tbuckley/cabot-search huggingface dataset:
Comparison of β-Cell Function Between Overweight/Obese Adults and Adolescents Across the Spectrum of Glycemia
Authors: Melinda E. Chen, Aaditya G. Chandramouli, Robert V. Considine, Tamara S. Hannon, Kieren J. Mather
Journal: Diabetes Care (2017)

OBJECTIVE Type 2 diabetes is a growing health problem among both adults and adolescents. To better understand the differences in the pathogenesis of diabetes between these groups, we examined differences in β-cell function along the spectrum of glucose tolerance. RESEARCH DESIGN AND METHODS We evaluated 89 adults and 50 adolescents with normal glucose tolerance (NGT), dysglycemia, or type 2 diabetes. Oral glucose tolerance test results were used for C-peptide and insulin/glucose minimal modeling. Model-derived and direct measures of insulin secretion and insulin sensitivity were compared across glycemic stages and between age-groups at each stage. RESULTS In adolescents with dysglycemia, there was marked insulin resistance (insulin sensitivity index: adolescents, median [interquartile range] 1.8 [1.1–2.4] × 10−4; adults, 5.0 [2.3–9.9]; P = 0.01). The nature of β-cell dysfunction across stages of dysglycemia differed between the groups. We observed higher levels of secretion among adolescents than adults (total insulin secretion: NGT, 143 [103–284] × 10−9/min adolescent vs. 106 [71–127], P = 0.001); adults showed stepwise impairments in static insulin secretion (NGT, 7.5 [4.0–10.3] × 10−9/min; dysglycemia, 5.0 [2.3–9.9]; type 2 diabetes, 0.7 [0.1–2.45]; P = 0.003), whereas adolescents showed diabetes-related impairment in dynamic secretion (NGT, 1,905 [1,630–3,913] × 10−9; dysglycemia, 2,703 [1,323–3,637]; type 2 diabetes, 1,189 [269–1,410]; P = 0.001). CONCLUSIONS Adults and adolescents differ in the underlying defects leading to dysglycemia, and in the nature of β-cell dysfunction across stages of dysglycemia. These results may suggest different approaches to diabetes prevention in youths versus adults.
P3.02b-097 Experience of Re-Biopsy (Biopsy at Progression) of EGFR Mutant Non-Small Cell Lung Cancer Patients in Japan: A Retrospective Study
Authors: Kaname Nosaki, Miyako Satouchi, Takayasu Kurata, Tatsuya Yoshida, Isamu Okamoto, Nobuyuki Katakami, Fumio Imamura, Kaoru Tanaka, Naoki Tashiro, Takashi Seto
Journal: Journal of Thoracic Oncology (2017)
Defining the Elements of Early Palliative Care That Are Associated With Patient-Reported Outcomes and the Delivery of End-of-Life Care
Authors: Michael Hoerger, Joseph A. Greer, Vicki A. Jackson, Elyse R. Park, William F. Pirl, Areej El-Jawahri, Emily R. Gallagher, Teresa Hagan, Juliet Jacobsen, Laura M. Perry, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2018)

Purpose We describe the key elements of early palliative care (PC) across the illness trajectory and examine whether visit content was associated with patient-reported outcomes and end-of-life care. Methods We performed a secondary analysis of patients with newly diagnosed advanced lung or noncolorectal GI cancer (N = 171) who were randomly assigned to receive early PC. Participants attended at least monthly visits with board-certified PC physicians and advanced practice nurses at Massachusetts General Hospital. PC clinicians completed surveys documenting visit content after each encounter. Patients reported quality of life (Functional Assessment of Cancer Therapy–General) and mood (Hospital Anxiety and Depression Scale and Patient Health Questionnaire-9) at baseline and 24 weeks. End-of-life care data were abstracted from the electronic health record. We summarized visit content over time and used linear and logistic regression to identify whether the proportion of visits addressing a content area was associated with patient-reported outcomes and end-of-life care. Results We analyzed data from 2,921 PC visits, most of which addressed coping (64.2%) and symptom management (74.5%). By 24 weeks, patients who had a higher proportion of visits that addressed coping experienced improved quality of life ( P = .02) and depression symptoms (Depression subscale of the Hospital Anxiety and Depression Scale, P = .002; Patient Health Questionnaire-9, P = .004). Patients who had a higher proportion of visits address treatment decisions were less likely to initiate chemotherapy ( P = .02) or be hospitalized ( P = .005) in the 60 days before death. Patients who had a higher proportion of visits addressing advance care planning were more likely to use hospice ( P = .03). Conclusion PC clinicians’ focus on coping, treatment decisions, and advance care planning is associated with improved patient outcomes. These data define the key elements of early PC to enable dissemination of the integrated care model.
P2.03a-017 Chemotherapy-Induced Nausea and Vomiting (CINV) in Italian Lung Cancer Patients: Assessment by Physician, Nurse and Patient
Authors: Simona Carnio, Domenico Galetta, Vieri Scotti, Diego Luigi Cortinovis, Andrea Antonuzzo, Salvatore Pisconti, Antonio Rossi, Olga Martelli, Alice Lunghi, Sara Pilotto, Alessandro Del Conte, Valeria Pegoraro, Elisabetta Sara Montagna, Juliana Topulli, Davide Pelizzoni, Simonetta Grazia Rapetti, Martina Gianetta, Maria Vittoria Pacchiana, Silvia Novello
Journal: Journal of Thoracic Oncology (2017)
Comment on Farren et al. The Prevention of Gestational Diabetes Mellitus With Antenatal Oral Inositol Supplementation: A Randomized Controlled Trial. Diabetes Care 2017;40:759–763
Authors: Basilio Pintaudi, Giacoma Di Vieste
Journal: Diabetes Care (2017)

