1.21; 95% CI, 1.07-1.37). Association with CVD events was also observed for several LDL and very-low-density lipoprotein subfractions but not for ion mobility-measured HDL subfractions. In statin-allocated participants, CVD events were associated with on-treatment LDL-C, non-HDL cholesterol, and apolipoprotein B; these were also associated with CVD/all-cause death, as were several LDL and very-low-density lipoprotein subfractions, albeit with a pattern of association that differed from the baseline risk.In JUPITER, baseline LDL-C was not associated with CVD events, in contrast with significant associations for non-HDL cholesterol and atherogenic particles: apolipoprotein B and ion mobility-measured non-HDL particles, LDL particles, and select subfractions of very-low-density lipoprotein particles and LDL particles. During high-intensity statin therapy, on-treatment levels of LDL-C and atherogenic particles were associated with residual risk of CVD/all-cause death.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.
Abstract 19338: Calcium Dose During Resuscitation from Asphyxial Cardiac Arrest in Developing Rats Affects Heart Rate and Blood Pressure but Not Survival
Authors: Michael Ricafort, Laura Sullivan, Michael Shoykhet
Journal: Circulation (2014)

Use of calcium during resuscitation from cardiac arrest remains controversial. Current AHA guidelines, drawing on small clinical studies, only recommend calcium use in hyperkalemia, hypocalcemia, hypermagnesemia and overdose of calcium-channel blockers. Yet, a large proportion of critical care physicians, especially in pediatrics, utilize IV calcium when cardiac arrest victims are resistant to epinephrine and vasopressin. We tested the effect of two different doses of calcium chloride - 10 mg/kg and 1 mg/kg - on blood pressure, heart rate, lactate and survival in a model of pediatric asphyxial cardiac arrest and resuscitation in developing rats. Seventeen to 19 days old Long Evans rats were anesthetized with isoflurane, endotracheally intubated and mechanically ventilated. The femoral artery and external jugular vein were cannulated for blood pressure monitoring and medication administration, respectively. EKG and EEG were continuously monitored. Anesthesia was discontinued 2 min prior to arrest to minimize confounding effect of isoflurane on outcomes. Asphyxial cardiac arrest was induced by discontinuing mechanical ventilation under neuromuscular blockade. After 9.5 minutes of asphyxia, rats were resuscitated using mechanical ventilation with 100% O2, chest compressions, epinephrine, NaHCO3, and either a standard resuscitation dose of 10 mg/kg CaCl2 (n=34) or a reduced dose of 1 mg/kg (n=40). Short-term (1 hr) survival did not differ between the two groups (85% in the 10 mg/kg group vs. 87% in the 1 mg/kg group, χ2, p > 0.05). Heart rate (HR) and mean arterial pressure (MAP) were calculated from 10 second intervals at 1, 5, 15 and 25 min post-resuscitation. Post-resuscitation HR was higher in the 10 mg/kg group (two-way ANOVA, p = 0.003 for calcium dose). Post-resuscitation MAP was also higher in the 10 mg/kg group (two-way ANOVA, p = 0.004 for calcium dose). Post-resuscitation whole blood lactate was lower in the 10 mg/kg group (5.8±1.1 mMol/L) compared to the 1 mg/kg group (6.8±2.1 mMol/L) ( t -test with unequal variances, p = 0.04). We conclude that in this clinically-realistic model of asphyxial cardiac arrest, lower dose CaCl2 during resuscitation does not affect short-term survival but is associated with lower post-resuscitation cardiac output.
Final response data of a phase II study of capecitabine and oxaliplatin (CAPOX) in advanced adenocarcinoma of the small bowel or ampulla of Vater
Authors: M. J. Overman, G. R. Varadhachary, E. Lin, J. Morris, R. Adinin, J. L. Abbruzzese, R. A. Wolff
Journal: Journal of Clinical Oncology (2008)

4538 Background: Small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC) are rare tumors. There is limited information regarding chemotherapy in advanced disease and no current standard of care. Methods: Patients with either metastatic or locally advanced unresectable SBA or AAC with adequate organ function, performance status (PS) ≤2 and measurable disease per RECIST were enrolled from 11/04 to 7/07. Prior use of 5-FU either as adjuvant therapy or as a radiosensitizer was allowed. CAPOX was administered as a 21 day cycle with oxaliplatin 130 mg/m2 IV on day 1 and capecitabine 750 mg/m2 PO BID days 1- 14. The planned sample size was 30 and the primary endpoint was overall response rate (ORR). Results: Thirty patients (12 AAC and 18 SBA) have been treated and 29 are evaluable for response. Patients had either locally advanced (5) or metastatic disease (25) and 5 had prior adjuvant 5-FU. The median age was 62 years (41–79); 40% females; 97% PS of 0–1. The median number of cycles administered was 5 (1 to 11); 4 patients remain on treatment. Common grade 3/4 toxicities included fatigue (7), neuropathy (2), granulocytopenia (3), vomiting (3), diarrhea (3), thrombocytopenia (2), and hypokalemia (2). Fifteen patients, 5 AAC and 10 SBA, had a confirmed response with an ORR of 52% (95% CI 33 to 71%); 11 patients had stable disease (SD). Six patients (20%) are currently without evidence of disease. Three patients with metastatic disease are alive in complete remission (CR), two following CAPOX alone and a third following consolidative radiation, at 31, 28, and 21 months, respectively. Three patients with locally advanced disease with SD or PR to CAPOX have since undergone surgery and are alive without evidence of disease at 8, 10, and 20 months. Median PFS is 9.8 m (95% CI 4.7 to 30+m). Twelve patients have died. With a median follow-up of 12.1 months, median overall survival is 20.3 m (95% CI 13 to 30+m). Conclusions: This prospective trial demonstrates that CAPOX delivered to good PS patients with advanced SBA or ACC is well tolerated and leads to the highest response rate and median survival ever reported from prospective trials in these tumor types. We believe, CAPOX should be considered the new standard regimen for advanced SBA and AAC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis
Lowered Cisplatin Dose and No Bleomycin in the Treatment of Pediatric Germ Cell Tumors: Results of the GCT-99 Protocol From the Brazilian Germ Cell Pediatric Oncology Cooperative Group
Authors: Luiz Fernando Lopes, Carla Renata Pacheco Donato Macedo, Simone dos Santos Aguiar, Jose Henrique S. Barreto, Gisele Eiras Martins, Viviane Sonaglio, Marcelo Milone, Eduardo Ribeiro Lima, Maria Teresa de Assis Almeida, Paula Maria Azevedo Allemand Lopes, Flora Mitie Watanabe, Maria Lydia Mello D´Andrea, Mara Albonei Pianovski, Renato Melaragno, Sonia Maria Rossi Vianna, Mauber Eduardo Schultz Moreira, Paula Bruniera, Cleyton Zanardo de Oliveira
Journal: Journal of Clinical Oncology (2016)

