tbuckley/cabot-search huggingface dataset:
Abstract 11027: Elevated Serum Testosterone Levels are Associated With Adverse Events in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia
Authors: Deniz Akdis, Ardan Muammer Saguner, Arnold von Eckardstein, HS Vincent Chen, Corinna Brunckhorst, Firat Duru
Journal: Circulation (2015)

Introduction: Sex hormones have been reported to play a role in the pathophysiology of ventricular arrhythmias. Hypothesis: We hypothesized that there may be a relationship between sex hormones and cardiovascular adverse events in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). Methods: Serum levels of testosterone, dehydroepiandrosterone, sex steroid-binding globulin, androstendione, estradiol, and progesterone were measured along with routine biochemical markers in 44 patients (33 male) from the Swiss ARVC/D Registry with a definite (n=29) or borderline (n=15) diagnosis of ARVC/D. Sex hormone levels were correlated with major adverse cardiovascular events (MACE), defined as the occurrence of cardiac death, heart transplantation, survived sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia or arrhythmogenic syncope. Results: Twenty-four patients experienced MACE within the last six months prior to determination of sex hormone levels. Testosterone levels were significantly higher in patients with MACE (mean±SD: 14nmol/l±9.6 versus 8.6nmol/l±5.9;p=0.03). In male patients with MACE, testosterone levels (18.7nmol/l±5.8 versus 11.3nmol/l±3.8; p=0.001) and sex steroid-binding globulin levels (48.9nmol/l±20.8 versus 32nmol/l±12.2; p=0.01) were significantly increased, whereas dehydroepiandrosterone levels were significantly decreased (4.0 micromol/l±2.6 versus 7.0 micromol/l±4.4; p=0.03). In females estradiol was lower in patients with MACE (14.1pmol/l±3.8 versus 396.6pmol/l±336.2; p=0.007). In bivariable analysis after adjusting for confounders such as body mass index, sports activity, and reduced RV/LV function, increased testosterone levels remained a significant independent predictor of MACE in males (odds ratio 1.4 per 1 nmol/l increase, 95% confidence interval 1.1-1.8, p= 0.005). A cut-off value for testosterone at 13.45 nmol/l predicted MACE with a sensitivity of 0.8 and a specificity of 0.7. Conclusion: In conclusion, our study suggests that sex hormones, in particular testosterone, are associated with adverse clinical events in patients with ARVC/D, and therefore, may play a role in risk stratification of this disease.
Genetics of rheumatoid arthritis: 2018 status
Authors: Yukinori Okada, Stephen Eyre, Akari Suzuki, Yuta Kochi, Kazuhiko Yamamoto
Journal: Annals of the Rheumatic Diseases (2018)

Study of the genetics of rheumatoid arthritis (RA) began about four decades ago with the discovery of HLA-DRB1 . Since the beginning of this century, a number of non-HLA risk loci have been identified through genome-wide association studies (GWAS). We now know that over 100 loci are associated with RA risk. Because genetic information implies a clear causal relationship to the disease, research into the pathogenesis of RA should be promoted. However, only 20% of GWAS loci contain coding variants, with the remaining variants occurring in non-coding regions, and therefore, the majority of causal genes and causal variants remain to be identified. The use of epigenetic studies, high-resolution mapping of open chromatin, chromosomal conformation technologies and other approaches could identify many of the missing links between genetic risk variants and causal genetic components, thus expanding our understanding of RA genetics.
Transmission of drug-resistant tuberculosis in HIV-endemic settings
Authors: Palwasha Y Khan, Tom A Yates, Muhammad Osman, Robin M Warren, Yuri van der Heijden, Nesri Padayatchi, Edward A Nardell, David Moore, Barun Mathema, Neel Gandhi, Vegard Eldholm, Keertan Dheda, Anneke C Hesseling, Valerie Mizrahi, Roxana Rustomjee, Alexander Pym
Journal: The Lancet Infectious Diseases (2018)
Direct <i>in vivo</i> application of induced pluripotent stem cells is feasible and can be safe
Authors: Meng Xiang, Meng Lu, Jing Quan, Ming Xu, Dan Meng, Anfeng Cui, Ning Li, Yingying Liu, Peng Lu, Xueling Kang, Xiaokai Wang, Ning Sun, Meng Zhao, Qiujuan Liang, Lili Le, Xinhong Wang, Jianyi Zhang, Sifeng Chen
Journal: Theranostics (2018)