We read with interest the study by Farren et al. (1) investigating the effect of a combination of myo -inositol and D -chiro-inositol on preventing gestational diabetes mellitus (GDM) in women with a family history of diabetes. The authors reported a not statistically different incidence of GDM in the intervention group compared with control subjects. However, it seems that important factors were not considered for the complete interpretation of results.

First, the selection of the study population was not limited to women with only a family history of diabetes as a risk factor for GDM. Women with other well-known risk factors (i.e., obesity, previous GDM) were also included. The presence/absence of previous macrosomia was not specified. With regard …
Targeting STUB1–tissue factor axis normalizes hyperthrombotic uremic phenotype without increasing bleeding risk
Authors: Moshe Shashar, Mostafa E. Belghasem, Shinobu Matsuura, Joshua Walker, Sean Richards, Faisal Alousi, Keshab Rijal, Vijaya B. Kolachalama, Mercedes Balcells, Minami Odagi, Kazuo Nagasawa, Joel M. Henderson, Amitabh Gautam, Richard Rushmore, Jean Francis, Daniel Kirchhofer, Kumaran Kolandaivelu, David H. Sherr, Elazer R. Edelman, Katya Ravid, Vipul C. Chitalia
Journal: Science Translational Medicine (2017)

Targeting mediators of the uremic thrombosis axis reverts the uremic hyperthrombotic phenotype without altering the bleeding risk.
What evidence do we need for biomarker qualification?
Authors: Chris Leptak, Joseph P. Menetski, John A. Wagner, Jiri Aubrecht, Linda Brady, Martha Brumfield, William W. Chin, Steve Hoffmann, Gary Kelloff, Gabriela Lavezzari, Rajesh Ranganathan, John-Michael Sauer, Frank D. Sistare, Tanja Zabka, David Wholley
Journal: Science Translational Medicine (2017)

Predictable steps are needed to determine the evidence required for confident use of a biomarker in drug development.
cGAS drives noncanonical-inflammasome activation in age-related macular degeneration
Authors: Nagaraj Kerur, Shinichi Fukuda, Daipayan Banerjee, Younghee Kim, Dongxu Fu, Ivana Apicella, Akhil Varshney, Reo Yasuma, Benjamin J Fowler, Elmira Baghdasaryan, Kenneth M Marion, Xiwen Huang, Tetsuhiro Yasuma, Yoshio Hirano, Vlad Serbulea, Meenakshi Ambati, Vidya L Ambati, Yuji Kajiwara, Kameshwari Ambati, Shuichiro Hirahara, Ana Bastos-Carvalho, Yuichiro Ogura, Hiroko Terasaki, Tetsuro Oshika, Kyung Bo Kim, David R Hinton, Norbert Leitinger, John C Cambier, Joseph D Buxbaum, M Cristina Kenney, S Michal Jazwinski, Hiroshi Nagai, Isao Hara, A Phillip West, Katherine A Fitzgerald, SriniVas R Sadda, Bradley D Gelfand, Jayakrishna Ambati
Journal: Nature Medicine (2017)
Sixty seconds on . . . potassium
Authors: Anne Gulland
Journal: BMJ (2017)

No, this is not about compost—this is about replacing sodium with potassium in food.

