tbuckley/cabot-search huggingface dataset:
Cardioprotective effect of the secretome of Sca-1+ and Sca-1− cells in heart failure: not equal, but equally important?
Authors: Stephanie Könemann, Luiz V Sartori, Stefan Gross, Stefan Hadlich, Jens-Peter Kühn, Rasmita Samal, Martin Bahls, Stephan B Felix, Kristin Wenzel
Journal: Cardiovascular Research (2019)

Both progenitor and differentiated cells were previously shown to secrete cardioprotective substances, but so far there has been no direct comparison of the paracrine effects of the two cell types on heart failure. The study sought to compare the paracrine effect of selected progenitors and the corresponding non-progenitor mononuclear cardiac cells on the cardiac function of transgenic heart failure mice. In addition, we aimed to further enhance the paracrine effect of the cells via pretreatment with the heart failure mediator aldosterone.Transgenic heart failure mice were injected with the supernatant of murine cardiac stem cell antigen-1 positive (Sca-1+) and negative (Sca-1-) cells with or without aldosterone pretreatment. Cardiac function was determined using small animal magnetic resonance imaging. In addition, heart failure markers were determined using enzyme-linked immunosorbent assay, RT-PCR, and bead-based multiplexing assay. While only the secretome of aldosterone pretreated Sca-1+ cells led to a significant improvement in cardiac function, N-terminal pro brain natriuretic peptide plasma levels were significantly lower and galectin-1 levels significantly higher in mice that were treated with either kind of secretome compared with untreated controls.In this first direct comparison of the paracrine effects of progenitor cells and a heterogeneous population of mononuclear cardiac cells the supernatants of both cell types showed cardioprotective properties which might be of great relevance for endogenous repair. During heart failure raised aldosterone levels might further increase the paracrine effect of progenitor cells.
Tryptophan catabolism differentiates breast cancer patients from healthy controls but does not predict outcome
Authors: C.E. Onesti, F. Boemer, C. Josse, S. Leduc, C. Poulet, V. Bours, G. Jerusalem
Journal: Annals of Oncology (2019)

Background: Indoleamine 2,3 dioxygenase (IDO) catalyzes the conversion of tryptophan (Trp) into kynurenine (Kyn), an immunosuppressive metabolite involved in T regulatory cell differentiation. IDO is expressed in many cancer types, including breast cancer (BC), but its association with prognosis is controversial. Here we analyze Kyn/Trp ratio, known as a surrogate indicator of IDO activity, in BC patients and in healthy control (CTRL). Methods: We prospectively enrolled 350 subjects, i.e. CTRL or BC patients (pts). All the subjects underwent a blood sample withdrawal at BC diagnosis or the day of the screening mammography for CTRL. After centrifugation, plasma was collected and stored at -80 °C. Kyn and Trp were determined on a TQ5500 tandem mass spectrometer after chromatographic separation. Statistical analysis was performed with SPSS v24 software. Results: We enrolled 146 CTRL and 204 stage I-III BC (85.1% ductal, 11.4% lobular, 3.5% other). The median age was 56 years (range 26-86). Overall, 29.7% of the cases were Luminal A, 44.1% Luminal B, 6.9% HER2-enriched and 19.3% triple negative. All the pts received surgery, 126 NAC with 43 pathological complete response (pCR), and 43 adjuvant chemotherapy. We observed significant higher Kyn, Trp and their ratio for CTRL vs BC (Table). We observed a higher Kyn/Trp ratio in estrogen receptor (0.042 ± 0.016 vs 0.038 ± 0.012, p 0.04) and progesterone receptor (0.041 ± 0.016 vs 0.038 ±0.012, p 0.048) negative pts, and a lower ratio for lobular histology (0.033 ± 0.008 vs 0.039 ± 0.014 in ductal vs 0.039 ± 0.008 in other, p 0.005). PCR was associated with higher Kyn (1.81 ± 0.47 µM/L vs 1.65 ± 0.59 µM/L, p 0.039), but not with Kyn/Trp ratio (p 0.367). Moreover, Kyn/Trp ratio was not predictive of disease free survival (p 0.194) and breast cancer specific survival (p 0.509). Table. Kyn and Trp in CTRL and BC pts. Table55PCTRLBCP valueKyn (µM/L)1.951 ± 0.7081.770 ± 0.535<0.0001Trp (µM/L)48.8 ± 14.244.6 ± 11.10.002Kyn/Trp0.041 ± 0.0190.038 ± 0.0130.019 Open table in a new tab Conclusions: Kyn/Trp ratio is not predictive of pCR and outcome. Kyn, Trp and their ratio are higher in CTRL than in BC pts. The concomitant reduction of Kyn and Trp suggest a rapid catabolism in presence of BC. Further studies, with the dosage of downstream metabolites are necessary to confirm it. Legal entity responsible for the study: Laboratory of Human Genetics, GIGA Institute, Liège, Belgium. Funding: FNRS. Disclosure: All authors have declared no conflicts of interest.
Smoking and Lung Cancer Mortality in the United States From 2015 to 2065
Authors: Richard J. Rosen
Journal: Annals of Internal Medicine (2019)