Increasing evidence suggests the consensus that direct in vivo application of induced pluripotent stem cells (iPSCs) is infeasible may not be true. Methods: Teratoma formation and fate were examined in 53 normal and disease conditions involving brain, lung, liver, kidney, islet, skin, hind limb, and arteries. Results: Using classic teratoma generation assays, which require iPSCs to be congregated and confined, all mouse, human, and individualized autologous monkey iPSCs tested formed teratoma, while iPSC-derived cells did not. Intravenously or topically-disseminated iPSCs did not form teratomas with doses up to 2.5×108 iPSCs/kg and observation times up to 18 months, regardless of host tissue type; autologous, syngeneic, or immune-deficient host animals; presence or absence of disease; disease type; iPSC induction method; commercial or self-induced iPSCs; mouse, human, or monkey iPSCs; frequency of delivery; and sex. Matrigel-confined, but not PBS-suspended, syngeneic iPSCs delivered into the peritoneal cavity or renal capsule formed teratomas. Intravenously administered iPSCs were therapeutic with a dose as low as 5×106/kg and some iPSCs differentiated into somatic cells in injured organs. Disseminated iPSCs trafficked into injured tissue and survived significantly longer in injured than uninjured organs. In disease-free animals, no intravenously administered cell differentiated into an unwanted long-lasting cell or survived as a quiescent stem cell. In coculture, the stem cell medium and dominant cell-type status were critical for iPSCs to form cell masses. Conclusion: Teratoma can be easily and completely avoided by disseminating the cells. Direct in vivo iPSC application is feasible and can be safe.
Patients at Intermediate Surgical Risk Undergoing Isolated Interventional or Surgical Aortic Valve Implantation for Severe Symptomatic Aortic Valve Stenosis
Authors: Nicolas Werner, Ralf Zahn, Andreas Beckmann, Timm Bauer, Sabine Bleiziffer, Christian W. Hamm, Raffi Berkeredjian, Alexander Berkowitsch, Friedrich W. Mohr, Sandra Landwehr, Hugo A. Katus, Wolfgang Harringer, Stephan Ensminger, Christian Frerker, Helge Möllmann, Thomas Walther, Steffen Schneider, Rüdiger Lange
Journal: Circulation (2018)

Background: Transcatheter aortic valve replacement (TAVR) is increasingly being used for treatment of severe aortic valve stenosis in patients at intermediate risk for surgical aortic valve replacement (SAVR). Currently, real-world data comparing indications and clinical outcomes of patients at intermediate surgical risk undergoing isolated TAVR with those undergoing SAVR are scarce. Methods: We compared clinical characteristics and outcomes of patients with intermediate surgical risk (Society of Thoracic Surgeons score 4%–8%) who underwent isolated TAVR or conventional SAVR within the prospective, all-comers German Aortic Valve Registry. Results: A total of 7613 patients at intermediate surgical risk underwent isolated TAVR (n=6469) or SAVR (n=1144) at 92 sites in Germany between 2012 and 2014. Patients treated by TAVR were significantly older (82.5±5.0 versus 76.6±6.7 years, P &lt;0.001) and had higher risk scores (logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation]: 21.2±12.3% versus 14.2±9.5%, P &lt;0.001; Society of Thoracic Surgeons score: 5.6±1.1 versus 5.2±1.0, P &lt;0.001). Multivariable analyses revealed that advanced age, coronary artery disease, New York Heart Association class III/IV, pulmonary hypertension, prior cardiac decompensation, elective procedure, arterial occlusive disease, no diabetes mellitus, and a smaller aortic valve area were associated with performing TAVR instead of SAVR (all P &lt;0.001). Unadjusted in-hospital mortality rates were equal for TAVR and SAVR (3.6% versus 3.6%, P =0.976), whereas unadjusted 1-year mortality was significantly higher in patients after TAVR (17.5% versus 10.8%, P &lt;0.001). After propensity score matching, the difference in 1-year mortality between patients with TAVR and SAVR was no longer significant (17.1% versus 15.7%, P =0.59). Conclusions: Patients at intermediate risk undergoing TAVR differ significantly from those treated with SAVR with regard to age and baseline characteristics. Isolated TAVR and SAVR were associated with an in-hospital mortality rate of 3.6%. In the propensity score analysis, there was no significant difference in 1-year mortality between patients with TAVR and SAVR.
A phase I dose escalation trial evaluating the impact of an in situ immunization strategy with intra-tumoral injections of Pexa-Vec in combination with ipilimumab in advanced solid tumors with injectable lesions
Authors: A. Marabelle, L. Eberst, C. Terret, F. Pilleul, C. Mastier, A. Bouhamama, L. Gilles-Afchain, S. Laurent, I. Delzano, C. Reynaud, C. Caux, C. Caux, G. Garin, A.-S. Bidaux, D. Perol, N. Stojkowitz, M. Homerin, H. Leenders, P. Cassier
Journal: Annals of Oncology (2018)

