tbuckley/cabot-search huggingface dataset:
Comparison of patient populations identified by different PD-L1 assays in in triple-negative breast cancer (TNBC)
Authors: M. Scott, P. Scorer, C. Barker, H. Al-Masri
Journal: Annals of Oncology (2019)

Background: TNBC represents an unmet clinical need; the IMPassion 130 and KEYNOTE-086 trials have demonstrated efficacy of PD-1/PD-L1 targeted therapeutics in the metastatic/unresectable first line setting, with increased response in PD-L1 high populations, defined using different diagnostic assays and algorithms. This work addresses the need to establish PD-L1 assay concordance in TNBC. Methods: 196 TNBC cases were stained by IHC using the VENTANA PD-L1 (SP263), VENTANA PD-L1 (SP142), Dako PD-L1 IHC 28-8 pharmDx and Dako PD-L1 IHC 22C3 pharmDx assays. A single pathologist scored the proportions of membrane staining tumour cells (TC), staining immune cells (IC) and tumour occupied by immune cells. The proportion of tumour occupied by staining immune cells (ICTA) and Combined Positive Score (CPS) were derived. Concordance between assays was evaluated using the Spearman coefficient ρ. Concordance in patient status was assessed using overall, positive and negative percent agreement (OPA/PPA/NPA) at matched algorithms and cut-offs. Results: SP263, 22C3 and 28-8 assays showed good analytical correlation for TC staining (ρ = 0.84–0.89), but lower for SP142 (0.44-0.46), whereas all assays showed good correlation for ICTA (0.77-0.96) and CPS (0.78-0.95). OPA ranged from 58%–97% at matched algorithms (Table). Prevalence for SP142 ICTA≥1% and 22C3 CPS≥1 was in-line with IMPassion 130 and KEYNOTE-086, respectively. Conclusions: Analytical performance between SP263, 22C3 and 28-8 is very similar; SP142 stains fewer TCs and ICs. In contrast to other cancer types, in TNBC, TC scores are lower and IC scores are higher. Care should be taken when interchanging PD-L1 assays and interpreting efficacy data derived with different algorithms in TNBC; whilst SP263 would identify largely the same PD-L1 patient population as on KEYNOTE-086, it could potentially identify 22% additional cases as PD-L1 high than on IMPassion 130. Legal entity responsible for the study: AstraZeneca. Funding: AstraZeneca. Disclosure: M. Scott, P. Scorer, C. Barker: Employee, shareholder: AstraZeneca. H. Al-Masri: Employee: Hematogenix. Table10O Prevalence (%) and OPA (%) of VENTANA SP263 with other assays at matched cut-offsSP26322C322C328-828-8SP142SP142Cut-offPrevalencePrevalenceOPAPrevalenceOPAPrevalenceOPATC ≥ 1%53509146881158ICTA≥1%54519652973278CPS≥164609261953571 Open table in a new tab
Development and Validation of an Esophageal Squamous Cell Carcinoma Detection Model by Large-Scale MicroRNA Profiling
Authors: Kazuki Sudo, Ken Kato, Juntaro Matsuzaki, Narikazu Boku, Seiichiro Abe, Yutaka Saito, Hiroyuki Daiko, Satoko Takizawa, Yoshiaki Aoki, Hiromi Sakamoto, Shumpei Niida, Fumitaka Takeshita, Takahiro Fukuda, Takahiro Ochiya
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Patients with late-stage esophageal squamous cell carcinoma (ESCC) have a poor prognosis. Noninvasive screening tests using serum microRNAs (miRNAs) to accurately detect early-stage ESCC are needed to improve mortality. <h3>Objective</h3> To establish a model using serum miRNAs to distinguish patients with ESCC from noncancer controls. <h3>Design, Setting, and Participants</h3> In this case-control study, serum miRNA expression profiles of patients with ESCC (n = 566) and control patients without cancer (n = 4965) were retrospectively analyzed to establish a diagnostic model, which was tested in a training set and confirmed in a validation set. Patients histologically diagnosed as having ESCC who did not receive prior therapy or have a past or concurrent cancer other than ESCC were enrolled from the National Cancer Center Hospital in Tokyo, Japan. Between October 2010 and November 2015, control samples were collected from the National Cancer Center Biobank, the Biobank of the National Center for Geriatrics and Gerontology, and the general population undergoing routine health examination. Data analysis was performed between August 2015 and October 2018. Serum samples were randomly divided into discovery and validation sets. <h3>Main Outcomes and Measures</h3> The expression of 2565 miRNAs was assessed in each sample. The discriminant model (named the EC index) was evaluated in the training set using Fisher linear discriminant analysis with a greedy algorithm. Receiver operating characteristic curve analysis evaluated the diagnostic ability of the model in the validation set. <h3>Results</h3> In the training set, 283 patients with esophageal cancer (median age, 67 years [range, 37-90 years]; 83.4% male) were compared with 283 control patients (median age, 54 years [range, 22-100 years]; 43.1% male), and the EC index was constructed using 6 miRNAs (miR-8073, miR-6820-5p, miR-6794-5p, miR-3196, miR-744-5p, and miR-6799-5p). The area under the receiver operating characteristic curve was 1.00, with sensitivity of 1.00 and specificity of 0.98. The validation set included 283 patients (median age, 66 years [range, 42-87 years]; 83.0% male) and 4682 control patients (median age, 68 years [range, 20-98 years]; 44.7% male), and the area under the receiver operating characteristic curve for the EC index was 1.00, with sensitivity of 0.96 and specificity of 0.98. <h3>Conclusions and Relevance</h3> What appears to be novel serum miRNA discriminant model was developed for the diagnosis of ESCC. A multicenter prospective study is ongoing to confirm the present observations.
DEVELOPMENT OF A MODIFIED SMSA SCORING SYSTEM WITH IMPROVED ACCURACY IN THE PREDICTION OF COMPLICATIONS OF ENDOSCOPIC MUCOSAL RESECTION IN THE COLON
Authors: JC Silva, J Rodrigues, R Pinho, M Sousa, AC Gomes, AP Silva, J Carvalho
Journal: Endoscopy (2019)

