tbuckley/cabot-search huggingface dataset:
Thinking outside the lungs: ‘other’ risk factors for pneumonia hospitalisation
Authors: C I Bloom, J K Quint
Journal: Thorax (2017)

The symptoms of pneumonic infection can be traced back through history; first being described during early Greek civilisation. But it wasn't until the 19th century the disorder was described in its own right, once causative bacteria were observed. Although mortality rates then rapidly declined, with the mass production of antibiotics, today it still remains a serious global problem.1

At the bedside, several determinants are now well recognised as severity markers for community-acquired pneumonia (CAP), such as age >65 years, COPD, smoking and dementia.2 In addition, we all look out for immunosuppressive treatments, and appreciate infection is often more severe in people who are immunocompromised, but other factors, such as androgen-deprivation therapy (ADT) may not usually be considered.

Respiratory clinicians are highly likely to treat patients with prostate cancer, the second most common cancer in the UK with a rapidly growing incidence (147/10 000 in 2014, predicted to be 233/100 000 in 2035).3 As prostate …
A Quality of Life Study Utilizing the EORTC QLQ-30 and EORTC QLQ-HDC29 Questionnaires for the Interview of 215 Patients Who Received Autologous or Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Akos G. Czibere, Verena Heymann, Ingmar Bruns, Thomas Schroeder, Roland Fenk, Fabian Zohren, Mustafa Kondakci, Sebastian Balleisen, Rainer Haas, Guido Kobbe
Journal: Blood (2009)
CD34+ Donor Chimerism and Wilms Tumor Gene 1 (WT1) Expression Provide an Early Indication of Relapse in Patients with Acute Leukemias and MDS after Hematopoietic Cell Transplantation (HCT) with Reduced-Intensity Conditioning.
Authors: Max Hubmann, Ralph Burkhardt, Georg Franke, Michael Cross, Markus Scholz, Sabine Leiblein, Joachim Thiery, Dietger W. Niederwieser, Thoralf Lange
Journal: Blood (2006)
Relationship of Race/Ethnicity and Survival After Single Umbilical Cord Blood Transplantation
Authors: Karen K. Ballen, John P. Klein, Tanya L. Pedersen, Joanne Kurtzberg, Hillard M. Lazarus, Charles F. LeMaistre, Paulette Mehta, Jeanne Palmer, Michelle Setterholm, John R. Wingard, Steven Joffe, Susan K. Parsons, Galen E. Switzer, Stephanie J. Lee, J. Douglas Rizzo, Navneet S. Majhail, for the Health Policy Working Committee of the CIBMTR
Journal: Blood (2010)
Spleen Tyrosine Kinase (SYK) Is Overexpressed and Represents a Potential Therapeutic Target in Chronic Lymphocytic Leukemia
Authors: Maike Buchner, Simon Fuchs, Gabriele Prinz, Dietmar Pfeifer, Kilian Bartholomé, Nina Chevalier, Laurent Vallat, Jens Timmer, John G Gribben, Hassan Jumaa, Hendrik Veelken, Christine Dierks, Katja Zirlik
Journal: Blood (2008)
CD14-CD15+, Possible Cells Are Potent Myeloid-Derived Suppressor Cells, Which Affect the Pathogenesis of Induction and Regression in Methotrexate-Mediated Lymphoproliferative Disorders
Authors: Michihide Tokuhira, Shuntaro Saito, Yuka Tanaka, Yasuyuki Takahashi, Yuta Kimura, Tatsuki Tomikawa, Tomoe Anan, Shuji Momose, Morihiro Higashi, Takayuki Shimizu, Takehiko Mori, Takayuki Tabayashi, Reiko Watanabe, Jun-ichi Tamaru, Shinichiro Okamoto, Masahiro Kizaki
Journal: Blood (2016)
Oxygen-Independent Stabilization of the Oxygen-Labile Transcription Factor HIF-1α with Dimethyloxalyl Glycine or FG-4497 Increases Hematopoietic Stem Cell Quiescence In Vivo and Mobilization in Response to G-CSF
Authors: Catherine Forristal, Bianca Nowlan, Valerie Barbier, Domenica McCarthy, Gail Walkinshaw, Ingrid G Winkler, Jean-Pierre Levesque
Journal: Blood (2011)
Inhibition of the Akt Pathway in MM Cell Lines by the Anti-TfR-IgG3-Avidin Fusion Protein (Anti-TfR-IgG3-Av): Role in Chemosensitization to CDDP-Induced Apoptosis
Authors: Eriko Suzuki, Kazuo Umezawa, Gustavo Helguera, Tracy R Daniels, Gary Schiller, James R. Berenson, Manuel L Penichet, Benjamin Bonavida
Journal: Blood (2008)
Enhanced Cytarabine and Daunorubicin Population Pharmacokinetics When Administered As CPX-351: A Novel Liposomal Formulation Not Requiring Dose Reduction for Mild Renal or Hepatic Dysfunction
Authors: Mina Nikanjam, Edmund Capparelli, Jeffrey E. Lancet, Jonathan E. Kolitz, Arthur C. Louie, Gary J. Schiller
Journal: Blood (2016)
Annals Story Slam - What Does One Remember After a Long Medical Career?
Authors: Eliot Nierman
Journal: Annals of Internal Medicine (2017)

