tbuckley/cabot-search huggingface dataset:
Abstract P228: MicroRNA Expression in Hypertension and Left Ventricular Hypertrophy in Rat
Authors: David Kain, Chana Yagil, Nathalie Landa-Rouben, Jasmine Jacob-Hirsch, Chen Dor, Yoram Yagil, Jonathan Leor
Journal: Circulation Research (2011)

Background: Heart injury and stress can cause a hypertrophic growth response in cardiac myocytes, which is characterized by an increase in cell size, enhanced protein synthesis, and activation of fetal genes, which can lead to heart failure (HF) and death. Given the emerging roles of microRNAs (miRNAs) in modulation of cellular phenotypes, we aimed to investigate miRNAs that are regulated during hypertension, left ventricular hypertrophy (LVH) and HF by using a rat model. Methods and Results: Male salt-sensitive (SBH/y) and salt-resistant (SBN/y) Sabra rats were obtained from the Israeli Rat Genome Center. Animals were salt-loaded with deoxycorticosterone-acetate (75 mg DOCA pellet s.c.) and 1% NaCl in drinking water for 16 weeks. Systolic blood pressure was determined by the tail-cuff method. Cardiac images were obtained using cardiac MRI using a specific small animal imaging protocol. Rats were sacrificed at different time points. miRNA expression was studied in the left ventricle using GeneChip miRNA Array (affymetrix). Expression of miRNAs related to cardiac hypertrophy or cell proliferation, including miR-132, miR-212, miR-29, miR-31and miR-205, increased more than 1.5 fold in salt-loaded SBH/y compared with salt-loaded SBN/y. In contrast, expression of MiR-182, miR-17-3p and miR-130b, known to be down-regulated in heart disease, diminished more than -1.5 fold in salt-loaded SBH/y compared with salt-loaded SBN/y. Conclusions: In animal model of salt-sensitive hypertension and LVH, up- and down-regulation of distinct miRNAs in the heart suggest novel therapeutic targets to prevent and reverse LVH and HF.
Trial of Tocilizumab in Giant-Cell Arteritis
Authors: John H. Stone, Katie Tuckwell, Sophie Dimonaco, Micki Klearman, Martin Aringer, Daniel Blockmans, Elisabeth Brouwer, Maria C. Cid, Bhaskar Dasgupta, Juergen Rech, Carlo Salvarani, Georg Schett, Hendrik Schulze-Koops, Robert Spiera, Sebastian H. Unizony, Neil Collinson
Journal: New England Journal of Medicine (2017)

Giant-cell arteritis commonly relapses when glucocorticoids are tapered, and the prolonged use of glucocorticoids is associated with side effects. The effect of the interleukin-6 receptor alpha inhibitor tocilizumab on the rates of relapse during glucocorticoid tapering was studied in patients with giant-cell arteritis.In this 1-year trial, we randomly assigned 251 patients, in a 2:1:1:1 ratio, to receive subcutaneous tocilizumab (at a dose of 162 mg) weekly or every other week, combined with a 26-week prednisone taper, or placebo combined with a prednisone taper over a period of either 26 weeks or 52 weeks. The primary outcome was the rate of sustained glucocorticoid-free remission at week 52 in each tocilizumab group as compared with the rate in the placebo group that underwent the 26-week prednisone taper. The key secondary outcome was the rate of remission in each tocilizumab group as compared with the placebo group that underwent the 52-week prednisone taper. Dosing of prednisone and safety were also assessed.Sustained remission at week 52 occurred in 56% of the patients treated with tocilizumab weekly and in 53% of those treated with tocilizumab every other week, as compared with 14% of those in the placebo group that underwent the 26-week prednisone taper and 18% of those in the placebo group that underwent the 52-week prednisone taper (P<0.001 for the comparisons of either active treatment with placebo). The cumulative median prednisone dose over the 52-week period was 1862 mg in each tocilizumab group, as compared with 3296 mg in the placebo group that underwent the 26-week taper (P<0.001 for both comparisons) and 3818 mg in the placebo group that underwent the 52-week taper (P<0.001 for both comparisons). Serious adverse events occurred in 15% of the patients in the group that received tocilizumab weekly, 14% of those in the group that received tocilizumab every other week, 22% of those in the placebo group that underwent the 26-week taper, and 25% of those in the placebo group that underwent the 52-week taper. Anterior ischemic optic neuropathy developed in one patient in the group that received tocilizumab every other week.Tocilizumab, received weekly or every other week, combined with a 26-week prednisone taper was superior to either 26-week or 52-week prednisone tapering plus placebo with regard to sustained glucocorticoid-free remission in patients with giant-cell arteritis. Longer follow-up is necessary to determine the durability of remission and safety of tocilizumab. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT01791153 .).
