tbuckley/cabot-search huggingface dataset:
Abstract MP36: Poverty Modifies the Association of Health-Related Fitness and School Absenteeism in New York City Middle School Girls
Authors: Emily M D'Agostino, Sophia E Day, Kevin J Konty, Michael Larkin, Subir Saha, Katarzyna Wyka
Journal: Circulation (2018)

Introduction: One-fifth to one-third of students in high-poverty, urban school districts do not attend school regularly (missing ≥6 days per year). Health related fitness is shown to be associated with absenteeism, although this relationship may differ across poverty and gender subgroups. Hypothesis: We hypothesized that area poverty would be a stronger effect modifier on the association of fitness (cardiorespiratory, muscular endurance, and muscular strength fitness composite percentile scores) and subsequent absenteeism (one-year lagged days absent) in girls compared with boys. Methods: Six cohorts of New York City public school students were followed from grades 5-8 during 2006/7-2012/13 (n=349,381). Stratified three-level longitudinal generalized linear mixed models were used to test the modification of poverty on the association of fitness changes and one-year lagged child-specific days absent across gender. Results: The fitness-absenteeism association was not significant in boys attending schools in high/very high (p=0.075) or low/mid poverty (p=0.454) areas. In girls attending schools in high/very high poverty areas, greater improvements in fitness the prior year were associated with greater improvements in attendance (p=0.034). Relative to the reference group (&gt;20% decrease in fitness composite percentile scores from the prior year), girls with a large increase in fitness (&gt;20%) demonstrated 10.3% fewer days absent (IRR 95% CI: 0.834, 0.964), followed by those who had a 10-20% increase in fitness (9.2%, IRR 95% CI: 0.835, 0.987), no change (5.4%, IRR 95% CI: 0.887, 1.007) and a 10-20% decrease in fitness (3.8%, IRR 95% CI: 0.885, 1.045). In girls attending schools in low/mid poverty areas, the fitness-attendance relationship was also positive, but no clear trend emerged. Conclusions: Fitness improvements may be more important to attendance improvements in high/very high poverty girls compared with low/mid poverty girls, and both high/very high and low/mid poverty boys. In conclusion, expanding school-based physical activity programs for girls in high-poverty neighborhoods may increase student attendance.
Impact of Sarcopenia on Adverse Outcomes After Allogeneic Hematopoietic Cell Transplantation
Authors: Saro H Armenian, Meisi Xiao, Jennifer Berano Teh, Brandyn Lee, Howard A Chang, Kristen Mascarenhas, Sean Lee, Alex Iukuridze, Jack J Xie, Jessica M Scott, Lee W Jones, F Lennie Wong, Stephen J Forman, Ryotaro Nakamura
Journal: JNCI Journal of the National Cancer Institute (2018)

Abstract Background High intensity treatments such as hematopoietic cell transplantation (HCT) can be curative for patients with hematologic malignancies, but this needs to be balanced by the high risk of nonrelapse mortality (NRM) during the first 2 years after HCT. Sarcopenia (low muscle mass) is associated with physical disability and premature mortality in individuals with nonmalignant diseases and may be a predictor of NRM and poor overall survival in patients undergoing HCT. Methods This was a retrospective cohort study of 859 patients with acute leukemia or myelodysplastic syndrome who underwent a first HCT as adults (≥18 years) between 2007 and 2014. Sarcopenia was assessed from pre-HCT abdominal computed tomography scans. Two-year cumulative incidence of NRM was calculated, with relapse/progression considered as a competing risk event. Fine-Gray subdistribution hazard ratio estimates and 95% confidence intervals (CI) were obtained and adjusted for relevant covariates. Kaplan-Meier method was used to examine overall survival. All statistical tests were two-sided. Results Median age at HCT was 51 years (range = 18–74 years); 52.5% had a high [≥3] HCT-comorbidity index; 33.7% had sarcopenia pre-HCT. Sarcopenia was an independent predictor of higher NRM risk (hazard ratio = 1.58, 95% CI = 1.16 to 2.16) compared with patients who were not. The 2-year incidence of NRM approached 30% in patients with sarcopenia and high (≥3) HCT-comorbidity index. Patients with sarcopenia had on average a longer hospitalization (37.2 days vs 31.5 days, P &lt; .001) and inferior overall survival at 2 years (55.2%, 95% CI = 49.5% to 61.0% vs 66.9%, 95% CI = 63.0% to 70.8%, P &lt; .001). Conclusions Sarcopenia is an important and independent predictor of survival after HCT, with potential additional downstream impacts on health-economic outcomes. This information can be used to facilitate treatment decisions prior to HCT and guide interventions to decrease the risk of treatment-related complications after HCT.
Abstract P3-01-17: PD-L1 expression on circulating epithelial tumor cells (CETCs) correlates with aggressiveness of tumor in breast cancer patients
Authors: D Schott, M Pizon, U Pachmann, K Pachmann
Journal: Cancer Research (2019)

