tbuckley/cabot-search huggingface dataset:
Comprehensive Molecular Profiling of Intrahepatic and Extrahepatic Cholangiocarcinomas: Potential Targets for Intervention
Authors: Maeve A. Lowery, Ryan Ptashkin, Emmet Jordan, Michael F. Berger, Ahmet Zehir, Marinela Capanu, Nancy E. Kemeny, Eileen M. O'Reilly, Imane El-Dika, William R. Jarnagin, James J. Harding, Michael I. D'Angelica, Andrea Cercek, Jaclyn F. Hechtman, David B. Solit, Nikolaus Schultz, David M. Hyman, David S. Klimstra, Leonard B. Saltz, Ghassan K. Abou-Alfa
Journal: Clinical Cancer Research (2018)

Purpose: Various genetic driver aberrations have been identified among distinct anatomic and clinical subtypes of intrahepatic and extrahepatic cholangiocarcinoma, and these molecular alterations may be prognostic biomarkers and/or predictive of drug response.Experimental Design: Tumor samples from patients with cholangiocarcinoma who consented prospectively were analyzed using the MSK-IMPACT platform, a targeted next-generation sequencing assay that analyzes all exons and selected introns of 410 cancer-associated genes. Fisher exact tests were performed to identify associations between clinical characteristics and genetic alterations.Results: A total of 195 patients were studied: 78% intrahepatic and 22% extrahepatic cholangiocarcinoma. The most commonly altered genes in intrahepatic cholangiocarcinoma were IDH1 (30%), ARID1A (23%), BAP1 (20%), TP53 (20%), and FGFR2 gene fusions (14%). A tendency toward mutual exclusivity was seen between multiple genes in intrahepatic cholangiocarcinoma including TP53:IDH1, IDH1:KRAS, TP53:BAP1, and IDH1:FGFR2 Alterations in CDKN2A/B and ERBB2 were associated with reduced survival and time to progression on chemotherapy in patients with locally advanced or metastatic disease. Genetic alterations with potential therapeutic implications were identified in 47% of patients, leading to biomarker-directed therapy or clinical trial enrollment in 16% of patients.Conclusions: Cholangiocarcinoma is a genetically diverse cancer. Alterations in CDKN2A/B and ERBB2 are associated with negative prognostic implications in patients with advanced disease. Somatic alterations with therapeutic implications were identified in almost half of patients. These prospective data provide a contemporary benchmark for guiding the development of targeted therapies in molecularly profiled cholangiocarcinoma, and support to the use of molecular profiling to guide therapy selection in patients with advanced biliary cancers. Clin Cancer Res; 24(17); 4154-61. ©2018 AACR.
Serum PD-L1 and outcomes in CCTG MA.31 phase 3 trial of anti-HER2 therapy in first-line HER2+ metastatic breast cancer patients (trastuzumab arm only).
Authors: Kim Leitzel, Suhail M. Ali, Lois E. Shepherd, Wendy R. Parulekar, Liting Zhu, Shakeel Virk, Dora Nomikos, Samuel Aparicio, Karen A. Gelmon, Joseph J. Drabick, Leah Cream, E Scott Halstead, Hyma Vani Polimera, Ashok Maddukuri, Aamnah Ali, Urmeel Hasmukh Patel, Joyson Poulose, Howard Spiegel, Bingshu E. Chen, Allan Lipton
Journal: Journal of Clinical Oncology (2018)

