tbuckley/cabot-search huggingface dataset:
Results of a Multicenter Phase II Study of Atezolizumab and Bevacizumab for Patients With Metastatic Renal Cell Carcinoma With Variant Histology and/or Sarcomatoid Features
Authors: Bradley A. McGregor, Rana R. McKay, David A. Braun, Lillian Werner, Kathryn Gray, Abdallah Flaifel, Sabina Signoretti, Michelle S. Hirsch, John A. Steinharter, Ziad Bakouny, Ronan Flippot, Xiao X. Wei, Atish Choudhury, Kerry Kilbridge, Gordon J. Freeman, Eliezer M. Van Allen, Lauren C. Harshman, David F. McDermott, Ulka Vaishampayan, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2019)

In this multicenter phase II trial, we evaluated atezolizumab combined with bevacizumab in patients with advanced renal cell carcinoma (RCC) with variant histology or any RCC histology with ≥ 20% sarcomatoid differentiation.Eligible patients may have received previous systemic therapy, excluding prior bevacizumab or checkpoint inhibitors. Patients underwent a baseline biopsy and received atezolizumab 1,200 mg and bevacizumab 15 mg/kg intravenously every 3 weeks. The primary end point was overall response rate (ORR) by RECIST version 1.1. Additional end points were progression-free survival (PFS), toxicity, biomarkers of response as determined by programmed death-ligand 1 (PD-L1) status, and on-therapy quality-of-life (QOL) metrics using the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 and the Brief Fatigue Inventory.Sixty patients received at least 1 dose of either study agent; the majority (65%) were treatment naïve. The ORR for the overall population was 33% and 50% in patients with clear cell RCC with sarcomatoid differentiation and 26% in patients with variant histology RCC. Median PFS was 8.3 months (95% CI, 5.7 to 10.9 months). PD-L1 status was available for 36 patients; 15 (42%) had ≥ 1% expression on tumor cells. ORR in PD-L1-positive patients was 60% (n = 9) v 19% (n = 4) in PD-L1-negative patients. Eight patients (13%) developed treatment-related grade 3 toxicities. There were no treatment-related grade 4-5 toxicities. QOL was maintained throughout therapy.In this study, atezolizumab and bevacizumab demonstrated safety and resulted in objective responses in patients with variant histology RCC or RCC with ≥ 20% sarcomatoid differentiation. This regimen warrants additional exploration in patients with rare RCC, particularly those with PD-L1-positive tumors.
Abstract 10723: A Plasma Phospholipid Omega-3 Fatty Acid Index > 4% Prevents Cognitive Decline in Cognitively Healthy Subjects With Coronary Artery Disease
Authors: Bhavya Vemuri, Abdulaziz Malik, Abdul Aziz A Asbeutah, Francine K Welty
Journal: Circulation (2019)

Introduction: Omega-3 fatty acids have shown benefit in cognitively impaired subjects, but the effect on cognitively healthy subjects is unclear. Effect of omega-3 fatty acids in patients with coro...
A Phase 3 Randomized Study (PRIMULA) of the Epigenetic Combination of Pracinostat, a Pan-Histone Deacetylase (HDAC) Inhibitor, with Azacitidine (AZA) in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) Unfit for Standard Intensive Chemotherapy (IC)
Authors: Guillermo Garcia-Manero, Maciej Kaźmierczak, Chun Yew Fong, Pau Montesinos, Adriano Venditti, Silvia Mappa, Riccardo Spezia, Lionel Ades
Journal: Blood (2019)
DESE: estimating driver tissues by selective expression of genes associated with complex diseases or traits
Authors: Lin Jiang, Chao Xue, Sheng Dai, Shangzhen Chen, Peikai Chen, Pak Chung Sham, Haijun Wang, Miaoxin Li
Journal: Genome biology (2019)

