tbuckley/cabot-search huggingface dataset:
A phase I study of MLN0128 and bevacizumab in patients with recurrent glioblastoma and other solid tumors.
Authors: Lakshmi Nayak, John L. Hays, Alona Muzikansky, Sarah C. Gaffey, Khanh Tu Do, Vinay K. Puduvalli, Eudocia Quant Lee, Mikael L. Rinne, Andrew David Norden, Rameen Beroukhim, Patrick Y. Wen, L. Austin Doyle, Helen X. Chen, Geoffrey Shapiro, David A. Reardon
Journal: Journal of Clinical Oncology (2016)

2013 Background: The P13K/Akt/mTOR signaling axis plays a central role in cell growth and survival in a variety of cancers. MLN0128 is an oral TORC1/2 inhibitor. Bevacizumab is a monoclonal antibody targeting VEGF with activity in some cancers, including glioblastoma (GBM). Methods: This ongoing Cancer Therapeutic Evaluation Program (CTEP)-sponsored phase I trial uses a 3+3 dose escalation design to determine the maximum tolerated dose (MTD/recommended phase 2 dose (RP2D) of MLN0128 when administered daily with bevacizumab (10 mg/kg every 2 weeks) and includes a dose expansion at the MTD/RP2D for recurrent GBM (n=10) and recurrent endometrial/ovarian cancer (n=30) patients (pts). Eligibility includes histologically confirmed recurrent GBM or other advanced solid tumors, >18 years old, KPS> 60, adequate bone marrow and organ function. The starting dose of MLN0128 was 3 mg daily. Results: Thirty-six pts have enrolled (12 in dose escalation and 24 in dose expansion). The median age and KPS were 56 (range: 25-74) and 80 (range 70-100), and 25 were women. Histologic diagnosis included GBM (n=16), ovarian (n=14) and endometrial (n=6) cancer. Three MLN0128 dose levels were evaluated including 3,4 and 5 mg daily. Only 1 dose limiting toxicity (DLT) occurred (grade 3 fatigue at the 5 mg dose level). There were 31 additional related grade 3 events and 1 grade 4 event. Most common toxicities were rash, hypercholesterolemia, gastrointestinal symptoms, lymphopenia and fatigue. Median number of completed cycles was 2 (range, 1-17). Sixteen pts came off for disease progression, 8 withdrew, 2 patient/physician's decision, 3 toxicity, 1 other; 6 remain on treatment. Best response to treatment among GBM pts was complete response (n=1), partial response (PR, n=3), stable disease (SD, n=6). Three ovarian cancer pts achieved PR and 8 SD, while 2 endometrial cancer pts achieved SD. Conclusions: The RP2D of daily MLN0128 is 5mg when combined with bevacizumab. The dose expansion phase continues to enroll. Clinical trial information: NCT02142803.
Fish Oils and Bleeding—Where Is the Evidence?
Authors: William S. Harris
Journal: JAMA Internal Medicine (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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal
Dichotomy in pulmonary graft-<i>versus</i>-host disease evident among allogeneic stem-cell transplant recipients undergoing lung transplantation
Authors: Mark Greer, Gerdt C. Riise, Lennart Hansson, Michael Perch, Pekka Hämmäinen, Antoine Roux, Sandrine Hirschi, Elodie Lhuillier, Martine Reynaud-Gaubert, Francois Philit, Johanna Claustre, Marc Stern, Jens Gottlieb, Are M. Holm
Journal: European Respiratory Journal (2016)

Allogeneic haematopoietic stem-cell transplantation (HSCT) has become a life-saving treatment option for numerous benign and malignant diseases, with more than 14 500 procedures being performed annually in Europe alone [1]. Late-onset noninfectious pulmonary complications (NIPCs) have emerged as the main hurdle to long-term survival, affecting up to 26% of HSCT recipients and conferring 2- and 5-year survival rates of 44% and 13%, respectively [2, 3]. Interstitial lung disease is a common, largely unrecognised feature of pulmonary GvHD after stem cell transplant <http://ow.ly/DWP4307mO3i>
Identification of a predictive biomarker for patritumab (P), an anti-HER3 monoclonal antibody, in advanced NSCLC.
Authors: Jeanne Mendell-Harary, Jens Ruhe, Matthias Schneider, Wenqin Feng, Daniel J. Freeman, Kenji Nakamaru, Xiaoping Jin, Zenta Tsuchihashi, Joachim Von Pawel, Catherine Copigneaux, Robert A. Beckman
Journal: Journal of Clinical Oncology (2014)