The SMSA (size, morphology, site, access) scoring system allows stratification of the complexity of endoscopic mucosal resections (EMR). However, the influence of other lesion characteristics in EMR outcomes is widely recognized. The aim of this study was to develop a modified SMSA scoring system with complementary lesion characteristics and determine its accuracy in the prediction of complications of EMR.
Progress Toward Polio Eradication — Worldwide, January 2017–March 2019
Authors: Sharon A. Greene, Jamal Ahmed, S. Deblina Datta, Cara C. Burns, Arshad Quddus, John F. Vertefeuille, Steven G.F. Wassilak
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Since the Global Polio Eradication Initiative (GPEI) began in 1988, transmission of wild poliovirus (WPV) has been interrupted in all countries except Afghanistan, Nigeria, and Pakistan. WPV type 2 (WPV2) was declared eradicated in 2015; WPV type 3 has not been detected since 2012 (1). After the certification of the eradication of WPV2, a global switch from trivalent oral poliovirus vaccine (tOPV, containing vaccine virus types 1, 2, and 3) to bivalent oral poliovirus vaccine (bOPV, containing types 1 and 3) was completed in April 2016. Nigeria last reported WPV type 1 (WPV1) cases in 2016. This report describes global progress toward poliomyelitis eradication during January 1, 2017-March 31, 2019, and updates previous reports (1,2). Afghanistan and Pakistan reported their lowest annual number of WPV cases (22) in 2017; however, 33 WPV1 cases were reported in 2018. During January-March 2019 (as of May 3), 12 WPV1 cases had been reported worldwide, four more than the eight reported during the corresponding period in 2018. The occurrence of polio cases caused by circulating vaccine-derived poliovirus (cVDPV) is rare and occurs where oral poliovirus vaccine (OPV) coverage has been low and vaccine virus reverts to neurovirulence (3). Eight countries (Democratic Republic of the Congo [DRC], Indonesia, Mozambique, Niger, Nigeria, Papua New Guinea, Somalia, and Syria) reported 210 cVDPV cases during 2017-2019 (as of May 3). Reaching children during supplemental immunization activities (SIAs), accessing mobile populations at high risk, and variations in surveillance performance represent ongoing challenges. Innovative efforts to vaccinate every child and strengthen coordination efforts between Afghanistan and Pakistan will help achieve eradication. For cVDPV outbreak responses to promptly stop transmission, intensified programmatic improvements are needed to make the responses more effective and limit the risk for generating future outbreaks.
Abstract 11090: Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells (icCDCs) Stimulates Endogenous Myocyte Proliferation and Inhibits Apoptosis in Swine with Ischemic Cardiomyopathy
Authors: Gen Suzuki, Merced M Leiker, Brian Weil, Rebeccah F Young, John M Canty
Journal: Circulation (2012)

