tbuckley/cabot-search huggingface dataset:
First-in-human phase I study of the oral PI3K inhibitor BEZ235 in patients (pts) with advanced solid tumors.
Authors: H. Burris, J. Rodon, S. Sharma, R. S. Herbst, J. Tabernero, J. R. Infante, A. Silva, D. Demanse, W. Hackl, J. Baselga
Journal: Journal of Clinical Oncology (2010)

3005 Background: The PI3K pathway plays a major role in cancer cell growth and survival, and is frequently aberrantly hyperactivated in tumors. BEZ235 is a potent and highly selective reversible PI3K pathway inhibitor with antiproliferative and apoptotic activity in cancer cells. BEZ235 strongly inhibited activation of downstream effectors (e.g. Akt) and displayed antitumor activity in xenograft models harboring PI3K pathway alterations. In preclinical toxicology studies, BEZ235 treatment was well tolerated. Methods: This phase I, multicenter, open-label, single-agent, dose-escalation, study was conducted in pts with histologically confirmed, advanced, unresectable solid tumors. BEZ235 was administered once daily as a gelatin capsule either fasted or fed (10-1,100 mg) until unacceptable toxicity or disease progression. Dose escalation was guided by a Bayesian logistic regression model with overdose control. Anti-tumor activity of BEZ235 was assessed by CT and PET. Early efficacy data are based on central review. Results: A total of 59 pts have entered the trial (13 breast [22%], 10 CRC [17%]). There were no DLTs with BEZ235 treatment. Frequently reported AEs included nausea, vomiting, diarrhea, fatigue/asthenia, anemia, and anorexia; they were mild or moderate, manageable, and reversible upon treatment discontinuation. AUC and Cmax increased non-proportionally with dose and were variable within and among pts. BEZ235 exhibited dose- and day-dependent PI3K inhibition as measured by elevation of plasma C-peptide levels. 2 PR (1 Cowden syndrome pt, 1 breast pt) and 16 MR were observed. 14 of 51 evaluable pts had stable disease ≥4 months; tumors from 6 of these 14 pts carried dysregulations of the PI3K pathway. 4 of the 14 (29%) patients with SD ≥4 months had breast cancer. 18 of 35 evaluable pts had detectable decreases of 18FDG- uptake. Conclusions: BEZ235 was well tolerated with a favorable safety profile. Available PD and efficacy data show that BEZ235 is active in pts (especially in those with PI3K pathway dysregulated tumors). Based on PK data, future studies will use a new formulation of BEZ235 with improved bioavailability and PK properties. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Exelixis, Merck, Novartis, Roche Novartis Novartis Novartis
Melanoma-Specific Antibodies Produced in Monkeys by Immunization With Human Melanoma Cell Lines2
Authors: Richard S. Metzgar, Paulo M. Bergoc, Marluce A. Moreno, Hilliard F. Seigler
Journal: JNCI Journal of the National Cancer Institute (1973)

Monkeys immunized with 2 tissue-culture cell lines, derived from human melanomas, produced antibodies which appeared to be specific for melanoma antigen(s). The antisera, after absorption with human erythrocytes, normal peripheral blood leukocytes, and HeLa cells, failed to react with normal human fibroblasts and lymphocytes or with nonmelanoma malignant cell lines but gave strong reactivity by cytotoxicity and mixed agglutination with 4 melanoma celilines.
Short term outcomes of pulmonary rehabilitation: A comparison between patients immediately after hospitalization for AECOPD and stable COPD patients
Authors: Michael Wittmann, Danijel Jelusic, Michael Schuler, Harma Alma, Corina De Jong, Thys Van Der Molen, Konrad Schultz
Journal: European Respiratory Journal (2014)

Background: Rehabilitation after hospitalization because of acute exacerbation of COPD (AECOPD) has proven to be highly effective. The current study compares the benefit of pulmonary rehabilitation (PR) in patients after AECOPD to the benefit in stable COPD patients.

Methods: We prospectively analyzed 311 COPD patients in PR, GOLD stage II-IV. Outcome measurements: walking distance (6MWD), dyspnea (mMRC, TDI), quality of life (CCQ, CAT) and the BODE score.