e19016 Background: HER3, an ErbB receptor with 6 docking sites for PI3K, is implicated in resistance to cancer treatment. P is a fully human mAb specific to HER3. Heregulin (HRG) is the ligand for HER3. In preclinical studies, HRG expression predicted sensitivity to P (Schneider et al., Yonesaka et al. ASCO 2014). P, in combination with erlotinib vs. erlotinib alone, was assessed in a randomized Ph2 study in advanced NSCLC (HERALD, von Pawel et al., ASCO 2014). Methods: Based on preclinical data after HERALD study initiation, HRG was identified as the primary predictive biomarker hypothesis for P clinical benefit prior to unblinding (prospective), albeit after subject enrollment (retrospective). Various methods were explored to measure HRG protein or mRNA in FFPE tissue, and a validated quantitative PCR assay for HRG mRNA measurment was developed. The median delta threshold cycle ΔCt value was specified as the cut-off for HRG high/low, prior to study unblinding. Other biomarkers were also measured, but not specified as the primary biomarker hypothesis. Results: Of the 215 FFPE samples collected in HERALD, 102 provided sufficient tumor sample for HRG mRNA measurement. Subjects in HERALD showed PFS improvement for P combined with erlotinib vs. erlotinib alone in the HRG high group (< ΔCt 3.9), but no PFS improvement in HRG low group, suggesting HRG is predictive for P benefit (von Pawel, ASCO 2014). A continuous relationship (Table) was observed between increased HRG mRNA expression (lower ΔCt) and greater clinical benefit in terms of PFS. Conclusions: Avalidated assay method was established to measure HRG mRNA in FFPE. Utilizing a prospective-retrospective approach in a Ph2 study, HRG mRNA appears to be a predictive biomarker for P, confirming preclinical data. The distribution of HRG mRNA in NSCLC will be further characterized and the cut-off refined to optimally define the recommended patient population that will benefit from P. Clinical trial information: NCT01211483. Cutoff for HRG high (ΔCt) N (#events) HR (pooled dose vs. Pbo) for PFS in HRG high group Log-rank p value 2.7 (1st quartile) 24 (18) 0.180 0.0039 3.0 33 (24) 0.177 0.0009 3.5 46 (36) 0.283 0.0009 3.9 (median) 51 (41) 0.324 0.0013 4.5 65 (50) 0.490 0.0190 5.0 (3rd quartile) 76 (58) 0.561 0.0429
Letter from Willey and Biviano Regarding Article, “Ablation Versus Amiodarone for Treatment of Persistent Atrial Fibrillation in Patients With Congestive Heart Failure and an Implanted Device: Results From the AATAC Multicenter Randomized Trial”
Authors: Joshua Z. Willey, Angelo Biviano
Journal: Circulation (2016)

We read the results of the AATAC trial (Ablation vs Amiodarone for Treatment of Persistent Atrial Fibrillation in Patients with Congestive Heart Failure and an Implanted ICD/CRTD) 1 as a stroke neurologist (Dr Willey) and cardiac electrophysiologist (Dr Biviano) with interest.The primary outcomes concerned improvements in heart failure-related symptoms, and a particular strength was having the presence of an atrial sensor to diagnose persistent atrial fibrillation.There was no mention of neurologic outcomes in the trial, however, and it may be tempting to stop anticoagulation in those patients who achieve freedom from atrial fibrillation depending on stroke risk and patient preference.Counter to current guidelines, 2 patients or providers may ask if ablation is available as an option to come off anticoagulation, particularly in instances where there may be a risk of intracerebral hemorrhage such as cerebral amyloid angiopathy.Although previous studies have demonstrated a low risk of stroke after atrial fibrillation ablation, 3,4 these studies may be limited by nonrandom allocation to stopping anticoagulation.Therefore, with the risk of stroke in mind, is there any information available on proportions treated with anticoagulation before and after the procedure?How many patients had ischemic stroke after the ablation procedure, and was there any association with stopping anticoagulation?Although difficult to gauge, how frequently was atrial fibrillation of <30 s detected, and, if so, was there any association with stopping anticoagulation or stroke risk? DISCLOSURESNone.
Screening strategies for lead poisoning
Authors: D. S. Blumenthal
Journal: JAMA (1993)