Background: In situ immunization is a strategy where immunomodulatory products are injected into one tumor site in order to use the tumor as its own vaccine and to trigger a systemic anti-tumor immune response. The Pexa-Vec (JX-594, Transgene) is an oncolytic virus genetically modified to secrete GM-CSF. We formulate the hypothesis that IT treatment with this oncolytic virus could synergize with anti-CTLA4 therapy via oncolytic virus-induced tumor cell death & tumor-antigen release, GM-CSF-induced recruitment/maturation/activation of antigen presenting cells, and anti-CTLA4-induced Treg blockade/depletion and reversion of T effectors inhibition. Trial design: ISI-JX is a multicentric, Phase I dose escalation trial followed by an extension part aiming to evaluate the safety, feasibility, and anti-tumor effects of an in situ immunization strategy with IT injections of ipilimumab with Pexa-Vec in adults patients (pts) with solid tumors. The trial is conducted in pts with at least one injectable lesion (≥2 and ≤8 cm) and one distant non-injected measurable target site. Pts are treated with an IT injection of Pexa-Vec alone (1 x 109pfu) at Week 1 (W1) Day 1 (D1) followed by 3 IT injections of Pexa-Vec (1 x 109pfu) + ipilimumab (4 dose levels: 2.5, 5, 7.5, 10 mg/injection) at W3 D1, W5 D1 and W9 D1. Primary endpoint for escalation part is the occurrence of Dose Limiting Toxicities (DLT) defined as the toxicities occurring during the DLT assessment window (the first 5 weeks) related to Pexa-Vec, Ipilimumab or both; and the objective response rate as per immune related Response Criteria after 3 months of treatment for extension part. Secondary endpoints include the disease control rate, duration of response, progression free survival and overall survival. The dose escalation part follows a classical 3 + 3 design with 3 to 6 pts at each DL depending of the number of DTL observed (maximum of 24 pts). In the extension part, according to on the first stage of a Gehan design, 12 patients per cohort (3) will be enrolled (maximum of 36 pts). Up to date, the dose escalation part is ongoing: 8 pts were enrolled (DL1 n = 3; DL2 n = 3; DL3 n = 2). Editorial acknowledgement: Bidaux As & Garin G; Centre Léon Bérard; DRCI Promotion Phase Précoce. Clinical trial identification: EudraCT: 2014-001692-32; NCT02977156. Legal entity responsible for the study: Centre Léon Bérard DRCI Promotion/Essais Précoces. Funding: Centre Léon Bérard & Transgene S.A. Disclosure: All authors have declared no conflicts of interest.
Efficacy of Ponatinib after Multiple Lines of Therapy for Chronic Myeloid Leukemia
Authors: Mahesh Swaminathan, Hagop M. Kantarjian, Koji Sasaki, Farhad Ravandi, Gautam Borthakur, Tapan M. Kadia, Guillermo Garcia-Manero, Courtney D. DiNardo, Marina Y. Konopleva, Zeev E. Estrov, Naveen Pemmaraju, Naval G. Daver, William G. Wierda, Alessandra Ferrajoli, Sherry A. Pierce, MD Emogene Dellasala, Elias J. Jabbour, Jorge E. Cortes
Journal: Blood (2018)
Myeloproliferative Neoplasms in Patients below 25 Years Old at Diagnosis: A Retrospective International Cooperative Work
Authors: Ianotto Jean-Christophe, Jean-Jacques Kiladjian, Marta Sobas, Parvis Sadjadian, Lee-Yung Shih, Maria Bieniaszewska, Ilona Seferynska, Mary Frances McMullin, Joanna Waclaw, Laurence Legros, Krzysztof Lewandowski, Mihnea Zdrenghea, Aitor Abuin Blanco, Anna Armatys, Jan Samuelsson, Adrianna Spalek, Anna Angola Figueras, Marie Lauermannova, María-Soledad Noya, Jarosław Czyż, Anna Szmigielska-Kaplon, Rajko Kusec, Joanna Gora Tybor, Anna Masternak, Jan J. Michiels, Malgorzata Skowronek, Jean-Loup Demory, Katell Le Du, Sonja Zweegman, Carlos Besses Raebel, Stephane Giraudier, Martin Griesshammer, Claire N. Harrison
Journal: Blood (2018)
Radical prostatectomy extends life expectancy in localised prostate cancer, trial finds
Authors: Susan Mayor
Journal: BMJ (2018)

