tbuckley/cabot-search huggingface dataset:
Abstract 19255: Double Knockout of Akt2 and AMPK Resists High Fat Diet-Induced Adiposity, Cardiac Dysfunction and Hepatic Steatosis
Authors: Shuyi Wang, Yingmei Zhang, Jun Ren
Journal: Circulation (2016)

Akt and AMPK are two essential sometimes reciprocal signaling regulatory machineries governing energy homeostasis and insulin action. This study was designed to examine the high fat diet intake-ind...
Palliative care and end-of-life health utilization in elder patients with pancreatic cancer.
Authors: Nizar Bhulani, Ang Gao, Arjun Gupta, Jenny Jing Li, Chad Guenther, Chul Ahn, M. Elizabeth Paulk, Stephanie Houck, Muhammad Shaalan Beg
Journal: Journal of Clinical Oncology (2018)

488 Background: Prospective trials have shown that palliative care is associated with improved survival and quality of life, with lower rate of end-of-life health care utilization and cost. We examined trends in palliative care utilization in older pancreatic cancer patients. Methods: Pancreatic cancer patients with and without palliative care consults were identified using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database between 2000 and 2009. Trend of palliative care use was studied. Emergency room and Intensive Care utilization and costs in the last 30 days of life were assessed. Statistical analyses were performed with SAS version 9.4 (SAS Institute, Inc., Cary, NC). Results: Of the 72205 patients with pancreatic cancer, 3383 (4.1%) received palliative care. The proportion of patients receiving palliative care increased from 1.8% in 2000 to 7.8% in 2009 (p for trend &lt; 0.001). Patients with palliative care were more likely to be Asian and women. Of those who received palliative care, 73% received it in the last 30 days of life, and only 11% at least 12 weeks before death. The average number of visits to the ED in the last 30 days of life were significantly higher for patients who received palliative care (0.93±0.62) versus those who did not (0.79±0.61), p &lt; 0.001, and had a significantly higher cost of care ($1317 vs $842, p &lt; 0.001). Intensive care unit length of stay in the last 30 days of life did not differ between patients who did and did not receive palliative care (1.14 days vs 1.04 days, p 0.08). Intensive care unit cost of care was significantly higher for patients with palliative care compared to their counterparts ($5202.641 vs $3896.750, p &lt; 0.001). Conclusions: Palliative care use for pancreatic cancer patients has increased between 2000 and 2009 in this study of Medicare patients. However, it was largely offered close to the end of life and was not associated with reduced health care utilization or cost. Early palliative care referral may be more beneficial.
Eribulin in BRAF V600E-mutant metastatic colorectal cancer: case series and potential rationale
Authors: T. Masuishi, H. Taniguchi, K. Sugiyama, K. Kato, S. Mitani, K. Honda, Y. Narita, S. Kadowaki, T. Ura, M. Ando, K. Muro
Journal: Annals of Oncology (2018)
A phase I study of MM-121 in combination with multiple anticancer therapies in patients with advanced solid tumors.
Authors: Monica Arnedos, Crystal Shereen Denlinger, Wael A. Harb, Olivier Rixe, John Charles Morris, Grace K. Dy, Alex A. Adjei, Joseph Pearlberg, Sarah Follows, Akos Gabor Czibere, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2013)

