tbuckley/cabot-search huggingface dataset:
Involvement of FER and FES in the Pathogenesis of Follicular Variant of Peripheral T-Cell Lymphoma
Authors: Iwona Wlodarska, Jo-Anne van der Krogt, Katrien Van Roosbroeck, Julio Finalet Ferreiro, Thomas Tousseyn, Carlos Graux, Daan Dierickx, Peter Vandenberghe, Jan Cools
Journal: Blood (2014)
Epidémie de Salmonella enteritis bongori 48:z35:- en Sicile
Authors: A Nastasi, C Mammina, L Salsa
Journal: Eurosurveillance (1999)

Salmonella bongori 48:z35:- a ete isolee pour la premiere fois en 1966 chez un lezard au Tchad et a alors ete classee comme une souche atypique sur le plan biochimique appartenant au sous-genre I de Kauffmann (1). Par la suite, d’autres souches partageant les memes proprietes biochimiques, mais se differenciant par leurs formules antigeniques ont ete identifiees et attribuees au groupe bongor du genre Salmonella (2). Plus recemment, sur la base de ses caracteristiques genetiques et biochimiques, S. bongori a ete definie comme une espece de salmonelle distincte (3).
Stereotyped Subset #4 In Chronic Lymphocytic Leukemia Is Associated With Distinct Gene and Microrna Transcriptional Profile
Authors: Francesco Maura, Laura Mosca, Giovanna Cutrona, Serena Matis, Marta Lionetti, Sonia Fabris, Massucco Carlotta, Daniele Reverberi, Massimo Gentile, Anna Grazia Recchia, Colombo Monica, Sabrina Bossio, Massimo Negrini, Pierfrancesco Tassone, Davide Rossi, Gianluca Gaidano, Francesco Di Raimondo, Fortunato Morabito, Manlio Ferrarini, Antonino Neri
Journal: Blood (2013)
Trends and In-Hospital Outcomes Associated With Adoption of the Subcutaneous Implantable Cardioverter Defibrillator in the United States
Authors: Daniel J. Friedman, Craig S. Parzynski, Paul D. Varosy, Jordan M. Prutkin, Kristen K. Patton, Ali Mithani, Andrea M. Russo, Jeptha P. Curtis, Sana M. Al-Khatib
Journal: JAMA Cardiology (2016)

<h3>Importance</h3> Trends and in-hospital outcomes associated with early adoption of the subcutaneous implantable cardioverter defibrillator (S-ICD) in the United States have not been described. <h3>Objectives</h3> To describe early use of the S-ICD in the United States and to compare in-hospital outcomes among patients undergoing S-ICD vs transvenous (TV)-ICD implantation. <h3>Design, Setting, and Participants</h3> A retrospective analysis of 393 734 ICD implants reported to the National Cardiovascular Data Registry ICD Registry, a nationally representative US ICD registry, between September 28, 2012 (US Food and Drug Administration S-ICD approval date), and March 31, 2015, was conducted. A 1:1:1 propensity-matched analysis of 5760 patients was performed to compare in-hospital outcomes among patients with S-ICD with those of patients with single-chamber (SC)–ICD and dual-chamber (DC)–ICD. <h3>Main Outcomes and Measures</h3> Analysis of trends in S-ICD adoption as a function of total ICD implants and comparison of in-hospital outcomes (death, complications, and defibrillation threshold [DFT] testing) among S-ICD and TV-ICD recipients. <h3>Results</h3> Of the 393 734 ICD implants evaluated during the study period, 3717 were S-ICDs (0.9%). A total of 109 445 (27.8%) of the patients were female; the mean (SD) age was 67.03 (13.10) years. Use of ICDs increased from 0.2% during the fourth quarter of 2012 to 1.9% during the first quarter of 2015. Compared with SC-ICD and DC-ICD recipients, those with S-ICDs were more often younger, female, black, undergoing dialysis, and had experienced prior cardiac arrest. Among 2791 patients with S-ICD who underwent DFT testing, 2588 (92.7%), 2629 (94.2%), 2635 (94.4%), and 2784 (99.7%) were successfully defibrillated (≤65, ≤70, ≤75, and ≤80 J, respectively). In the propensity-matched analysis of 5760 patients, in-hospital complication rates associated with S-ICDs (0.9%) were comparable to those of SC-ICDs (0.6%) (<i>P</i> = .27) and DC-ICD rates (1.5%) (<i>P</i> = .11). Mean (SD) length of stay after S-ICD implantation was comparable to that after SC-ICD implantation (1.1 [1.5] vs 1.0 [1.2] days;<i>P</i> = .77) and less than after DC-ICD implantation (1.1 [1.5] vs 1.2 [1.5] days;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> The use of S-ICDs is rapidly increasing in the United States. Early adoption has been associated with low complication rates and high rates of successful DFT testing despite frequent use in patients with a high number of comorbidities.
A New Prognostic Scoring System Including Transfusion Dependency and Cytogenetic Abnormalities for Patients with Chronic Myelomonocytic Leukemia.
Authors: Esperanza Such, Jose Cervera, Benet Nomdedeu, Carmen Pedro, Javier Bueno, Teresa Bernal, Felix Carbonell, Mohamed Belkaid, Leonor Senent, Francesc Sole, Elisa Luño, Teresa Vallespi, Rosa Collado, Teresa Ardanaz, Fernando Ramos, Mar Tormo, Reyes Sancho-Tello, Maria Consuelo del Cañizo, Blanca Xicoy, Victor Marco, Valle Gomez, Santiago Bonanad, Ana Valencia, Mar Mallo, Luis Benlloch, Guillermo Sanz
Journal: Blood (2009)
Autologous Cord Blood Infusion for the Treatment of Brain Injury in Children with Cerebral Palsy
Authors: Jessica Sun, Mohamad Mikati, Jesse Troy, Kathryn Gustafson, Ryan Simmons, Ricki Goldstein, Jodi Petry, Colleen McLaughlin, Barbara Waters-Pick, Laura Case, Gordon Worley, Joanne Kurtzberg
Journal: Blood (2015)
A Rapid and Robust Molecular Diagnostic Approach For Multiple Myeloma – Results From a Large Trial Cohort
Authors: Martin F. Kaiser, Dil Begum, Paula Proszek, Nasrin Dahir, David Gonzalez de Castro, Charlotte Pawlyn, Annamaria Brioli, Suvi Savola, Walter Gregory, Roger G. Owen, Graham H. Jackson, Faith E Davies, Brian A Walker, Gareth J Morgan
Journal: Blood (2013)
Insights into CYP2B6-mediated drug–drug interactions
Authors: William D. Hedrich, Hazem E. Hassan, Hongbing Wang
Journal: Acta Pharmaceutica Sinica B (2016)