Radical prostatectomy is associated with significantly more years of life gained than watchful waiting in men with localised prostate cancer, long term follow-up results from a randomised trial have shown.1

“In clinically detected prostate cancer, the benefit of radical prostatectomy in otherwise healthy men can be substantial, with a mean gain of almost three years of life after 23 years of follow-up,” said the study authors, led by Anna Bill-Axelson, from Uppsala University Hospital in Sweden. But they warned that the benefit is highly dependent on a man’s baseline risk, which can now be better assessed with modern diagnostic procedures than in the past.

Radical prostatectomy is known …
The Innate Immune Sensor NLRC3 Acts as a Rheostat that Fine-Tunes T Cell Responses in Infection and Autoimmunity
Authors: Toru Uchimura, Yoshitaka Oyama, Meng Deng, Haitao Guo, Justin E. Wilson, Elena Rampanelli, Kevin D. Cook, Ichiro Misumi, Xianming Tan, Liang Chen, Brandon Johnson, Jason Tam, Wei-Chun Chou, W. June Brickey, Alex Petrucelli, Jason K. Whitmire, Jenny P.Y. Ting
Journal: Immunity (2018)

Appropriate immune responses require a fine balance between immune activation and attenuation. NLRC3, a non-inflammasome-forming member of the NLR innate immune receptor family, attenuates inflammation in myeloid cells and proliferation in epithelial cells. T lymphocytes express the highest amounts of Nlrc3 transcript where its physiologic relevance is unknown. We show that NLRC3 attenuated interferon-γ and TNF expression by CD4+ T cells and reduced T helper 1 (Th1) and Th17 cell proliferation. Nlrc3−/− mice exhibited increased and prolonged CD4+ T cell responses to lymphocytic choriomeningitis virus infection and worsened experimental autoimmune encephalomyelitis (EAE). These functions of NLRC3 were executed in a T-cell-intrinsic fashion: NLRC3 reduced K63-linked ubiquitination of TNF-receptor-associated factor 6 (TRAF6) to limit NF-κB activation, lowered phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and diminished glycolysis and oxidative phosphorylation. This study reveals an unappreciated role for NLRC3 in attenuating CD4+ T cell signaling and metabolism.
Gimema Registry of Conception/Pregnancy in Adult Italian Patients Diagnosed with Chronic Myeloid Leukemia (CML): Report on 166 Outcomes
Authors: Elisabetta Abruzzese, Chiara Elena, Fausto Castagnetti, Carlo Gambacorti-Passerini, Mario Annunziata, Luigia Luciano, Giorgina Specchia, Alessandra Iurlo, Isabella Capodanno, Patrizia Pregno, Antonella Gozzini, Simona Sica, Mario Tiribelli, Sara Galimberti, Monica Bocchia, Clementina Caracciolo, Giovanna Rege Cambrin, Micaela Bergamaschi, Anna Rita Scortechini, Alessandro Rambaldi, Diamante Turri, Claudio Fozza, Mariella D'adda, Lucia Mastrullo, Marzia Salvucci, Caterina Musolino, Gianluca Gaidano, Filippo Gherlinzoni, Anna d'Emilio, Paola Fazi, Michele Baccarani
Journal: Blood (2018)
Treatment of chronic hepatitis C virus infection in Rwanda with ledipasvir–sofosbuvir (SHARED): a single-arm trial
Authors: Neil Gupta, Aimable Mbituyumuremyi, Jules Kabahizi, Fabien Ntaganda, Claude Mambo Muvunyi, Fabienne Shumbusho, Emmanuel Musabeyezu, Constance Mukabatsinda, Cyprien Ntirenganya, Jennifer Ilo Van Nuil, Fredrick Kateera, Gregory Camus, Makuza Jean Damascene, Sabin Nsanzimana, Joia Mukherjee, Philip M Grant
Journal: The Lancet. Gastroenterology & hepatology (2018)
Genetic profiling of basal cell carcinomas detects postzygotic mosaicism in basal cell naevus syndrome
Authors: M.G.H.C. Reinders, B. Cosgun, L.M.C. Gijezen, C.N. Oosterhoud, N.W.J. Kelleners‐Smeets, E. Vermander, M. Vreeburg, P.M. Steijlen, K. Mosterd, M. Geel
Journal: British Journal of Dermatology (2018)