Abstract Background: Strategies to improve the efficacy of the immune system against malignant tumors represent a major innovation focusing on the programmed death-1 receptor (PD-1), with its two ligands PD-L1 and PD-L2. The expression of PD-L1 has been evaluated in a number of different tumor types and can be used as a predictive biomarker for PD-1/PD-L1 checkpoint inhibitor treatment response. We used a non-invasive, real-time liquid biopsy to better characterize PD-L1 expression on circulating epithelial tumor cells (CETCs) in breast cancer patients. Methods: CETCs were determined from blood of 72 patients suffering from breast cancer. The number of vital CETCs and their expression of PD-L1 was investigated using the maintrac® method. Results: PD-L1 expressing CETCs were detected in 94.5 % of breast cancer patients. Breast cancer patients with metastatic disease had significantly more PD-L1 positive CETCs as compared to patients without metastasis (median 75% vs. 61.1%; p&amp;lt;0.05). Furthermore, patients with positive lymph node status had significantly more PD-L1 positive CETCs as compared to patients with negative lymph nodes (median 60% vs. 93%, p&amp;lt;0,05). Moreover, we observed a significant heterogeneity in PD-L1 immunostaining intensity across CETCs from the same patients. Conclusion: Breast cancer patients have detectable CETCs with a high frequency of PD-L1 which correlates with progression of cancer disease. PD-L1 seems to be a major factor in immune evasion and may be a promising target of anticancer therapies. Monitoring the frequency of PD-L1 positive CETCs could reflect individual patient's response to an anti-PD-1/PD-L1 therapy. Citation Format: Schott D, Pizon M, Pachmann U, Pachmann K. PD-L1 expression on circulating epithelial tumor cells (CETCs) correlates with aggressiveness of tumor in breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-01-17.
<i>BRCA1</i> Promoter Methylation Is Linked to Defective Homologous Recombination Repair and Elevated <i>miR-155</i> to Disrupt Myeloid Differentiation in Myeloid Malignancies
Authors: Weijie Poh, Robert L. Dilley, Alison R. Moliterno, Jaroslaw P. Maciejewski, Keith W. Pratz, Michael A. McDevitt, James G. Herman
Journal: Clinical Cancer Research (2019)

Defective homologous recombination (HR) has been reported in multiple myeloid disorders, suggesting a shared dysregulated pathway in these diverse malignancies. Because targeting HR-defective cancers with PARP inhibition (PARPi) has yielded clinical benefit, improved understanding of HR defects is needed to implement this treatment modality.We used an ex vivo irradiation-based assay to evaluate HR repair, HR gene promoter methylation, and mRNA expression in primary myeloid neoplastic cells. In vitro BRCA1 gene silencing was achieved to determine the consequences on HR repair, sensitivity to PARPi, and expression of miR-155, an oncogenic miRNA.Impaired HR repair was frequently detected in myeloid neoplasm samples (9/21, 43%) and was linked to promoter methylation-mediated transcriptional repression of BRCA1, which was not observed for other members of the HR pathway (BRCA2, ATM, ATR, FANC-A). In vitro BRCA1 knockdown increased sensitivity to PARP inhibition, and BRCA1 expression is inversely correlated with miR-155 expression, a finding reproduced in vitro with BRCA1 knockdown. Increased miR-155 was associated with PU.1 and SHIP1 repression, known myeloid differentiation factors that are frequently downregulated during leukemic transformation.This study demonstrates frequent defective HR, associated with BRCA1 epigenetic silencing, in a broad range of myeloid neoplasms. The increased prevalence of BRCA1 promoter methylation, resulting in repressed BRCA1, may have an additional role in leukemogenesis by increasing miR-155 expression, which then inhibits transcription factors associated with normal myeloid differentiation. Further study of HR defects may facilitate the identification of HR-defective myeloid neoplasms sensitive to PARPi.
TNF-Induced Vaso-Occlusive and Inflammatory Processes in Mice with Sickle Cell Anemia Are Abrogated By the Platelet Activation Inhibitor, Prasugrel
Authors: Hanan Chweih, Juliete A.F. Silva, Erica M.F. Gotardo, Pamela L. Brito, Guilherme G.O. Barbosa, Flavia Garcia, Wilson A. Ferreira, Flavia C. Leonardo, Carla F. Franco-Penteado, Fernando F. Costa, Nicola Conran
Journal: Blood (2018)
Physician Burnout in the Electronic Health Record Era
Authors: Donald E. Girard
Journal: Annals of Internal Medicine (2019)