Mounting evidence demonstrates that CYP2B6 plays a much larger role in human drug metabolism than was previously believed. The discovery of multiple important substrates of CYP2B6 as well as polymorphic differences has sparked increasing interest in the genetic and xenobiotic factors contributing to the expression and function of the enzyme. The expression of CYP2B6 is regulated primarily by the xenobiotic receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) in the liver. In addition to CYP2B6, these receptors also mediate the inductive expression of CYP3A4, and a number of important phase II enzymes and drug transporters. CYP2B6 has been demonstrated to play a role in the metabolism of 2%–10% of clinically used drugs including widely used antineoplastic agents cyclophosphamide and ifosfamide, anesthetics propofol and ketamine, synthetic opioids pethidine and methadone, and the antiretrovirals nevirapine and efavirenz, among others. Significant inter-individual variability in the expression and function of the human CYP2B6 gene exists and can result in altered clinical outcomes in patients receiving treatment with CYP2B6-substrate drugs. These variances arise from a number of sources including genetic polymorphism, and xenobiotic intervention. In this review, we will provide an overview of the key players in CYP2B6 expression and function and highlight recent advances made in assessing clinical ramifications of important CYP2B6-mediated drug–drug interactions.
Giant Thrombosed Intracranial Aneurysm
Authors: Yasunori Nagahama, Matthew A Howard
Journal: New England Journal of Medicine (2016)

A 79-year-old woman presented with gradual neurologic decline involving confusion, memory loss, imbalance, and incontinence. On examination, she was oriented only to self and had mild nonfluent aphasia. CT revealed a large left frontotemporal mass with areas of calcification.
Screening for Lipid Disorders in Children and Adolescents
Authors: Edward H. Livingston
Journal: JAMA (2016)

US Preventive Services Task Force; Kirsten Bibbins-Domingo, PhD, MD, MAS; David C. Grossman, MD, MPH; Susan J. Curry, PhD; Karina W. Davidson, PhD, MASc; John W. Epling Jr, MD, MSEd; Francisco A. R. García, MD, MPH; Matthew W. Gillman, MD, SM; Alex R. Kemper, MD, MPH, MS; Alex H. Krist, MD, MPH; Ann E. Kurth, PhD, RN, MSN, MPH; C. Seth Landefeld, MD; Michael LeFevre, MD, MSPH; Carol M. Mangione, MD, MSPH; Douglas K. Owens, MD, MS; William R. Phillips, MD, MPH; Maureen G. Phipps, MD, MPH; Michael P. Pignone, MD, MPH; Albert L. Siu, MD, MPH
“Adaptive pathways” to drug authorisation: adapting to industry?
Authors: Courtney Davis, Joel Lexchin, Tom Jefferson, Peter Gøtzsche, Martin McKee
Journal: BMJ (2016)

