tbuckley/cabot-search huggingface dataset:
Abstract 16554: Rapid Identification of Familial Hypercholesterolemia From Electronic Health Records
Authors: Maya S Safarova, Hongfang Liu, Iftikhar J Kullo
Journal: Circulation (2015)

Background: Familial hypercholesterolemia (FH) is an important public health burden as it is a relatively common Mendelian genetic disorder which is associated with dramatically increased lifetime risk for premature atherosclerotic cardiovascular disease (ASCVD) due to elevated plasma low-density lipoprotein cholesterol (LDL-C) levels. Little is known about prevalence and control of FH in the US. Objective: To develop an electronic phenotyping algorithm for rapid identification of FH in electronic health records (EHRs) and thereby address knowledge gaps in prevalence and control of FH. Methods: We identified patients in the Mayo Employee and Community Health (ECH) system who met the following inclusion criteria: 1) gave research authorization, 2) any LDL-C in EHR ≥190 mg/dL; 2) triglycerides &lt;400 mg/dL; 3) absence of secondary causes of hyperlipidemia (hypothyroidism, cholestatic liver diseases, nephrotic syndrome, renal failure, and pregnancy). Next we applied the Dutch Lipid Clinic Network (DLCN) criteria to ascertain FH cases. ASCVD-related diagnosis codes, laboratory data, and medications were obtained from structured EHR datasets. We used the Mayo natural language processing (NLP) system to ascertain presence of family and personal history of premature ASCVD, xanthomas and corneal arcus from clinical text notes. Results: Of a total of 131,000 patients seen in ECH clinics between July 1993 and December 2014, 6018 met the inclusion criteria. Implementing the electronic phenotyping algorithm for FH in these patients identified 178 definite and 369 probable cases (DLCN score &gt;8 and 6-8 points, respectively) with an overall FH prevalence of 0.4% (1:240). Blinded expert review of 160 randomly chosen patients showed positive and negative predictive values for electronic phenotyping algorithm at 85% and 90%, respectively. Only 40% of these patients achieved LDL-C ≤100 mg/dL on treatment. Conclusions: 1) An EHR-based phenotyping algorithm that included NLP had reasonable accuracy in ascertaining FH cases. 2) Implementing this algorithm revealed the prevalence of FH in the study cohort to be nearly twice the current estimate of 1:500 in the general population. 3) Less than half of the FH patients had optimal LDL-C levels on treatment.
Global Lung Function Initiative 2012 reference equations for spirometry in the Norwegian population
Authors: Arnulf Langhammer, Ane Johannessen, Turid L. Holmen, Hasse Melbye, Sanja Stanojevic, May B. Lund, Morten N. Melsom, Per Bakke, Philip H. Quanjer
Journal: European Respiratory Journal (2016)

We studied the fit of the Global Lung Function Initiative (GLI) all-age reference values to Norwegians, compared them with currently used references (European Community for Steel and Coal (ECSC) and Zapletal) and estimated the prevalence of obstructive lung disease. Spirometry data collected in 30 239 subjects (51.7% females) aged 12–90 years in three population-based studies were converted to z-scores. We studied healthy non-smokers comprising 2438 adults (57.4% females) aged 20–90 years and 8725 (47.7% female) adolescents aged 12–19 years. The GLI-2012 prediction equations fitted the Norwegian data satisfactorily. Median± sd z-scores were respectively 0.02±1.03, 0.01±1.04 and −0.04±0.91 for forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC) and FEV 1 /FVC in males, and −0.01±1.02, 0.07±0.97 and −0.21±0.82 in females. The ECSC and Zapletal references significantly underestimated FEV 1 and FVC. Stricter criteria of obstruction (FEV 1 /FVC &lt;GLI-2012 lower limit of normal (LLN)) carried a substantially higher risk of obstructive characteristics than FEV 1 /FVC &lt;0.7 and &gt;GLI-2012 LLN. Corresponding comparison regarding myocardial infarction showed a four-fold higher risk for women. The GLI-2012 reference values fit the Norwegian data satisfactorily and are recommended for use in Norway. Correspondingly, the FEV 1 /FVC GLI-2012 LLN identifies higher risk of obstructive characteristics than FEV 1 /FVC &lt;0.7.
<i>Annals</i> Graphic Medicine - Today's Doctor–Patient Relationship
Authors: Kartik A. Valluri
Journal: Annals of Internal Medicine (2016)