Web Exclusives7 March 2017Annals On Being a Doctor Story Slam - What Does One Remember After a Long Medical Career?FREEEliot Nierman, MDEliot Nierman, MDFrom Penn Internal Medicine University City, Philadelphia, Pennsylvania.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0033 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - What Does One Remember After a Long Medical Career? "What Does One Remember After a Long Medical Career?," by Dr. Eliot Nierman (Duration 8:19)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From Penn Internal Medicine University City, Philadelphia, Pennsylvania.Current Author Address: Eliot Nierman, MD; e-mail, eliot.[email protected]upenn.edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 March 2017Volume 166, Issue 5Page: SS1 ePublished: 7 March 2017 Issue Published: 7 March 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...
Importance of genetic heterogeneity in curing adult acute leukemia (AL)
Authors: Clara D. Bloomfield
Journal: Journal of Clinical Oncology (2009)

s1 Forty-five years ago adult AL was incurable. Since then we have discovered the striking heterogeneity of AL and its importance in selecting therapy, resulting in cure of increasing numbers of patients. Publication of the French-American-British classification 34 years ago resulted in acceptance that morphology and cytochemistry separated AL into two different diseases, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), that required separate treatment. During the next 15–20 years the importance of cytogenetics in dissecting ALL and AML into entities requiring different therapies became widely accepted, resulting in 2001 in their first incorporation into the World Health Organization (WHO) classification of AL. Over the last 10 years, discovery of molecular abnormalities within cytogenetic groups has further increased our ability to selectively treat and increasingly cure AL. The most striking example of increased curability of AL is acute promyelocytic leukemia, in which targeted therapy combined with chemotherapy has increased survival from a 2-week median to an 80% cure rate. Recognition of increased sensitivity of a genetic subtype of AML to high-dose cytarabine (HiDAC) has increased the cure rate of core-binding factor (CBF) AML from &lt;10%–25% to 55%–60%. Recent discovery of the adverse impact of KIT mutations in CBF AML may allow the addition of tyrosine kinase inhibitors to HiDAC to substantially further increase cure. Among adult de novo AML 40%–45% are cytogenetically normal (CN); the striking molecular heterogeneity of CN-AML is now being recognized and promises to allow individualized approaches that improve substantially upon the current cure rate of 40%. In adult ALL the major adverse subgroup has a Philadelphia chromosome (PH+). New molecularly targeted approaches are allowing remissions in over 90% of PH+ elderly patients and appear likely to substantially cure an increasing fraction of younger PH+ adults. New approaches to studying the leukemia genome and epigenome should improve our understanding of AL heterogeneity, identify new therapeutic targets, and allow the cure of most patients.
Treatment of Lower Risk MDS with Del 5q by Lenalidomide, with or without G-CSF: Current Results of the French Patient Named Program (ATU)
Authors: Fabien Lebras, Marie Sebert, Virginie Eclache, Thierry Lamy, Jacques Delaunay, Sorin Visanica, Francois Dreyfus, Anne Banos, Michel Blanc, Caroline Besson, Xavier Thomas, Philippe Rodon, Norbert Vey, Martine Gardembas, Frederic Bauduer, Jean-Francois Ramee, Alain Delmer, Delphine Rea, Pascal Turlure, Odile Beyne-Rauzy, Agnes Guerci, Joel Ceccaldi, J. Dugay, Pierre Fenaux, Lionel Ades
Journal: Blood (2008)
Incremental Value of Cocktail 18F-FDG and 18F-NaF PET/CT Over 18F-FDG PET/CT Alone for Characterization of Skeletal Metastases in Breast Cancer
Authors: Mohan J. Roop, Baljinder Singh, Harmandeep Singh, Ankit Watts, Pavneet S. Kohli, Bhagwant R. Mittal, Gurpreet Singh
Journal: Clinical Nuclear Medicine (2017)