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S42 Transbronchial cryobiopsies in the diagnosis of Interstitial Lung Diseases- first UK experience: Abstract S42 Table 1
Authors: TA Mikolasch, E Borg, R Thakrar, V Holmes, HL Booth, JC Porter, N Navani
Journal: Thorax (2015)

<h3>Introduction</h3> Despite radiological advancements histology is often needed in the diagnosis of Interstitial Lung Disease (ILD). In order to obtain lung biopsies of adequate size and quality patients traditionally undergo a surgical lung biopsy associated with a mean hospital stay of 3.5 days and a complication rate of up to 28%.<sup>1</sup> We are the first UK centre to have set up a minimally invasive, day case transbronchial cryobiopsy service in the diagnosis of ILDs. <h3>Aims</h3> To establish a transbronchial cryobiopsy service for ILDs and assess complication rates and diagnostic yield. <h3>Methods</h3> Patients were selected following discussion at the Interstitial Lung Disease Multidisciplinary Team meeting. Only patients in whom significant diagnostic doubt remained after thorough clinic-radiological work up were considered. All procedures were performed with the patient self-ventilating under deep sedation with propofol using a flexible bronchoscope and 2.4 mm cryoprobe (ERBE). All but one procedure was performed under fluoroscopy guidance. All but the first two cases were performed following intubation with an uncuffed ET tube (Bronchoflex, Rusch). We introduced prophylactic IV tranexamic acid 1 g as premedication and endobronchial adrenaline routinely as part of our protocol after the first 5 cases. 1–5 samples were taken per procedure from several sub-segments of one lobe pre-selected by CT imaging. <h3>Results</h3> 14 procedures were carried out on 13 patients. 9 patients were male. Mean age 63, mean predicted TLCO 50%; mean number of biopsies 2.7; mean aggregate biopsy size 624 mm<sup>3</sup>. <i>Complications:</i> 2 pneumothoraces requiring chest drain insertion; 1 case of moderate bleeding and 1 case of severe bleeding managed with endobronchial adrenaline and suction only. All cases were performed as outpatient day cases with patients discharged home 2– 4 h after the procedure except the 2 patients requiring chest drains. <h3>Conclusions</h3> Our transbronchial cryobiopsy service is comparable in complication rates and diagnostic yield with larger case series from established centres outside the UK. Transbronchial cryobiopsy provides potential for minimally-invasive acquisition of sizeable lung biopsies. Further research is needed to establish whether transbronchial cryobiopsy should replace surgical lung biopsy in selected cases. <h3>Reference</h3> 1 Morris D, Zamvar V. The efficacy of video-assisted thoracoscopic surgery lung biopsies in patients with interstitial lung disease: a retrospective study of 66 patients.<i> J Cardiothorac Surg</i>. 2014;<b>9</b>:45
Two Superb Vaccines Against Hepatitis B in Mexican Standoff-Reply
Authors: Robert J. Gerety
Journal: JAMA (1988)

<h3>In Reply.</h3> —To clarify and extend major points in our previous letter,<sup>1</sup>both Heptavax-B and Recombivax-HB (the only hepatitis B vaccines licensed in the United States) have been well tolerated, highly immunogenic, and equally effective in preventing hepatitis B when used at their respective recommended doses (Heptavax-B, 20 μg for adults and 10 μg for children; Recombivax-HB, 10μg for adults and 5 μg for children). Although antibody titers after three-dose regimens of Heptavax-B generally have been somewhat higher than after administration of Recombivax-HB, there are no significant differences between them with respect to seroconversion rates in healthy adults or children. Similarly, while persistence of vaccine-induced antibodies seems to be directly related to peak titer after vaccination, decline in titer over time is of no concern in terms of protection against clinically significant infections.<sup>2</sup>The long incubation period of hepatitis B provides sufficient time for anamnestic antibody responses in
Induction of Cancer Testis Antigen Expression in Circulating Acute Myeloid Leukemia Blasts Following Hypomethylating Agent Monotherapy
Authors: Pragya Srivastava, Benjamin E. Paluch, Junko Matsuzaki, Smitha R. James, Golda Collmat-Lai, Nadja Blagitko-Dorfs, Laurie Ann Ford, Rafeh Naqash, Michael Luebbert, Adam R. Karpf, Michael J. Nemeth, Elizabeth A. Griffiths
Journal: Blood (2015)
Clinical Significance of a Positive Antineutrophil Cytoplasmic Antibody (ANCA) Test
Authors: Viet L. Bui, Tanaz A. Kermani
Journal: JAMA (2016)