Results: 228 stable patients (56.6±7.1 years, O FEV1 53.1%pred., 64% male) and 83 patients after hospitalization for AECOPD (59.0±6.1 years, O FEV1 47.9%pred., 60% male) were included. The results are shown in the table. No differences between the groups were found.

![Figure][1] 



Discussion: All patients improved in most outcomes, with no difference between the patient groups.

 [1]: pending:yes
Systemic inflammatory response and the incidence of bacteremia during biochemotherapy in metastatic melanoma
Authors: G. H. Kloecker, M. V. Jaglal, J. Chesney, F. Arnold, D. M. Miller
Journal: Journal of Clinical Oncology (2008)

9615 Background: Standard of care calls for blood cultures to be drawn in patients with systemic inflammatory response syndrome (SIRS). Signs of SIRS, such as fevers, are expected using biochemotherapy with IL-2 and Interferon. This study evaluates the usefulness of routine blood cultures in patients who develop temperatures of 38.5o C or higher while treated with biochemotherapy. Methods: Charts of patients treated with biochemotherapy or high dose IL-2 for metastatic melanoma were reviewed at the University of Louisville from 2005 to 2007. The study objective was to estimate the frequency of true and false positive blood cultures. Results: A total of 205 blood cultures in 46 patients (27 male, 19 female) were reviewed. The average age was 63 years (25–71 years). The patients had an average of three cycles of biochemotherapy. The mean temperature of the febrile episodes was 38.7°C. The mean absolute neutrophil count was 5.1 K/mm3;, with extreme lows of less than 0.5 K/mm3; during treatment. Most patients had central lines placed at the initiation of treatment and had their central lines pulled at the end of the cycle. No patient was started on biochemotherapy while on antibiotics for a recent or acute infection. Out of these 205 febrile episodes only one blood culture was true positive. The patient had methicillin sensitive staph aureus bacteremia. There were five positive blood cultures thought to be false positive by the treating physician. 434 further febrile episodes on biochemotherapy were documented without blood cultures drawn. None of these patents were found to be infected during their biochemotherapy. Conclusions: Blood cultures during biochemotherapy/ IL-2 therapies are very inefficient in diagnosing clinically relevant bacteremia. The yield of true positive blood cultures in this setting is less than 3% (95% CI, 0–3%).There was however a significant number of false positive blood cultures. Unnecessary phlebotomies are an inconvenience to patients, are expensive and may be misleading by giving false positive results. No significant financial relationships to disclose.
Clinical Sequelae of Ebola
Authors: M. J. Friedrich
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 13833: Postconditioning Effect of Granulocyte Colony-Stimulating Factor is Mediated Through Activation of RISK Pathway and Opening of the Mitochondrial KATP Channels
Authors: Shohei Sumi, Shinya Minatoguchi, Masamitsu Iwasa, Takahiko Yamaki, Yoshihisa Yamada, Hiroaki Ushikoshi, Kazuhiko Nishigaki, Genzou Takemura
Journal: Circulation (2010)

Background: Granulocyte-colony-stimulating factor(G-CSF) has been reported to improve cardiac function after myocardial infarction(MI). However, whether postinfarct acute effect of G-CSF is mediated through the same signaling pathways as those of ischemic postconditioning is still unclear. We examined the postinfarct acute effect of G-CSF on myocardial infarct size and its precise molecular mechanism. Method: Japanese white rabbits underwent 30 min of ischemia and 48 hour of reperfusion. Rabbits were intravenously injected 10 μg/kg of G-CSF (G-CSF group), saline(control group) immediately after reperfusion. The wortmannin+G-CSF, PD98059+G-CSF, L-NAME+G-CSF, and 5-HD+G-CSF groups were respectively injected with wortmannin(0.6mg/kg), PD98059(0.3mg/kg), L-NAME(10mg/kg) and 5-HD(5mg/kg), 5 min before G-CSF administration. Myocardial infarct size was calculated as a percentage of the risk area of the left ventricle. Western blot analysis was performed to examine the signals such as Akt, ERK, eNOS, p70S6K and G...
Abstract 12728: Common Variant Near <i>Hey2</i> as a Protective Modifier of Ventricular Fibrillation in Brugada Syndrome by Modurating QTc Interval
Authors: Yukiko Nakano, Hidenori Ochi, Masaaki Toshisige, Takehito Tokuyama, Hiroshi Kawazoe, Yoshikazu Watanebe, Masaya Matumura, Shunsuke Tomomori, Shinji Kishimoto, Hiroki Ikenaga, Noboru Oda, Kazuaki Chayama, Yasuki Kihara
Journal: Circulation (2014)