To the Editor.  —Gellert et al1declare that pediatric lead poisoning is not a major problem affecting Orange County  because only 7.25% of a sample of 5115 such children (aged 12 to 72 months) had blood lead levels of 0.50 μmol/L (10 μg/dL) or higher, and only 0.12% had blood lead levels higher than 1.20 μmol/L (25 μg/dL). They then suggest that in Orange County and other locales with such low prevalence rates universal screening for lead could be replaced by testing only those children with a history of lead exposure or a history of risk factors for lead poisoning. Gellert et al present no information on the percentage of children with elevated blood lead levels in their sample that would have been identified by such a history; experience and older literature2suggest that history is a poor predictor of children with elevated blood lead levels. In
P1064 : Association between PNPLA3 I148M polymorphism and Nonalcoholic Fatty Liver Disease (NAFLD) in the Indian Continent
Authors: D. Rangegowda, S. Sharma, K.N. Chandan Kumar, R. Maiwal, C. Vashista, M.K. Sharma, V. Bhatia, A.S. Bhadoria, A. Rastogi, S. Sarin
Journal: Journal of Hepatology (2015)
Carfilzomib (CFZ), a Novel Proteasome Inhibitor for Relapsed or Refractory Multiple Myeloma, Is Associated with Minimal Peripheral Neuropathic Effects.
Authors: Ravi Vij, Luhua Wang, Robert Z Orlowski, A. Keith Stewart, Sundar Jagannath, Sagar Lonial, Suzanne Trudel, Andrzej J Jakubowiak, Andrew Belch, Melissa Alsina, Nizar J Bahlis, Mai H. Le, Scott Cruickshank, Mark K Bennett, Susan Molineaux, Michael Kauffman, David Siegel
Journal: Blood (2009)
Nomenclature in Translational Research
Authors: Kevin Fiscella
Journal: JAMA (2008)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Characterizing release mechanisms of leuprolide acetate-loaded PLGA microspheres for IVIVC development I: In vitro evaluation
Authors: Keiji Hirota, Amy C. Doty, Rose Ackermann, Jia Zhou, Karl F. Olsen, Meihua R. Feng, Yan Wang, Stephanie Choi, Wen Qu, Anna S. Schwendeman, Steven P. Schwendeman
Journal: Journal of Controlled Release (2016)
Measurement properties of quality-of-life measurement instruments for infants, children and adolescents with eczema: a systematic review
Authors: D. Heinl, C.A.C. Prinsen, T. Sach, A.M. Drucker, R. Ofenloch, C. Flohr, C. Apfelbacher
Journal: British Journal of Dermatology (2016)

Quality of life (QoL) is one of the core outcome domains identified by the Harmonising Outcome Measures for Eczema (HOME) initiative to be assessed in every eczema trial. There is uncertainty about the most appropriate QoL instrument to measure this domain in infants, children and adolescents. To systematically evaluate the measurement properties of existing measurement instruments developed and/or validated for the measurement of QoL in infants, children and adolescents with eczema. A systematic literature search in PubMed and Embase, complemented by a thorough hand search of reference lists, retrieved studies on measurement properties of eczema QoL instruments for infants, children and adolescents. For all eligible studies, we judged the adequacy of the measurement properties and the methodological study quality with the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. Results from different studies were summarized in a best-evidence synthesis and formed the basis to assign four degrees of recommendation. Seventeen articles, three of which were found by hand search, were included. These 17 articles reported on 24 instruments. No instrument can be recommended for use in all eczema trials because none fulfilled all required adequacy criteria. With adequate internal consistency, reliability and hypothesis testing, the U.S. version of the Childhood Atopic Dermatitis Impact Scale (CADIS), a proxy-reported instrument, has the potential to be recommended depending on the results of further validation studies. All other instruments, including all self-reported ones, lacked significant validation data. Currently, no QoL instrument for infants, children and adolescents with eczema can be highly recommended. Future validation research should primarily focus on the CADIS, but also attempt to broaden the evidence base for the validity of self-reported instruments.
Massive rearrangements of cellular MicroRNA signatures are key drivers of hepatocyte dedifferentiation
Authors: Volker M. Lauschke, Sabine U. Vorrink, Sabrina M.L. Moro, Fatemah Rezayee, Åsa Nordling, Delilah F.G. Hendriks, Catherine C. Bell, Rowena Sison‐Young, B. Kevin Park, Christopher E. Goldring, Ewa Ellis, Inger Johansson, Souren Mkrtchian, Tommy B. Andersson, Magnus Ingelman‐Sundberg
Journal: Hepatology (2016)