2609 Background: MM-121 is a fully human monoclonal antibody targeting the epidermal growth factor receptor family member ErbB3. ErbB3 has been implicated in driving cancer growth and in the development of resistance to conventional chemotherapies across multiple malignancies. Here we present results of an open-label, Phase 1, multicenter, non-randomized, dose-escalation trial which recently completed enrollment evaluating MM-121 in combination with one of the following chemotherapies: Gemcitabine (Arm A, n=11), carboplatin (Arm B, n=11), pemetrexed (Arm C, n=10), or cabazitaxel (Arm D, n=11). Methods: Patients were treated in a dose escalation “3+3” design to assess the safety, tolerability and pharmacokinetics (PK) of MM-121 administered weekly in combination with anticancer therapies in subjects with advanced cancer. Doses were escalated until the maximum tolerated dose (MTD) was identified or the combination was shown to be tolerable at the highest planned doses. Secondary objectives included: Determining the objective response rate, clinical benefit rate, PK and immunogenicity of MM-121. Data summarized are as of 1/17/2013 from a live database. Results: Overall, 43 patients, [22 (51%) female and 21 (49%) male] have been treated with a median treatment duration of 57 days (range 1-302). The median age was 59 years (range 42-84) and patients had received a median of four prior lines of therapy (range 0-13). Common (&gt;20%) adverse events of any grade and causality across all arms included diarrhea (74%), nausea (54%), fatigue (51%), anemia (44%), vomiting (33%), hypokalemia (30%), decreased appetite (26%), thrombocytopenia (26%), peripheral edema (23%), neutropenia (21%), and constipation (21%). Four DLTs were observed: Two in combination with carboplatin (G4 thrombocytopenia and G3 rash), one with gemcitabine (G4 thrombocytopenia), and one with pemetrexed (G4 hyperuricemia). Overall 38 (88%) patients were evaluable for response and the overall clinical benefit rate (PR or SD &gt;18 weeks), is 32% (12/38). Conclusions: MM-121 can be combined at its recommended single agent dose with standard doses of gemcitabine, pemetrexed, and cabazitaxel and adapted doses of carboplatin. Clinical trial information: NCT01447225.
Unusual diagnoses made by convex-probe endobronchial ultrasound-guided transbronchial needle aspiration
Authors: S. Fernandez-Bussy, H. Inaty, I. Caviedes, G. Labarca, M.R. Vial, A. Majid
Journal: Pulmonology (2018)

Endobronchial ultrasound-guided transbronchial needle biopsy (EBUS-TBNA) has proven to be an effective and minimally invasive tool to diagnose and stage lung cancer. However, its use for the diagnosis of rare mediastinal and lung pathologies has been rarely described. Hereby we describe a retrospective chart review of our EBUS-TBNA database for unusual diagnosis made between July 2012 and October 2016. Those conditions considered unusual for EBUS-TBNA diagnosis were identified and their medical records reviewed.
A Child With a Blistering Rash
Authors: Christina N. Kraus, Pooja Sodha, A. Yasmine Kirkorian
Journal: JAMA Pediatrics (2018)

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 Pediatrics 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 Pediatrics journal
Evaluating Vaccination Strategies for Zika Virus in the Americas
Authors: David P. Durham, Meagan C. Fitzpatrick, Martial L. Ndeffo-Mbah, Alyssa S. Parpia, Nelson L. Michael, Alison P. Galvani
Journal: Annals of Internal Medicine (2018)

Background: Mosquito-borne and sexually transmitted Zika virus has become widespread across Central and South America and the Caribbean. Many Zika vaccine candidates are under active development. Objective: To quantify the effect of Zika vaccine prioritization of females aged 9 to 49 years, followed by males aged 9 to 49 years, on incidence of prenatal Zika infections. Design: A compartmental model of Zika transmission between mosquitoes and humans was developed and calibrated to empirical estimates of country-specific mosquito density. Mosquitoes were stratified into susceptible, exposed, and infected groups; humans were stratified into susceptible, exposed, infected, recovered, and vaccinated groups. Age-specific fertility rates, Zika sexual transmission, and country-specific demographics were incorporated. Setting: 34 countries and territories in the Americas with documented Zika outbreaks. Target Population: Males and females aged 9 to 49 years. Intervention: Age- and sex-targeted immunization using a Zika vaccine with 75% efficacy. Measurements: Annual prenatal Zika infections. Results: For a base-case vaccine efficacy of 75% and vaccination coverage of 90%, immunizing females aged 9 to 49 years (the World Health Organization target population) would reduce the incidence of prenatal infections by at least 94%, depending on the country-specific Zika attack rate. In regions where an outbreak is not expected for at least 10 years, vaccination of women aged 15 to 29 years is more efficient than that of women aged 30 years or older. Limitation: Population-level modeling may not capture all local and neighborhood-level heterogeneity in mosquito abundance or Zika incidence. Conclusion: A Zika vaccine of moderate to high efficacy may virtually eliminate prenatal infections through a combination of direct protection and transmission reduction. Efficiency of age-specific targeting of Zika vaccination depends on the timing of future outbreaks. Primary Funding Source: National Institutes of Health.
TNF-driven adaptive response mediates resistance to EGFR inhibition in lung cancer
Authors: Ke Gong, Gao Guo, David E. Gerber, Boning Gao, Michael Peyton, Chun Huang, John D. Minna, Kimmo J. Hatanpaa, Kemp Kernstine, Ling Cai, Yang Xie, Hong Zhu, Farjana J. Fattah, Shanrong Zhang, Masaya Takahashi, Bipasha Mukherjee, Sandeep Burma, Jonathan Dowell, Kathryn Dao, Vassiliki A. Papadimitrakopoulou, Victor Olivas, Trever G. Bivona, Dawen Zhao, Amyn A. Habib
Journal: Journal of Clinical Investigation (2018)