Web Exclusives4 October 2016Annals Graphic Medicine - Today's Doctor–Patient RelationshipFREEKartik A. Valluri, MDKartik A. Valluri, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G16-0014 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: The author has disclosed no conflicts of interest. Form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G16-0014.Author Information: Kartik A. Valluri, MD, is Chief Medical Resident at the University of Miami Miller School of Medicine at Holy Cross Hospital. He is passionate about innovating medical education and believes in the ability of artwork to showcase the greatest medical challenges of today. He can be reached at s.[email protected]miami.edu.Author Contributions: Conception and design: K.A. Valluri. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 October 2016Volume 165, Issue 7Page: W12KeywordsConflicts of interestDisclosureHealth careHospital medicineMedical education ePublished: 4 October 2016 Issue Published: 4 October 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A genome-wide association study identifies risk loci for childhood acute lymphoblastic leukemia at 10q26.13 and 12q23.1
Authors: J Vijayakrishnan, R Kumar, M Y R Henrion, A V Moorman, P S Rachakonda, I Hosen, M I da Silva Filho, A Holroyd, S E Dobbins, R Koehler, H Thomsen, J A Irving, J M Allan, T Lightfoot, E Roman, S E Kinsey, E Sheridan, P D Thompson, P Hoffmann, M M Nöthen, S Heilmann-Heimbach, K H Jöckel, M Greaves, C J Harrison, C R Bartram, M Schrappe, M Stanulla, K Hemminki, R S Houlston
Journal: Leukemia (2016)

Genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of childhood acute lymphoblastic leukemia (ALL). To identify new susceptibility loci for the largest subtype of ALL, B-cell precursor ALL (BCP-ALL), we conducted a meta-analysis of two GWASs with imputation using 1000 Genomes and UK10K Project data as reference (totaling 1658 cases and 7224 controls). After genotyping an additional 2525 cases and 3575 controls, we identify new susceptibility loci for BCP-ALL mapping to 10q26.13 (rs35837782, LHPP, P=1.38 × 10-11) and 12q23.1 (rs4762284, ELK3, P=8.41 × 10-9). We also provide confirmatory evidence for the existence of independent risk loci at 9p21.3, but show that the association marked by rs77728904 can be accounted for by linkage disequilibrium with the rare high-impact CDKN2A p.Ala148Thr variant rs3731249. Our data provide further insights into genetic susceptibility to ALL and its biology.
Impact of salvage surgery and radiotherapy on overall survival in patients with recurrent primary urethral cancer.
Authors: Georgios Gakis, Todd Matthew Morgan, Siamak Daneshmand, Kirk A. Keegan, Rebecca Helen Clayman, Johannes Mischinger, Harras B Zaid, Jan Hrbacek, Bedeir Ali-El-Dein, Sigolene Galland, Kola Olugbade, Michael Rink, Hans-Martin Fristche, Maximilian Burger, Sam Chang, Marek Babjuk, George N. Thalmann, Arnulf Stenzl, Jason Alexander Efstathiou
Journal: Journal of Clinical Oncology (2015)