Letters5 February 2019Physician Burnout in the Electronic Health Record EraDonald E. Girard, MDDonald E. Girard, MDOregon Health & Science University, Portland, Oregon (D.E.G.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L18-0602 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:As an older general internist, I have lived through the many issues that Downing and colleagues (1) discuss. I remember with some humor that our academic center's intramural news sites circulated a photograph of me at a computer to show that even the oldest among us could learn to use the electronic health record (EHR). I succeeded in mastering the basics; however, facing increasing and seemingly needless requirements and less time with patients (and students, residents, and other learners), I left the struggle. In truth, my failure to meet the local EHR requirements ended my academic practice. ...Reference1. Downing NL, Bates DW, Longhurst CA. Physician burnout in the electronic health record era: are we ignoring the real cause? Ann Intern Med. 2018;169:50-1. [PMID: 29801050]. doi:10.7326/M18-0139 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Oregon Health & Science University, Portland, Oregon (D.E.G.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L18-0602. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoPhysician Burnout in the Electronic Health Record Era: Are We Ignoring the Real Cause? N. Lance Downing , David W. Bates , and Christopher A. Longhurst Physician Burnout in the Electronic Health Record Era N. Lance Downing , David W. Bates , and Christopher A. Longhurst Physician Burnout in the Electronic Health Record Era Mukesh Kapoor Metrics Cited byDigitalization in Medicine: Are German Medical Students Well Prepared for the Future?National Trends in Daily Ambulatory Electronic Health Record Use by Otolaryngologists 5 February 2019Volume 170, Issue 3Page: 215-216KeywordsComputersConflicts of interestDisclosureElectronic medical recordsEmotionsProspective studies ePublished: 5 February 2019 Issue Published: 5 February 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Broad IgG repertoire in patients with chronic rhinosinusitis with nasal polyps regulates proinflammatory IgE responses
Authors: Mohamed H. Shamji, Irene Thomsen, Janice A. Layhadi, Jasper Kappen, Gabriële Holtappels, Umit Sahiner, Amy Switzer, Stephen R. Durham, Oliver Pabst, Claus Bachert
Journal: Journal of Allergy and Clinical Immunology (2019)
Prognostic and predictive factors after failure of two drug lines for metastatic gastric adenocarcinomas: A French retrospective study.
Authors: Benjamin Boussac, Ludovic Evesque, Jocelyn Gal, Renaud Schiappa, Jerome Doyen, Emmanuel Benizri, Angelique Saint, Gerard Cavaglione, Eric Francois
Journal: Journal of Clinical Oncology (2019)

149 Background: There is no therapeutic consensus after failure of two drug lines for metastatic gastric adenocarcinoma. The theoretical benefit of a third-line chemotherapy has to be weighed with the potential toxicity it could generate. It is essential to have prognostic and predictive factors to better select the candidate patients for a 3 rd line chemotherapy. Methods: The medical records of patients (pts) treated in our institute from 2008 to 2018 who received at least two chemotherapy lines have been retrospectively analyzed. The main objective was to look for prognostic factors after failure of two chemotherapy lines. The secondary objectives were to look for predictive factors of progression-free survival, global survival, and RECIST response in 3 rd line. Results: Out of a total of 153 pts identified, 68 received at least 2 chemotherapy lines and were eligible for analysis (44%). A third line was initiated for 41 pts (27%). Overall survival from the date of failure of a 2 nd line treatment was 4.4 months (95% CI: 3.2-6.2). The median of progression-free survival in 3 rd line was 1.68 months (CI 95%: 1.5-3.5 months), 5% of the patients responded to the treatment. In multivariate analysis, a period of less than 12 months between the administration of the 1 st line of chemotherapy and the failure of a 2 nd line was associated with a Hazard Ratio (HR) for death of 2.7 (p &lt; 0.001; 95% CI 1.44 – 5.1). Pts who did not receive a 3 rd line and female patients had a HR for death of 3.7 (p &lt; 0.001; CI 95%: 1,9–7.3), and 2.8 (p &lt; 0.001; 95% CI: 1,3–5.8) respectively. For patients who started a 3 rd line: a PS ≥ 2 increased the risk of progression by 4.05 (p &lt; 0.001; 95% CI: 1.1–15.7). Conclusions: Nearly one-third of pts were able to receive a third line chemotherapy. However, the benefit of this chemotherapy is low given the RECIST response rate, and the short overall and progression-free survival medians. Our results suggest that the administration of a third-line chemotherapy should only be considered for pts with 12 months or older ongoing metastatic lesions and whose general health condition is unaltered.
<i>Prevotella copri</i> in individuals at risk for rheumatoid arthritis
Authors: Deshire Alpizar-Rodriguez, Till Robin Lesker, Achim Gronow, Benoît Gilbert, Elena Raemy, Celine Lamacchia, Cem Gabay, Axel Finckh, Till Strowig
Journal: Annals of the Rheumatic Diseases (2019)