The Addition of Rituximab Eliminates the Negative Prognostic Impact of PMBCL Compared to DLBCL in Young Patients with CD20-Positive Aggressive Lymphomas Receiving a CHOP-Like Chemotherapy: Results of a Subgroup Analysis of the Mabthera International Trial Group (MInT) Study
Authors: Marek Trneny, Michael Rieger, Anders Osterborg, Ruth Pettengel, Darrell J White, Devinder Gill, Jan Walewski, Evelyn Kuhnt, Markus Loeffler, Michael Pfreundschuh, Anthony D. Ho
Journal: Blood (2008)
Enhanced Prophylaxis plus Antiretroviral Therapy for Advanced HIV Infection in Africa
Authors: James Hakim, Victor Musiime, Alex J. Szubert, Jane Mallewa, Abraham Siika, Clara Agutu, Simon Walker, Sarah L. Pett, Mutsa Bwakura-Dangarembizi, Abbas Lugemwa, Symon Kaunda, Mercy Karoney, Godfrey Musoro, Sheila Kabahenda, Kusum Nathoo, Kathryn Maitland, Anna Griffiths, Margaret J. Thomason, Cissy Kityo, Peter Mugyenyi, Andrew J. Prendergast, A. Sarah Walker, Diana M. Gibb
Journal: New England Journal of Medicine (2017)

In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%.
A feasibility study on hepatic arterial infusion (HAI) of oxaliplatin followed by I-folinic acid modulated continuous HAI of 5-fluorouracil as second line chemotherapy for stage IV colorectal cancer limited to the liver
Authors: Bart Neyns, Yves Van Nieuwenhove, Christel Fontaine, Joanna Vermeij, Erica Sermijn, Dennis Schallier, Johan De Mey, Frederik Vandenbroucke, Georges Delvaux, Jacques De Greve
Journal: Annals of Oncology (2004)
Abstract P127: Carnitine Palmitoyltransferase 1b Deficiency Leads to Exacerbated Cardiac Dysfunction and Hypertrophy in Mice Subjected to Pressure Overload
Authors: Lan He, Teayoun Kim, Jian Liu, Peiyong Wang, Philip A Wood, Qinglin Yang
Journal: Circulation Research (2011)

Carnitine palmitoyltransferase 1 (CPT1) is a primary rate-limiting enzyme that controls the entry of long-chain fatty acids into the mitochondrial matrix. CPT1b is the predominant isoform in the heart essential for myocardial fatty acid oxidation (FAO). Inhibition of myocardial FAO by specific CPT1 inhibitors has been proposed to be cardioprotective, but with mixed results from animal and human studies. To gain more specific insights, the present study investigates the effect of CPT1b deficiency in mice subjected to transverse aorta constriction (TAC)-induced pressure-overload. Because homozygous knockout of CPT1b causes embryonic lethality, we used the overtly normal heterozygous CPT1b knockout (CPT1b+/−) mice and their wild type (WT) littermates for the study. Under a severe pressure-overload condition, CPT1b+/− hearts showed substantially increased mortality compared with WT hearts. Under a milder pressure-overload condition, CPT1b+/− mice showed more pronounced cardiac hypertrophy than WT mice. Echocardiographic measurement revealed greater increases of posterior wall thickness at diastole, left ventricular (LV) internal dimension at systole and LV mass in CPT1b+/− than in WT mice. Stroke volume, ejection fraction and fraction shorting were also further decreased in CPT1b+/− mice. Based on assessments of heart-weight to body-weight ratio, molecular markers of cardiac hypertrophy, the cross-sectional area of cardiomyocytes, fibrosis and cardiomyocyte apoptosis, cardiac pathological hypertrophy was more pronounce in CPT1b+/− than in WT mice. Transmission electron microscope assessment revealed a reduced mitochondrial volume in CPT1b+/− compared with WT hearts after TAC. CPT1b+/− heart sections exhibited dramatic myocardial lipid accumulation with numerous lipid droplets. Moreover, CPT1b+/− hearts exhibited substantially elevated triglycerides and ceramide contents compared with WT hearts. Therefore, we conclude that CPT1b deficiency is detrimental to the heart under the pressure-overload condition with exacerbated cardiac dysfunction and progressive development of pathological hypertrophy due to lipotoxicity, thus cautious should be taken in evaluating CPT1b as a therapeutic target for heart disease.