4568 Background: To evaluate the impact of salvage therapy (ST) on overall survival (OS) in recurrent primary urethral cancer (PUC). Methods: A series of 154 patients (109 men, 45 women; median age: 66, IQR: 58-76) were diagnosed with PUC at ten referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank was used to estimate the impact of ST on OS. The median follow-up was 21 months (mean: 32 months; IQR: 4-48). Results: The modality of primary treatment was cystectomy+urethrectomy in 43 (27.9%), total/partial urethrectomy in 39/6 (25.3/3.9%), transurethral resection in 39 (25.3%), chemoradiotherapy (CRT), radiotherapy (RT), chemotherapy (CT) and other in 9 (5.8%), 4 (2.6%), 3 (1.9%) and 9 (5.8%) patients, respectively. Neoadjuvant CT/CRT and adjuvant CT were administered to 16/9 (10.4/5.8%) and 23 (14.9%) patients, respectively. The locations of recurrences were: urethral in 28 (18.2%), lymph nodes (LN) in 18 (11.7%), LN+distant in 12 (7.8%), LN+distant+urethral in 9 (5.8%), LN+urethral in 6 (3.9%), distant in 5 (3.3%), distant+urethral in 4 (2.6%) and no recurrence in 72 (46.8%). In the 82 patients with recurrences, the modality of ST was surgery in 32 (39.0%), RT in 8 (9.8%), surgery+RT in 5 (6.1%) and none in 37 (45.1%). The 3-year OS for patients free of any recurrence (I), with solitary and/or concomitant urethral recurrence (II) and non-urethral recurrence (III) were 86.7%, 74.5/% and 41.7% respectively (p < 0.001 for I vs. III, p = 0.001 for II vs. III, p = 0.53 for I vs. II). In patients with recurrences, those who underwent ST had similar 3-year OS (surgery: 84.9%, RT: 80%, surgery+RT: 80%) compared to patients with no recurrence (86.7%, p = 0.79), and exhibited superior 3-year OS compared to patients who did not undergo ST (27.6%; p < 0.001 compared to surgery; p = 0.016 to RT-based ST; p = 0.53 for surgery vs. RT-based ST). Receipt of perioperative CT/CRT (N = 16) did not impact on 3-year OS after ST (79.3%) compared to no CT/CRT (N = 29, 85.5%, p = 0.95). Conclusions: In this study, patients who underwent surgery or RT-based ST for recurrent PUC demonstrated improved OS compared to those who did not receive ST and exhibited similar survival to those who never developed recurrence after primary treatment.
Multimodality determination of HPV status in head and neck cancers (HNC) and development of an HPV signature.
Authors: Zhixiang Zuo, Michaela K. Keck, Arun Khattri, Rajesh D. Patel, Kim Walter, Mark W. Lingen, Kevin P. White, Peter S. Hammerman, Ezra E.W. Cohen, Kerstin Stenson, Elizabeth A. Blair, David S. Shames, Everett E. Vokes, Tanguy Y. Seiwert
Journal: Journal of Clinical Oncology (2013)

6008 Background: Determination of HPV status is prognostically important, and various testing modalities are commonly used. Discordant results are occasionally observed and a gold standard (for research purposes) is E6/E7 mRNA expression. We aimed to evaluate accuracy of multiple research HPV tests compared to p16 expression/anatomic site, and developed a new HPV signature that we hypothesize will capture HPV-related oncogenic processes independent for all HPV types. Methods: HNCsamples from 136 patients were evaluated by: 1) nested E6 PCR (DNA) (Sotlar 2004), 2) qPCR for E6, E7 (HPV16), E6, L1 (HPV18) (mRNA), 3) p16 expression by IHC and/or mRNA. Results were correlated with anatomic site. A gene expression (GE) signature was developed based on Agilent 4x44Kv2 data and validated in a second cohort. In equivocal cases mutational status of TP53 was evaluated. Results: p16/CDKN2A expression was unreliable outside the oropharynx (OP) (81% false-positives in non-OP tumors, compared to 12% for OP tumors). Anatomic site as described by clinical reports was unreliable. In our cohort, 52 out 77 OP (67.6%) were HPV positive by DNA and RNA based approaches, 3 only by DNA. DNA and RNA based approaches appeared to be similarly accurate and concordant in 97% of samples. The newly developed HPV-GE signature was highly accurate, and allowed to reconcile discrepant cases, suggesting that the DNA-based approach overcalled HPV(+) in 2 tumors while the RNA based approach underreported HPV status in two cases. Expression levels of E6/E7 mRNA showed extensive variability in HPV(+) samples. Interestingly the HPV-GE signature suggested continuous/overlapping biology for a minority of cases. Two tumors (1 supraglottis/HPV18, 1 oropharynx/HPV16) tested HPV(+) by DNA/RNA, p16/CDKN2A, and HPV-GE signature while at the same time having TP53 mutations. Conclusions: p16 should not be used outside the oropharynx and anatomic allocation may also be inaccurate. DNA and mRNA based approaches perform equally well and can be reconciled using the HPV-GE signature. The HPV-GE signature supports the hypothesis that HPV(+) and HPV(-) biology may overlap in a minority of cases.
Cytomegalovirus reactivation enhances the virulence of Staphylococcus aureus pneumonia in a mouse model
Authors: S. Hraiech, J. Bordes, J.L. Mège, X. de Lamballerie, R. Charrel, Y. Bechah, B. Pastorino, C. Guervilly, J.M. Forel, M. Adda, J.M. Rolain, H. Lepidi, D. Raoult, S. Lehingue, L. Papazian
Journal: Clinical Microbiology and Infection (2016)
Abstract 3666: Synthesis and evaluation of itraconazole analogues for hedgehog pathway inhibition
Authors: Jennifer Pace, M. Kyle Hadden
Journal: Cancer Research (2015)