Background: Previous studies have demonstrated the efficacy of autologous icCDCs in swine with healed infarction as well as chronic hibernating myocardium. We tested the hypothesis that unmatched a...
The incidence of metastases detected on a staging CT scan prior to neoadjuvant chemotherapy in early stage breast cancer
Authors: R. Broadbent, S. Ralston, A. Armstrong, C. O’Brien, A.M. Wardley, G. Wilson, S. Howell
Journal: Annals of Oncology (2019)

Background: The role of neoadjuvant chemotherapy (NACT) in the treatment of early stage breast cancer is well established. Guidelines differ in their recommendation for staging work-up prior to NACT. Our institutional guidelines recommend CT thorax abdomen and pelvis scan for all such patients and we sought to evaluate the rate of metastatic disease by breast cancer stage. Methods: All cases identified for potentially curative NACT by the Multidisciplinary Team between 1/1/15-31/12/17 were included. Clinical records were reviewed. Those without a CT, inoperable when referred, with a diagnosis other than breast cancer or with loco-regional recurrence were excluded. Rates of metastases by tumour size (greatest by MRI, USS and mammography), lymph node stage (MRI and USS), receptor status and multifocality were calculated. Results: 185 patients were identified and 22 were excluded (no CT scan (6), inoperable (5), referred for adjuvant therapy (7), locoregional recurrence (3) and angiosarcoma (1)). 104/163 (64%) patients had a normal CT scan. 7/163 (4%) patients had definite metastases identified on their staging CT and 52/163 (32%) had an equivocal scan with further imaging required. Following additional imaging a further 10 patients had metastatic disease confirmed giving an overall incidence of of 10% (17 patients). The incidence of metastatic disease by stage (M1/total), (N + = node positive): T0N+ 0/1; T1N0 0/11; T1N+ 0/12; T2N0 1/42 (2%); T2N+ 9/53 (17%); T3N0 1/8 (12.5%);. T3N+ 4/32 (12.5%); T4N0 1/1 (100%); T4N+ 1/3 (33%). T2N0M1 and T3N0M1 patients both had triple negative disease. Multifocal disease: 7/163 of which 4/7 (57%) were metastatic. All 4 of multifocal M1 were node positive. For patients with an equivocal CT scan, 72 additional scans were arranged: ultrasound (16), MR (25), CT (20), bone scan (6), PETCT (5). Conclusions: The incidence of metastatic disease detected on imaging during work-up for NACT was 10%. The rate of metastatic diagnosis increases with T stage in patients with clinical N0 disease. Staging can be omitted in patients T1/2N0 at diagnosis. Omission of staging CT scans in the T1-2N0 cohort would have reduced the imaging frequency across all modalities by 30% when both initial and additional imaging are considered. Legal entity responsible for the study: Sacha Howell. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
ENDOSCOPIC BAND LIGATION FOR THE TREATMENT OF REFRACTORY RADIATION PROCTITIS
Authors: I Maestro Prada, EM Quintanilla Lázaro, C García-Ramos García, P Chaudarcas Castiñeira, M Álvarez Sánchez, JL Castro Urda
Journal: Endoscopy (2019)