Introduction: A recent genome-wide association study (GWAS) identified that three loci, SCN10A (rs10428132), SCN5A (rs11708996), and one downstream from HEY2 gene (rs9388451) were associated with Brugada syndrome. Methods: We investigated these 3 single nucleotide polymorphisms (SNPs) in 94 Japanese patients diagnosed with Brugada syndrome and 1,978 healthy controls. Results: Both rs10428132 at SCN10A and rs9388451near HEY2 were associated with Brugada syndrome [ P = 6.13 х 10 –14 ;odds ratio (OR), 8.0 and P = 8.0 х 10 –4 ; OR, 2.5, respectively). However, the C HEY2 allele was more frequent in Brugada syndrome patients without ventricular fibrillation (VF) than those with VF (53.7% vs. 40%, P = 0.04). This suggests a protective effect of this allele against VF occurrence, which may conflict with previous GWAS findings. The QTc interval was significantly longer in patients with the HEY2 risk allele than those without it (CC: 422 ± 3.8 vs. CT: 409 ± 4.8 vs. TT: 381 ± 9.5 ms, P = 0.0004). The other electrocardiogram parameters were unrelated to the HEY2 allele. PQ interval was longer in patients with the SCN10A risk allele than those without it (CC: 157 ± 2.5 vs. CT: 172 ± 5.3 vs. TT: 172 ± 3.5 ms, P = 0.0019), but the SCN10A SNP was not associated with clinical severity of Brugada syndrome. Conclusions: These results suggest that the HEY2 SNP may be a prognostic marker for Brugada syndrome, protecting VF occurrence presumably by regulating repolarization current.
PWE-148 Combined effects of reoperation and venous thromboembolism in gastrointestinal surgery: evaluation of postoperative complications using linked hospital and primary care data
Authors: G Bouras, EM Burns, A Bottle, J Clarke, T Athanasiou, A Darzi
Journal: Gut (2015)

<h3>Introduction</h3> Trends towards early hospital discharge mean that complications such as venous thromboembolism (VTE) may increasingly occur in the primary care setting. Guidelines recommend thromboprophylaxis after hospital discharge in patients undergoing gastrointestinal cancer resection. However factors other than the presence of malignancy may prolong VTE risk. Previous studies have shown increased VTE risk with reoperation. The combined effect of VTE and reoperation on mortality has not been reported. <h3>Method</h3> Thirty-day reoperation, 90-day VTE and 90-day mortality was measured using linked Clinical Practice Research Datalink (CPRD), Hospital Episodes Statistics (HES), Office of National Statistics (ONS) and National Cancer Intelligence Network databases. The effect of different types of reoperation on VTE risk adjusted for length of hospital stay and other short-term complications was evaluated in adults undergoing one of seven gastrointestinal surgical procedures. The combined effect of VTE and reoperation on mortality was evaluated in benign and cancer patients separately. <h3>Results</h3> 76334 procedures over fifteen years were evaluated. Thirty-day reoperation was recorded in 3.18% (2426/76334) of procedures. There were 721/76334 (0.94%) VTE events recorded after 90 days of surgery (0.51% - 294/58036 in procedures for benign disease, 2.33% - 427/18298 in procedures for cancer). Over half (57.7%, 416/721) of VTE were recorded after hospital discharge. Reoperation was an independent predictor of 90-day VTE in benign (OR=1.88, p &lt; 0.05) but not in cancer (OR=1.17) patients. Reoperation for bleeding (OR=1.20 in benign, OR=1.55 in cancer), peritoneal drainage (OR=1.75 in benign, OR=1.45 in cancer) and organ resection (OR=2.01 in benign, OR=1.22 in cancer) were associated with greater odds of VTE in both groups. Cox regression analysis revealed that VTE together with reoperation was a stronger predictor of poor survival (OR=2.70) than reoperation (OR=2.44) or VTE (OR=2.22) alone in patients undergoing surgery for cancer. These synergistic effects of VTE and reoperation on mortality were not observed in patients undergoing surgery for benign disease. <h3>Conclusion</h3> Reoperation increased VTE risk in patients undergoing gastrointestinal surgery for benign conditions, while reoperation and VTE acted synergistically to increase mortality in patients undergoing surgery for cancer. Reoperation was therefore associated with significant harm from VTE extending into the out-patient setting, which may infer the need for additional thromboprophylaxis in some patients. <h3>Disclosure of interest</h3> None Declared.
Erratum. Risks of Psychiatric Disorders and Suicide Attempts in Children and Adolescents With Type 1 Diabetes: A Population-Based Cohort Study. Diabetes Care 2015;38:453–459
Authors: Agnieszka Butwicka, Louise Frisén, Catarina Almqvist, Björn Zethelius, Paul Lichtenstein
Journal: Diabetes Care (2016)