Abstract The hedgehog (Hh) pathway is a developmental signaling pathway that plays a key role in embryonic development. While the pathway is generally quiescent during adult life, dysregulation of the Hh pathway can lead to cell proliferation and tumor growth. This abnormal Hh signaling is typically responsible for tumors associated with basal cell carcinoma (BCC) and medulloblastoma (MB) and inhibiting the Hh pathway is a valid target to develop novel chemotherapeutic agents. Most Hh inhibitors identified to date target the protein smoothened (SMO), a crucial component of the Hh pathway. Vismodegib is a SMO inhibitor that was recently approved by the FDA for the treatment of advanced BCC. However, there has been an emergence of resistance to Vismodegib; this resistance is a result of a point mutation in SMO. This occurrence of Vismodegib-resistant SMO mutations highlights the therapeutic need for new Hh pathway inhibitors. Itraconazole (ITZ), a well-known antifungal agent, was recently determined to be a potent inhibitor of the Hh pathway in vitro and in vivo; ITZ was also found to be a potent inhibitor of wild type SMO and Vismodegib-resistant SMO. ITZ is well-characterized and there is a good understanding of its potential side effects. This well-known safety profile makes ITZ a desirable drug candidate. Our ongoing studies on the ITZ scaffold are focused on exploring the regions of ITZ that are required for potent Hh pathway inhibition. The design, synthesis, and preliminary in vitro evaluation of these ITZ analogues will be reported herein. Citation Format: Jennifer Pace, M. Kyle Hadden. Synthesis and evaluation of itraconazole analogues for hedgehog pathway inhibition. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3666. doi:10.1158/1538-7445.AM2015-3666
Simultaneous Targeting of the Insulin-Like Growth Factor 1 Receptor (IGF-1R) and Anaplastic Lymphoma Kinase (ALK) in Embryonal and Alveolar Rhabdomyosarcoma
Authors: J.C. van Gaal, Y.M.H. Versleijen-Jonkers, M.H.S. Roeffen, U.E. Flucke, G. van der Heijden, A.J.H. Suurmeijer, E.S.J.M. De Bont, W.T.A. van der Graaf
Journal: Annals of Oncology (2012)
The role of postoperative PET-CT in the evaluation of patients with high-risk stage III colon cancer (CC).
Authors: Y. Kundel, B. Brenner, Y. Asman, N. Vaserberg
Journal: Journal of Clinical Oncology (2010)

e14089 Background: Routine PET-CT evaluation is still not indicated for stage III colon cancer (CC). However, accumulating data suggest that it may modify the staging and treatment of these patients (pts). Methods: Retrospective chart review of stage III CC pts who underwent PET-CT for being at high risk for systemic disease attributable to: early T stage (T < 3), grade > 3, < 12 lymph-nodes examined, > 3 involved lymph nodes, elevated pre- or postoperative CEA and/or CA-19.9. Demographic and clinicopathological data of pts found to have metastatic disease were compared to those who were negative. Results: Fifty-three pts, (22 males, median age 68 (36-88) years) were included. Pathologic FDG-uptake was observed in 23 (43%) pts, including 6 (11%) who had clear postoperative changes. The results of the PET-CT modified the management of 17 pts (32%): 10 (19%) were upstaged with altered treatment protocol (true positive) and 7 (13%) required further work-up which was negative (false-positive). Of all the parameters tested, only elevated postoperative CEA and CA-19.9 levels correlated with positive CT-PET (p = 0.001 and p = 0.0512, respectively). With a median follow-up of 25 months (range, 2-60 months), overall survival was 90% among both groups. Three pts in the positive group were disease free following metastectomy, 6 were alive with disease and one pt died of disease. Conclusions: Selective postoperative PET-CT influenced staging/therapy in 19% of Pts with high-risk stage III colon cancer. Postoperative CEA and Ca- 19.9 levels may play a role in selecting eligible pts. Failure to identify other parameters may be related to the preexisting selection bias and the small cohort. No significant financial relationships to disclose.
Retrospective analyses of m-RNA gene expression profile from formalin fixed paraffin embedded (FFPE) specimens in colorectal cancer (CRC) and correlation with chemoresponsiveness
Authors: M. G. Ghi, A. Paccagnella, G. Stanta, B. Murer, F. Petrera, S. Busato, S. Bonin, M. Medici, R. Carnuccio, R. Biason
Journal: Journal of Clinical Oncology (2007)