Abstract The driver tissues or cell types in which susceptibility genes initiate diseases remain elusive. We develop a unified framework to detect the causal tissues of complex diseases or traits according to selective expression of disease-associated genes in genome-wide association studies (GWASs). This framework consists of three components which run iteratively to produce a converged prioritization list of driver tissues. Additionally, this framework also outputs a list of prioritized genes as a byproduct. We apply the framework to six representative complex diseases or traits with GWAS summary statistics, which leads to the estimation of the lung as an associated tissue of rheumatoid arthritis.
Is running associated with a lower risk of all-cause, cardiovascular and cancer mortality, and is the more the better? A systematic review and meta-analysis
Authors: Zeljko Pedisic, Nipun Shrestha, Stephanie Kovalchik, Emmanuel Stamatakis, Nucharapon Liangruenrom, Jozo Grgic, Sylvia Titze, Stuart JH Biddle, Adrian E Bauman, Pekka Oja
Journal: British Journal of Sports Medicine (2019)

To investigate the association of running participation and the dose of running with the risk of all-cause, cardiovascular and cancer mortality.Systematic review and meta-analysis.Journal articles, conference papers and doctoral theses indexed in Academic Search Ultimate, CINAHL, Health Source: Nursing/Academic Edition, MasterFILE Complete, Networked Digital Library of Theses and Dissertations, Open Access Theses and Dissertations, PsycINFO, PubMed/MEDLINE, Scopus, SPORTDiscus and Web of Science.Prospective cohort studies on the association between running or jogging participation and the risk of all-cause, cardiovascular and/or cancer mortality in a non-clinical population of adults were included.Fourteen studies from six prospective cohorts with a pooled sample of 232 149 participants were included. In total, 25 951 deaths were recorded during 5.5-35 year follow-ups. Our meta-analysis showed that running participation is associated with 27%, 30% and 23% lower risk of all-cause (pooled adjusted hazard ratio (HR)=0.73; 95% confidence interval (CI) 0.68 to 0.79), cardiovascular (HR=0.70; 95% CI 0.49 to 0.98) and cancer (HR=0.77; 95% CI 0.68 to 0.87) mortality, respectively, compared with no running. A meta-regression analysis showed no significant dose-response trends for weekly frequency, weekly duration, pace and the total volume of running.Increased rates of participation in running, regardless of its dose, would probably lead to substantial improvements in population health and longevity. Any amount of running, even just once a week, is better than no running, but higher doses of running may not necessarily be associated with greater mortality benefits.
Domestic Violence Against Women
Authors: Jean Abbott
Journal: JAMA (1995)

