tbuckley/cabot-search huggingface dataset:
Moving From Clinical Trials to Precision Medicine
Authors: Michael J. Pencina, Eric D. Peterson
Journal: JAMA (2016)

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Health literacy and quality of life in an inner city laryngectomy population
Authors: K. L. Jacobson, M. J. Connolly, A. Y. Chen, P. A. S. Johnstone
Journal: Journal of Clinical Oncology (2005)

8191 Background: Treatment for advanced laryngeal cancer is either total laryngectomy (TL) or a combination of chemotherapy and radiation. In order to make a treatment choice, patients must have functional health literacy (HL), the ability to successfully read, understand and apply medical instructions. Previous data indicate low literacy among adults ≥50 years old (when head and neck cancers occur most). Thus, we hypothesize that HL will be similarly deficient in this age group. This study describes the prevalence of inadequate HL and quality of life among an inner-city indigent cancer TL population. Methods: The records of the Grady Memorial Hospital Tumor Registry were reviewed for all patients having undergone TL for cancer between 01–01-88 and 12–31-02. Patients were invited to participate in face-to-face interviews measuring sociodemographics, health status (SF-12), and HL (S-TOFHLA). Of 30 eligible patients, 4 were deceased or too sick to participate, 4 refused, 10 could not be located or lived out of state, and 4 were unable to be reached (n=8; 27% response rate). Results: No patients had evidence of disease recurrence at time of interview, with a median follow-up since diagnosis of 4.3 years. Half had pT3N0 disease, and half had pT4N0; none had received chemotherapy, and 75% had received adjuvant radiation therapy. Of patients interviewed, 75% were black, 88% were male, and 50% had less than a high school education, with a median annual household income of <$10,000. Median age was 59.5 years, and only 37.5% reported having excellent or very good health. Over one-third of patients had severely inadequate HL skills (median score of 12, where scores up to 53 are ranked inadequate). Half were unable to correctly identify at what time to take medications, nearly two-thirds (63%) were unable to correctly interpret an appointment card, and one-third could not correctly interpret how to take medicine on an empty stomach. Conclusions: In the presence of fair quality of life, many inner-city TL patients have inadequate HL skills. HL should be considered in the initial management of such patients because after TL, individuals who struggle with low health literacy have lost a primary mean of communication. Supported by NCMHD grant 5P60-MD-000525. No significant financial relationships to disclose.
A Biobank for Long-Term and Sustainable Research in the Field of Congenital Heart Disease in Germany
Authors: Thomas Pickardt, Eva Niggemeyer, Ulrike M.M. Bauer, Hashim Abdul-Khaliq
Journal: Genomics Proteomics & Bioinformatics (2016)

Congenital heart disease (CHD) is the most frequent birth defect (0.8%-1% of all live births). Due to the advance in prenatal and postnatal early diagnosis and treatment, more than 90% of these patients survive into adulthood today. However, several mid- and long-term morbidities are dominating the follow-up of these patients. Due to the rarity and heterogeneity of the phenotypes of CHD, multicenter registry-based studies are required. The CHD-Biobank was established in 2009 with the aim to collect DNA from patients and their parents (trios) or from affected families, as well as cardiovascular tissues from patients undergoing corrective heart surgery for cardiovascular malformations. Clinical/phenotype data are matched to the International Paediatric and Congenital Cardiac Code (IPCCC) and the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10). The DNA collection currently comprises samples from approximately 4200 participants with a wide range of CHD phenotypes. The collection covers about 430 trios and 120 families with more than one affected member. The cardiac tissue collection comprises 1143 tissue samples from 556 patients after open heart surgery. The CHD-Biobank provides a comprehensive basis for research in the field of CHD with high standards of data privacy, IT management, and sample logistics.
Hypertension, Proteinuria and Overall Survival in Elderly Cancer Patients Treated with Bevacizumab
Authors: V. Launay-Vacher, N. Janus, I.L. Ray-Coquard, J. Gligorov, F. Selle, P. Beuzeboc, C. Daniel, J. Spano, J. Thery, F. Goldwasser, O. Mir, J. Rey, C. Jouannaud, J. Morere, S. Oudard, F. Scotte, M. Azizi, R. Dorent, G. Deray
Journal: Annals of Oncology (2014)
A phase I trial of intravesical antisense oligonucleotide targeting heat shock protein 27 (OGX-427) for the treatment of non-muscle-invasive bladder cancer.
Authors: Alan I. So, Peter C. Black, Kim N. Chi, Antonio Hurtado-Col, Martin E. Gleave
Journal: Journal of Clinical Oncology (2012)