15039 Background: Patients with chemoresponsive tumors are more likely to have a survival advantage, consequently a great interest is being placed on the identification of predictive markers. Currently, the improving in the extraction techniques allow the detection of gene profile at the mRNA level from FFPE materials. The purpose of the study was to analyse the m-RNA level of specific genes from FFPE (Stanta et al, BioTechniques 1998), both primary tumor (T) and locoregional lymphnodes (N) in CRC patients treated with chemotherapy (CT), and to relate it with chemoresponsiveness. Material and Methods: RNA was extract from FFPE tumor specimen both in T and N. RNA was reversing transcribed to cDNA. From the cDNA sample, BRCA1, ERCC1, CES2 and TS gene transcripts were specifically amplified by PCR. ERCC1 and BRCA1 are involved in platinum-compound resistance; TS is involved in responses to 5Fluorouracil (5FU) and CES2 level expression was recently related to Irinotecan pro-drug activation. Eligible patients included metastatic CRC patients treated from March 2000 to December 2003 as first line CT with Oxaliplatin/5FU or Irinotecan/5FU or 5FU alone. Results: Forty-five consecutive patients were retrospectively analysed. 15 of them received Oxaliplatin/5FU, 15 Irinotecan/5FU and the other 15 5FU alone. Median age was 64 (range 46–75). 13 patients (28%) had received adjuvant CT. 32 patients (72%) had metastatic disease at the time of surgery. Global Response Rate was 44%. All 45 patients received 5FU and they were analysed for the level of TS expression. With Multiple Regression Analysis, no statistical significant relation between TS level expression and response to 5FU was observed (P=0.36). A strong relation was observed between ERCC1 and response to Oxaliplatin (P=0.006) and a possible correlation of BRCA1-exon11 level expression and response to Irinotecan (P=0.06). The analyses of CES2 and the relation between gene expression and survival are ongoing. Conclusions: The analyses of mRNA gene expression profile from FFPE could be use to predicting response to CT in CRC patients. To test this hypothesis, a randomized phase II-III prospective study of tailored therapy in metastatic CRC is planned. No significant financial relationships to disclose.
Cancer-Related Fatigue in Patients With and Survivors of Hodgkin Lymphoma: The Impact on Treatment Outcome and Social Reintegration
Authors: Karolin Behringer, Helen Goergen, Horst Müller, Indra Thielen, Corinne Brillant, Stefanie Kreissl, Teresa Veronika Halbsguth, Julia Meissner, Richard Greil, Peter Moosmann, Oluwatoyin Shonukan, Jens Ulrich Rueffer, Hans-Henning Flechtner, Michael Fuchs, Volker Diehl, Andreas Engert, Peter Borchmann
Journal: Journal of Clinical Oncology (2016)

Purpose Cancer-related fatigue occurs frequently in patients with Hodgkin lymphoma (HL) and has a major impact on their quality of life. We hypothesized that severe fatigue (sFA) might have an impact on patients’ treatment outcome and social reintegration. Methods Of 5,306 patients enrolled in the German Hodgkin Study Group’s fifth generation of clinical trials in HL (HD13, HD14, and HD15; nonqualified and older [&gt; 60 years] patients excluded), 4,529 provided data on health-related quality of life. We describe sFA (defined as a score ≥ 50 on the 0 to 100 scale from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30) before and up to 9 years after therapy and analyze its impact on treatment outcome and social reintegration. Results The proportion of patients reporting sFA was 37% at baseline and ranged from 20% to 24% during follow-up. Baseline sFA was associated with significantly impaired progression-free survival and a trend to impaired overall survival, which can be overcome in patients receiving highly effective HL therapies as applied in our fifth-generation trials. Our analysis revealed a significant negative association of sFA and employment in survivors: 5 years after therapy, 51% and 63% of female and male survivors, respectively, with sFA were working or in professional education, compared with 78% and 90% without sFA, respectively ( P &lt; .001 adjusted for age, sex, stage, baseline employment status, and treatment outcome). sFA was also associated with financial problems and the number of visits to a general practitioner and medical specialists. Conclusion sFA is an important factor preventing survivors from social reintegration during follow-up. This observation underscores the need to address fatigue as a significant diagnosis when treating patients with and survivors of cancer.