Although aberrant EGFR signaling is widespread in cancer, EGFR inhibition is effective only in a subset of non–small cell lung cancer (NSCLC) with EGFR activating mutations. A majority of NSCLCs express EGFR wild type (EGFRwt) and do not respond to EGFR inhibition. TNF is a major mediator of inflammation-induced cancer. We find that a rapid increase in TNF level is a universal adaptive response to EGFR inhibition in NSCLC, regardless of EGFR status. EGFR signaling actively suppresses TNF mRNA levels by inducing expression of miR-21, resulting in decreased TNF mRNA stability. Conversely, EGFR inhibition results in loss of miR-21 and increased TNF mRNA stability. In addition, TNF-induced NF-κB activation leads to increased TNF transcription in a feed-forward loop. Inhibition of TNF signaling renders EGFRwt-expressing NSCLC cell lines and an EGFRwt patient-derived xenograft (PDX) model highly sensitive to EGFR inhibition. In EGFR-mutant oncogene-addicted cells, blocking TNF enhances the effectiveness of EGFR inhibition. EGFR plus TNF inhibition is also effective in NSCLC with acquired resistance to EGFR inhibition. We suggest concomitant EGFR and TNF inhibition as a potentially new treatment approach that could be beneficial for a majority of lung cancer patients.
Second-line chemotherapy in patients with advanced biliary tract cancer.
Authors: Naminatsu Takahara, Yousuke Nakai, Hiroyuki Isayama, Takashi Sasaki, Kazunaga Ishigaki, Kei Saito, Suguru Mizuno, Hirofumi Kogure, Minoru Tada, Kazuhiko Koike
Journal: Journal of Clinical Oncology (2018)

429 Background: The current standard of care for patients with advanced biliary tract cancer (BTC) is a palliative chemotherapy. Although the survival benefit of first-line chemotherapy (CT1) including gemcitabine and cisplatin (GC) had been established in prospective randomized trials, the safety and efficacy of second-line chemotherapy (CT2) have yet to be elucidated. Methods: Consecutive advanced BTC patients receiving CT1 followed by CT2 between 2000 and 2016 were enrolled. We investigated factors associated with receiving CT2, treatment outcomes of CT2, and the prognostic factors for overall survival (OS) with CT2 to determine which patients could be expected to benefit from CT2. Results: Among 309 advanced BTC patients receiving CT1, including those with 108 intrahepatic bile duct cancer, 96 gallbladder cancer, 88 extrahepatic bile duct cancer and 17 papilla cancer, CT2 was given in 139 patients (45%). Compared to patients without CT2, younger patients (median; 67 vs. 70 years, p &lt; 0.01) and patients with better PS (PS 0-1; 98% vs. 94%, p = 0.06), and those who achieved higher tumor response by CT1 (response rate; 19% vs. 7%, p &lt; 0.01) had higher chance to receive CT2. Objective response rate and disease control rate of CT2 were 4% and 50%, respectively. Median progression-free survival (PFS) and overall survival (OS) from the beginning of CT2 were 2.8 and 7.7 months, respectively. Prognostic factors impacting OS with CT2 were PS (0 vs. 1-2, hazard ratio [HR] 1.28, p=0.05), tumor response to CT1 (PR-SD vs. PD, HR 1.62, p = 0.02), and CEA (&lt;5.0 vs. ≥5.0 IU/mL, HR 1.52, p = 0.03). Conclusions: Although the efficacy of CT2 was modest at present, it may deserve to be considered in patients who maintained systemic condition in clinical practice. Further investigations are necessary both to to develop more effective regimens and to select patient who will benefit from CT2 in order to maximize the efficacy and to avoid unnecessary toxicity and expense.
Molecular Diagnosis of Diffuse Gliomas through Sequencing of Cell-Free Circulating Tumor DNA from Cerebrospinal Fluid
Authors: Francisco Martínez-Ricarte, Regina Mayor, Elena Martínez-Sáez, Carlota Rubio-Pérez, Estela Pineda, Esteban Cordero, Marta Cicuéndez, Maria A. Poca, Nuria López-Bigas, Santiago Ramon y Cajal, María Vieito, Joan Carles, Josep Tabernero, Ana Vivancos, Soledad Gallego, Francesc Graus, Juan Sahuquillo, Joan Seoane
Journal: Clinical Cancer Research (2018)