286 Background: The treatment options to prevent recurrence and progression in patients with non-muscle invasive bladder cancer (NMIBC) are limited. Heat Shock Protein 27 (Hsp27) is a cytoprotective protein that has been shown to be important in a variety of malignancies, including bladder cancer (BCa), where it has been linked to therapeutic resistance and disease progression. OGX-427 is a 2nd generation (2’-MOE) antisense oligonucleotide that potently inhibits Hsp27 expression in vitro and in vivo. Methods: We initiated a phase I clinical study to assess the safety, pharmacokinetic (pk), pharmacodynamic (pd) and biologic effects of intravesical treatments of OGX-427 using a presurgical dose-escalating design for patients with BCa. Eligible patients include patients with Ta, T1 or carcinoma-in-situ and candidates for transurethral resection of the bladder tumor (TURBT), or patients with muscle invasive BCa (&gt;cT2) and candidates for radical cystectomy (RC). Patients are treated with intravesical OGX-427 on days 1,3,5, and 8 and then undergo surgery on day 9-12. Dose is escalated after tolerability and safety assessment for each cohort at 20uM, 50 uM, 100uM, 250uM, 500uM, and 750uM. Results: To date, we have enrolled 13 patients in the trial and have completed the 250uM cohort. 12 patients had NMIBC and one had cT2 disease and underwent a cystectomy. No significant drug-related adverse events have been reported; no dose limiting toxicity was observed and only one patient developed gross hematuria (grade 1) within 24 hours of administration of drug that spontaneously resolved. Pathological staging of surgical specimens revealed that five patients (38%) had complete responses (p0). The remaining NMIBC patients had pTa tumors that ranged from G1-G2; the sole patient undergoing cystectomy had pT2aG3 bladder cancer. Accrual of the two remaining cohorts will be complete shortly and the pd and pk analysis will be performed once all specimens are available. Conclusions: OGX-427 is well tolerated intravesically with minimal toxicity. Our results indicate early evidence of activity of OGX-427 against bladder cancer that requires confirmation in phase II/III studies.
Over half of qualified GPs are now women, show HSCIC data
Authors: Abi Rimmer
Journal: BMJ (2016)

Over 50% of qualified GPs in England are now women, data from the Health and Social Care Information Centre have shown.

Provisional experimental figures released by the HSCIC showed that the proportion of female GPs, excluding GP registrars, retainers, and locums, rose from 49.9% in 2014 to 51.9% in 2015.1

When salaried GPs, registrars, and retainers were included, women accounted for 54.4% of the workforce in 2015, up from 52.4% in …
Abstract 18789: A Learning Collaborative Model to Improve Door to Needle Time for Stroke Thrombolysis in Chicago
Authors: Shyam Prabhakaran, Kathleen O’Neill
Journal: Circulation (2014)