Letters21 May 2019Smoking and Lung Cancer Mortality in the United States From 2015 to 2065Richard J. Rosen, MDRichard J. Rosen, MDCone Health, Greensboro, North Carolina (R.J.R.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0065 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:It is reassuring that the downward trend in smoking and lung cancer mortality noted by Jeon and colleagues (1) will continue into the next half-century if efforts to prevent smoking initiation and promote smoking cessation are maintained at current levels. Although an ounce of prevention may be worth several pounds of cure when it comes to lung cancer, the authors do not consider potential progress in the treatment of this condition in the next 50 years. Recent advances in therapy are exciting. Recognition of molecular subgroups susceptible to target therapy has caused substantial responses that may herald ...References1. Jeon J, Holford TR, Levy DT, Feuer EJ, Cao P, Tam J, et al. Smoking and lung cancer mortality in the United States from 2015 to 2065. A comparative modeling approach. Ann Intern Med. 2018;169:684-93. [PMID: 30304504]. doi:10.7326/M18-1250 LinkGoogle Scholar2. Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ, Wu YL, et al. Lung cancer: current therapies and new targeted treatments. Lancet. 2017;389:299-311. [PMID: 27574741] doi:10.1016/S0140-6736(16)30958-8 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Cone Health, Greensboro, North Carolina (R.J.R.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0065. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoSmoking and Lung Cancer Mortality in the United States From 2015 to 2065 Jihyoun Jeon , Theodore R. Holford , David T. Levy , Eric J. Feuer , Pianpian Cao , Jamie Tam , Lauren Clarke , John Clarke , Chung Yin Kong , and Rafael Meza Metrics Cited byAssociation of Silica Dust Exposure and Cigarette Smoking With Mortality Among Mine and Pottery Workers in ChinaCrosstalk between let-7a-5p and BCL-xL in the Initiation of Toxic Autophagy in Lung Cancer 21 May 2019Volume 170, Issue 10Page: 740KeywordsCancer preventionCancer screeningCancer treatmentConflicts of interestDisclosureLung and intrathoracic tumorsMortalityRespiratory system proceduresSmoking cessation ePublished: 21 May 2019 Issue Published: 21 May 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Defining EGFR amplification status for clinical trial inclusion
Authors: Pim J French, Marica Eoli, Juan Manuel Sepulveda, Iris de Heer, Johan M Kros, Annemiek Walenkamp, Jean-Sebastien Frenel, Enrico Franceschi, Paul M Clement, Michael Weller, Peter Ansell, Jim Looman, Earle Bain, Marie Morfouace, Thierry Gorlia, Martin van den Bent
Journal: Neuro-Oncology (2019)