1031 Background: In MA.31 the lapatinib-taxane combination led to shorter PFS than trastuzumab-taxane in HER2+ metastatic breast cancer. We previously reported the positive prognostic utility of pretreatment serum PD-L1 in 63 trastuzumab-treated patients (ASCO 2017, #1024), and here we evaluated it in the trastuzumab arm of MA.31. Methods: MA.31 accrued 652 centrally and/or locally-identified HER2-positive patients; in the trastuzumab arm 186 patients had pretreatment serum available.TheELLA immunoassay platform (ProteinSimple, San Jose, CA) was used to quantitate serum PD-L1. Stratified step-wise forward Cox multivariate analysis was used for PFS and OS. Results: In univariate analysis for PFS, serum PD-L1 was not a significant biomarker for PFS. In univariate analysis for OS, higher serum PD-L1 was a significant biomarker for shorter OS (continuous PD-L1: HR 3.86, p = 0.044; quartiles of PD-L1: HR 1.55, p = 0.002; median cutpoint PD-L1: HR 2.16, p = 0.014). In multivariate analysis for OS [14 covariates included: age, race, ECOG status, anthracyclines, other chemo, endocrine, radio, other prior adjuvant therapy, disease status, ER status, PR status, Ki67 (log transformed), CK5, EGFR, serum PD-L1], elevated serum PD-L1 was a significant independent covariate [continuous PD-L1: HR 22.7, p = 0.001; median cutpoint PD-L1: HR 2.91, p = 0.0061 (Table)]. Conclusions: In the CCTG MA.31 trial, elevated pretreatment serum PD-L1was associated with a shorter OS (but not PFS) with trastuzumab treatment. Immune evasion by the tumor may decrease the effectiveness of trastuzumab therapy. Elevated serum PD-L1 may identify patients who would benefit from addition of an immune checkpoint inhibitor. Multivariate significant independent covariates for OS (186 patients). Covariate p-value Hazard Ratio Lower 95% CI Higher 95% CI Prior adjuvant/metastatic endocrine therapy (yes vs no) 0.001 4.07 1.75 9.46 Performance status (0 vs 1 or 2) 0.002 0.30 0.14 0.65 Central Review ER status (continuous IHC score) 0.006 0.99 0.98 0.99 Serum PD-L1 (pretreatment) ( > median vs < median) 0.006 2.91 1.36 6.25 Prior adjuvant / metastatic radiotherapy (yes vs no) 0.049 0.44 0.19 0.99
Impact of immigration status on health behaviors and perceptions in cancer survivors.
Authors: Sophia Yijia Liu, Lin Lu, Karmugi Balaratnam, Dan Pringle, Mary Mahler, Chongya Niu, Hiten Naik, Kyoko Tiessen, Henrique Hon, M Catherine Brown, Peter Selby, Doris Howell, Wei Xu, Shabbir M.H. Alibhai, Jennifer M. Jones, Geoffrey Liu, Lawson Eng
Journal: Journal of Clinical Oncology (2018)

27 Background: Health behaviors including smoking cessation, physical activity (PA) and alcohol moderation are key aspects of cancer survivorship. Disparities in health literacy and cancer screening behaviors have been reported between immigrant and native-born cancer patients. However, disparities in health behaviors in cancer survivorship has not been explored. We compared health behaviors and perceptions about these behaviors between immigrant and native-born cancer survivors. Methods: Adult cancer patients from Princess Margaret Cancer Centre (Toronto, Canada) were surveyed on their smoking, PA, and alcohol habits and perceptions of the effects of these behaviors on quality of life (QoL), 5-year survival, and fatigue. Multivariable models evaluated the effect of immigration status on behaviors and perceptions. The effect of originating from a Western vs. non-Western country was also evaluated. Results: Of 1275 patients, 27% self-identified as foreign-born. At 1 year before diagnosis (baseline), 17% smoked, 69% were physically inactive, and 58% consumed alcohol. Although immigration status was not associated with smoking at baseline (P &gt; 0.05), immigrants were less likely to perceive that smoking was harmful on QoL (adjusted odds ratio [aOR] 0.58, P = 0.008), survival (aOR 0.56, P = 0.002), and less so for fatigue (aOR 0.75, P = 0.11). Immigrants were less likely to meet PA guidelines at baseline (aOR = 0.70, P = 0.08), and perceive that PA improved fatigue (aOR 0.62, P = 0.04) and survival (aOR 0.64, P = 0.08). Immigrants were also less likely to drink alcohol at baseline (aOR = 0.47, P = 0.001), but alcohol perceptions did not differ between immigrants and native-born. Those from non-Western countries were less likely to smoke (aOR 0.63, P = 0.03), drink alcohol (aOR 0.48, P = 0.006), or meet PA guidelines at baseline (aOR 0.44, P = 0.006). Conclusions: Immigrants were less likely to perceive continued smoking as harmful and less likely to be aware of the benefits of PA. Patients from non-Western countries were less likely to meet PA guidelines, but were also less likely to smoke or drink at baseline. Culturally tailored counselling should be considered for immigrants who smoke or are physically inactive at baseline.
Letter by Koh Regarding Article, “Low-Density Lipoprotein Cholesterol Lowering for the Primary Prevention of Cardiovascular Disease Among Men With Primary Elevations of Low-Density Lipoprotein Cholesterol Levels of 190 mg/dL or Above: Analyses From the WOSCOPS (West of Scotland Coronary Prevention Study) 5-Year Randomized Trial and 20-Year Observational Follow-Up”
Authors: Kwang Kon Koh
Journal: Circulation (2018)
Meningeal hemangiopericitoma (HPC): Treatment outcome in a retrospective series in a single institution.
Authors: Alejandro Daniel Muggeri, BERNADETTE CALABRESE, Sebastian Cerrato, Andres Cervio, Blanca D. Diez
Journal: Journal of Clinical Oncology (2012)

