tbuckley/cabot-search huggingface dataset:
PTU-061 Utility of endoscopic retrograde cholangiography to diagnose IgG4-associated cholangitis: an international, double blind, randomised, multicentre study: Abstract PTU-061
Authors: E Kalaitzakis, G J Johnson, M Levy, T Kamisawa, T H Baron, M D Topazian, N Takahashi, A Kanno, K Okazaki, N Egawa, K Uchida, K Sheikh, Z Amin, T Shimosegawa, N S Sandanayake, N I Church, M H Chapman, A R Hatfield, S P Pereira, S Chari, G J Webster
Journal: Gut (2010)

<h3>Introduction</h3> IgG4 associated cholangitis (IAC) may have similar radiographic appearances to primary sclerosing cholangitis (PSC) and cholangiocarcinoma (CCA). Making the diagnosis is important as IAC usually responds favourably to steroids (in contrast to PSC) and erroneous treatment for presumed CCA may be avoided. We assessed whether specialists familiar with these diseases could reliably distinguish between them based on endoscopic retrograde cholangiograms (ERC). <h3>Methods</h3> ERCs (n=104) of patients with a definitive diagnosis of IAC, PSC and CCA from centres in the US, Japan and UK were screened for quality by an experienced endoscopist unaware of clinical diagnoses. A final set of 48 ERCs (20 IAC, 10 PSC, 10 CCA and 8 duplicates) were arranged in random order and presented to 18 reviewers unaware of the diagnosis. Reviewers noted presence or absence of key ERC features and provided their three most probable diagnoses given as per cent confidence (95%, 75%, 50%, 25% and 5%, totalling 100%). We used a ≥75% confidence in the diagnosis of IAC to determine sensitivity and specificity for that condition. The κ statistic for intra- and inter-observer agreement was also calculated. <h3>Results</h3> The specificity of ERC for detecting IAC was high and did not differ significantly between centres (Abstract 061), but sensitivity was uniformly low. Neither reviewer speciality (endoscopist, radiologist, HPB physician) nor years of experience had any statistically significant effect on reporting success. Although intraobserver agreement was generally very good, interobserver agreement was poor (Abstract 061). <h3>Conclusion</h3> High specificity for diagnosing IAC using ERC suggests that particular cholangiographic features support the diagnosis. However, poor sensitivity suggests that, based on ERC, many patients with IAC, who might benefit from steroid therapy, may be misdiagnosed with PSC or CCA. Additional diagnostic strategies, including pathological sampling, are likely to be vital in distinguishing these diseases.
Is Next Generation Sequencing (NGS) Ready for Routine Clinical Practice in Gliomas? Results of a Prospective Study Utilizing the MSK-IMPACT Assay
Authors: Antonio Marcilio Padula Omuro, Ahmet Zehir, Donavan T. Cheng, Michael F. Berger, David Michael Hyman, David B. Solit, Jose Baselga, Marc Ladanyi, Maria E. Arcila, Meera Hameed, Paul Sabbatini, Lisa Marie DeAngelis, Philip H. Gutin, Marc Rosenblum, Ingo K. Mellinghoff, Viviane Tabar, Timothy An-thy Chan, Samuel Briggs, Jason T. Huse, Cameron W. Brennan
Journal: Journal of Clinical Oncology (2015)