Abstract Background Precision medicine trials targeting the epidermal growth factor receptor (EGFR) in glioblastoma patients require selection for EGFR-amplified tumors. However, there is currently no gold standard in determining the amplification status of EGFR or variant III (EGFRvIII) expression. Here, we aimed to determine which technique and which cutoffs are suitable to determine EGFR amplification status. Methods We compared fluorescence in-situ hybridization (FISH) and real-time quantitative (RT-q)PCR data from patients screened for trial inclusion into the Intellance 2 clinical trial, with data from a panel-based next generation sequencing (NGS) platform (both DNA and RNA). Results By using data from &gt;1000 samples, we show that at least 50% of EGFR amplified nuclei should be present to define EGFR gene amplification by FISH. Gene amplification (as determined by FISH) correlates with EGFR expression levels (as determined by RT-qPCR) with receiver operating characteristics analysis showing an area under the curve of up to 0.902. EGFR expression as assessed by RT-qPCR therefore may function as a surrogate marker for EGFR amplification. Our NGS data show that EGFR copy numbers can strongly vary between tumors, with levels ranging from 2 to more than 100 copies per cell. Levels exceeding 5 gene copies can be used to define EGFR-amplification by NGS; below this level, FISH detects very few (if any) EGFR amplified nuclei and none of the samples express EGFRvIII. Conclusion Our data from central laboratories and diagnostic sequencing facilities, using material from patients eligible for clinical trial inclusion, help define the optimal cutoff for various techniques to determine EGFR amplification for diagnostic purposes.
Author’s reply to Iliffe and Manthorpe
Authors: Rajvinder Samra
Journal: BMJ (2019)

Thank you Iliffe and Manthorpe for your thoughtful response to my editorial on burnout.12 I note your points that we do not know what burnout is, as long as studies are measuring it differently, and that the effect of burnout on patient care is not clear.

In relation to the first point, …
Prognostic Implications of Plaque Characteristics and Stenosis Severity in Patients With Coronary Artery Disease
Authors: Joo Myung Lee, Ki Hong Choi, Bon-Kwon Koo, Jonghanne Park, Jihoon Kim, Doyeon Hwang, Tae-Min Rhee, Hyung Yoon Kim, Hae Won Jung, Kyung-Jin Kim, Kawase Yoshiaki, Eun-Seok Shin, Joon-Hyung Doh, Hyuk-Jae Chang, Yun-Kyeong Cho, Hyuck-Jun Yoon, Chang-Wook Nam, Seung-Ho Hur, Jianan Wang, Shaoliang Chen, Shoichi Kuramitsu, Nobuhiro Tanaka, Hitoshi Matsuo, Takashi Akasaka
Journal: Journal of the American College of Cardiology (2019)
Abstract 18367: Association of Neighborhood Socioeconomic Status With Smoking Cessation Assistance Provided in the Cardiology Practices: Insights From the NCDR PINNACLE Registry
Authors: Mayank Sardana, Yuanyuan Tang, Jared W Magnani, Phillip G Jones, Jeroan J Allison, Ira S Ockene, Thomas M Maddox, Salim S Virani, David D McManus
Journal: Circulation (2017)

Background: Disadvantaged neighborhood socioeconomic status (SES) is associated with increased cardiovascular risk, including smoking. We hypothesized that neighborhood SES is also associated with ...
Development and Validation of a Cytogenetic Prognostic Index Predicting Survival in Multiple Myeloma
Authors: Aurore Perrot, Valérie Lauwers-Cances, Elodie Tournay, Cyrille Hulin, Marie-Lorraine Chretien, Bruno Royer, Mamoun Dib, Olivier Decaux, Arnaud Jaccard, Karim Belhadj, Sabine Brechignac, Jean Fontan, Laurent Voillat, Hélène Demarquette, Philippe Collet, Philippe Rodon, Claudine Sohn, François Lifermann, Frédérique Orsini-Piocelle, Valentine Richez, Mohamad Mohty, Margaret Macro, Stéphane Minvielle, Philippe Moreau, Xavier Leleu, Thierry Facon, Michel Attal, Hervé Avet-Loiseau, Jill Corre
Journal: Journal of Clinical Oncology (2019)