<h3>Objective.</h3> —To determine the incidence, 1-year prevalence, and cumulative prevalence of domestic violence (DV) among female emergency department (ED) patients. <h3>Design.</h3> —Descriptive written survey. <h3>Setting.</h3> —Two teaching EDs, two hospital walk-in clinics, and one private hospital ED in Denver, Colo. <h3>Participants.</h3> —Of 833 women presenting during 30 randomly selected 4-hour time blocks, 648 (78%) agreed to participate. Most respondents were young (median age, 34 years) and unemployed (62%); half (49%) had annual household incomes less than $10000. <h3>Main Outcome Measures.</h3> —Domestic violence was defined as an assault, threat, or intimidation by a male partner. Acute DV (incidence) and past DV exposure (1-year prevalence and cumulative prevalence) were determined. <h3>Results.</h3> —The incidence of acute DV among the 418 women with a current male partner was 11.7% (95% confidence interval [CI], 8.7% to 15.2%). Only 11 (23%) of these 47 women subjected to acute DV presented for care because of trauma, and only six (13%) either told staff about DV or were asked about DV by ED professionals. Among 230 women without current partners, 13 (5.6%) reported an episode of DV within the previous 30 days. For the entire sample, the cumulative lifetime prevalence of DV exposure was 54.2% (95% CI, 50.2% to 58.1%). Women exposed to acute or prior DV were more likely than unexposed women to have made suicide attempts (26% vs 8%;<i>P</i>&lt;.001) and to report excessive ethanol use (24% vs 13%;<i>P</i>=.001). <h3>Conclusions.</h3> —The incidence of acute DV is not as common among women visiting an ED as previously reported, although the cumulative prevalence of DV is strikingly high. Women who have experienced DV are seldom identified by ED professionals. (<i>JAMA</i>. 1995;273:1763-1767)
NCMP-13. BRAIN MRI FINDINGS IN PATIENTS TREATED WITH CHIMERIC ANTIGEN RECEPTOR T-CELLS (CAR-T) DURING SEVERE NEUROTOXICITY
Authors: Sepideh Mokhtari, John Arrington, Justin Asquith, Christina Bachmeier, Frederick Locke, Aleksandr Lazaryan
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Severe neurotoxicity occurs in ~30% of Diffuse Large B Cell Lymphoma (DLBCL) patients treated with CAR-T cell therapy. Brain MRI is used to assess and manage patients during neurotoxicity. Brain MRI can help understand which brain locations are affected during neurotoxicity. However, in majority of patients brain MRI is normal. It is unclear if the MRI findings are time dependent. Here we review our institutional experience with MRI findings. METHOD We reviewed MRI brain of 38 patients who received CAR-T at Moffitt Cancer Center from October, 2017 to March, 2019. RESULTS We identified 8 patients (21%) who had abnormal MRI findings. Five (63%) of these patients showed increased T2 FLAIR changes in bilateral mesial temporal lobes consistent with limbic encephalitis. One patient showed restricted diffusion and abnormal T2 FLAIR and T2 weighted images within the splenium of the corpus callosum plus increased T2 FLAIR changes in bilateral mesial temporal lobe, which resolved with follow up MRI in a month. One patient showed increased FLAIR signal intensity in left lateral cerebellum and cerebellar vermis. Two patients showed multiple new tiny areas of acute ischemic changes post CAR-T. One patient had several small and subtle areas of increased FLAIR signal intensity in bilateral frontal and parietal cortex on day 5 post CAR-T and multiple tiny areas of acute ischemia on day 10 post CAR-T. The median time to performing brain MRI was 8 days (range: 5–14). CONCLUSIONS MRI can show T2 FLAIR changes consistent with limbic encephalitis mostly in temporal lobes but also in frontal, parietal lobes, and cerebellum. The MRI changes can happen anytime from day 5 to day 14 post CAR-T infusion. We need larger, controlled studies to have better understanding of MRI findings and whether they are time dependent in relation to when CAR-T was given.
Deficiency of Cardiac Natriuretic Peptide Signaling Promotes Peripartum Cardiomyopathy-Like Remodeling in the Mouse Heart
Authors: Kentaro Otani, Takeshi Tokudome, Chizuko A. Kamiya, Yuanjie Mao, Hirohito Nishimura, Takeshi Hasegawa, Yuji Arai, Mari Kaneko, Go Shioi, Junji Ishida, Akiyoshi Fukamizu, Tsukasa Osaki, Chiaki Nagai-Okatani, Naoto Minamino, Takuya Ensho, Jun Hino, Shunsuke Murata, Misa Takegami, Kunihiro Nishimura, Ichiro Kishimoto, Mikiya Miyazato, Mariko Harada-Shiba, Jun Yoshimatsu, Kazuwa Nakao, Tomoaki Ikeda, Kenji Kangawa
Journal: Circulation (2019)