2057 Background: NGS is becoming increasingly available but its relevance in clinical practice has been questioned. In this prospective, IRB-approved study (NCT01775072), we utilized the MSK-IMPACT assay to analyze gliomas in a routine practice setting. The MSK-IMPACT, performed in a CLIA-compliant laboratory, is a multiplexed assay (Illumina HiSeq) providing full exon coverage of 341 cancer related genes, detecting base substitutions, small indels, copy number and select gene rearrangements. Methods: After written consent, tumor and germline DNA were analyzed. Mutations were catalogued and compared to TCGA data. Comparison with other profiling methods, i.e. IHC (IDH-1 R132H mutation), RT-PCR (EGFRvIII), Sanger sequencing (IDH-1/2 mutations) and FISH (EGFR amplification, 1p/19q co-deletion) was performed. Participation in clinical trials was recorded. Results: N = 104 pts were enrolled (48 glioblastomas, 39 grade III, 9 grade II and 3 grade I gliomas). The mutational landscape was in line with TCGA, including mutations in TERT (59%), TP53 (55%), IDH-1 (35%), ATRX (27%), PTEN (22%) EGFR (17%), PIK3CA (12%) and BRAF (2%); four pts displayed a hypermutator genotype. MSK-IMPACT identified all IDH1/2 mutations, including one IDH2 R172K in an IDH-1 R132H IHC-negative tumor. All pure oligodendrogliomas (N = 13) displayed 1p/19q codeletion on MSK-IMPACT. Three pts had 1p/19q codeletion on FISH but not on MSK-IMPACT, but mutational profile/ histology favored non-codeleted glioma, suggesting false-positive FISH results. All FISH EGFR amplifications were detected by MSK-IMPACT. Among EGFR amplified tumors, MSK-IMPACT disclosed EGFRvIII in 55%. To date, 33 pts have been enrolled in trials, including 4 extreme responders in whom results are guiding further drug development. Conclusions: NGS with MSK-IMPACT is a highly useful profiling tool, providing prognostic and therapeutically relevant information and guiding patient selection/ interpretation of clinical trials. Given lower cost, higher accuracy and wider range of information provided, this assay replaces with advantages other profiling tools, and is ready for incorporation into routine clinical practice. Clinical trial information: NCT01775072.
Chemoresistance in Pancreatic Cancer Is Driven by Stroma-Derived Insulin-Like Growth Factors
Authors: Lucy Ireland, Almudena Santos, Muhammad S. Ahmed, Carolyn Rainer, Sebastian R. Nielsen, Valeria Quaranta, Ulrike Weyer-Czernilofsky, Danielle D. Engle, Pedro A. Perez-Mancera, Sarah E. Coupland, Azzam Taktak, Thomas Bogenrieder, David A. Tuveson, Fiona Campbell, Michael C. Schmid, Ainhoa Mielgo
Journal: Cancer Research (2016)

Tumor-associated macrophages (TAM) and myofibroblasts are key drivers in cancer that are associated with drug resistance in many cancers, including pancreatic ductal adenocarcinoma (PDAC). However, our understanding of the molecular mechanisms by which TAM and fibroblasts contribute to chemoresistance is unclear. In this study, we found that TAM and myofibroblasts directly support chemoresistance of pancreatic cancer cells by secreting insulin-like growth factors (IGF) 1 and 2, which activate insulin/IGF receptors on pancreatic cancer cells. Immunohistochemical analysis of biopsies from patients with pancreatic cancer revealed that 72% of the patients expressed activated insulin/IGF receptors on tumor cells, and this positively correlates with increased CD163+ TAM infiltration. In vivo, we found that TAM and myofibroblasts were the main sources of IGF production, and pharmacologic blockade of IGF sensitized pancreatic tumors to gemcitabine. These findings suggest that inhibition of IGF in combination with chemotherapy could benefit patients with PDAC, and that insulin/IGF1R activation may be used as a biomarker to identify patients for such therapeutic intervention. Cancer Res; 76(23); 6851-63. ©2016 AACR.
TCT-787 Evaluation of Cell Proliferation in Adaptive Neointimal Remodeling Following Arteriovenous Fistula in a Large Animal Model
Authors: Armando Tellez, Krista N. Dillon, Scott T. Wilson, Jan Guerrero, Dane A. Brady, Will Grundy, Joan Wicks, Serge D. Rousselle
Journal: Journal of the American College of Cardiology (2015)
Assessment of Changes in Gene Expression Caused by Insertions of a Globin Lentiviral Vector Containing Globin Regulatory Elements or a Lentiviral Vector Containing Retroviral LTR Elements.
Authors: Phillip W. Hargrove, Steven Kepes, Hideki Hanawa, Cheng Cheng, Geoff Neale, Arthur W. Nienhuis, Derek A. Persons
Journal: Blood (2004)
Clinical Factors Predicting the Response of Acute Graft-Versus-Host Disease to Corticosteroid Therapy.
Authors: Makoto Murata, Hideki Nakasone, Junya Kanda, Takahiko Nakane, Tatsuo Furukawa, Takahiro Fukuda, Shuichi Taniguchi, Takehiko Mori, Tetsuya Eto, Yasuo Morishima, Tokiko Nagamura-Inoue, Hiromasa Yabe, Yoshiko Atsuta, Hisashi Sakamaki, Ritsuro Suzuki
Journal: Blood (2012)
Association of Histopathologic Phenotype of Periampullary Adenocarcinomas With Survival
Authors: Jennifer L. Williams, Carmen K. Chan, Paul A. Toste, Irmina A. Elliott, Charles R. Vasquez, Dharma B. Sunjaya, Eric A. Swanson, Jamie Koo, O. Joe Hines, Howard A. Reber, David W. Dawson, Timothy R. Donahue
Journal: JAMA Surgery (2016)