Rheumatoid arthritis (RA) has been associated with a relative expansion of faecal Prevotellaceae. To determine the microbiome composition and prevalence of Prevotella spp. in a group of individuals at increased risk for RA, but prior to the development of the disease.In an ongoing cohort study of first-degree relatives (FDRs) of patients with RA, we identified 'FDR controls', asymptomatic and without autoantibodies, and individuals in pre-clinical RA stages, who had either developed anticitrullinated peptide antibodies or rheumatoid factor positivity and/or symptoms and signs associated with possible RA. Stool sampling and culture-independent microbiota analyses were performed followed by descriptive statistics and statistical analyses of community structures.A total of 133 participants were included, of which 50 were categorised as 'FDR controls' and 83 in 'pre-clinical RA stages'. The microbiota of individuals in 'pre-clinical RA stages' was significantly altered compared with FDR controls. We found a significant enrichment of the bacterial family Prevotellaceae, particularly Prevotella spp., in the 'pre-clinical RA' group (p=0.04).Prevotella spp. enrichment in individuals in pre-clinical stages of RA, before the onset of RA, suggests a role of intestinal dysbiosis in the development of RA.
Anti-CD117 antibody depletes normal and myelodysplastic syndrome human hematopoietic stem cells in xenografted mice
Authors: Wendy W. Pang, Agnieszka Czechowicz, Aaron C. Logan, Rashmi Bhardwaj, Jessica Poyser, Christopher Y. Park, Irving L. Weissman, Judith A. Shizuru
Journal: Blood (2019)
Abstract P255: Use of Novel Oral Anticoagulants Among Patients With Atrial Fibrillation Increased Even in Those With Severely Impaired Kidney Function
Authors: Jung-Im Shin, Alex Secora, Josef Coresh, Alex R Chang, Morgan E Grams
Journal: Circulation (2017)

Novel oral anticoagulants (NOACs) are increasingly prescribed as substitutes for warfarin in patients with atrial fibrillation (AF). All of the NOACs are at least partially renally cleared, but most trials excluded patients with severe kidney dysfunction. Despite this, labels include dosing for creatinine clearance 15-30 ml/min. The objective of the study was to estimate the prevalence of NOAC use over time among people with AF, stratified by stage of chronic kidney disease (CKD). Study population included 17,280 patients with AF and at least one prescribed anticoagulant (warfarin, dabigatran, rivaroxaban, or apixaban) between 2010 and 2016 in the Geisinger Health System, a large rural health care system in Pennsylvania. Medication information was obtained from both medication orders and records. Average age of the study population was 73.6 years, 46.6% (N=8,044) were women, 98.4% (N=17,009) were Non-Hispanic White, and average estimated glomerular filtration rate (eGFR) was 70.2 ml/min/1.73 m 2 . Over the course of 2010-2016, 3.0% (N=513), 6.9% (N=1,184) and 4.6% (N=792) received at least one prescription for dabigatran, rivaroxaban, or apixaban. NOAC ever-users (N=2,392) were younger (69.1 vs. 74.3 years, P &lt;0.001) and had a higher eGFR (77.7 vs. 69.9 ml/min/1.73 m 2 ) than warfarin-only users (N=14,888). Prescription of NOACs increased from 0% to 14.7% from 2010 to 2016 ( P &lt;0.001). Prescription of NOACs increased in each category of CKD (G1-2, G3 and G4-5, all P &lt;0.001) (Figure 1). The most frequently prescribed NOAC in 2016 was rivaroxaban (8.2%) among those with eGFR&gt;60 ml/min/1.73 m 2 and apixaban (5.9% and 4.9%) among those with eGFR 30-60 ml/min/1.73 m 2 and eGFR&lt;30 ml/min/1.73 m 2 , respectively. Among the 22 patients prescribed apixaban with eGFR&lt;30 ml/min/1.73 m 2 in 2016, 22.7% (5 of 22) had eGFR&lt;15 ml/min/1.73 m 2 . In conclusion, NOAC prescriptions increased among patients with AF in all stages of CKD. Further studies to quantify the effectiveness and safety of NOACs compared to warfarin by stage of CKD are warranted.
Differential immune profiles distinguish the mutational subtypes of gastrointestinal stromal tumor
Authors: Gerardo A. Vitiello, Timothy G. Bowler, Mengyuan Liu, Benjamin D. Medina, Jennifer Q. Zhang, Nesteene J. Param, Jennifer K. Loo, Rachel L. Goldfeder, Frederic Chibon, Ferdinand Rossi, Shan Zeng, Ronald P. DeMatteo
Journal: Journal of Clinical Investigation (2019)