The epidemiology of metaplastic breast cancer: A review of 2,500 cases from the national cancer database.
Authors: Brittany Morgan Campbell, Samantha Marie Thomas, Cecilia Tuongquang Ong, Rachel Adams Greenup, Jennifer Kay Plichta, Laura Horst Rosenberger, Jeremy Meyer Force, Terry Hyslop, Eun-Sil Shelley Hwang, Oluwadamilola Motunrayo Fayanju
Journal: Journal of Clinical Oncology (2017)

1570 Background: Metaplastic breast cancer (MBC) is a rare, aggressive, sarcomatoid breast cancer that was first described in 1973 but only became recognized as a histologically distinct entity in 2000. Given the paucity of data on the epidemiology of MBC, we performed a population-based analysis to delineate sociodemographic and clinicopathological characteristics associated with increased likelihood of MBC diagnosis. Methods: Adult female breast cancer patients with stage I-III MBC and non-MBC histology diagnosed between 2010 and 2013 were identified in the National Cancer Database (NCDB). Multivariate logistic regression was used to identify factors associated with diagnosis of MBC, and Cox proportional hazards modeling was used to estimate the effect of MBC on overall survival. Results: 2,451 MBC and 568,057 non-MBC patients were identified. After adjusting for receptor status (ER, PR, HER2), age, stage, grade, and treatment variables, MBC patients had worse survival than non-MBC patients (HR 1.45, p &lt; 0.001). Compared to non-MBC patients, a higher proportion of MBC patients were non-Hispanic black (16.7% vs 10.5%), had an annual income &lt; $35k (29.0% vs 25.5%), had lower high school completion rates (36.7% vs 33.9%), were treated at academic centers (35.5% vs 30.8%), and had government-sponsored insurance (48.8% vs 43.7%, all p &lt; 0.01). MBC diagnosis was more likely in patients with triple-negative breast cancer (OR 20.71), higher clinical T stage (cT4 vs cT1: OR 6.18), and lower clinical N stage (cN1 vs cN0: OR 0.38, all p &lt; 0.001). MBC patients were also more likely to be diagnosed based on pathology from their first operation rather than preoperatively (OR 1.41, p &lt; 0.001). Conclusions: Black women and women of low socioeconomic status were at increased risk for diagnosis with MBC. Though MBC was more likely to be treated at academic centers, MBC was less likely to be diagnosed prior to surgical intervention. Many of the sociodemographic factors associated with MBC have also been associated with triple-negative breast cancer. Additional research is needed to determine the contribution of sociodemographic factors to the epidemiology of MBC independent of receptor status.