The aim of this study was to evaluate the incremental value of cocktail F-FDG/F-NaF PET/CT over F-FDG PET/CT alone for detection of skeletal metastases in breast cancer patients.Seventy patients with locally advanced/recurrent breast cancer were prospectively included. All patients underwent whole-body F-FDG PET/CT and cocktail F-FDG/F-NaF PET/CT within a span of 1 week. Both studies were evaluated to detect presence of skeletal/marrow metastases on PET/CT images by 2 nuclear medicine physicians. Clinical and radiological correlation/follow-up was used as criterion standard.Of 70 patients, 50 (71.0%) had locally advanced breast cancer, and 20 had recurrent breast cancer. On patient-wise analysis, both cocktail PET/CT and F-FDG PET/CT identified skeletal/marrow lesions in 23 (32.8%) of 70 patients. In 8 patients (11.4%), only cocktail PET/CT identified skeletal/marrow lesions, whereas F-FDG PET/CT was negative. In the rest of the 39 patients (55.8%), no skeletal/marrow lesion was identified on both scans. Good correlation was noted between cocktail PET/CT and F-FDG PET/CT results (r = 0.785, P < 0.0001). Cocktail PET/CT detected lesions in significantly more number of patients than F-FDG PET/CT alone (P = 0.007). On lesion-wise analysis, cocktail PET/CT detected more number of lesions in 20 patients as compared with F-FDG-PET/CT alone. Both scans detected same number of lesions in the rest of 11 patients with positive findings. A total of 32 additional lesions were identified on cocktail PET/CT imaging as compared with F PET/CT alone (P < 0.0001).Cocktail F-FDG and F-NaF PET/CT is superior to F-FDG PET/CT alone for the detection of skeletal/marrow metastases in breast cancer. It can be a better alternative to F-FDG PET/CT alone in facilities where both tracers are available.
Abstract OT2-01-16: Evaluating targets in localized and advanced breast cancer by sequencing tumor DNA at diagnosis and after progression (ELSA)
Authors: AG Gaba, SF Powell, WL Jennifer, LL Megan, C Chun-Hung, BJ Lora, JM Ford
Journal: Cancer Research (2017)

Abstract Background: Breast cancer therapy exerts strong selection pressure that shapes the evolution of the cancer. Despite the importance of these treatment-induced changes for the success of subsequent therapy, tumors have been rarely resampled and reanalyzed, with the exception of hematopoietic malignancies. The availability of next generation sequencing (NGS) has made it possible to get highly accurate sequencing that allows detection of mutations and other genetic alterations not only from tumor biopsies but also from circulating DNA fragments. Objectives: To demonstrate the evolution of the molecular genotype of breast cancer as patients are diagnosed, treated, and upon relapse. This will be accomplished by NGS of the tumor at key time points during the natural history of the disease. The molecular profile at diagnosis will be compared to the profile at recurrence/metastasis and after treatment for metastasis. Correlation with treatment response and adverse clinical outcomes will be determined. Study Design and Eligibility: We have initiated a prospective observational study in patients with a new diagnosis of Stage I, II and III breast cancer and an ECOG performance status of 0, 1 or 2. Patients should be medically suitable to give informed consent for a biopsy or surgical procedure. Enrollment will occur at community-based cancer centers with inclusion of under-served populations. Methodology: Tumor samples and blood samples are collected at - initial diagnosis/definitive surgery, first local relapse, diagnosis of metastasis and at first progression after treatment for metastatic disease. Molecular genotype will be analyzed from the tumor samples and from the circulating tumor DNA (ctDNA) in blood samples at each of the time points. ctDNA will also be assessed on blood samples collected annually till the diagnosis of metastasis and then more frequently at 3-6 month intervals in patients with high risk breast cancer. Statistical Design/Size of study sample: Formal sample size calculations are not required for this study as by design, it is based on participation. There is no discrete endpoint that can be powered by sample size calculation for this study. We are screening all patients who are diagnosed with breast cancer at our facility. The proposed enrollment is 300 patients per year. The study launched in December 2015 at 4 of our community-based cancer centers. Current enrollments is 46 patients. Citation Format: Gaba AG, Powell SF, Jennifer WL, Megan LL, Chun-Hung C, Lora BJ, Ford JM. Evaluating targets in localized and advanced breast cancer by sequencing tumor DNA at diagnosis and after progression (ELSA) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-01-16.
The European Medicines Agency and Publication of Clinical Study Reports
Authors: Anna L. Davis, James Dabney Miller
Journal: JAMA (2017)