Purpose: Diffuse gliomas are the most common primary tumor of the brain and include different subtypes with diverse prognosis. The genomic characterization of diffuse gliomas facilitates their molecular diagnosis. The anatomical localization of diffuse gliomas complicates access to tumor specimens for diagnosis, in some cases incurring high-risk surgical procedures and stereotactic biopsies. Recently, cell-free circulating tumor DNA (ctDNA) has been identified in the cerebrospinal fluid (CSF) of patients with brain malignancies.Experimental Design: We performed an analysis of IDH1, IDH2, TP53, TERT, ATRX, H3F3A, and HIST1H3B gene mutations in two tumor cohorts from The Cancer Genome Atlas (TCGA) including 648 diffuse gliomas. We also performed targeted exome sequencing and droplet digital PCR (ddPCR) analysis of these seven genes in 20 clinical tumor specimens and CSF from glioma patients and performed a histopathologic characterization of the tumors.Results: Analysis of the mutational status of the IDH1, IDH2, TP53, TERT, ATRX, H3F3A, and HIST1H3B genes allowed the classification of 79% of the 648 diffuse gliomas analyzed, into IDH-wild-type glioblastoma, IDH-mutant glioblastoma/diffuse astrocytoma and oligodendroglioma, each subtype exhibiting diverse median overall survival (1.1, 6.7, and 11.2 years, respectively). We developed a sequencing platform to simultaneously and rapidly genotype these seven genes in CSF ctDNA allowing the subclassification of diffuse gliomas.Conclusions: The genomic analysis of IDH1, IDH2, TP53, ATRX, TERT, H3F3A, and HIST1H3B gene mutations in CSF ctDNA facilitates the diagnosis of diffuse gliomas in a timely manner to support the surgical and clinical management of these patients. Clin Cancer Res; 24(12); 2812-9. ©2018 AACR.
Abstract 14165: Nocturnal Blood Pressure Detected by Home Blood Pressure Monitoring as a Novel Independent Predictor Oo Cardiovascular Events in the Japanese General Practice Population: The J-HOP Study
Authors: Kazuomi Kario, Satoshi Hoshide, Yukie Okawara, Naoko Tomitani, Yuichiro Yano, Kazuo Eguchi
Journal: Circulation (2016)

Background:  Nocturnal blood pressure (BP) measured by ambulatory BP monitoring has been shown as a robust predictor of incident cardiovascular disease (CVD) in high-risk populations. However, the clinical relevance of nocturnal BP measured by home BP monitoring (HBPM) in general practice remains unknown.   Objective:  To study whether nocturnal HBP is associated with CVD risk independently of clinic BP and morning and evening HBPs in general practice.   Methods:  We used data from the nationwide practice-based Japan Morning Surge-Home Blood Pressure (J-HOP) Nocturnal BP Study that included 2545 Japanese with a history of or risk factors for CVD, or both (mean age 63.3 years; 82.9% on antihypertensive medications). Patients measured their nocturnal HBP at 3 time points during sleep (AM2:00, AM3:00, AM4:00) using our automatic Medinote HBPM device.   Results:  Ninety-three CVD events (46 stroke, 47 coronary events) occurred during the 4.0-year follow-up period. A 10-mmHg increase in nocturnal home systolic BP (HSBP) (average of the values at AM2:00 and AM3:00) was associated with a significant increase in CVD events of 26.9% (p=0.007) by Cox regression analysis, even after controlling for covariates including both clinic and morning HBPs. These associations were stronger for stroke than coronary events. Compared with the well-controlled group with morning HSBP 115mmHg) both with (HR=2.43, p=0.012) or without (HR=2.39, p=0.021) morning HSBP   Conclusion:  Higher nocturnal SBP detected by HBPM, regardless of office or morning SBP level, is a strong and independent risk for CVD events in the general practice population. Nocturnal HBPM is useful in identifying those at higher risk of developing adverse CVD outcomes in clinical practice.
IL-17–producing ST2+ group 2 innate lymphoid cells play a pathogenic role in lung inflammation
Authors: Ting Cai, Jinxin Qiu, Yan Ji, Wenjing Li, Zhaoyun Ding, Caixia Suo, Jiali Chang, Jingjing Wang, Rui He, Youcun Qian, Xiaohuan Guo, Liang Zhou, Huiming Sheng, Lei Shen, Ju Qiu
Journal: Journal of Allergy and Clinical Immunology (2018)
Immunoscore to provide prognostic information in low- (T1-3N1) and high-risk (T4 or N2) subsets of stage III colon carcinoma patients treated with adjuvant FOLFOX in a phase III trial (NCCTG N0147; Alliance).
Authors: Frank A. Sinicrope, Qian Shi, Fabienne Hermitte, Erica N Heying, Al Bowen Benson, Sharlene Gill, Richard Goldberg, Morton S. Kahlenberg, Suresh Nair, Anthony Frank Shields, Daniel J. Sargent, Jerome Galon, Steven R. Alberts
Journal: Journal of Clinical Oncology (2018)