Hepatocytes are dynamic cells that, upon injury, can alternate between nondividing differentiated and dedifferentiated proliferating states in vivo . However, in two‐dimensional cultures, primary human hepatocytes (PHHs) rapidly dedifferentiate, resulting in loss of hepatic functions that significantly limits their usefulness as an in vitro model of liver biology, liver diseases, as well as drug metabolism and toxicity. Thus, understanding the underlying mechanisms and stalling of the dedifferentiation process would be highly beneficial to establish more‐accurate and relevant long‐term in vitro hepatocyte models. Here, we present comprehensive analyses of whole proteome and transcriptome dynamics during the initiation of dedifferentiation during the first 24 hours of culture. We report that early major rearrangements of the noncoding transcriptome, hallmarked by increased expression of small nucleolar RNAs, long noncoding RNAs, microRNAs (miRNAs), and ribosomal genes, precede most changes in coding genes during dedifferentiation of PHHs, and we speculated that these modulations could drive the hepatic dedifferentiation process. To functionally test this hypothesis, we globally inhibited the miRNA machinery using two established chemically distinct compounds, acriflavine and poly‐ l ‐lysine. These inhibition experiments resulted in a significantly impaired miRNA response and, most important, in a pronounced reduction in the down‐regulation of hepatic genes with importance for liver function. Thus, we provide strong evidence for the importance of noncoding RNAs, in particular, miRNAs, in hepatic dedifferentiation, which can aid the development of more‐efficient differentiation protocols for stem‐cell‐derived hepatocytes and broaden our understanding of the dynamic properties of hepatocytes with respect to liver regeneration. Conclusion: miRNAs are important drivers of hepatic dedifferentiation, and our results provide valuable information regarding the mechanisms behind liver regeneration and possibilities to inhibit dedifferentiation in vitro . (H epatology 2016;64:1743‐1756)
Multiple Mutations of CEBPA Contribute to Leukemogenesis: The Donor Origin of Leukemia Relapse After Allogeneic Hematopoietic Cell Transplantation.
Authors: Haowen Xiao, Jimin Shi, Yi Luo, Yamin Tan, Jingsong He, Wanzhuo Xie, Weiyan Zheng, Gaofeng Zheng, Xiaoyan Han, Lifei Zhang, Yingjia Wang, Lizhen Liu, Kangni Wu, Xiaohong Yu, Zhen Cai, Maofang Lin, Xiujin Ye, He Huang
Journal: Blood (2010)
Functional outcomes after cisplatin (C)-based concurrent chemoradiation (CCRT) in patients (pts) with human papillomavirus (HPV)-related squamous cell carcinoma of the orophrarynx (SCCOP).
Authors: C. P. Rodriguez, D. J. Adelstein, L. A. Rybicki, J. P. Saxton, J. Scharpf, B. Burkey, B. J. Wood, P. D. Knott, A. P. Hoschar, D. I. Ives
Journal: Journal of Clinical Oncology (2010)