Patients with periampullary adenocarcinomas have widely variable survival. These cancers are traditionally categorized by their anatomic location of origin, namely, the duodenum, ampulla, distal common bile duct (CBD), or head of the pancreas. However, they can be alternatively subdivided histopathologically into intestinal or pancreaticobiliary (PB) types, which may more accurately estimate prognosis.To identify factors associated with survival in patients with periampullary adenocarcinomas and to compare survival between those having intestinal-type or PB-type cancers originating from the duodenum, ampulla, or distal CBD with those having pancreatic ductal adenocarcinoma (PDAC).This study was a retrospective analysis of medical records in a prospectively maintained database. Three pathologists separately evaluated histopathologic phenotypes at a university-based tertiary referral center. Study participants were all patients (N = 510) who underwent pancreatoduodenectomy for adenocarcinoma between January 1995 and December 2014.Overall survival.This study identified 510 patients (mean [SD] age, 66.1 [10.9] years; 245 female [48%]) who underwent pancreatoduodenectomy for adenocarcinomas: 13 duodenal, 110 ampullary, 43 distal CBD, and 344 PDAC. The median overall survival was 61.2 (interquartile range [IQR], 22.0-111.0), 70.4 (IQR, 26.7-147.7), 40.6 (IQR, 15.2-59.6), and 31.4 (IQR, 17.3-86.3) months for patients with cancers of the duodenum, ampulla, distal CBD, or pancreas, respectively (P = .01), indicating a significant difference between the 4 tumor anatomic locations. Most duodenal (61.5% [8 of 13]) and ampullary (51.8% [57 of 110]) cancers were intestinal type, and most distal CBD tumors were PB type (86.0% [37 of 43]). Those with intestinal-type duodenal, ampullary, or distal CBD adenocarcinomas had longer median overall survival than those with PB type (71.7 vs 33.3 months, P = .02) or PDAC (31.4 months, P = .003). There was no survival difference between PB-type cancers and PDAC (33.3 vs 31.4 months, P = .66). On multivariable analysis, histologic grade (hazard ratio [HR], 1.98; 95% CI, 1.56-2.52; P < .001), histopathologic phenotype (HR, 1.75; 95% CI, 1.16-2.64; P = .008), and nodal status (HR, 1.45; 95% CI, 1.12-1.87; P = .05) were significantly associated with survival, while anatomic location was not.Histopathologic phenotype is a better prognosticator of survival in patients with periampullary adenocarcinomas than tumor anatomic location. Those with PB-type duodenal, ampullary, or distal CBD adenocarcinomas have survival similar to those with PDAC.
Hernia Mesh Repair and Global Surgery—Reply
Authors: Joseph D. Forrester, Jared A. Forrester, George P. Yang
Journal: JAMA Surgery (2016)