In the research design and methods section of the article cited above, page 454, the sentences “We used data from the Swedish Childhood Diabetes Register (SCDR), Swedish National Diabetes Register (NDR), and the Swedish National Patient Register (NPR) to identify patients (probands) born in Sweden from 1964 onward with onset of type 1 diabetes before 18 years of age. Since 1 July 1977, the SCDR has recorded …
The genome sequences of Arachis duranensis and Arachis ipaensis, the diploid ancestors of cultivated peanut
Authors: David John Bertioli, Steven B Cannon, Lutz Froenicke, Guodong Huang, Andrew D Farmer, Ethalinda K S Cannon, Xin Liu, Dongying Gao, Josh Clevenger, Sudhansu Dash, Longhui Ren, Márcio C Moretzsohn, Kenta Shirasawa, Wei Huang, Bruna Vidigal, Brian Abernathy, Ye Chu, Chad E Niederhuth, Pooja Umale, Ana Cláudia G Araújo, Alexander Kozik, Kyung Do Kim, Mark D Burow, Rajeev K Varshney, Xingjun Wang, Xinyou Zhang, Noelle Barkley, Patrícia M Guimarães, Sachiko Isobe, Baozhu Guo, Boshou Liao, H Thomas Stalker, Robert J Schmitz, Brian E Scheffler, Soraya C M Leal-Bertioli, Xu Xun, Scott A Jackson, Richard Michelmore, Peggy Ozias-Akins
Journal: Nature Genetics (2016)

David Bertioli and colleagues report the genomes of Arachis duranensis and Arachis ipaensis, the diploid ancestors of cultivated peanut, Arachis hypogaea. Their analyses are a first step in understanding the evolution of the peanut's tetraploid genome. Cultivated peanut (Arachis hypogaea) is an allotetraploid with closely related subgenomes of a total size of ∼2.7 Gb. This makes the assembly of chromosomal pseudomolecules very challenging. As a foundation to understanding the genome of cultivated peanut, we report the genome sequences of its diploid ancestors (Arachis duranensis and Arachis ipaensis). We show that these genomes are similar to cultivated peanut's A and B subgenomes and use them to identify candidate disease resistance genes, to guide tetraploid transcript assemblies and to detect genetic exchange between cultivated peanut's subgenomes. On the basis of remarkably high DNA identity of the A. ipaensis genome and the B subgenome of cultivated peanut and biogeographic evidence, we conclude that A. ipaensis may be a direct descendant of the same population that contributed the B subgenome to cultivated peanut.
Disease-free survival (DFS) as surrogate end point for overall survival (OS) in adjuvant aromatase inhibitors (AIs) trials for breast cancer (BC): Meta-analysis of 10 randomized clinical trials (RCTs) exploring the magnitude of the benefit
Authors: M. Ciccarese, E. Bria, F. Cuppone, C. Nisticò, P. Carlini, I. Sperduti, V. Lorusso, E. Terzoli, F. Cognetti, D. Giannarelli
Journal: Journal of Clinical Oncology (2007)