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Higher Titer of Anti-EBV Nuclear Antigen Antibodies Might be a Marker of Poorer Prognosis in Patients with Peripheral T-Cell Lymphoma, Not Otherwise Specified
Authors: Yoshiharu Kusano, Yasuhito Terui, Kyoko Ueda, Yuko Mishima, Noriko Nishimura, Masahiro Yokoyama, Hideaki Nitta, Tadahiro Gunji, Norihito Inoue, Anna Takahasi, Kengo Takeuchi, Kiyohiko Hatake
Journal: Blood (2015)
ABBV-399, a c-Met Antibody–Drug Conjugate that Targets Both <i>MET</i>–Amplified and c-Met–Overexpressing Tumors, Irrespective of <i>MET</i> Pathway Dependence
Authors: Jieyi Wang, Mark G. Anderson, Anatol Oleksijew, Kedar S. Vaidya, Erwin R. Boghaert, Lora Tucker, Qian Zhang, Edward K. Han, Joann P. Palma, Louie Naumovski, Edward B. Reilly
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Despite the importance of the MET oncogene in many malignancies, clinical strategies targeting c-Met have benefitted only small subsets of patients with tumors driven by signaling through the c-Met pathway, thereby necessitating selection of patients with MET amplification and/or c-Met activation most likely to respond. An ADC targeting c-Met could overcome these limitations with potential as a broad-acting therapeutic. Experimental Design: ADC ABBV-399 was generated with the c-Met–targeting antibody, ABT-700. Antitumor activity was evaluated in cancer cells with overexpressed c-Met or amplified MET and in xenografts including patient-derived xenograft (PDX) models and those refractory to other c-Met inhibitors. The correlation between c-Met expression and sensitivity to ABBV-399 in tumor and normal cell lines was assessed to evaluate the risk of on-target toxicity. Results: A threshold level of c-Met expressed by sensitive tumor but not normal cells is required for significant ABBV-399–mediated killing of tumor cells. Activity extends to c-Met or amplified MET cell line and PDX models where significant tumor growth inhibition and regressions are observed. ABBV-399 inhibits growth of xenograft tumors refractory to other c-Met inhibitors and provides significant therapeutic benefit in combination with standard-of-care chemotherapy. Conclusions: ABBV-399 represents a novel therapeutic strategy to deliver a potent cytotoxin to c-Met–overexpressing tumor cells enabling cell killing regardless of reliance on MET signaling. ABBV-399 has progressed to a phase I study where it has been well tolerated and has produced objective responses in c-Met–expressing non–small cell lung cancer (NSCLC) patients. Clin Cancer Res; 23(4); 992–1000. ©2016 AACR.
The initial report of RTOG 0436: A phase III trial evaluating the addition of cetuximab to paclitaxel, cisplatin, and radiation for patients with esophageal cancer treated without surgery.
Authors: Mohan Suntharalingam, Kathryn Winter, David H. Ilson, Adam Dicker, Lisa A. Kachnic, Andre A. Konski, Bapsi Chakravarthy, David K. Gaffney, Harish V. Thakrar, Margit Naomi Horiba, Melvin Deutsch, Vivek Kavadi, Adam Raben, Kevin S. Roof, Gregory M. M. Videtic, Jondavid Pollock, Howard Safran, Christopher H. Crane
Journal: Journal of Clinical Oncology (2014)