The wide heterogeneity in multiple myeloma (MM) outcome is driven mainly by cytogenetic abnormalities. The current definition of high-risk profile is restrictive and oversimplified. To adapt MM treatment to risk, we need to better define a cytogenetic risk classification. To address this issue, we simultaneously examined the prognostic impact of del(17p); t(4;14); del(1p32); 1q21 gain; and trisomies 3, 5, and 21 in a cohort of newly diagnosed patients with MM.Data were obtained from 1,635 patients enrolled in four trials implemented by the Intergroupe Francophone du Myélome. The oldest collection of data were used for model development and internal validation. For external validation, one of the two independent data sets was used to assess the performance of the model in patients treated with more current regimens. Six cytogenetic abnormalities were identified as clinically relevant, and a prognostic index (PI) that was based on the parameter estimates of the multivariable Cox model was computed for all patients.In all data sets, a higher PI was consistently associated with a poor survival outcome. Dependent on the validation cohorts used, hazard ratios for patients in the high-risk category for death were between six and 15 times higher than those of patients in the low-risk category. Among patients with t(4;14) or del(17p), we observed a worse survival in those classified in the high-risk category than in those in the intermediate-risk category. The PI showed good performance for discriminating between patients who died and those who survived (Harrell's concordance index greater than 70%).The cytogenetic PI improves the classification of newly diagnosed patients with MM in the high-risk group compared with current classifications. These findings may facilitate the development of risk-adapted treatment strategies.
Abstract 5814: Association between <i>ADH1B</i> and <i>ADH1C</i> haplotype tag SNPs and breast cancer risk, and the interaction with alcohol drinking
Authors: Catalin Marian, Lara Sucheston, Jing Nie, Amy Millen, David Goerlitz, Maurizio Trevisan, M Russell, T Nochajski, CB Ambrosone, A Hutson, SB Edge, D Vito, Peter G Shields, Jo L Freudenheim
Journal: Cancer Research (2008)

Abstract Alcohol consumption has been found to be associated with breast cancer with some consistency. Alcohol dehydrogenase is rate limiting in alcohol metabolism. We investigated the association of haplotype tag SNPs in ADH1B and ADH1C with breast cancer risk and the interaction with alcohol drinking in a population-based case control study (the WEB Study) conducted in western New York between 1996 and 2001. Genomic DNA and SNP genotyping was performed by allelic discrimination real time PCR for 991 cases and 1698 controls. Haplotype tag SNPs were selected from the Caucasian HapMap data. Lifetime alcohol consumption was queried by interview. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Backwards selection was employed to obtain the most parsimonious model starting with the full model with interactions. Two tag SNPs, rs1042026 in ADH1B and rs1614972 in ADH1C, were associated with risk for postmenopausal women. The ADH1B SNP rs1042026 located in the 3’UTR is in LD with several functional SNPs from ADH6, ADH1A, ADH1B and ADH1C. This SNP was in Hardy Weinberg equilibrium in the postmenopausal control and not in postmenopausal cases, which strengthens the evidence of association. This SNP showed evidence of significant interaction with alcohol consumption. The OR for postmenopausal breast cancer in women with both CC genotype and who consume alcohol versus without the AA genotype and who abstain was 1.94, 95%CI 1.13-3.30. In addition, we found evidence of a trend for dose response depending on the amount of alcohol consumption when alcohol consumption was examined in three categories of abstainers, low and high consumption (p=0.08). The ADH1C SNP rs1614972 located in intron 8 is in LD with other six nonsynonymous exonic SNPs including the functional I350V (rs698). There was an interaction with alcohol consumption with the presence of the CC genotype and risk conferring a protective effect varying inversely proportional with the drinking level (p=0.0092). Moreover, the CC genotype decreased the odds of breast cancer in women who consume alcohol versus those that abstain regardless of the menopausal status (OR=0.56, 95%CI 0.35-0.90). In conclusion, haplotype tag SNPs in ADH1B and ADH1C were associated with breast cancer risk especially in postmenopausal women, and showed evidence of significant interaction with alcohol consumption. Supported by the following grants: DAMD-17-03-1-0446, DAMD-17-00-1-0417 and NCI-RO1CA92040 Marian C. was supported by an AVON-AACR International Scholar in Breast Cancer Research award
Former GP partner is jailed for 10.5 years for sexually molesting patients over two decades
Authors: Clare Dyer
Journal: BMJ (2019)