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TCT-239 Effects of Statin Therapy on Clinical Outcomes of Survivors of Acute Myocardial Infarction with Severe Systolic Heart Failure
Authors: Jong Shin Woo, Hyun Soo Kim, Chang-Bum Park, Jin-Man Cho, Chong-Jin Kim, Myung Ho Jeong, Weon Kim
Journal: Journal of the American College of Cardiology (2015)
Salvage Treatment with Ofatumumab and ESHAP (O-ESHAP) for Patients with Relapsed or Refractory Classical Hodgkin's Lymphoma After First-Line Chemotherapy: Interim Analysis of a Phase II Trial of the Spanish Group of Lymphoma and Bone Marrow Transplantation (GELTAMO)
Authors: Carmen Martinez, Mercedes Rodriguez-Calvillo, María José Terol, Blanca Xicoy, Ramón García-Sanz, Elena Perez-Ceballos, Alberto Cantalapiedra, Eva Domingo-Domènech, Miguel Hernández, Antonia Sampol, Manuel Espeso, Javier Briones, Javier Lopez, Anna Sureda
Journal: Blood (2012)
Bimodal Induction of NK Cell Reactivity Against Acute Myeloid (AML) and Chronic Lymphoid Leukemia (CLL) by Fc-Engineered GITR-Fc Fusion Proteins.
Authors: Julia Steinbacher, Benjamin J Schmiedel, Antje Werner, Tina Nuebling, Corina Buechele, Ludger Grosse-Hovest, Lothar Kanz, Helmut R Salih
Journal: Blood (2012)
BCL-2 Expression May Adversely Affect Outcome in HIV-Associated Systemic Diffuse Large B Cell Lymphoma.
Authors: Hatoon Ezzat, J. Doug Filipenko, Linda M. Vickars, Paul F. Galbraith, Charles H. Li, Kevin Murphy, Julio Montaner, Marianne Harris, Robert Hogg, Suzanne Vercauteren, Chantal S. Leger, Leslie Zypchen, Heather A. Leitch
Journal: Blood (2005)
The Potential of Aurora Kinases A and B As Therapeutic Targets in Pediatric Acute Leukemia
Authors: Stefanie A. Hartsink-Segers, C. Michel Zwaan, Carla Exalto, Mirjam W.J. Luijendijk, Valerie S. Calvert, Emanuel F. Petricoin, William E. Evans, Dirk Reinhardt, Válerie de Haas, Maj Hedtjärn, Bo R. Hansen, Troels Koch, Huib N. Caron, Rob Pieters, Monique L. Den Boer
Journal: Blood (2012)
Non-specific effects of childhood vaccines
Authors: Chee Fu Yung
Journal: BMJ (2016)

Evidence of any “off target” effects remains weak and vulnerable to biases

Non-specific effects of vaccines or “off target effects” as they are sometimes called can be defined as effects of a vaccine beyond their intended target pathogen or disease. These effects can be beneficial as well as harmful.1 2 3 The published evidence on non-specific effects of childhood vaccines remain confusing, so the linked systematic reviews by Higgins and colleagues (doi:10.1136/bmj.i5170)4 and Kandasamy and colleagues (doi:10.1136/bmj.i5225)5 looking at clinical and immunological non-specific effects are welcome.

The systematic reviews were commissioned by the WHO Strategic Advisory Group of Experts (SAGE) to decide if there was enough evidence to consider changes in scheduling or co-administration of certain vaccines.6 It is important to emphasise that the systematic reviews were not intended or designed to assess if these vaccines are safe or should continue to be recommended for children. It is beyond debate that BCG, diphtheria, tetanus, pertussis (DPT), and measles containing vaccines (MCV) are safe. These vaccines have …
Polyclonal hematopoietic reconstitution in leukemia patients at remission after suppression of specific gene rearrangements [see comments]
Authors: F Lo Coco, PG Pelicci, F D'Adamo, D Diverio, G Alimena, E Montefusco, W Arcese, G Avvisati, L De Felice, G Meloni
Journal: Blood (1993)
FIP1L1-PDGFRA Positive Secondary Acute Myeloid Leukemia.
Authors: Georgia Metzgeroth, Helena Popp, Christoph Walz, Martin C. Müller, Jürgen Mix, Peter Paschka, Lothar Müller, Martin Steder, Francisco Del Valle, Walter E. Aulitzky, Harro Benke, Claudia Schoch, Torsten Haferlach, Rüdiger Hehlmann, Andreas Hochhaus, Andreas Reiter
Journal: Blood (2005)
TCT-644 Comparison of the new balloon-expandable SAPIEN 3 versus the SAPIEN XT. 30-day clinical outcome and echocardiographic data after transfemoral aortic valve implantation
Authors: Suzanne Fateh-Moghadam, Sabrina Voesch, Tobias Geisler, Meinrad Gawaz, Wolfgang Bocksch
Journal: Journal of the American College of Cardiology (2015)
Rapid Immune Reconstitution Following Unmanipulated Haploidentical BMT with Post-Transplant High Dose Cyclophosphamide
Authors: Alida Dominietto, Anna Maria Raiola, Barbara Bruno, Maria Teresa van Lint, Francesco Frassoni, Carmen Di Grazia, Francesca Gualandi, Stefania Bregante, Riccardo Varaldo, Anna Ghiso, Andrea Bacigalupo
Journal: Blood (2011)
Theranostic Treatment of Metastatic Bone Pain With 177Lu-DOTMP
Authors: Tapas Das, Ajit Shinto, Koramadai Karuppuswamy Kamaleshwaran, Sharmila Banerjee
Journal: Clinical Nuclear Medicine (2016)