5579 Background: Late treatment-related toxicity and organ dysfunction are well-recognized after CCRT for locally advanced head and neck squamous cell cancer (LAHNSCC). Whether these outcomes are different in the subset of pts with HPV-related SCCOP is unknown and explored in this single-institution retrospective study. Methods: Pts with insitu hybridization demonstrated high-risk HPV+, stage III-IVB SCCOP treated with CCRT at the Cleveland Clinic were identified. Treatment consisted of radiation therapy (RT) administered once or twice daily to a total dose of 66-72 Gy, concurrent with either C (100 mg/m2) q3 weeks × 3, or with 96 hour infusions of C (20 mg/m2/day) and 5-fluorouracil (1,000mg/m2/day) given during the first and fourth weeks of RT. Feeding tube dependence (FTD), narcotic use, dietary limitation, trismus, and neck range of motion (ROM), were assessed at 3, 6, 12, and 24 months (m) after initiation of CCRT and retrospectively compared to a historical cohort of HPV-unknown, CCRT treated LAHNSCC patients using Fisher's exact test. Results: Between 1/06 and 7/09, 47 pts with HPV-related SCCOP were identified and treated with CCRT. The median age was 56 (range 42-69) years; 42 (89%) were male, and 45 (96%) were Caucasian. Four (9%) pts had stage III, 27( 58%) stage IVA, and 16 (34%) stage IVB disease. There were 15 (32%) never, 24 (51%) former, and 8 (17%) current smokers. Twenty (43%) received C alone, and RT was delivered once daily in 35 (74%). With a median follow-up of 15 (range 4-42) m, the 2-year projected survival is 98%. Late toxicity is detailed in the Table. Compared to our historical cohort, pts with HPV-related SCCOP had significantly lower rates of FTD at 3 m (66% vs. 4% p<0.001) and 6 m (31% vs. 0, p<0.001) and less dietary limitation at 3 m (76% vs. 29%, p<0.001) and 6 m (45% vs. 19% p=0.003). Conclusions: This retrospective review suggests the possibility that late toxicity and organ dysfunction is less frequent in pts with HPV-related SCCOP treated with C-based CCRT. Late toxicity 3 m 6 m 12 m 24 m FTD 4% 0 0 0 Narcotic use 40% 7% 0 0 Dietary limitation 29% 19% 6% 9% Trismus 11% 15% 19% 18% Impaired neck ROM 2% 5% 13% 20% Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, sanofi-aventis
P121 Characteristics of COPD patients with and without maintenance treatment at baseline, by GOLD stage: TONADO: Abstract P121 Table 1
Authors: S Korn, R Abrahams, L Grönke, L Korducki, VC Amatto, R Buhl
Journal: Thorax (2015)

<h3>Rationale</h3> The efficacy and safety of the once-daily combination of tiotropium (T), a long-acting muscarinic antagonist (LAMA), and olodaterol (O), a long-acting β<sub>2</sub>-agonist (LABA), for the treatment of chronic obstructive pulmonary disease (COPD) has been established. We investigated whether there was a difference in the characteristics of COPD patients with and without baseline maintenance treatment. <h3>Methods</h3> Two replicate, randomised, 52-week, double-blind, parallel-group, Phase III trials (NCT01431274; NCT01431287; n = 5162) assessed the efficacy and safety of once-daily treatment with T+O (2.5/5 μg; 5/5 μg; Respimat® inhaler) compared to the individual components. Baseline characteristics of COPD patients within Global initiative for chronic Obstructive Lung Disease (GOLD) subgroups 2 and 3/4, with/without maintenance treatment (prior LABA, LAMA or both at baseline), are presented, based on data from the pooled set. <h3>Results</h3> Most patients received baseline maintenance treatment (3037 vs 2121) and of those, there was a greater proportion of GOLD 3/4 compared to GOLD 2 patients (52.58% vs 47.42%, respectively). An opposite trend was observed in patients not receiving maintenance treatment (GOLD 3/4, 45.87% vs GOLD 2, 54.13%). The proportion of current smokers was lower in GOLD 3/4 than GOLD 2 patients, as expected (Table); nevertheless, irrespective of GOLD stage, there was a greater proportion of smokers without maintenance treatment than with maintenance treatment (42.81% vs 32.86%, respectively). As expected, pulmonary function was reduced in GOLD 3/4 compared to GOLD 2 patients, although it appeared comparable between patients with and without maintenance treatment. Of the patients with maintenance treatment, a considerably greater proportion received inhaled steroids compared to those without prior LAMA/LABA treatment (69.67% vs 15.51%, respectively). Furthermore, a smaller proportion of patients without prior LAMA/LABA treatment received short-acting β-adrenergics compared to those with maintenance treatment (Table 1). Of the GOLD 3/4 patients without baseline maintenance treatment, 43.4% were not receiving any other pulmonary medication. <h3>Conclusions</h3> A high proportion of GOLD 3/4 patients not receiving maintenance treatment were not receiving any other pulmonary medication. One could hypothesise that these patients had either been diagnosed recently or that they were not treated according to current COPD guidelines.
Haploidentical Second Allogeneic Hematopoietic Stem Cell Transplantation for the Treatment of Acute Leukemia Relapse after First Allo-HSCT: A Retrospective Registry Analysis of 60 Patients on Behalf of the German Cooperative Transplant Group
Authors: Maximilian Christopeit, Johanna Tischer, Martin Bornhäuser, Lutz Uharek, Christian Pfrepper, Gerhard Behre, Dietger Niederwieser, Nicolaus Kröger, Wolf Rösler, Stefan A. Klein, Dietrich Beelen, Andreas Hausmann, Wolfgang Bethge, Christoph Schmid
Journal: Blood (2014)