The Department of Health for England asked the Scientific Advisory Committee on Nutrition to investigate the benefits and risks of reducing the salt content in foods through the use of catchily named potassium based sodium replacers.1 A review of the evidence found that if the salt content was replaced with potassium by 15% to 25% there would be significant …
Lomustine and Bevacizumab in Progressive Glioblastoma
Authors: Wolfgang Wick, Thierry Gorlia, Martin Bendszus, Martin Taphoorn, Felix Sahm, Inga Harting, Alba A. Brandes, Walter Taal, Julien Domont, Ahmed Idbaih, Mario Campone, Paul M. Clement, Roger Stupp, Michel Fabbro, Emilie Le Rhun, Francois Dubois, Michael Weller, Andreas von Deimling, Vassilis Golfinopoulos, Jacoline C. Bromberg, Michael Platten, Martin Klein, Martin J. van den Bent
Journal: New England Journal of Medicine (2017)

Bevacizumab is approved for the treatment of patients with progressive glioblastoma on the basis of uncontrolled data. Data from a phase 2 trial suggested that the addition of bevacizumab to lomustine might improve overall survival as compared with monotherapies. We sought to determine whether the combination would result in longer overall survival than lomustine alone among patients at first progression of glioblastoma.We randomly assigned patients with progression after chemoradiation in a 2:1 ratio to receive lomustine plus bevacizumab (combination group, 288 patients) or lomustine alone (monotherapy group, 149 patients). The methylation status of the promoter of O6-methylguanine-DNA methyltransferase (MGMT) was assessed. Health-related quality of life and neurocognitive function were evaluated at baseline and every 12 weeks. The primary end point of the trial was overall survival.A total of 437 patients underwent randomization. The median number of 6-week treatment cycles was three in the combination group and one in the monotherapy group. With 329 overall survival events (75.3%), the combination therapy did not provide a survival advantage; the median overall survival was 9.1 months (95% confidence interval [CI], 8.1 to 10.1) in the combination group and 8.6 months (95% CI, 7.6 to 10.4) in the monotherapy group (hazard ratio for death, 0.95; 95% CI, 0.74 to 1.21; P=0.65). Locally assessed progression-free survival was 2.7 months longer in the combination group than in the monotherapy group: 4.2 months versus 1.5 months (hazard ratio for disease progression or death, 0.49; 95% CI, 0.39 to 0.61; P<0.001). Grade 3 to 5 adverse events occurred in 63.6% of the patients in the combination group and 38.1% of the patients in the monotherapy group. The addition of bevacizumab to lomustine affected neither health-related quality of life nor neurocognitive function. The MGMT status was prognostic.Despite somewhat prolonged progression-free survival, treatment with lomustine plus bevacizumab did not confer a survival advantage over treatment with lomustine alone in patients with progressive glioblastoma. (Funded by an unrestricted educational grant from F. Hoffmann-La Roche and by the EORTC Cancer Research Fund; EORTC 26101 ClinicalTrials.gov number, NCT01290939 ; Eudra-CT number, 2010-023218-30 .).
Outcomes of Positive Airway Pressure for Sleep Apnea
Authors: David T. Plante, William T. Hoyt
Journal: JAMA (2017)

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Randomized, Multicenter, Placebo-Controlled Clinical Trial of Duloxetine Versus Placebo for Aromatase Inhibitor–Associated Arthralgias in Early-Stage Breast Cancer: SWOG S1202
Authors: N. Lynn Henry, Joseph M. Unger, Anne F. Schott, Louis Fehrenbacher, Patrick J. Flynn, Debra M. Prow, Carl W. Sharer, Gary V. Burton, Charles S. Kuzma, Anna Moseley, Danika L. Lew, Michael J. Fisch, Carol M. Moinpour, Dawn L. Hershman, James L. Wade
Journal: Journal of Clinical Oncology (2017)