Basal cell naevus syndrome (BCNS) is associated with germline mutations in the PTCH1 gene. Postzygotic mosaicism can also cause BCNS. Here we describe two patients, one with multiple basal cell carcinomas (BCCs) and one with clinical BCNS, who had no PTCH1 mutation in DNA extracted from blood. In both patients, we performed genetic analysis on different BCCs, revealing the presence of a shared PTCH1 mutation in all tumours. Our findings show that in patients with symptoms of BCNS and initial absence of a PTCH1 mutation in blood, genetic profiling of BCCs can detect postzygotic mosaicism. What's already known about this topic? Basal cell naevus syndrome (BCNS) is associated with germline mutations in the PTCH1 gene, but it can also be caused by low-grade postzygotic mosaicism in PTCH1. What does this study add? In patients suspected of having BCNS or patients with multiple basal cell carcinomas (BCCs) with a special distribution on the body and no mutation detected in blood, it is worthwhile to search for a shared PTCH1 mutation in their BCCs as this can detect postzygotic mosaicism. This information is important to ensure proper surveillance programmes, choose the right therapy and provide adequate genetic counselling.
A Rare Case of Neutrophil-Rich, ALK-Negative Anaplastic Large Cell Lymphoma in the Lung Mimicking a Pulmonary Abscess on 18F-FDG PET/CT
Authors: Li-Juan Wang, Hu-Bing Wu, Yin Zhang, Wen-Lan Zhou, Quan-Shi Wang
Journal: Clinical Nuclear Medicine (2018)

A 21-year-old man complained of cough, fever, and hemoptysis for 15 days. Peripheral neutrophil cell (33.8 × 10/L) was markedly increased, and a mass in the left lung was detected by chest radiography. F-FDG PET/CT was referred for characterizing the lesion and found a large mass with multiple cavities in the left lung, which had markedly high uptake of F-FDG, mimicking pulmonary abscess. Surprisingly, the lesion was eventually proved to be neutrophil-rich anaplastic large cell lymphoma. After 4 cycles' chemotherapy, the lesion shrank significantly.
Abstract 20515: Clinical Course, Risk Stratification and Response to Beta-Blockers in Patients With Long QT Syndrome Type 3
Authors: Riccardo Maragna, Andrea Mazzanti, Gaetano Vacanti, Maira Marino, Massimo Morini, Nicola Monteforte, Raffaella Bloise, Carlo Napolitano, Silvia G Priori
Journal: Circulation (2017)