Radiation proctitisis a known complication following radiation therapy for pelvic malignancy. The majority of cases are treated with conservative management, including endoscopic treatment.
Trends in Suicide Among Youth Aged 10 to 19 Years in the United States, 1975 to 2016
Authors: Donna A. Ruch, Arielle H. Sheftall, Paige Schlagbaum, Joseph Rausch, John V. Campo, Jeffrey A. Bridge
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Suicide is a leading cause of death among youth aged 10 to 19 years in the United States, with rates traditionally higher in male than in female youth. Recent national mortality data suggest this gap may be narrowing, which warrants investigation. <h3>Objective</h3> To investigate trends in suicide rates among US youth aged 10 to 19 years by age group, sex, race/ethnicity, and method of suicide. <h3>Design, Setting, and Participants</h3> Cross-sectional study using period trend analysis of US suicide decedents aged 10 to 19 years from January 1, 1975, to December 31, 2016. Data were analyzed for periods defined by statistically significant changes in suicide rate trends. Suicide rates were calculated using population estimates. <h3>Main Outcomes and Measures</h3> Period trends in suicide rates by sex and age group were assessed using joinpoint regression. Incidence rate ratios (IRRs) were estimated using negative binomial regression comparing male and female suicide rates within periods. <h3>Results</h3> From 1975 to 2016, we identified 85 051 youth suicide deaths in the United States (68 085 male [80.1%] and 16 966 female [19.9%]) with a male to female IRR of 3.82 (95% CI, 3.35-4.35). Following a downward trend until 2007, suicide rates for female youth showed the largest significant percentage increase compared with male youth (12.7% vs 7.1% for individuals aged 10-14 years; 7.9% vs 3.5% for individuals aged 15-19 years). The male to female IRR decreased significantly across the study period for youth aged 10 to 14 years (3.14 [95% CI, 2.74-3.61] to 1.80 [95% CI, 1.53-2.12]) and 15 to 19 years (4.15 [95% CI, 3.79-4.54] to 3.31 [95% CI, 2.96-3.69]). Significant declining trends in the male to female IRR were found in non-Hispanic white youth aged 10 to 14 years (3.27 [95% CI, 2.68-4.00] to 2.04 [95% CI, 1.45-2.89]) and non-Hispanic youth of other races aged 15 to 19 years (4.02 [95% CI, 3.29-4.92] to 2.35 [95% CI, 2.00-2.76]). The male to female IRR for firearms increased significantly for youth aged 15 to 19 years (χ<sup>2</sup> = 7.74;<i>P</i> = .02 for sex × period interaction). The male to female IRR of suicide by hanging or suffocation decreased significantly for both age groups (10-14 years: χ<sup>2</sup> = 88.83;<i>P</i> &lt; .001 for sex × period interaction and 15-19 years: χ<sup>2</sup> = 82.15;<i>P</i> &lt; .001 for sex × period interaction). No significant change was found in the male to female IRR of suicide by poisoning across the study period. <h3>Conclusions and Relevance</h3> A significant reduction in the historically large gap in youth suicide rates between male and female individuals underscores the importance of interventions that consider unique differences by sex. Future research examining sex-specific factors associated with youth suicide is warranted.
Docetaxel plus cisplatin and S-1 versus cisplatin and S-1 in patients with advanced gastric cancer (JCOG1013): an open-label, phase 3, randomised controlled trial
Authors: Yasuhide Yamada, Narikazu Boku, Junki Mizusawa, Satoru Iwasa, Shigenori Kadowaki, Norisuke Nakayama, Mizutomo Azuma, Takeshi Sakamoto, Kohei Shitara, Takao Tamura, Keisho Chin, Hiroaki Hata, Mikihito Nakamori, Hiroki Hara, Hirofumi Yasui, Hiroshi Katayama, Haruhiko Fukuda, Takaki Yoshikawa, Mitsuru Sasako, Masanori Terashima
Journal: The Lancet. Gastroenterology & hepatology (2019)
Disruption of the Scaffolding Function of mLST8 Selectively Inhibits mTORC2 Assembly and Function and Suppresses mTORC2-Dependent Tumor Growth <i>In Vivo</i>
Authors: Yoonha Hwang, Laura C. Kim, Wenqiang Song, Deanna N. Edwards, Rebecca S. Cook, Jin Chen
Journal: Cancer Research (2019)

Abstract mTOR is a serine/threonine kinase that acts in two distinct complexes, mTORC1 and mTORC2, and is dysregulated in many diseases including cancer. mLST8 is a shared component of both mTORC1 and mTORC2, yet little is known regarding how mLST8 contributes to assembly and activity of the mTOR complexes. Here we assessed mLST8 loss in a panel of normal and cancer cells and observed little to no impact on assembly or activity of mTORC1. However, mLST8 loss blocked mTOR association with mTORC2 cofactors RICTOR and SIN1, thus abrogating mTORC2 activity. Similarly, a single pair of mutations on mLST8 with a corresponding mutation on mTOR interfered with mTORC2 assembly and activity without affecting mTORC1. We also discovered a direct interaction between mLST8 and the NH2-terminal domain of the mTORC2 cofactor SIN1. In PTEN-null prostate cancer xenografts, mLST8 mutations disrupting the mTOR interaction motif inhibited AKT S473 phosphorylation and decreased tumor cell proliferation and tumor growth in vivo. Together, these data suggest that the scaffolding function of mLST8 is critical for assembly and activity of mTORC2, but not mTORC1, an observation that could enable therapeutic mTORC2-selective inhibition as a therapeutic strategy. Significance: These findings show that mLST8 functions as a scaffold to maintain mTORC2 integrity and kinase activity, unveiling a new avenue for development of mTORC2-specific inhibitors.
Questioning the Higher Abscess Rate and Overall Cost of Care Associated With Nonoperative Management of Uncomplicated Acute Appendicitis—Reply
Authors: Lindsay A. Sceats, Cindy Kin, Kristan L. Staudenmayer
Journal: JAMA Surgery (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Immunogenicity of full and fractional dose of inactivated poliovirus vaccine for use in routine immunisation and outbreak response: an open-label, randomised controlled trial
Authors: Cynthia J Snider, Khalequ Zaman, Concepcion F Estivariz, Mohammad Yunus, William C Weldon, Kathleen A Wannemuehler, M Steven Oberste, Mark A Pallansch, Steven GF Wassilak, Tajul Islam A Bari, Abhijeet Anand
Journal: The Lancet (2019)
ENDOSCOPIC FULL-THICKNESS RESECTION OF THE COLORECTAL LESIONS – A CZECH MULTICENTER EXPERIENCE
Authors: P Falt, P Fojtik, T Hucl, P Drastich, J Martinek, I Tacheci, S Suchanek, M Lukas, M Bortlik, F Neumann, P Volsansky, O Urban
Journal: Endoscopy (2019)