Background: Door-to-needle (DTN) times have remained suboptimal despite overall increases in tissue plasminogen activator use (tPA) for stroke in Chicago. The American Heart Association’s (AHA) Quality Enhancement for Speedy Thrombolysis in Stroke (QUESTS) initiative aimed to identify barriers to reduce DTN times at Chicago’s 15 primary stroke centers (PSCs) and increase the proportion of patients treated with tPA within 60 minutes of hospital arrival. Methods: Starting in January 2013, we used face-to-face and on-site meetings with each PSC’s stroke team members to share AHA Target Stroke best practices and strategies to reduce DTN time. A survey of current practice was completed at each site to determine opportunities for improvement and repeated at 1 year to assess implementation of new strategies. We used the Get With The Guidelines (GWTG) Stroke registry to aggregate baseline data DTN times and track performance in each quarter of 2013. Results: At baseline, 5 strategies were notably under-utilized at Chicago’s 15 PSCs: 1) Direct to CT scanner (baseline: 0 sites; 1 year: 5 sites); 2) pre-mixing tPA (baseline: 1 site; 1 year: 14 sites); 3) tPA prior to laboratory results (baseline: 3 sites; 1 year: 7 sites); 4) stroke code activation at triage (baseline: 4 sites; 1 year: 13 sites); and 5) streamlined consent process (baseline: 0 sites; 1 year: 12 sites. The proportion of patients treated within 60 minutes increased in each quarter of 2013 from 25% in quarter 1 to 60% in quarter 4 (p&lt;0.01). The median DTN time decreased from 89.5 minutes in quarter 1 to 55 minutes in quarter 4 (p&lt;0.01). Conclusions: Using a learning collaborative model to implement strategies to reduce DTN times among 15 PSCs in Chicago, we observed major improvements within a few months. Regional collaboration and best practices sharing should be a model for rapid and sustainable system-wide quality improvement.
Case 6-1976
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Christopher Longcope, Robert E. Scully
Journal: New England Journal of Medicine (1976)

Presentation of CaseA 44-year-old woman was admitted to the hospital because of virilization.Her menarche had appeared at the age of eight years and was not affected by monthly injections of an unknown medication. By the age of 11 years she had well developed breasts and dense axillary and pubic hair. During her first pregnancy at the age of 19 years she gained 28 kg and noticed the development of several black hairs on her chin. After delivery she could not nurse because of scanty lactation, and subsequently the hair on her chin increased slowly in amount. During the . . .
RNA-seq Identification of RACGAP1 as a Metastatic Driver in Uterine Carcinosarcoma
Authors: Shijun Mi, Mingyan Lin, Jurriaan Brouwer-Visser, Jennifer Heim, David Smotkin, Tiffany Hebert, Marc J. Gunter, Gary L. Goldberg, Deyou Zheng, Gloria S. Huang
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Uterine carcinosarcoma is a rare aggressive malignancy frequently presenting at advanced stage of disease with extrauterine metastases. Median survival is less than 2 years due to high relapse rates after surgery and poor response to chemotherapy or radiotherapy. The goal of this study was to identify novel therapeutic targets. Experimental Design: We applied RNA-seq analysis to prospectively collected uterine carcinosarcoma tumor samples from patients undergoing primary surgical resection and for comparison, normal endometrial tissues from postmenopausal women undergoing hysterectomy for benign indications. Functional assays were done in primary carcinosarcoma cell lines developed from patients and in established cell lines, as well as a cell line–derived xenograft model. Validation was done by analysis of an independent cohort of patients with uterine carcinosarcoma from The Cancer Genome Atlas (TCGA). Results: Rac GTPase–activating protein 1 (RACGAP1) was identified to be highly upregulated in uterine carcinosarcoma. Functional assays showed that RACGAP1 mediates motility and invasion via regulation of STAT3 phosphorylation and survivin expression. RACGAP1 depletion or survivin inhibition abrogated motility and invasiveness of carcinosarcoma cells, while RACGAP1 overexpression conferred invasiveness to endometrial adenocarcinoma cells. In the TCGA cohort, RACGAP1 expression correlated with survivin expression and extrauterine spread of disease. Conclusions: The RACGAP1–STAT3–survivin signaling pathway is required for the invasive phenotype of uterine carcinosarcoma and is a newly identified therapeutic target in this lethal disease. Clin Cancer Res; 22(18); 4676–86. ©2016 AACR.
ATNT-02DETERMINANTS OF RESPONSES AND RESISTANCE TO ABT-414: RESULTS OF NEXT-GENERATION SEQUENCING
Authors: Andrew M. Scott, Lisa Roberts-Rapp, Hui K. Gan, Xin Lu, Andrew B. Lassman, Martin van den Bent, Kyriakos P. Papadopoulos, Ryan Merrell, Priya Kumthekar, David A. Reardon, Irina Sokolova, Minghao Song, Rupinder Kular, Erica Gomez, JuDee Fischer, Anahita Bhathena, Kyle Holen, Rose Lai, Peter Ansell
Journal: Neuro-Oncology (2015)