Background: Long QT syndrome type 3 (LQT3) represents a rare and lethal variant of long QT syndrome (LQTS) caused by gain-of-function mutations in the SCN5A gene. Objective: 1) To describe the clin...
Re: Nudleman et al.: Glaucoma after lens-sparing vitrectomy for advanced retinopathy of prematurity (Ophthalmology. 2018;125:671-675)
Authors: Ta C. Chang, Elizabeth A. Hodapp, Alana L. Grajewski, Elizabeth A. Vanner, Audina M. Berrocal, Sharon F. Freedman
Journal: Ophthalmology (2018)
Review: In chronic noncancer pain, cannabinoids reduce pain (NNT 24) but increase adverse events (NNH 6)
Authors: Anupam Goel
Journal: Annals of Internal Medicine (2018)

Source Citation Stockings E, Campbell G, Hall WD, et al. Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: a systematic review and meta-analysis of controlled and observational studies. Pain. 2018;159:1932-54. 29847469
P083 Efficacy of EGFR-TKIs in Patients Harboring EGFR Mutations with Non-Adenocartinoma Histology
Authors: T. Yamaguchi, S. Morikawa, O. Yuko, K. Asada, T. Oguri, N. Inui, K. Ito, T. Kimura, E. Kunii, T. Matsui, A. Kubo, T. Kato, J. Shindo, T. Tsuda, M. Okuno, T. Hida, K. Imaizumi
Journal: Journal of Thoracic Oncology (2018)
Abstract 16282: Coronary Fibromuscular Dysplasia Angiographic Manifestations
Authors: Jacqueline Saw, Hiram Bezerra, Heather Gornik, Lindsay Machan, GB John Mancini
Journal: Circulation (2015)

Background: We previously described a strong association between fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection (SCAD). Angiographic manifestation of coronary FMD aside from dissection was reported to be rare. However, we observed several non-dissection coronary angiographic abnormalities in patients with multifocal FMD. Methods: Baseline demographics and imaging of patients with suspected non-dissection coronary FMD at Vancouver General Hospital were retrospectively reviewed. Presence of multifocal FMD in non-coronary territories was confirmed by 3 specialists. Coronary angiograms with suspected coronary FMD changes (excluding dissected segments) were reviewed and classified by 2 experienced angiographers for: (1) irregular stenosis (beading) - multiple areas of stenosis in a focal or diffuse pattern and with/without systolic accentuation, (2) smooth stenosis - diffuse or focal, (3) segmental dilatation/ectasia, and (4) tortuosity. Optical coherence tomography (OCT), if performed, were reviewed by 2 specialists. Results: Of 28 patients with multifocal FMD and suspected coronary involvement on angiography, 23 were women (82.1%), mean age was 58.6 ± 9.5, and mean BMI was 24.6. Sixteen presented with myocardial infarction (10 due to SCAD), 12 underwent angiography for stable or atypical angina. The observed coronary angiographic abnormalities were: irregular stenosis (beading) in 14 (12 diffuse, 2 focal, 3 with systolic accentuation), smooth stenosis in 6 (4 diffuse, 2 focal), segmental dilatation/ectasia in 14 (majority with multi-segmental, diffuse enlargement in an entire vessel), and tortuosity in 25 cases. Fourteen patients had OCT of the abnormal segments showing abnormalities distinct from atherosclerosis. These included multiple areas of patchy or diffuse intimal, medial or adventitial abnormalities with disorganized fibrotic thickening, proteoglycan accumulation, macrophage infiltration, loss of elastic membranes, and cavitation. Conclusions: This is the first case series describing angiographic manifestations of coronary FMD, which can be categorized into irregular stenosis, smooth stenosis, dilatation and tortuosity, representing features that are additional to dissection.
Molecular Profiling of Pancreatic Cancer Patients—Response
Authors: Michael J. Pishvaian, Emanuel Petricoin
Journal: Clinical Cancer Research (2018)

We appreciate the opportunity to address the comments raised by Drs. Sahin and Elias. First, we are aware of the data surrounding the use of PARP inhibitors for HR-deficient pancreatic ductal adenocarcinoma (PDA; refs. [1, 2][1]). We acknowledge that for patients with HR-deficient disease whose
Administration of BPX-501 Cells Following Αβ T and B-Cell-Depleted HLA-Haploidentical HSCT (haplo-HSCT) in Children with Malignant or Non-Malignant Disorders
Authors: Mattia Algeri, Pietro Merli, Waseem Qasim, Mary Slatter, Melissa Kuhn, Franco Locatelli
Journal: Blood (2018)