Radiochemical studies and biological evaluation in animal models have shown superior radiochemical properties and better clearance pattern for 177Lu-DOTMP compared with 177Lu-EDTMP, an agent recently proven to be efficacious and safe for metastatic bone pain palliation. This prompted us to initiate the clinical evaluation of 177Lu-DOTMP. The images represent the whole-body scans of a prostate cancer patient (man, 67 years) with skeletal metastases recorded after administering 3.7 GBq (100 mCi) of 177Lu-DOTMP.
Targeted Deep Sequencing of Genetic Alterations Identified By Whole Exome Sequencing Reveals Clonal Evolution in Pediatric T-Lymphoblastic Leukemia
Authors: Joachim Kunz, Obul R Bandapalli, Tobias Rausch, Adrian Stuetz, Paulina Pechanska, Yassen Assenov, Juliane Eilers, Elena Orlova, Judit Sagi, Martin Stanulla, Martin Schrappe, Rupert Handgretinger, Renate Kirschner-Schwabe, Jana Hof, Cornelia Eckert, Smadar Avigad, Rolf Koehler, Martina U. Muckenthaler, Jan Korbel, Andreas E Kulozik
Journal: Blood (2014)
GW27-e1160 Ultrasound-targeted Microbubble Destruction Enhances the PHD2-shRNA to restore Myocardial Function following Ischemic Injury in Rats via Improving the Efficacy of Therapeutic Angiogenesis
Authors: Xhang Li, Zhenxing Sun, Mingxing Xie
Journal: Journal of the American College of Cardiology (2016)
TCT-528 Bioabsorbable Vascular Scaffold Overexpansion: Insights from in-vitro post-expansion experiments
Authors: Nicolas Foin, Renick D. Lee, Alessio Mattesini, Jing Ni Chan, Yingying Huang, Gianluca Caiazzo, Enrico Fabris, Ismail D. Kilic, Subbu S. Venkatraman, Carlo Di Mario, Philip Wong, Holger Nef
Journal: Journal of the American College of Cardiology (2015)
Effect of Experience and Training on the Concordance and Precision of Strain Measurements
Authors: Tomoko Negishi, Kazuaki Negishi, Paaladinesh Thavendiranathan, Goo-Yeong Cho, Bogdan A. Popescu, Dragos Vinereanu, Koji Kurosawa, Martin Penicka, Thomas H. Marwick, Svend Aakhus, Manish Bansal, Andreea Calin, Jelena Čelutkienė, Nobuyuki Fukuda, Krassimira Hristova, Masaki Izumo, Andre La Gerche, Julie Lemieux, Diana Mihalcea, Philip Mottram, Ryoko Morimoto Ichikawa, Mark Nolan, Tomas Ondrus, Stéphanie Seldrum, Mitra Shirazi, Evgeny Shkolnik, Babitha Thampinathan, Liza Thomas, Hirotsugu Yamada, Satoshi Yuda
Journal: JACC. Cardiovascular imaging (2016)
Reduced intensity conditioning and allogeneic stem cell transplantation (RI AlloSCT) in children and adolescents with malignancies following unrelated cord blood and matched family donor AlloSCT results in ≥90% achieving ≥98% donor chimerism
Authors: G. Del Toro, P. Satwani, M. B. Bradley, D. George, D. Yamashiro, J. Garvin, D. Skerrett, O. Bessmertny, C. Van de Ven, M. S. Cairo
Journal: Journal of Clinical Oncology (2004)