The purpose of the analysis was to evaluate feasibility, efficacy and safety of endoscopic full-thickness resection (FTR) of the colorectal lesions performed in the Czech Republic.
Counter-traction using clips and rubber banding for endoscopic submucosal dissection of a laterally spreading tumor involving a diverticulum in the colon
Authors: Jérémie Albouys, Sophie Geyl, Aurélie Charissoux, Romain Legros, Denis Sautereau, Mathieu Pioche, Jérémie Jacques
Journal: Endoscopy (2019)

In addition to the possibility of en bloc resection without size limitations, endoscopic submucosal dissection (ESD) is also a novel option for endoscopic treatment of lesions involving a diverticulum in the colon [1] or appendix [2]. Generally, when employing endoscopic mucosal resection, these types of lesions have a high risk of perforation or incomplete resection.
Review: In adults, general health checks do not reduce all-cause, cardiovascular, or cancer mortality
Authors: Joel M. Schectman
Journal: Annals of Internal Medicine (2019)

ACP Journal Club21 May 2019Review: In adults, general health checks do not reduce all-cause, cardiovascular, or cancer mortalityJoel M. Schectman, MD, MPHJoel M. Schectman, MD, MPHUniversity of Virginia Health System, Charlottesville, Virginia, USA (J.M.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ201905210-052 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationKrogsbøll LT, Jørgensen KJ, Gøtzsche PC. General health checks in adults for reducing morbidity and mortality from disease. Cochrane Database Syst Rev. 2019;1:CD009009. https://pubmed.ncbi.nlm.nih.gov/30699470Clinical Impact RatingsGIM/FP/GP: Public Health: References1 Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: Executive Summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:1269-324. [PMID: 29133354] Google Scholar2 Chou R, Dana T, Blazina I, Daeges M, Jeanne TL. Statins for prevention of cardiovascular disease in adults: evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2016;316:2008-24. [PMID: 27838722] Google Scholar3 Ebrahim S, Taylor F, Ward K, et al. Multiple risk factor interventions for primary prevention of coronary heart disease. Cochrane Database Syst Rev. 2011;(1):CD001561. [PMID: 21249647] Google Scholar4 Smith RA, Andrews KS, Brooks D, et al. Cancer screening in the United States, 2018: a review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin. 2018;68:297-316. [PMID: 29846940] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Virginia Health System, Charlottesville, Virginia, USA (J.M.S.)This article was published at Annals.org on 7 May 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byManaging the moral expansion of medicine 21 May 2019Volume 170, Issue 10Page: JC52KeywordsGrading of Recommendations Assessment Development and EvaluationHealth screeningIschemic strokeMedical risk factorsMorbidityMortalityPrevention, policy, and public healthPrimary careResearch designRisk ratio ePublished: 21 May 2019 Issue Published: 21 May 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Cash for publication is discriminatory, unscientific, and dangerous
Authors: Andrew N Bamji
Journal: BMJ (2019)

Plan S aims to achieve open access science publishing without paywalls.1 I don’t often write scientific papers. Much of what I submit to journals is comment or related to medical history. But a recent experience made me uneasy.

I submitted a paper to a prestigious journal. It was rejected. I don’t get hung up about rejection; one is always convinced by the brilliance of one’s own work. I suspect many people have suffered similarly. But …