We describe the results of a risk-adapted, response-based therapeutic approach from the Brazilian GCT-99 study on germ cell tumors.From May 1999 to October 2009, 579 participants were enrolled in the Brazilian GCT-99 study. Treatment, defined as specific chemotherapy regimen and number of cycles, was allocated by means of risk-group assignment at diagnosis with consideration for stage and primary tumor site. Patients at low risk received no chemotherapy. Patients at intermediate risk (IR) with a good response (GR) received four cycles of platinum and etoposide (PE), for total doses of platinum 420 mg/m(2) and etoposide 2,040 mg/m(2). Patients at IR with a partial response (PR) received three cycles of PE plus three cycles of ifosfamide, vinblastine, and bleomycin. Patients at high risk (HR) with a GR received four cycles of PE and ifosfamide (PEI) at total doses of platinum 420 mg/m(2), etoposide 1,200 mg/m(2), and ifosfamide 30 g/m(2). Patients at HR with a PR received six cycles of PEI.The risk-group distribution was 213 LR, 138 IR, and 129 HR for 480 evaluable patients. Overall survival (OS) and event-free survival (EFS) rates at 10 years were, respectively, 90% and 88.6% in the IR-GR group (n = 126) and 74.1% and 74.1% in the IR-PR group (n = 12). Ten-year rates for the HR-GR group (n = 86) were an OS of 66.8% and an EFS of 62.5%. The HR-PR group (n = 43) had an OS of 74.8% and an EFS of 73.4%. In univariable and multivariable analysis, increased serum lactate dehydrogenase level and histology for a metastatic immature teratoma were prognostic of a worsened outcome.Reduction of therapy to two drugs did not compromise survival outcomes for patients in the IR-GR group, and escalation of therapy with PEI did not significantly improve OS and EFS in patients at HR.
Association of time delays to radical cystectomy by use of neoadjuvant chemotherapy with higher rates of progression.
Authors: William P. Parker, Avinash Nehra, Joshua Griffin, Ernesto Lopez-Corona, Jeffrey M. Holzbeierlein
Journal: Journal of Clinical Oncology (2014)

345 Background: Neoadjuvant chemotherapy (NC) is utilized to improve survival for patients with muscle invasive bladder cancer. However, this results in a protracted treatment course of 3−4 chemotherapy cycles given over several months. Previous series have suggested that delays in radical cystectomy (RC) from initial diagnosis are associated with inferior survival rates. We investigated if similar trends are seen in a population of patients treated with neoadjuvant chemotherapy. Methods: A retrospective review of our RC database was performed to identify patients treated with NC over the last five years. Time interval was calculated from date of initial diagnosis of muscle invasive disease to date of surgery. Kaplan Meier and multivariate analysis methods were used to assess recurrence free and cancer specific survival based on pathologic stage, nodal status, margin status, and time to RC with estimation of hazard ratios for those variables. Results: 72 patients from 2006−2012 were identified. Mean age was 64 years and 80% were male. 79% of the cohort had 3 or more cycles of NC, with gemcitabine−cisplatin as the most common regimen (75%). Mean time from diagnosis to RC was 173 days. Pathologic stage distribution was T2−20.8%, T3−20.8%, T4− 18.1% and T0 status was obtained in 27.8%. 95% was of pure urothelial carcinoma histology. Node positive disease was found in 30%. At most recent follow up 33% of the cohort had died and 13% had recurrent disease. Higher tumor stage and positive nodal status were associated with lower recurrence free and cancer specific survival. When stratifying the cohort by time to RC (1−4 months, 5months, 6 months) there was no statistical difference in recurrence free or cancer specific survival. However, on multivariate analysis patients who had RC less than 5 months from diagnosis had lower rates of progression (OR 0.14; 95% CI .02−.08, p 0.038) compared to those with RC after 5 months (OR 4.86 95% CI 0.9−26, p 0.06). Conclusions: Time delays associated with use of NC of greater than five months correlated with lower recurrence free survival in our cohort but there did not appear to be any effect on cancer specific survival. This should be further validated with a larger multicenter analysis.