The maternal circulatory system and hormone balance both change dynamically during pregnancy, delivery, and the postpartum period. Although atrial natriuretic peptides and brain natriuretic peptides produced in the heart control circulatory homeostasis through their common receptor, NPR1, the physiologic and pathophysiologic roles of endogenous atrial natriuretic peptide/brain natriuretic peptide in the perinatal period are not fully understood.To clarify the physiologic and pathophysiologic roles of the endogenous atrial natriuretic peptide/brain natriuretic peptide-NPR1 system during the perinatal period, the phenotype of female wild-type and conventional or tissue-specific Npr1-knockout mice during the perinatal period was examined, especially focusing on maternal heart weight, blood pressure, and cardiac function.In wild-type mice, lactation but not pregnancy induced reversible cardiac hypertrophy accompanied by increases in fetal cardiac gene mRNAs and ERK1/2 (extracellular signaling-regulated kinase) phosphorylation. Npr1-knockout mice exhibited significantly higher plasma aldosterone level than did wild-type mice, severe cardiac hypertrophy accompanied by fibrosis, and left ventricular dysfunction in the lactation period. Npr1-knockout mice showed a high mortality rate over consecutive pregnancy-lactation cycles. In the hearts of Npr1-knockout mice during or after the lactation period, an increase in interleukin-6 mRNA expression, phosphorylation of signal transducer and activator of transcription 3, and activation of the calcineurin-nuclear factor of the activated T cells pathway were observed. Pharmacologic inhibition of the mineralocorticoid receptor or neuron-specific deletion of the mineralocorticoid receptor gene significantly ameliorated cardiac hypertrophy in lactating Npr1-knockout mice. Anti-interleukin-6 receptor antibody administration tended to reduce cardiac hypertrophy in lactating Npr1-knockout mice.These results suggest that the characteristics of lactation-induced cardiac hypertrophy in wild-type mice are different from exercise-induced cardiac hypertrophy, and that the endogenous atrial natriuretic peptide/brain natriuretic peptide-NPR1 system plays an important role in protecting the maternal heart from interleukin-6-induced inflammation and remodeling in the lactation period, a condition mimicking peripartum cardiomyopathy.
Oral Contraceptives and Breast Cancer
Authors: J. J. Shipman
Journal: BMJ (1964)

Sir-Recently one of my former registrars Mr. A.E.J. Mullins described in a letter to me a young lady with a rapidly growing carcinoma of the breast who was taking oral contraceptives.  I recently had a young patients aged 34 with a small carcinoma which appeared to be implicating the deep fascia although it was small in size.  She was taking oral contraceptives and asked me if they had caused the growth or should she continue taking them.  I do feel that these drugs should be discontinued if carcinoma is thought or known to be present.  Quite a proportion of the carcinomas of the breast are known to be hormone sensitive and may be influenced adversely if the hormone is continued.  Whether or not these hormones favour the origin of the growth or the viability and persistence of secondaries is open to question but at this stage I feel that as they are known to cause occasionally an increased blood flow to the breast in  the premenstrual phase it might be advisable to discontinue their use in suspected or proved carcinoma of the breast.  -I am etc.(FULL TEXT)
Mannosylation of the Tumor Immunoglobulin Variable Region Informs Cell of Origin and Environmental Interactions in DLBCL Subsets
Authors: Giorgia Chiodin, Joel Allen, Philip J Rock, Enrica Antonia Martino, Beatriz Valle Argos, Graham Packham, Patrick Duriez, Teunis Geijtenbeek, Carl Figdor, Richard Burack, Max Crispin, Freda K Stevenson, Francesco Forconi
Journal: Blood (2019)
MCT1 As Molecularly Validated Predictive Marker for Lenalidomide-Maintenance Therapy in Multiple Myeloma
Authors: Jacob Stroh, Anja Seckinger, Michael Heider, Ruth Eichner, Martina Emde, Hans Salwender, Uta Bertsch, Hartmut Goldschmidt, Katja Weisel, Christof Scheid, Dirk Hose, Florian Bassermann
Journal: Blood (2019)
Mandated Imaging Appropriate Use Criteria
Authors: David M. Mitchell
Journal: Annals of Internal Medicine (2019)