BACKGROUND: ABT-414 is an EGFR-targeted antibody conjugated to the toxic antimicrotubule agent monomethylauristatin F. In an ongoing phase I study (abstract by Gan et al), all confirmed responses as determined by RANO criteria have been restricted to patients whose tumors harbor EGFR amplification. Genomic analysis was performed to explore mechanisms associated with innate sensitivity and acquired resistance. METHODS: Whole exome sequencing (WES) of diagnostic tumor samples from relapsed glioblastoma patients treated with ABT-414 + temozolomide (TMZ) or ABT-414 alone was performed. WES data were correlated with EGFR amplification and EGFRvIII as determined by FISH and RT-PCR, respectively. To explore acquired resistance, tissue was collected prior to starting ABT-414/TMZ from a patient who had a complete response and again postrelapse. WES and RNAseq of collected tissue were performed to identify mutations and associated transcriptional changes occurring at relapse. RESULTS: WES has been completed for 13 patients (14 samples) and is ongoing for 11 additional samples. Of the 9 samples determined to be EGFR amplified by FISH, 8 were amplified by WES. All 5 samples determined to be EGFRvIII positive by RT-PCR were positive by WES. In the patient with serial tumor collection, EGFR amplification and EGFRvIII expression was not significantly altered postprogression. Mutations in 25 genes were detected only in the postrelapse biopsy including in TOP2A and TOPORS, both of which are reported to be associated with chemotherapeutic resistance. RNAseq demonstrated a 1.7-fold upregulation of TUBGCP4 at the time of relapse. Given the involvement of TUBGCP4 in tubulin biology, this may potentially influence sensitivity to ABT-414's microtubule toxin. CONCLUSIONS: To date, EGFR amplification is necessary but not sufficient for response to ABT-414. Genomic profiling of longitudinally collected tissue may suggest factors involved in treatment sensitivity and acquired resistance. Ongoing mutation analysis in additional samples will be presented.
Effect of nivolumab (NIVO) on quality of life (QoL) in patients (pts) with treatment-naïve advanced melanoma (MEL): results of a phase III study (CheckMate 066)
Authors: G.V. Long, V. Atkinson, P.A. Ascierto, C. Robert, J.C. Hassel, P. Rutkowski, K.J. Savage, F. Taylor, C. Coon, I. Gilloteau, H.B. Dastani, I. Waxman, A.P. Abernethy
Journal: Annals of Oncology (2015)
P0925 : Pharmacological evaluation of pioglitazone and candesartan cilexetil in a novel mouse model of nonalcoholic steatohepatitis, modified choline-deficient, amino acid-defined diet fed LDL Receptor knockout mice
Authors: S. Tsuchiya, Y. Amano, O. Isono, M. Imai, F. Shimizu, M. Asada, S. Imai, A. Harada, Y. Yasuhara, R. Tozawa, H. Nagabukuro
Journal: Journal of Hepatology (2015)
Nailfold Videocapillaroscopic Features and Other Clinical Risk Factors for Digital Ulcers in Systemic Sclerosis: A Multicenter, Prospective Cohort Study
Authors: Maurizio Cutolo, Ariane L. Herrick, Oliver Distler, Mike O. Becker, Emma Beltran, Patrick Carpentier, Clodoveo Ferri, Murat Inanç, Panayiotis Vlachoyiannopoulos, Harbajan Chadha‐Boreham, Emmanuelle Cottreel, Thomas Pfister, Daniel Rosenberg, Juan V. Torres, Vanessa Smith
Journal: Arthritis & Rheumatology (2016)