Identification of Anti-Lymphoma Biomarkers of Response to the Anti-CD37 Antibody Drug Conjugate (ADC) IMGN529
Authors: Eugenio Gaudio, Chiara Tarantelli, Alberto Arribas, Luciano Cascione, Ivo Kwee, Andrea Rinaldi, Maurilio Ponzoni, Roberta Pittau Bordone, Georg Stussi, Davide Rossi, Emanuele Zucca, Anastasios Stathis, Callum Sloss, Francesco Bertoni
Journal: Blood (2016)
The Significance of the Next Generation Targeted Sequencing in the Precise Diagnosis of Pediatric Acquire Aplastic Anemia and Inherited Bone Marrow Failure Syndromes
Authors: Wenbin An, Ye Guo, Yumei Chen, Yao Zou, Xiaojuan Chen, Wenyu Yang, Lixian Chang, Yang Wan, Xiaofan Zhu
Journal: Blood (2016)
Re: 18F-FDG PET/CT Versus Contrast-Enhanced CT for Staging and Prognostic Prediction in Patients With Salivary Gland Carcinomas
Authors: Siamak Sabour
Journal: Clinical Nuclear Medicine (2017)

Safety Promotion and Injury Prevention Research Center and Department of Clinical Epidemiology, School of Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran [email protected] Conflicts of interest and sources of funding: none declared.
THU0362 Effect of biotechnological drugs on extra-articular manifestations of ankylosing spondylitis: systematic review
Authors: ALR Pinto, CV Pessoa, LS Inês
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Treatment with biotechnological agents (infliximab, etanercept, adalimumab, golimumab and certolizumab pegol) in ankylosing spondylitis (AS) is effective. However, evidence regarding the potential efficacy of these anti-TNF drugs in the extra-articular manifestations of ankylosing spondylitis, namely in uveitis (UV), inflammatory bowel disease (IBD) and dactylitis is scarce. <h3>Objectives</h3> To analyze evidence on efficacy of anti-TNF drugs approved for AS treatment in UV, IBD and dactylitis associated with AS. <h3>Methods</h3> A systematic literature review was performed using the PubMed and Cochrane Library databases. Randomized controlled trials (RCT), meta-analyzes and observational studies (OS) reporting efficacy of anti-TNF agents in extra-articular manifestations of AS were included. <h3>Results</h3> Fifty studies were included (seventeen RCTs, six meta-analyses and twenty seven observational studies). From the RCT we extracted the results presented in Table 1 for uveitis and in Table 2 for IBD. None reported results for dactylitis. Of the meta-analyzes included, only one presents results. These one shows that the incidence of uveitis is lower in patients taking etanercept than placebo (incidence of 8.6 and 19.3 per 100 patients per year, respectively; p value =0.03). In OS comparing different drugs, in one the risk of developing uveitis was 1.9 times higher in patients under etanercept compared to those under adalimumab (p value =0.0223) and a risk similar to those under infliximab and those under adalimumab. In another we have a percentage of patients with uveitis, during the course of the study, under etanercept of 8.0% and under infliximab of 4.0%. In the OS, the percentage of patients with UV events with infliximab was in a range of 0.0%&gt;3.1% with a follow-up interval between 2 years and 5 years; with etanercept was 0.9%&gt;29.6% and a follow-up time interval between 12 weeks to 7 years; with adalimumab there is only one study with duration of 2 years reporting 3.9% UV events. Regarding IBD reported in OS, there was 3.7%&gt;7.7% patients with events under treatment with etanercept over a follow-up time of 3.2–7 years; with adalimumab only a 2-year study reported IBD in 0.6% of cases. We did not find results regarding for other extra-articular manifestations or anti-TNF drugs. <h3>Conclusions</h3> Efficacy of anti-TNF drugs on extra-articular manifestations of AS is under-reported in RCTs. Available data suggests possible efficacy of infliximab, adalimumab and certolizumab in UV, and of certolizumab in IBD. No evidence is available about anti-TNF efficacy in AS-associated dactylitis. Future studies with anti-TNF drugs should better report on extra-articular manifestations in AS. <h3>Disclosure of Interest</h3> None declared
ILC2s regulate adaptive Th2 cell functions via PD-L1 checkpoint control
Authors: Christian Schwartz, Adnan R. Khan, Achilleas Floudas, Sean P. Saunders, Emily Hams, Hans-Reimer Rodewald, Andrew N.J. McKenzie, Padraic G. Fallon
Journal: The Journal of Experimental Medicine (2017)

Group 2 innate lymphoid cells (ILC2s) are important effector cells driving the initiation of type 2 immune responses leading to adaptive T helper 2 (Th2) immunity. Here we show that ILC2s dynamically express the checkpoint inhibitor molecule PD-L1 during type 2 pulmonary responses. Surprisingly, PD-L1:PD-1 interaction between ILC2s and CD4+ T cells did not inhibit the T cell response, but PD-L1-expressing ILC2s stimulated increased expression of GATA3 and production of IL-13 by Th2 cells both in vitro and in vivo. Conditional deletion of PD-L1 on ILC2s impaired early Th2 polarization and cytokine production, leading to delayed worm expulsion during infection with the gastrointestinal helminth Nippostrongylus brasiliensis Our results identify a novel PD-L1-controlled mechanism for type 2 polarization, with ILC2s mediating an innate checkpoint to control adaptive T helper responses, which has important implications for the treatment of type 2 inflammation.