614 Background: A consensus interpretation of the IDEA colon cancer study results suggested that risk categories based on T/N stage grouping be used to guide decision-making for duration (3 vs 6 months) of adjuvant FOLFOX or CapeOX chemotherapy. Given the prognostic potential of immune biomarkers, we examined the immunoscore and individual T and B lymphocyte markers in low and high risk T/N subsets of stage III colon carcinoma patients (N=600) treated with adjuvant FOLFOX. Methods: Immunoscore (CD3 + , CD8 + ) and individual T-cell and CD20 + B-cell immunostain densities in central tumor (CT) and invasive margin (IM) of FFPE sections were quantified by image analysis. A predetermined immunoscore categorization was used [high (2-4) vs low (0-1)]. Individual markers were analyzed by backwards selection wherein CD3 + IM was most robust for prognosis and an optimized cutoff was then determined. Associations with disease-free survival (DFS) were analyzed by multivariable Cox regression adjusting for age, T/N stage, sidedness, KRAS/BRAF, and DNA mismatch repair. Results: In low and high risk T/N patient subsets, the immunoscore and CD3 + IM were each significantly discriminant for prognosis. Among low risk (T 1-3 N 1 ) patients, a high vs low immunoscore was associated with a 91% vs 77% 3-year DFS [HR 0.57, 95% confidence interval (CI) 0.34-0.95, adjusted (adj) P= 0.026]. Among high risk (T 4 or N 2 ) patients, a high vs low immunoscore was associated with a 68% vs 54% 3-year DFS (HR 0.64, 95% CI 0.42-0.98, P adj = 0.034]. Similarly, a high vs low intratumoral CD3 + density at the invasive margin (IM) was significantly associated with prognosis in low risk [HR 0.37, 95% CI 0.21- 0.66), P adj &lt; 0.0003] and in high risk [HR 0.47, 95% CI, 0.27- 0.80), P adj &lt; 0.0028] patient subsets. Conclusions: Immunoscore and CD3 + IM were shown to prognostically stratify FOLFOX-treated patients within both low and high risk T/N subsets. These data underscore limitations of the T/N risk classification for adjuvant treatment decisions in stage III patients, and demonstrate the ability of T-cell markers to enhance prognostication to guide clinical decision-making.
Does metabolic health status affect the optimal starting age for colorectal cancer screening? A Korean nationwide cross-sectional study.
Authors: Yoon Jin Choi, Dong Ho Lee
Journal: Journal of Clinical Oncology (2018)

573 Background: The association between metabolic syndrome and colorectal cancer (CRC) has been suggested as one of causes for the increasing incidence of CRC, particularly in younger age groups. The present study examined whether the current age threshold (50 years) for colorectal cancer (CRC) screening in Korea requires modification when considering metabolic syndrome. Methods: We examined data from the National Health Insurance Corporation database, which covers ~97% of the population in Korea. CRC risk was analyzed with stratification based on age and the presence/absence of relevant metabolic syndrome components (diabetes, dyslipidemia, and hypertension). The incidence of CRC was determined for four, 2-year time periods. Results: A total of 51,612,316 subjects enrolled during 2014-2015 were analyzed. Among them, 19.3% had diabetes, hypertension, dyslipidemia, or some combination thereof. This population had a higher incidence of CRC than did those without these conditions and this was more prominent in subjects &lt; 40 years of age. The optimal cut-off age for detecting CRC, based on the highest Youden index, was 45 years among individuals without diabetes, dyslipidemia, and hypertension, and 62 years among individuals with at least one of these components of metabolic syndrome. Resetting the cut-off age from 50 years to 45 years achieved a 6% increment in sensitivity for CRC detection among the total population. Conclusions: An earlier start of CRC screening, namely at 45 rather than at 50 years of age, may improve secondary prevention of CRC in Korea.