Gastrointestinal stromal tumor (GIST) is the most common human sarcoma, frequently characterized by an oncogenic mutation in the KIT or PDGFRA gene. We performed RNA sequencing of 75 human GIST tumors from 75 patients, comprising what we believe to be the largest cohort of GISTs sequenced to date, in order to discover differences in the immune infiltrates of KIT- and PDGFRA-mutant GIST. Through bioinformatics, immunohistochemistry, and flow cytometry, we found that in PDGFRA-mutant GISTs, immune cells were more numerous and had higher cytolytic activity than in KIT-mutant GISTs. PDGFRA-mutant GISTs expressed many chemokines, such as CXCL14, at a significantly higher level when compared with KIT-mutant GISTs and exhibited more diverse driver-derived neoepitope:HLA binding, both of which may contribute to PDGFRA-mutant GIST immunogenicity. Through machine learning, we generated gene expression–based immune profiles capable of differentiating KIT- and PDGFRA-mutant GISTs, and identified additional immune features of high–PD-1– and –PD-L1–expressing tumors across all GIST mutational subtypes, which may provide insight into immunotherapeutic opportunities and limitations in GIST.
Single-shot celiac plexus radiosurgery in pancreatic cancer: Palliative and functional outcomes—Final results of a prospective clinical trial.
Authors: Yaacov Richard Lawrence, Einat Shacham Shmueli, Liat Hammer, Ofir Morag, Maoz Ben-Ayun, Ofer Margalit, Naama Halpern, Nirit Yarom, Ben Boursi, Galia Jacobson, Zvi Symon, Kinneret Shefer, Inessa Yanovsky, Talia Golan, David Hausner
Journal: Journal of Clinical Oncology (2019)

309 Background: Pancreatic cancer is characterized by severe epigastric/lower back pain caused by infiltration of the celiac plexus. The celiac plexus is a network of nociceptive nerves, located along the abdominal aorta. Contemporary approaches (opioids, celiac plexus chemical neurolysis, systemic chemotherapy) are often inadequate. We hypothesized that ablative radiation targeted to the celiac plexus would alleviate pain. Here we report results for pancreatic cancer patients treated with a single fraction of radiation. Methods: We conducted a single-institution single-arm prospective clinical trial. Eligible cancer patients had celiac-pain &gt; 4/10 on Numerical Rating Scale (NRS) and completed treatment per protocol with at least one post-treatment visit. The celiac plexus was irradiated from D12 to L2. Radiation was given as a single-fraction 25 Gy. The primary endpoint was NRS pain 3 weeks post-treatment. Secondary endpoints were toxicity, pain at 6w, analgesic use, and pain interference with daily activities as evaluated by the ‘The Brief Pain Inventory’. Analgesia was not restricted. Total daily dose of opioids was measured in morphine milligram equivalents (MME). Results: Seventeen patients were evaluable, 65% female, median age 68 yr (range 51-79), three had undergone pancreatic resection, nine had liver metastases, median ECOG = 1. Sixteen patients reported 3-week outcomes, and 10 reported 6-week outcomes. At time of treatment subjects were a median of 8.2 months from diagnosis, and had received a median of one systemic treatment (range 0-3). Toxicity was limited to grade 1. Median baseline pain was 6/10 (IQR 5-7), was reduced to 2.3/10 (IQR 0.9-3.6) (p &lt; 0.0005) at 3 w, and to 2.5/10 (IQR 0-3.1) at 6 w post-treatment, for both p &lt; 0.001. Median opioid consumption numerically decreased (baseline 52.9 MME, 3 w 43.9 MME, 6 w 37.5 MME, NS). ‘BPI pain interference’ improved significantly: median baseline score 7.1 dropped to 1.1 at 3 weeks and 0 at 6 weeks (p &lt; 0.01 for both time points). Conclusions: Celiac plexus radiosurgery alleviates pain, and improves quality of life among patients with pancreatic cancer. A follow-up international trial is accruing. Clinical trial information: NCT02356406.