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Systemic Heme and Iron Overload Results in Depletion of Serum Hemopexin, Haptoglobin and Transferrin and Correlates with Markers of Endothelial Activation and Lipid Oxidation in Beta Thalassemia Major and Intermedia
Authors: Francesca Vinchi, Gregory M Vercellotti, John D. Belcher, Eitan Fibach, Hala Zreid, Rushdy Rasras, Hussam Ghoti, Martina U. Muckenthaler, Eliezer A. Rachmilewitz
Journal: Blood (2016)
Association Between Diabetes and 1-Year Adverse Clinical Outcomes in a Multinational Cohort of Ambulatory Patients With Chronic Heart Failure: Results From the ESC-HFA Heart Failure Long-Term Registry
Authors: Marco Dauriz, Giovanni Targher, Cécile Laroche, Pier Luigi Temporelli, Roberto Ferrari, Stephan Anker, Andrew Coats, Gerasimos Filippatos, Maria Crespo-Leiro, Alexandre Mebazaa, Massimo F. Piepoli, Aldo P. Maggioni, Luigi Tavazzi
Journal: Diabetes Care (2017)

OBJECTIVE Diabetes mellitus is associated with an increased risk of cardiovascular disease (CVD) and death. Because the prevalence of diabetes is rising worldwide and chronic heart failure (CHF) is becoming increasingly common with the aging population, it is timely to examine the impact of diabetes per se on 1-year adverse outcomes in patients with CHF. RESEARCH DESIGN AND METHODS We prospectively assessed whether diabetes status independently affected the 1-year risk of all-cause and CVD mortality and first hospitalization for worsening heart failure (HF) in a multinational cohort of 9,428 outpatients with CHF enrolled in the European Society of Cardiology and Heart Failure Association Long-Term Registry. RESULTS Compared with those patients without diabetes, patients with diabetes (n = 3,440, 36.5%) had higher cumulative rates of 1-year all-cause death (9.4% vs. 7.2%; adjusted hazard ratio [HR] 1.28; 95% CI 1.07–1.54), CVD death (4.8% vs. 3.8%; adjusted HR 1.28; 95% CI 0.99–1.66), and HF hospitalization (13.8% vs. 9.3%; adjusted HR 1.37; 95% CI 1.17–1.60), all independent of age, sex, BMI, smoking, systolic blood pressure, estimated glomerular filtration rate, hemoglobin, HF etiology, left ventricular ejection fraction, hypertension, statin use, and prior stroke or chronic obstructive pulmonary disease. Among CHF patients with HbA1c measurements available at baseline (n = 2,567), there was a significant and independent association between increasing HbA1c levels and the risk of 1-year survival outcomes. CONCLUSIONS The presence of diabetes markedly increases the risk of 1-year adverse clinical outcomes in outpatients with CHF independent of multiple common risk factors. More effective and personalized treatment for diabetes should be considered in this particularly high-risk patient population.
Abstract P3-04-23: Combination therapy of targeted anticancer pathways and estrogen receptor ligands and their responses in <i>de novo</i> andtamoxifen resistant cell models
Authors: LM Gutgesell, R Xiong, GRJ Thatcher, DA Tonetti
Journal: Cancer Research (2017)