A former senior partner in a GP practice who sexually molested patients over two decades in the guise of medical examinations has been jailed for 10 and a half years.

Alan Tutin, 71, targeted women and girls who consulted him for minor ailments such as a wart on a foot and a cold, asking them to strip off for unnecessary breast or internal examinations at his Merrow Park surgery in Guildford, Surrey, between the early 1980s and 2003.1

The father …
Prognostic and predictive value of phosphorylated HER2, HER3 and PTEN expression in patients with HER2-positive breast cancer treated with trastuzumab
Authors: S. Debska-Szmich, R. Kusinska, M. Krakowska, R. Czyzykowski, U. Czernek, A. Zadrozna, P. Potemski
Journal: Annals of Oncology (2019)

Background: Trastuzumab improves survival in HER2-positive breast cancer patients. But there are no other predictive markers for the treatment and only half of patients benefit from it. Our aim is to evaluate an association between expression of proteins engaged into HER2-signaling pathway and overall survival of patients treated with trastuzumab. Methods: A retrospective analysis of 81 patients with breast cancer treated with trastuzumab in adjuvant (n = 45) or palliative (as a 1st to 5th line; n = 36) regimens in our institution from 2003 to 2010 was done. Immunohistochemistry staining for expression of phosphorylated HER2 (p-HER2), HER3 and PTEN was performed. We analyzed an association between expression of the proteins and overall survival (OS) and overall survival from start of trastuzumab treatment (OStrast) defined, respectively, as a time from date of diagnosis or time from start of trastuzumab to date of death or last observation. The relationship between tested parameters and survival was analyzed by the Cox regression models. We used Kruskall-Wallis analysis of variance and Fisher's exact test to verify correlation between the proteins expression and clinical features of the patients. Statistical significance was assumed when p < 0.05. Results: 55.6%, 32% and 34.6% of the tumors were positive for HER3, PTEN and p-HER2, respectively. Positivity of HER3 and PTEN correlated with larger size of tumors (p = 0.016 and p = 0.008, respectively) and p-HER2-positivity - with more advanced clinical stage (p = 0.032). Median follow-up was 141 months. We recorded, respectively, 14 and 34 deaths in adjuvant and in palliative group. We have not found any correlation between the expressions of the proteins and survival neither for patients treated with palliative nor adjuvant regimen. For 27 patients treated palliatively with trastuzumab in 1st or 2nd line we have shown a trend toward worse OStrast in p-HER2-positive subgroup (HR 2.39; 95%: 0.99 to 5.79; p = 0.053). For patients treated with adjuvant trastuzumab numerically higher mortality rate was recorded for p-HER2-positive patients (7/15 v. 7/30). Conclusions: p-HER2 may have predictive value for trastuzumab treatment but this observation needs validation. Legal entity responsible for the study: Medical University of Lodz Study was approved by Bioethical Committee of Medical University of Lodz (No. RNN/138/09/KE 12-05-.2009). Funding: Study was financed by means of European Social Fund (Integrated Regional Operational Program - Grants for innovative PhD studies) and statutory activities no. 503-1034-2. Disclosure: M. Krakowska: Sponsorship of a participation in conferences: Merck, Roche. R. Czyzykowski, U. Czernek: Investigator in clinical trial sponsored by Roche. P. Potemski: Lecture fees, travel support: Roche. All other authors have declared no conflicts of interest.
PAN-ENTERIC CAPSULE IN PATIENTS WITH MELENA AND A NEGATIVE UPPER ENDOSCOPY: A PILOT STUDY
Authors: A Mussetto, R Arena, O Triossi
Journal: Endoscopy (2019)