Purpose Adherence to aromatase inhibitor (AI) therapy for early-stage breast cancer is limited by AI-associated musculoskeletal symptoms (AIMSS). Duloxetine is US Food and Drug Administration approved for treatment of multiple chronic pain disorders. We hypothesized that treatment of AIMSS with duloxetine would improve average joint pain compared with placebo. Methods This randomized, double-blind, phase III trial included AI-treated postmenopausal women with early-stage breast cancer and who had average joint pain score of ≥ 4 out of 10 that developed or worsened since AI therapy initiation. Patients were randomly assigned 1:1 to duloxetine or placebo for 13 weeks. The primary end point was average joint pain through 12 weeks, examined using multivariable linear mixed models, adjusted for stratification factors (baseline pain score of 4 to 6 v 7 to 10 and prior taxane use). Clinically significant change in average pain was defined as a ≥ 2-point decrease from baseline. Results Of 299 enrolled patients, 127 patients treated with duloxetine and 128 who received placebo were evaluable for the primary analysis. By 12 weeks, the average joint pain score was 0.82 points lower for patients who received duloxetine compared with those who received placebo (95% CI, -1.24 to -0.40; P = .0002). Similar patterns were observed for worst joint pain, joint stiffness, pain interference, and functioning. Rates of adverse events of any grade were higher in the duloxetine-treated group (78% v 50%); rates of grade 3 adverse events were similar. Conclusion Results of treatment with duloxetine for AIMSS were superior to those of placebo among women with early-stage breast cancer, although it resulted in more frequent low-grade toxicities.
Abstract 20138: What is a Realistically Low Mortality in Cardiogenic Shock?
Authors: Torvind O Naesheim, Kaja Terese Hansen, Anja Blakar, Truls Myrmel
Journal: Circulation (2016)

Background:  In geographic areas with abundant revascularization options, both the incidence and mortality of cardiogenic shock (CS) seem to be decreasing. However, an aggressive revascularization strategy for ischemic heart disease seems to bring acute CS-mortality only to a sub 40% level and therefore a need for improvement still exists. We have established a “cardiogenic shock-team” with the intent to institute ECMO-treatment early in patients deemed insufficiently supported with medical treatment and acute revascularization.   Methods:  We evaluated 1497 patients diagnosed with cardiac failure admitted to the University Hospital of Northern Norway 2013 and 2014, after the systematic ECMO-algorithm was established, to find cases of cardiogenic shock and postcardiotomia heart failure. These patients were compared to an earlier study in our institution during the years 2003 and 2004.   Results:  Our pre-ECMO results demonstrated a 30 day mortality of 38% in 126 patients with cardiogenic shock and postcardiotomia heartfailure treated in a 2 year periode. Twelve % (n=15) of the diseased patients were deemed to be potential candidates for ECMO-treatment.  In the two year period since establishing the ECMO-team model we treated 73 patients using identical criteria for CS. 12 patients (16%) were treated with ECMO. CS hospital mortality during the last period was 28%, . Among the nonsurvivors ECMO was declined because of age in 32%, preexisting co morbidity in 9%, uncontrolled bleeding in 5% and multi organ failure in 27%. Hospital mortality among the ECMO patients was 25% and 30-day mortality was 33%. Kaplan-Meier curves comparing ECMO vs non ECMO patients show no difference in long term survival.  We identified 5 nonsurviving non-ECMO patients who potentially could have been selected for ECMO-treatment by our contemporary ECMO-protocol.   Conclusion:  Establishing a cardiogenic shock-team has improved the survival of these patients. Our retrospective analysis indicates that the triage of these patients can be even more refined. However, given some of these patients age and comorbidity, a close to zero mortality does not seem clinically realistic.
Abstract 21011: Crispr/ndcas9 Adenoviral Vector System as a Tool for Promoting Mitochondrial Biogenesis in Cardiomyocytes
Authors: Deepthi Ashok, Agnieszka Sidor, Brian O'Rourke
Journal: Circulation (2017)