Abstract Approximately 75% of breast cancers are classified as Estrogen Receptor positive (ER+). Tamoxifen, a selective estrogen receptor modulator (SERM), is the standard of care for many of these ER+ breast cancer patients. Unfortunately, tamoxifen resistance occurs in almost 50% of patients within 5 years of treatment, and endocrine-independence accompanying resistance also negates the effects of aromatase inhibitors. Combination therapy is increasingly used in non-cytotoxic therapeutic approaches in many types of cancer. The potential exists that endocrine resistance can be lessened, eliminated, or overcome through targeted therapy in combination with endocrine therapy. Inhibition of kinase signaling (e.g. via CDK4/6 or PI3K) and other pathways (e.g. HSP90) are expected to be effective in combination with endocrine therapy. We have discovered a variety of ER ligands with potential as endocrine therapeutic agents, based upon a single chemical scaffold with a diverse set of pharmacological responses: including SERMs, selective ER downregulators (SERDs), selective estrogen mimics (SEMs), and selective human ER partial agonists (ShERPAs). To predict which agents in combination with these endocrine-targeted ligands would be of potential therapeutic benefit it was necessary to develop 3D spheroidal cultures of ER+ breast cancer cell lines: including endocrine-dependent lines; and cell lines made endocrine-independent either by extended exposure to tamoxifen or extended deprivation of estradiol. In contrast to 2D cultures, drug response in 3D spheroidal cell cultures was predictive of response to treatment in mouse xenograft studies. Growth of endocrine-dependent cell lines was, as expected, inhibited by SERDs; and endocrine-independent, tamoxifen-resistant cell lines were also sensitive to SERD treatment, although one cell line was largely resistant. Growth of all three tamoxifen-resistant cell lines was inhibited by SEMs/ShERPAs. Importantly, regardless of the type of endocrine therapeutic agent studied, concentrations leading to saturation of the target (ER) did not cause cell death. Equally, all endocrine therapies studied benefited from combination treatment with other agents, leading to enhanced cell death. Citation Format: Gutgesell LM, Xiong R, Thatcher GRJ, Tonetti DA. Combination therapy of targeted anticancer pathways and estrogen receptor ligands and their responses in de novo andtamoxifen resistant cell models [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-04-23.
Abstract P4-12-07: <i>CCND1</i> amplification in early breast cancer patients: Correlation with subtypes and prognosis
Authors: DC Hanf, PA Fasching, IE Villalobos, A Gasparyan, D Wachter, A Santiago, R Guzman, S Weihbrecht, V Hanf, A Hartmann, MW Beckmann, MF Press
Journal: Cancer Research (2017)

Abstract Background: Mechanisms of progress and recurrence of early breast cancer (BC) have gained importance since several targeted therapeutic options in metastatic breast cancer have been introduced over the last years, especially in hormone receptor positive BC. This study investigates the amplification of cell cycle regulator cyclin D1 gene (CCND1) amplification as one possible progression mechanism. Patients &amp; Methods: Patients from an unselected cohort of early BC patients were included into this study. A tissue microarray (TMA) was available for n=832 patients with early breast cancer. CCND1 amplification was assessed after FISH (Abbott Vysis LSI CCND1 SpectumOrange/CEP11 SpectrumGreen Probes Kit). A CCND1/CEP11-ratio ≥ 2.0 was considered as amplification. Staining was successful in 545 tumor cores. Amplification results were correlated with clinical patient and tumor characteristics and survival analyses were performed with regard to distant disease free survival and overall survival. Results: CCND1 amplification was found in 13.6% of patients. Triple negative, luminal A like, luminal B like and HER2 positive tumors were amplified in 7.5%, 7.8%, 18.6% and 15.7% respectively (p = 0.010). CCDN1 amplification was significantly associated with a higher grading and a higher body mass index. Furthermore an amplification was seen more frequently in lobular BC and ductal BC than other histological subtypes. Survival analysis showed a reduced DDFS for patients with CCDN1-amplification. 5 year DDFS rates were 90.6% for non-amplified tumors and 86.0% for amplified tumors (p, log-rank =0.066 ). 5 year OS rates were 93.0% for non-amplified tumors and 90.1% for amplified tumors (p, log-rank =0.119). Adjusted for age, tumor size, nodal status and molecular subtype, cox regression showed HR of 1.3 (95% CI: 0.76-2.5, p=0.46) for DDFS and a HR of 1.33 (95% CI: 0.7-2.53, p=0.38) for OS. Conclusion: With a 13.6% prevalence in all breast cancer patients, mainly present in luminal B like cancers, CCND1-amplification is a genetic aberration associated with an unfavorable prognosis. Within hormone receptor positive women CCDN1 amplification might play a role in treatment resistance mechanisms in early breast cancer patients. Citation Format: Hanf DC, Fasching PA, Villalobos IE, Gasparyan A, Wachter D, Santiago A, Guzman R, Weihbrecht S, Hanf V, Hartmann A, Beckmann MW, Press MF. CCND1 amplification in early breast cancer patients: Correlation with subtypes and prognosis [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-12-07.
High Resolution Purification and Characterization of Human Cord Blood-Derived CD34–negative SCID-Repopulating Cells with a Very Immature Phenotype.
Authors: Mari Murakami, Yoshikazu Matsuoka, Ryusuke Nakatsuka, Masaya Takahashi, Tsuyoshi Nakamoto, Katsuhiko Yasuda, Kazuo Matsui, Yasushi Uemura, Yutaka Sasaki, Takashi Tsuji, Shirou Fukuhara, Yoshiaki Sonoda
Journal: Blood (2009)