To identify nailfold videocapillaroscopic features and other clinical risk factors for new digital ulcers (DUs) during a 6-month period in patients with systemic sclerosis (SSc).In this multicenter, prospective, observational cohort study, the videoCAPillaroscopy (CAP) study, we evaluated 623 patients with SSc from 59 centers (14 countries). Patients were stratified into 2 groups: a DU history group and a no DU history group. At enrollment, patients underwent detailed nailfold videocapillaroscopic evaluation and assessment of demographic characteristics, DU status, and clinical and SSc characteristics. Risk factors for developing new DUs were assessed using univariable and multivariable logistic regression (MLR) analyses.Of the 468 patients in the DU history group (mean ± SD age 54.0 ± 13.7 years), 79.5% were female, 59.8% had limited cutaneous SSc, and 22% developed a new DU during follow-up. The strongest risk factors for new DUs identified by MLR in the DU history group included the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs (categorized as 0, 1, 2, or ≥3), and the presence of critical digital ischemia. The receiver operating characteristic (ROC) of the area under the curve (AUC) of the final MLR model was 0.738 (95% confidence interval [95% CI] 0.681-0.795). Internal validation through bootstrap generated a ROC AUC of 0.633 (95% CI 0.510-0.756).This international prospective study, which included detailed nailfold videocapillaroscopic evaluation and extensive clinical characterization of patients with SSc, identified the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs at enrollment, and the presence of critical digital ischemia at enrollment as risk factors for the development of new DUs.
Abstract P6-09-08: Exposure to multiple sources of polycyclic aromatic hydrocarbon and breast cancer incidence
Authors: AJ White, PT Bradshaw, AH Herring, SL Teitelbaum, J Beyea, SD Stellman, SE Steck, I Mordukhovich, SM Eng, LS Engel, K Conway, M Hatch, AI Neugut, RM Santella, MD Gammon
Journal: Cancer Research (2016)

Abstract Background. Previous epidemiologic studies, including our own, have consistently linked long-term exposure to single-source polycyclic aromatic hydrocarbons (PAHs) to increased breast cancer incidence. It is unclear whether single sources, specific groups, or all PAH sources should be targeted for breast cancer risk reduction. This study considers the impact on breast cancer incidence from multiple PAH exposure sources in a single model, which better reflects exposure to these complex mixtures. Methods. In a population-based case-control study conducted on Long Island, New York (N=1,508 breast cancer cases/1,556 controls), a Bayesian hierarchical regression approach was used to estimate adjusted posterior means and credible intervals (CrI) for the adjusted odds ratios (ORs) for PAH exposure sources, considered singly and as groups: active smoking; residential environmental tobacco smoke (ETS); indoor and outdoor air pollution; and grilled/smoked meat intake. Results. Most women were exposed to PAHs from multiple sources. In a hierarchical model, breast cancer incidence was positively associated with ETS from a spouse (OR=1.20, 95%CrI=1.03, 1.42) and residential synthetic firelog burning (OR=1.30, 95%CrI=1.06, 1.60). Additionally, PAH exposure groups, including ingestion (OR=1.45, 95%CrI=1.16, 1.79), indoor stove/fireplace use (OR=1.30, 95%CrI=1.02, 1.62), and total indoor sources (active smoking, ETS from spouse, grilled/smoked meat intake, stove/fireplace use, OR=1.46, 95%CrI=1.03, 2.05), were associated with increased breast cancer incidence. Conclusions. Groups of PAH sources, especially those for ingestion and indoor sources, were associated with a 30-50% increase in breast cancer incidence. PAH exposure is ubiquitous and a potentially modifiable breast cancer risk factor. Citation Format: White AJ, Bradshaw PT, Herring AH, Teitelbaum SL, Beyea J, Stellman SD, Steck SE, Mordukhovich I, Eng SM, Engel LS, Conway K, Hatch M, Neugut AI, Santella RM, Gammon MD. Exposure to multiple sources of polycyclic aromatic hydrocarbon and breast cancer incidence. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-09-08.
House dust mite–induced asthma causes oxidative damage and DNA double-strand breaks in the lungs
Authors: Tze Khee Chan, Xin Yi Loh, Hong Yong Peh, W.N. Felicia Tan, W.S. Daniel Tan, Na Li, Ian J.J. Tay, W.S. Fred Wong, Bevin P. Engelward
Journal: Journal of Allergy and Clinical Immunology (2016)
261P Tolerability and efficacy of neoadjuvant chemotherapy with three-weekly interval methotrexate, doxorubicin, vinblastine and cisplatin regimen for patients with locally advanced bladder cancer
Authors: S. Arai, T. Hara, H. Hashimoto, Y. Shinoda, M. Komiyama, T. Otsuka, H. Fujimoto, Y. Hayashi
Journal: Annals of Oncology (2015)