Mitochondrial dysfunction contributes to heart failure. Our recent work revealed that genes in mitochondrial biogenesis and quality control, such as the peroxisome proliferator activated receptor gamma coactivator-1α(PGC-1α) and mitochondrial transcription factor A(TFAM), are downregulated in a rodent model of heart failure. Here, we apply CRISPR/Cas9 technology as a transcriptional activator to target sequences upstream of the start site to promote transcription of PGC-1α or TFAM. Since cardiomyocytes are difficult to transduce, we developed an adenoviral gene delivery system for expression of the CRISPR/Cas9 activating complex and a targeting gRNA to modulate expression of any gene of interest in differentiated cardiomyocytes, with our initial focus on activating the metabolic gene program. We use nuclease-dead Cas9 (ndCas9) fused to an activation domain VP64 and guide RNAs for activation of target genes. Proof-of-principle evidence was obtained by activating a cyclic AMP response element (CRE)-driven luciferase reporter gene and activation of endogenous CRE-regulable genes (PCK1 and PGC-1α). Next, we constructed ndCas9-gRNA adenoviral vectors to target PGC-1α and TFAM in the rat genome to determine if transcription of these genes can be increased. Functional effects of viral gene transduction in H9C2 cells and neonatal rat ventricular myocytes are assessed by determining mitochondrial DNA copy number (mtDNA)/genomic DNA ratio, and mtDNA quantity by picogreen labeling. Results: We have successfully upregulated the luciferase gene and endogenous CRE-regulated gene PCK1 in the same reporter cell line with ndCas9-VP64, as evidenced by significant increases in mRNA and protein expression levels. We have constructed and delivered adenoviral vectors with ndCas9 that are efficiently expressed by the host cells (NRVMs and H9c2 cells) and showed increased expression of PGC1a and TFAM in H9c2 cells. Importantly, an increase in mtDNA copy number was evoked by TFAM activation. For the first time, we show that the CRISPR/ndCas9 system can be used as a powerful tool for modulating transcription of native genes involved in mitochondrial biogenesis in cardiac cells, opening the door to developing novel therapeutic approaches for heart failure
P3.02b-115 Clinical Activity of Osimertinib in EGFR Mutation Positive Non-Small Cell Lung Cancer (NSCLC) Patients (Pts) Previously Treated with Rociletinib
Authors: Shirish Gadgeel, Wei Chen, Zofia Piotrowska, Jonathan W. Goldman, Heather Wakelee, D. Ross Camidge, Andrea Varga, Helena Yu, Vassiliki Papadimitrakopoulou, Joel Neal, Jean-Charles Soria, Antoinette Wozniak, Gregory Riely, Vignesh Narayanan, Melody Mendenhall, Lecia Sequist
Journal: Journal of Thoracic Oncology (2017)
Opioid epidemic or pain crisis? Exploring prescription opioid medication utilization for patients with cancer in rural Southwest Virginia.
Authors: Virginia T. LeBaron, Tareq Fabian Camacho, Kyle Russell, Marianne Beare, Aaron M. Gilson
Journal: Journal of Clinical Oncology (2017)

210 Background: The U.S. is in the throes of two concurrent epidemics: too many people die from opioid-related fatalities, but too many people continue to suffer in pain. In certain regions this dilemma is particularly pronounced. For example, Southwest (SW) Virginia is a rural area with disproportionately high cancer mortality rates and high rates of opioid fatalities. Little is known about how to most effectively and safely manage pain in a region where there exists both a high cancer burden and significant opioid misuse. Purpose: Describe prescription opioid medication (POM) use for patients with cancer in SW Virginia and potential harms. Methods: This is a longitudinal, exploratory, secondary data analysis using the Virginia All Payers Claims Database (APCD), which includes paid medical and pharmacy claims data on 4 million individuals in the Commonwealth of Virginia. Patients with a diagnosis of cancer who lived in far, rural SW Virginia between 2011–2015 were included. Outpatient prescription data were linked to hospitalization admission claims data to explore potential opioid-related harms. Analysis was conducted at the patient, prescription and prescriber level (SAS 9.4, STATA 13.1) to identify predictors of POM use and opioid-related substance use admissions. Results: Within the APCD, POMs represent 7.23% of all medications prescribed for patients with cancer, with hydrocodone- and oxycodone-combinations, oxycodone, fentanyl transdermal patch and morphine sulfate being the most common. Over 50% of patients were prescribed a POM at least once during the study period. Multi-level logistic regressions suggest age, payer source, cancer type, gender, prescriber type and specialty were all significant (p &lt; .001) predictors of being prescribed POMs. Preliminary analyses of hospitalized cancer patients found no association between POM use and opioid-related substance use hospitalization. Conclusions: A clearer view of geographic patterns and predictors of both POM use and potential harms can inform targeted clinical interventions and policy initiatives that achieve a balanced approach to POMs – ensuring access for patients in need, while reducing risk.
Control de la rubéola en Francia
Authors: D Lévy-Bruhl, C Six, I Parent du Châtelet
Journal: Eurosurveillance (2004)

La introduccion en 1983 de la vacunacion contra la rubeola en el programa de inmunizacion de Francia dio lugar a una impresionante reduccion en la incidencia de infecciones por rubeola durante el embarazo y en el sindrome de rubeola congenita, como lo demuestra la red de vigilancia en la que participan todos los laboratorios que realizan pruebas de IgM de rubeola. Sin embargo, la cobertura vacunal de nivel inferior al optimo tanto en ninos como en mujeres en edad fertil permite, respectivamente, la persistencia de la transmision de la rubeola y la incidencia anual de docenas de infecciones por rubeola durante el embarazo. Deben mantenerse las actividades recientemente destinadas a incrementar la cobertura, para prevenir futuros brotes debidos al gran nivel de susceptibilidad en mujeres jovenes.