8506 Background: Although RI AlloSCT induces complete donor chimerism in adults with hematological malignancies (Slavin et al, Blood 91:756–763, 1998), there is little data in children and adolescents. We determined the degree of engraftment following RI AlloSCT in 14 children with malignant diseases following matched-family donor (MFD) and umbilical cord blood transplants (UCBT). Methods: Donors included: 8 unrelated UCB, 1 related UCB, and 5 related peripheral blood stem cells (PBSC). RI conditioning consisted of: fludarabine and busulfan +/- rabbit anti-thymocyte globulin (r-ATG) or alemtuzumab (N=12); and fludarabine, melphalan +/- horse ATG (N=2). Graft-vs.-host disease (GVHD) prophylaxis consisted of tacrolimus and mycophenolate mofetil. Demographics were as follows: median age 14.5 (0.5–21) yrs; 6 pts. with Hodgkin's disease (3 in 2nd CR, 1 in PR, 2 pts with PD), 1 pt with non-Hodgkin's lymphoma in PR, 2 pts with neuroblastoma - 1 in CR and one with PD, 2 pts with Wilms' tumor and PD, 1 pt with chronic myelogenous leukemia in chronic phase, and 2 pts with acute myelogenous leukemia in 1st CR. The UCB median cell dose was 3.43 × 107 NC/kg (0.9–10.8). The PBSC dose was 5.7 × 108 NC/kg (4.3–9.9). Results: Maximal donor chimerism (MDC) following UCBT was 100% for 7 pts, 98% for 1 pt, and 55% for 1 pt (died of PD on day +79), and 100% for all 5 pts after PBSC transplant. Graft failure was not observed. There was one non-infectious grade 4 toxicity (hepatic) secondary to busulfan, which resolved. The probability of developing acute GVHD grade II-IV in UCB vs. PBSC transplants was 11.11% (CI, 0–31.64) vs. 60.0% (CI, 38.1–81.9). The overall probability of chronic GVHD was 32.5% (CI, 0–73.2). The probability of 1-yr OS is 67.7 % (CI, 48.69–99.45). 1-yr OS for good-risk patients vs. poor-risk patients was 100% vs. 33.3% (CI, 20.47–93.81). Conclusions: RI AlloSCT is feasible and tolerable in children and adolescents with malignancies. Evaluation of graft-vs.-malignancy effect is ongoing, but 4 patients with active disease responded. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Pharmaceuticals
Magnetic Resonance Imaging–Detected Features of Inflammation and Erosions in Symptom‐Free Persons From the General Population
Authors: L. Mangnus, H. W. van Steenbergen, M. Reijnierse, A. H. M. van der Helm‐van Mil
Journal: Arthritis & Rheumatology (2016)

The use of magnetic resonance imaging (MRI)-detected inflammation and joint damage in the diagnosis of rheumatoid arthritis is recommended by a European League Against Rheumatism imaging task force. This recommendation is based on the sensitivity of MRI and not on specificity. Knowledge of the prevalence of MRI-detected features in symptom-free persons, however, is pivotal when considering MRI for diagnostic purposes.From November 2013 to December 2014, 196 symptom-free persons of different ages were recruited from the general population. Inclusion criteria were no history of inflammatory arthritis, no joint symptoms during the previous month, and no clinically detectable arthritis on physical examination. Contrast-enhanced MRIs of the dominant metacarpophalangeal (MCP), wrist, and metatarsophalangeal (MTP) joints were obtained using a 1.5T scanner and scored by 2 readers for synovitis, bone marrow edema, tenosynovitis, and erosions. For analyses at the joint level, MRI-detected inflammation was considered present if both readers scored the image as positive.Of 193 persons scanned (ages 19-89 years), only 28% had no single inflammatory feature and 22% had no erosions. Primarily low-grade features were observed. All MRI features were positively correlated with age (P < 0.001). Preferential locations for synovitis were MCP2, MCP3, the wrists, and MTP1. Bone marrow edema was frequently present in MCP3, the scaphoid, and MTP1. Tenosynovitis was infrequent, except for in the extensor carpi ulnaris. Preferential locations for erosions were MCP2, MCP3, MCP5, the distal ulna, MTP1, and MTP5. Tables with age-, location-, and inflammation type-dependent frequencies were constructed. Simultaneous colocalized presence of synovitis, bone marrow edema, tenosynovitis, or erosions occurred.MRI-detected inflammation and erosions are prevalent in symptom-free persons from the general population, especially at older ages and at preferential locations.