e12511 Background: HPC is a rare malignant tumor with a high proclivity toward recurrence and metastasis. Methods: The purpose of this study was to analyse retrospectively a series of eighteen patients with HPC treated between January 1992 and Oct 2011 with respect to clinical presentation, treatment results and long-term follow-up outcomes.Survival rate and PFS were analyzed by Kaplan-Meier method, with the use of two-sided log-rank test statistics Results: Twelve were females with a median age of 44.5 years (21-62). In 17 the tumor was intracranial, in one in the spinal cord. Median follow-up was 75,5 months (4 -314). Eight underwent gross total resection (GTR) and 2 of them received adjuvant radiotherapy. Ten had subtotal resection (STR) and 2 of them received RT. Three of 6 with GTR without RT relapsed. All patients with STR suffered local progression (2 after RT). Five developed systemic metastases after reiterate surgical resection (more than 3); three of them are alive with disease after further treatment at 11, 18 and 28 month. The median progression free survival (PFS) was 42,5 months (4-264), with 2 and 5-year PFS rates of 88% and 27% respectively. The 2, 5 and 10-year survival rates was 100, 93 and 81% respectively. All patients with GTR are alive (median follow-up: 60,5 months, range 30-125) and 3 of 10 patients with STR died (median follow-up: 81,5 months, range 4-314). Conclusions: When safe and feasible, GTR should be pursued as an initial surgical strategy to maximize overall survival. Adjuvant RT may show promise in preventing tumor progression in GTR patients. In metastatic disease long term survival could be achieved. The lack of a standard of care for HPC patients makes it especially important to do a complete workup, especially among patients presenting with recurrent HPC.
The enteric microbiota regulates jejunal Paneth cell number and function without impacting intestinal stem cells
Authors: Alexi A. Schoenborn, Richard J. von Furstenberg, Smrithi Valsaraj, Farah S. Hussain, Molly Stein, Michael T. Shanahan, Susan J. Henning, Ajay S. Gulati
Journal: Gut Microbes (2018)

Paneth cells (PCs) are epithelial cells found in the small intestine, next to intestinal stem cells (ISCs) at the base of the crypts. PCs secrete antimicrobial peptides (AMPs) that regulate the commensal gut microbiota. In contrast, little is known regarding how the enteric microbiota reciprocally influences PC function. In this study, we sought to characterize the impact of the enteric microbiota on PC biology in the mouse small intestine. This was done by first enumerating jejunal PCs in germ-free (GF) versus conventionally raised (CR) mice. We next evaluated the possible functional consequences of altered PC biology in these experimental groups by assessing epithelial proliferation, ISC numbers, and the production of AMPs. We found that PC numbers were significantly increased in CR versus GF mice; however, there were no differences in ISC numbers or cycling activity between groups. Of the AMPs assessed, only Reg3γ transcript expression was significantly increased in CR mice. Intriguingly, this increase was abrogated in cultured CR versus GF enteroids, and could not be re-induced with various bacterial ligands. Our findings demonstrate the enteric microbiota regulates PC function by increasing PC numbers and inducing Reg3γ expression, though the latter effect may not involve direct interactions between bacteria and the intestinal epithelium. In contrast, the enteric microbiota does not appear to regulate jejunal ISC census and proliferation. These are critical findings for investigators using GF mice and the enteroid system to study PC and ISC biology.
Acute Kidney Injury
Authors: Tom Finucane
Journal: Annals of Internal Medicine (2018)