539 Background. The issue regarding the eventual correlation of DFS with OS has not actually been explored in trials addressing the role of AIs. For this purpose, we meta-analyzed all RCTs in which patients were randomized to receive standard tamoxifen or AIs, whatever applied strategies. Methods. A literature-based meta-analysis was accomplished, and event-based relative risk ratios (RRs) with 95% confidence interval (CI) were derived. A fixed- (FEM) and a random-effect (REM) model and heterogeneity test were applied as well. Absolute benefits (AB) and the Number of patients Needed to Treat (NNT) were calculated. A linear regression model considering both each single outcome pair (5-years DFS and OS) has been adopted to explore for correlation, estimated according to Pearson, R 2 (parametric) and Spearman (non-parametric) coefficients. Results. Ten RCTs were gathered (27,653 patients); two RCTs did not report the OS result, so they were not evaluable. DFS was significantly improved with AIs, with a AB of 2.3–3.5%, which translate into 29–43 NNT. OS was significantly improved in both overall and early switch strategy, with an AB of 0.8–1.61%, which translate into 120 and 62 NNT, respectively. A strong correlation was found between DFS and OS in the overall (r=0.78, R 2 =0.60, p=0.001; Rho=0.77, p=0.001) and in the early switch strategy (r=0.83, R 2 =0.68, p=0.003; Rho=0.84, p=0.002). Although a stronger correlation was found in the upfront strategy, the low number of RCTs did not allow to reaching statistical significance. Conclusions. The strong correlation between DFS and OS in AIs adjuvant endocrine treatment for early BC underlines the choice of DFS as a surrogate end-point for OS. The predictive value of earlier DFS (3-years) estimation for overall survival deserves a further analysis. [Table: see text] No significant financial relationships to disclose.
Then and now: The effect of tyrosine kinase inhibitors on survival in patients with metastatic renal cell carcinoma in Alberta, Canada
Authors: M. A. Warren, P. M. Venner, S. A. North, D. Finch, S. Ghosh, A. Venner, C. Venner, T. Cheng
Journal: Journal of Clinical Oncology (2008)

16033 Background: Tyrosine kinase inhibitors (TKIs) improve progression free survival in both first line (sunitinib) and second line (sorafenib) treatment of metastatic renal cell carcinoma (mRCC). We performed a Retrospective Population based study to assess the impact of TKIs on overall survival (OS) in patients (pts) treated for mRCC in Alberta, Canada. Methods: 130 pts were identified who commenced either sorafenib, or sunitinib between December 2003 and June 2007 for mRCC at one of two referral cancer centres in Alberta. Survival was compared to that of an earlier cohort of 141 pts treated with Interferon α (IFN) at the same centres between May 1995 and March 2003. Data was collected enabling stratification into risk categories according to the MSKCC prognostic model. The primary endpoint was OS measured from date of commencement of TKI in the recent cohort, and IFN in the earlier cohort. The Kaplan Meier method was used to determine OS, with Cox Regression analysis used to determine hazard ratios (HR) and confidence intervals (CI). Results: Of the 130 pts treated with a TKI, 78 received treatment in the first line setting, whereas 52 received treatment after prior IFN therapy. All 141 pts from the IFN cohort received treatment in the 1st line setting. Patients treated on TKIs had an improved OS compared with the earlier IFN cohort with a HR of 0.621 (95% CI .45–.857, p=0.004). Median OS was 16.5 months and 10.2 months, respectively. There was no significant impact on OS based on whether the TKI was received after prior IFN therapy or in first line (HR .774, 95% CI .451–1.327, p=.351). Survival according to MSKCC risk groups is outlined in Table 1. Factors associated with improved survival on multivariate analysis were treatment with a TKI, time between diagnosis and treatment greater than 12 months, LDH ≤ 1.5 ULN, normal Hb, normal corr. Ca++ and Karnofsky PS ≥80%. Conclusions: TKIs improve OS compared with IFN in mRCC with significant benefits in favourable and intermediate risk groups. Risk Group No. pts TKI/IFN HR 95% CI P value Favourable 46/21 .311 .115-.84 .021 Intermediate 45/66 .559 .332-.94 .028 Poor 28/25 .814 .46-1.442 .559 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Pfizer Oncology Pfizer Oncology