LBA6 Background: RTOG 0436 is a randomized Ph III trial designed to evaluate the benefit of cetuximab added to the concurrent chemoradiation for patients undergoing non-operative management of esophageal carcinoma. Methods: Pts with biopsy-proven squamous cell or adenocarcinoma of the esophagus (T1N1M0; T2-4 AnyN M0; Any T/N M1a) were randomized to weekly concurrent cisplatin (50 mg/m2), paclitaxel (25 mg/m2), and daily radiation 50.4 Gy/1.8 Gy fractions ± weekly cetuximab (400 mg/m2 day 1 then weekly 250 mg/m2). Patients were stratified by histology, tumor size (&lt; 5 cm vs &gt; 5cm), and the status of celiac lymph nodal involvement. Overall survival (OS) was the primary endpoint, with a planned accrual of 420 pts to detect an increase in 2-year OS from 41% to 53%; 80% power and 1-sided 0.025 alpha. An interim analysis of cCR was planned for the first 150 of each histology. Results: The study accrued 344 pts from 2008-2013 and 328 were eligible. Based on interim analyses, the study stopped accruing adeno pts in 5/2012 and SCC pts in 1/2013. Pts were well matched for pretreatment characteristics: 80% with T3/4 disease, 66% N1, and 19% with celiac nodal involvement. Incidence of grade 3/4/5 treatment (tx) related AEs was 45%, 22%, 4% in Arm 1 (cetuximab) and 49%, 17%, 1% in Arm 2 (no cetuximab). A cCR rate of 56% was observed in Arm 1 vs 59% in Arm 2 (p=0.72). No differences were seen in cCR between tx arms for either histology. The 12 and 24 mo OS rates for cCR pts were 79% and 58% vs 53% and 30% for those with residual disease (p&lt;0.0001). Median follow-up for all pts is 15.4 mos. The 12 and 24 mo OS (95% CI) for Arm 1 is 64% (56%, 71%) and 44% (36%, 52%) vs 65% (57%, 72%) and 42% (34%, 50%) for Arm 2 (p=0.70). Adeno pts (n=203) had a 12 and 24 mo OS of 65% and 43% for Arm 1 vs 64% and 41% for Arm 2 (p=0.37). The 12 and 24 mo OS for the 125 SCC pts was 62% and 46% for Arm 1 vs 67% and 43% for Arm 2 (p=0.97). Conclusions: The addition of cetuximab to concurrent chemoradiation did not improve OS. There were no differences in cCR rates by tx arm. These Ph III results point to little benefit for current EGFR targeted agents in the tx of esophageal cancer. Supported by RTOG CA21661 and CCOP CA3742 NCI grants and Bristol Myers Squibb. Clinical trial information: NCT00655876.
Phase II trial of bevacizumab and pemetrexed for recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer.
Authors: Andrea R. Hagemann, Israel Zighelboim, Akiva Pesach Novetsky, Feng Gao, L. Stewart Massad, Premal H. Thaker, Matthew A. Powell, David Gardner Mutch, Jason D. Wright
Journal: Journal of Clinical Oncology (2012)

5013 Background: This phase II clinical trial evaluated the efficacy and safety of the combination of bevacizumab, a VEGF inhibitor, and pemetrexed, a multi-targeted antifolate agent inhibiting thymidylate synthase, for recurrent or persistent epithelial ovarian, fallopian tube (FT) or primary peritoneal (PP) cancer. Methods: Patients with measurable recurrent/persistent epithelial ovarian, FT or PP cancer after at least one prior platinum- and taxane-containing regimen were eligible. Patients might have received &lt; 2 prior cytotoxic chemotherapy regimens but no prior bevacizumab. Pemetrexed 500 mg/m 2 IV and bevacizumab 15 mg/kg IV were given every 3 weeks until progression, unacceptable adverse effects, or patient/physician choice. 32 patients were needed to have 90% power to detect the primary endpoint of 6-month PFS ≥ 40% with a two-sided 0.05 significance. Secondary endpoints included toxicity and response by RECIST and CA-125 criteria. Results: Thirty-four patients received a median of 7 treatment cycles (range, 2-26). Twenty-eight patients (82%, 95% CI: 66-92) were platinum-sensitive. Median follow-up was 17.1 months (range, 2.7-31.2). The 6-month PFS was 58.2% (95%CI: 40-73) for all patients and 50% (19-81) for platinum-resistant patients. Objective response rates by RECIST criteria included (%; 95%CI): 0 CR, 14 PR (41%; 25-59), 18 SD (53%; 35-70) and 2 PD (6%; 1-20). Of 27 patients evaluable by CA-125, levels declined ≥50% in 17 (62%; 44-79), and ≥75% in 8 (30%; 16-49). 12-month OS was 88% (95%CI: 71-95) and median PFS was 7.8 months (95%CI: 4.7-10.7). Of the 34 patients, grade 3-4 hematologic toxicities occurred in 53% (neutropenia 50%, leukopenia 26%, thrombocytopenia 12%, anemia 9%). Other grade 3-4 toxicities included metabolic (29%), constitutional (18%), pain (18%) and gastrointestinal (15%). No bowel perforations occurred. Conclusions: Combined bevacizumab/pemetrexed is well tolerated and highly active for the treatment of recurrent ovarian cancer. The dose and schedule tested here warrant further investigation in phase III trials.