Letters5 June 2018Acute Kidney InjuryTom Finucane, MDTom Finucane, MDJohns Hopkins University, Baltimore, Maryland (T.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L18-0016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Drs. Levey and James (1) note that “decreased kidney perfusion is the most common cause of community-acquired [acute kidney injury (AKI)]” and recommend evaluation for volume depletion, an important cause of decreased perfusion. They also state, “Increased [glomerular filtration rate (GFR)] within hours of volume repletion with oral or [intravenous] fluids confirms the diagnosis.” However, consider a patient who develops volume depletion, decreased perfusion, and a consequent decrease in GFR who then recovers fully with volume repletion. Do the authors believe that this patient with “AKI” actually had a kidney injury? I believe instead that his or ...Reference1. Levey AS, James MT. Acute kidney injury. Ann Intern Med. 2017;167:ITC66-80. [PMID: 29114754]. doi:10.7326/AITC201711070 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Johns Hopkins University, Baltimore, Maryland (T.F.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L18-0016. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAcute Kidney Injury Andrew S. Levey and Matthew T. James Acute Kidney Injury Andrew S. Levey and Matthew T. James Acute Kidney Injury Joana Gameiro , Sofia Jorge , and José António Lopes Metrics 5 June 2018Volume 168, Issue 11Page: 836KeywordsAcute kidney injuryAcute renal failureComaConflicts of interestDisclosureGlomerular filtration rateKidneysRenal failure ePublished: 5 June 2018 Issue Published: 5 June 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Impact of quality of life on employment and marital status in long-term cancer survivors treated in a referral center in Mexico.
Authors: Yuly Andrea Remolina Bonilla, Alejandra Armengol Alonso, Raul Rogelio Trejo rosales
Journal: Journal of Clinical Oncology (2018)

122 Background: Worldwide there is an increasing number of cancer survivors (CS); in the United States in 2016 there were more than 15 million CS and are predicted to increase to 20 million in 2026. In Mexico (GLOBOCAN 2012), new cancer cases were 148.000 and at least 69.000 will survive. Therefore, it is necessary to focus on cancer survivor’s quality of life (QOL) and its effects in social aspects. Methods: A cross-sectional study was performed including 205 CS with history of non-metastatic cancer (aged ≤65 years, ≥ 2 years from diagnosis and off chemo- or radiotherapy). The QOL-CS questionnaire developed by City of Hope Medical Center was used to measure QOL. Participants reported employment and marital status changes during or after cancer treatment. The aim of this study was to evaluate QOL in CS and its association with employment and marital status. A multivariate logistic regression analysis was conducted to estimate odds ratios (OR). Results: Of the 205 CS 70.2% were women and 29.8% men. Median age at the time of the study was 56 years. Median survival time from diagnosis was 83.6 months. 37.1% had history of invasive breast, 18% colorectal and 8.8% testicular cancers. Disease-related marital status changes presented in 15.6%, 26.8% lost or changed work and 36.6% decreased their work hours. Distress about initial diagnosis, cancer treatment, family and financial burden had the worst score in the QOL-CS. We found no differences in QOL between gender, income, age at diagnosis or type of tumor, but having received chemotherapy was associated with worst QOL (OR 7.33 CI 95% 1.99-26.96 p = 0.003) as well as self-reported neuropathy (OR 2.34 CI 95% 1.06-5.19 p = 0.032). Those with low QOL-CS scores (≤6) were more likely to have a disease-related change in employment (OR 2.34 CI 95% 1.19-4.61 p = 0.014). Disease-related marital status changes were higher in who experienced work status variations (OR 3.87 CI 95% 1.21-12.4 p = 0.023). Conclusions: this is one of the first studies in Mexican CS that associate QOL with relevant social roles. In this cohort having received chemotherapy has the greatest impact in QOL. CS with low QOL were more likely to have changes in employment and therefore, in the marital status.
Consolidative Local Ablative Therapy Improves the Survival of Patients With Synchronous Oligometastatic NSCLC Harboring EGFR Activating Mutation Treated With First-Line EGFR-TKIs
Authors: Qinghua Xu, Fei Zhou, Hui Liu, Tao Jiang, Xuefei Li, Yaping Xu, Caicun Zhou
Journal: Journal of Thoracic Oncology (2018)
Automatic emotion and attention analysis of young children at home: a ResearchKit autism feasibility study
Authors: Helen L. Egger, Geraldine Dawson, Jordan Hashemi, Kimberly L. H. Carpenter, Steven Espinosa, Kathleen Campbell, Samuel Brotkin, Jana Schaich-Borg, Qiang Qiu, Mariano Tepper, Jeffrey P. Baker, Richard A. Bloomfield, Guillermo Sapiro
Journal: npj Digital Medicine (2018)