A novel “hitch-and-ride” deep biliary cannulation method during rendezvous endoscopic ultrasound-guided ERCP technique
Authors: Yousuke Nakai, Hiroyuki Isayama, Saburo Matsubara, Hirofumi Kogure, Suguru Mizuno, Tsuyoshi Hamada, Naminatsu Takahara, Tomoka Nakamura, Tatsuya Sato, Tsuyoshi Takeda, Ryunosuke Hakuta, Kazunaga Ishigaki, Kei Saito, Minoru Tada, Kazuhiko Koike
Journal: Endoscopy (2017)

Abstract Background and study aim Endoscopic ultrasound-guided rendezvous (EUS-RV) is increasingly reported as a treatment option after failed endoscopic retrograde cholangiopancreatography. We developed a novel “hitch-and-ride” catheter for biliary cannulation to reduce the risk of guidewire loss during EUS-RV. Patients and methods We retrospectively evaluated safety and technical success of EUS-RV between June 2011 and May 2016. Biliary cannulation during EUS-RV using three methods – over-the-wire, along-the-wire, and hitch-and-ride – were compared. Results A total of 30 EUS-RVs were attempted and the technical success rate was 93.3 %, with two failures (one bile duct puncture and one guidewire insertion). After 28 cases of successful guidewire passage, cannulation was attempted by the over-the-wire (n = 13), along-the-wire (n = 4) or hitch-and-ride (n = 11) method. Only the hitch-and-ride method achieved biliary cannulation without guidewire loss or conversion to the other methods. Time to cannulation was shorter with the hitch-and-ride method (4 minutes) than with over-the-wire and along-the-wire methods (9 and 13 minutes, respectively). The adverse event rate of EUS-RV was 23.3 %. Conclusion A novel hitch-and-ride catheter was feasible for biliary cannulation after EUS-RV.