Melena can be caused both by bleeding from upper sources and from mid/lower gastrointestinal bleeding. Colonoscopy is frequently used to investigate melena after a non-diagnostic EGD but retrospective studies showed that its diagnostic and therapeutic yield is low. Aim of our study was to perform a pan-enteric capsule endoscopy (PCE) with PillCam Colon2 capsule and evaluate its ability to avoid unnecessary colonoscopies when performed on patients with melena after an initial negative upper endoscopy.
Les résultats de la résection endoscopique dans les cancers colorectaux superficiels sont-ils comparables à ceux des séries intéressant principalement les adénomes? Reste-t-il une place pour la résection piecemeal dans cette indication?
Authors: JP Ratone, E Bories, C Zemmour, F Caillol, C Pesenti, S Hoibian, S Godat, C De Chaisemartin, B Lelong, H Meillat, F Poizat, M Giovannini
Journal: Endoscopy (2019)

Ces deux dernières décennies, la résection endoscopique est devenue la première ligne de traitement des lésions prénéoplasiques colorectales. Peu de séries occidentales se sont intéressées uniquement aux cancers superficiels (4 – 4 et 5 de la classification de Vienne modifiée). Nous avons voulu rapporter nos résultats à moyen et long terme sur la prise en charge endoscopique de ces cancers. L'objectif principal était la survie sans récidive après résection endoscopique (GSSR). Les objectifs secondaires étaient la survie sans récidive (SSR) à moyen terme (3 à 6 mois, C1), la survie sans récidive à long terme (> 12 mois, C2), le taux de morbidité, le taux de chirurgie pour anatomopathologie non interprétable, la recherche de facteurs prédictifs d'échec et la gestion des récidives.
Combined immunodeficiency in a patient with c-Rel deficiency
Authors: Sarah Beaussant-Cohen, Faris Jaber, Michel J. Massaad, Sabrina Weeks, Jennifer Jones, Mohammed F. Alosaimi, Jacqueline Wallace, Waleed Al-Herz, Raif S. Geha, Janet Chou
Journal: Journal of Allergy and Clinical Immunology (2019)
La papille diverticulaire est-elle un facteur d'échec du cathétérisme de la voie biliaire principale dans la pathologie lithiasique? Expérience d'un service Marocain
Authors: S Jamal, H Seddik, F Nejjari, K Loubaris, F Bouhamou, H Boutallaka, S Morabit, A Aomari, I El Koti, A Benkirane
Journal: Endoscopy (2019)

Les diverticules duodénaux sont fréquents (6 à 20%). Ils siègent préférentiellement dans la région papillaire, ils sont alors appelés, juxta-, péri-, para-papillaires ou valériens. Ces derniers peuvent constituer une difficulté au cathétérisme de la voie biliaire principale (VBP) et sont plus fréquents en cas de lithiase biliaire associée.
COLON POLYPECTOMY: PROSPECTIVE ANALYSIS OF RISK FACTORS FOR MAJOR COMPLICATIONS
Authors: F Taveira, M Areia, M João, L Elvas, S Alves, D Brito, S Saraiva, AT Cadime
Journal: Endoscopy (2019)

Endoscopic excision of lesions in the colon is generally safe and decisively contributes for avoiding colorectal cancer. Complications such bleeding or perforation are well established. We intend to study the complications after colon polypectomy at our unit and to understand the risk factors associated.