Current tools for objectively measuring young children's observed behaviors are expensive, time-consuming, and require extensive training and professional administration. The lack of scalable, reliable, and validated tools impacts access to evidence-based knowledge and limits our capacity to collect population-level data in non-clinical settings. To address this gap, we developed mobile technology to collect videos of young children while they watched movies designed to elicit autism-related behaviors and then used automatic behavioral coding of these videos to quantify children's emotions and behaviors. We present results from our iPhone study Autism & Beyond, built on ResearchKit's open-source platform. The entire study-from an e-Consent process to stimuli presentation and data collection-was conducted within an iPhone-based app available in the Apple Store. Over 1 year, 1756 families with children aged 12-72 months old participated in the study, completing 5618 caregiver-reported surveys and uploading 4441 videos recorded in the child's natural settings. Usable data were collected on 87.6% of the uploaded videos. Automatic coding identified significant differences in emotion and attention by age, sex, and autism risk status. This study demonstrates the acceptability of an app-based tool to caregivers, their willingness to upload videos of their children, the feasibility of caregiver-collected data in the home, and the application of automatic behavioral encoding to quantify emotions and attention variables that are clinically meaningful and may be refined to screen children for autism and developmental disorders outside of clinical settings. This technology has the potential to transform how we screen and monitor children's development.
Polymorphic Erythematous Macules and Plaques With Dysesthesia
Authors: Cesar Daniel Villarreal-Villarreal, Jorge Ocampo-Candiani, Oliverio Welsh
Journal: JAMA Dermatology (2018)

A woman in her 50s presented with a 2-year history of disseminated dermatosis involving the trunk and limbs; the dermatosis was characterized by polymorphic erythematous macules and plaques with elevated and indurated borders without evanescence to pressure. What is your diagnosis?
Leveraging survivorship care to identify recurrent melanoma.
Authors: Andrew Joseph Ward, James M. McLoughlin, James M. Lewis
Journal: Journal of Clinical Oncology (2018)

181 Background: The University of Tennessee Medical Center in Knoxville, Tennessee is the regions only academic medical center. This includes the Cancer Institute, where in 2013 a division dedicated to melanoma and soft tissue tumors (MASTT) was created. Since 2013, the number of melanoma cases treated at UTMCK treated has increased in excess of 300%. One critical aspect of the MASTT service was to provide survivorship care to all patients treated. This has given MASTT a unique opportunity to determine how survivorship care has impacted detection of recurrence in melanoma. Methods: Tumor registry data was retrospectively reviewed from a prospectively maintained database. All melanoma patients treated from 2011 to 2015 were identified. This cohort was selected because all of these patients would have been eligible for survivorship care. These patients were then stratified into stage and sub-stage, recurrence status, stage at recurrence, and whether alive or dead. Median and range of time to recurrence were calculated as well. Results: A total of 758 patients were treated for melanoma between 2011 and 2015 at UTMCK by the MASTT service. From this overall sample, a total of 37 patients demonstrated recurrence (4.88% overall). Local recurrence was noted in 9 cases (1.2%), regional recurrence in 4 cases (0.53%) and distant in 15 cases (2.0%). Seven of the recurrent cases were not specified. Median time to recurrence was 12 months (6-40 months). Overall mortality rate for patients with recurrent melanoma was 18/37 (48.6%). Nationally, local recurrence rates are reported between 3 – 5%. Conclusions: A retrospective analysis of tumor registry data for melanoma patients treated at UTMCK CI by the MASTT service line shows that offering survivorship care to this population is beneficial in detecting recurrence. This is key in getting patients evaluated and established for immunotherapy and/or other treatment options at the earliest time of recurrence, which can potentially improve their response to treatment by.
18F-FDG PET/CT and MRI of a Mediastinal Malignant Granular Cell Tumor With Associated Recurrent Pericarditis
Authors: Ludovic D’hulst, Christophe Deroose, David Strybol, Johan Coolen, Olivier Gheysens
Journal: Clinical Nuclear Medicine (2018)

We report a rare case of a mediastinal malignant granular cell tumor in a 41-year-old man presenting with dyspnea, retrosternal chest pain, and recurrent pericardial effusion under treatment with corticosteroids. Because of recurrent episodes, further investigations with chest MRI and F-FDG PET/CT revealed a large infiltrating and strongly hypermetabolic mass in the mediastinum with pericarditis. Histopathology and immunohistochemical analysis showed large cells with greater pleomorphism and eosinophilic granular cytoplasm with positive staining for S100 protein and CD68 as well as high Ki67 proliferative index (15%) confirming the diagnosis of a malignant granular cell tumor.