IL33-mediated ILC2 activation and neutrophil IL5 production in the lung response after severe trauma: A reverse translation study from a human cohort to a mouse trauma model
Authors: Jing Xu, Jesse Guardado, Rosemary Hoffman, Hui Xu, Rami Namas, Yoram Vodovotz, Li Xu, Mostafa Ramadan, Joshua Brown, Heth R. Turnquist, Timothy R. Billiar
Journal: PLoS Medicine (2017)

Background The immunosuppression and immune dysregulation that follows severe injury includes type 2 immune responses manifested by elevations in interleukin (IL) 4, IL5, and IL13 early after injury. We hypothesized that IL33, an alarmin released early after tissue injury and a known regulator of type 2 immunity, contributes to the early type 2 immune responses after systemic injury. Methods and findings Blunt trauma patients admitted to the trauma intensive care unit of a level I trauma center were enrolled in an observational study that included frequent blood sampling. Dynamic changes in IL33 and soluble suppression of tumorigenicity 2 (sST2) levels were measured in the plasma and correlated with levels of the type 2 cytokines and nosocomial infection. Based on the observations in humans, mechanistic experiments were designed in a mouse model of resuscitated hemorrhagic shock and tissue trauma (HS/T). These experiments utilized wild-type C57BL/6 mice, IL33-/- mice, B6.C3(Cg)-Rorasg/sg mice deficient in group 2 innate lymphoid cells (ILC2), and C57BL/6 wild-type mice treated with anti-IL5 antibody. Severely injured human blunt trauma patients (n = 472, average injury severity score [ISS] = 20.2) exhibited elevations in plasma IL33 levels upon admission and over time that correlated positively with increases in IL4, IL5, and IL13 (P < 0.0001). sST2 levels also increased after injury but in a delayed manner compared with IL33. The increases in IL33 and sST2 were significantly greater in patients that developed nosocomial infection and organ dysfunction than similarly injured patients that did not (P < 0.05). Mechanistic studies were carried out in a mouse model of HS/T that recapitulated the early increase in IL33 and delayed increase in sST2 in the plasma (P < 0.005). These studies identified a pathway where IL33 induces ILC2 activation in the lung within hours of HS/T. ILC2 IL5 up-regulation induces further IL5 expression by CXCR2+ lung neutrophils, culminating in early lung injury. The major limitations of this study are the descriptive nature of the human study component and the impact of the potential differences between human and mouse immune responses to polytrauma. Also, the studies performed did not permit us to make conclusions about the impact of IL33 on pulmonary function. Conclusions These results suggest that IL33 may initiate early detrimental type 2 immune responses after trauma through ILC2 regulation of neutrophil IL5 production. This IL33–ILC2–IL5–neutrophil axis defines a novel regulatory role for ILC2 in acute lung injury that could be targeted in trauma patients prone to early lung dysfunction.
Italian cohort of nivolumab Expanded Access Programme (EAP): Preliminary data from a real-world population.
Authors: Lucio Crino, Paolo Bidoli, Angelo Delmonte, Francesco Grossi, Filippo De Marinis, Francesca Sperandi, Fabiana Vitiello, Milena Vitali, Hector J. Soto Parra, Simone Scagnoli, Gabriele Minuti, Luana Calabrò, Marcello Tiseo, Daniele Turci, Silvia Quadrini, Paola Antonelli, Anna Manzo, Irene Prediletto, Diana Giannarelli, Domenico Galetta
Journal: Journal of Clinical Oncology (2016)

3067 Background: Nivolumab is the first checkpoint inhibitor approved for the treatment of squamous non small cell lung cancer (Sq-NSCLC) to show a survival benefit in a randomised phase III trial. The experience of patients and physicians in routine clinical practice is often different from those in a controlled clinical trial setting. The purpose of this analysis is to evaluate nivolumab use in real world setting. Methods: Nivolumab was available upon physician request for patients (pts) aged ≥ 18 years who had relapsed after a minimum of one prior systemic treatment for stage IIIB/stage IV Sq-NSCLC. Nivolumab 3 mg/kg is administered intravenously every 2 weeks to a maximum of 24 months. Pts included in the analysis had received ≥ 1 dose of nivolumab and were monitored for adverse events using Common Terminology Criteria for Adverse Events. Results: In total, 371 Italian pts participated in the EAP across 96 centres. Table 1 shows pts baseline characteristics. With a median follow-up of 2 months (range 0-7), 139 pts are not yet evaluable for response; the disease control rate (DCR) among others 232 pts evaluable for response is 35.8%: one patient (0,4%) with complete response, 32 pts (13.8%) with partial response and 50 pts (21.6%) with stable disease. DCR is comparable among pts regardless previous lines of therapy, brain metastasis, age and smoking habits. To date, median time of treatment is 2 months, with 42 patients treated beyond progression. Among 370 pts, 99 pts (27%) discontinued treatment for any reason except toxicity; 16 out of 370 discontinued due to AE (4%). Conclusions: To date, this is the largest clinical experience with nivolumab in current clinical practice: nivolumab seems to be an effective and safe therapy for pre-treated pts with Sq-NCSLC. These preliminary data provide insights into routine clinical use of nivolumab and seems to confirm data from pivotal trials.