Letters5 November 2019Mandated Imaging Appropriate Use CriteriaDavid M. Mitchell, MD, PhDDavid M. Mitchell, MD, PhDNorton Community Hospital, Norton, Virginia (D.M.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0531 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read Hentel and colleagues' article (1) with interest. As an associate program director of a small internal medicine residency program in a small community hospital, I recently met with our primary radiologist to discuss enhancing our residents' education in radiology. She quickly noted that better education was definitely needed, because the number of computed tomography scans of the abdomen and pelvis with the indication “retroperitoneal bleed” had markedly increased. Our facility had recently implemented a clinical decision support (CDS) system, so it was not difficult to recognize the reason: Retroperitoneal bleeding is 1 of the decision ...Reference1. Hentel KD, Menard A, Mongan J, et al. What physicians and health organizations should know about mandated imaging appropriate use criteria. Ann Intern Med. 2019;170:880-5. [PMID: 31181572]. doi:10.7326/M19-0287 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Norton Community Hospital, Norton, Virginia (D.M.M.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0531. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoWhat Physicians and Health Organizations Should Know About Mandated Imaging Appropriate Use Criteria Keith D. Hentel , Andrew Menard , John Mongan , Jeremy C. Durack , Pamela T. Johnson , Ali S. Raja , and Ramin Khorasani Mandated Imaging Appropriate Use Criteria Keith D. Hentel , Andrew Menard , John Mongan , Jeremy C. Durack , Ali S. Raja , and Ramin Khorasani Metrics 5 November 2019Volume 171, Issue 9Page: 682KeywordsChartsClinical decision support systemsEmergency departmentHemorrhageHospital medicineInpatientsMedicarePelvisRadiologistsResidency ePublished: 5 November 2019 Issue Published: 5 November 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Association of Baclofen With Encephalopathy in Patients With Chronic Kidney Disease
Authors: Flory T. Muanda, Matthew A. Weir, Lavanya Bathini, Peter G. Blake, Kianna Chauvin, Stephanie N. Dixon, Eric McArthur, Jessica M. Sontrop, Louise Moist, Amit X. Garg
Journal: JAMA (2019)

At least 30 case reports have linked the muscle relaxant baclofen to encephalopathy in patients with chronic kidney disease (CKD).To compare the 30-day risk of encephalopathy in patients with CKD and newly prescribed baclofen at greater than or equal to 20 mg per day vs less than 20 mg per day. The secondary objective was to compare the risk of encephalopathy in baclofen users vs nonusers.Retrospective population-based cohort study in Ontario, Canada (2007-2018) using linked health care data. Participants comprised 15 942 older adults (aged 66 years or older) with CKD (defined as an estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 but not receiving dialysis). The primary cohort was restricted to patients who were newly prescribed baclofen; participants in the secondary cohort were new users and nonusers.Prescription for oral baclofen greater than or equal to 20 mg per day vs less than 20 mg per day.Hospital admission with encephalopathy, defined as a main diagnosis of delirium, disorientation, transient alteration of awareness, transient cerebral ischemic attack, or unspecified dementia within 30 days of starting baclofen. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on indicators of baseline health. Weighted risk ratios (RRs) were obtained using modified Poisson regression and weighted risk differences (RDs) using binomial regression. Prespecified subgroup analyses were conducted by eGFR category.The primary cohort comprised 15 942 patients with CKD (9699 [61%] women; median age, 77 years [interquartile range, 71-82]; 9707 [61%] patients started baclofen at ≥20 mg/d and 6235 [39%] at <20 mg/d). The primary outcome, hospitalization with encephalopathy, occurred in 108/9707 (1.11%) patients who started baclofen at greater than or equal to 20 mg per day and in 26/6235 (0.42%) who started baclofen at less than 20 mg per day; weighted RR, 3.54 (95% CI, 2.24 to 5.59); weighted RD, 0.80% (95% CI, 0.55% to 1.04%). In subgroup analysis, the absolute risk increased progressively at lower eGFR (weighted RD eGFR 45-59, 0.42% [95% CI, 0.19%-0.64%]; eGFR 30-44, 1.23% [95% CI, 0.62%-1.84%]; eGFR <30, 2.90% [95% CI, 1.30%-4.49%]; P for interaction, <.001]). In the secondary comparison with 284 263 nonusers, both groups of baclofen users had a higher risk of encephalopathy (<20 mg/d weighted RR, 5.90 [95% CI, 3.59 to 9.70] and ≥20 mg/d weighted RR, 19.8 [95% CI, 14.0 to 28.0]).Among older patients with CKD who were newly prescribed baclofen, the 30-day incidence of encephalopathy was increased among those prescribed higher doses compared with lower doses. If verified, these risks should be balanced against the benefits of baclofen use.
A Pilot Study of an Oral Anticoagulant, Apixaban, in Secondary Prophylaxis of Venous Thromboembolism (VTE) in Children and Adolescents
Authors: Ashley Pinchinat, Neida Otero, Harshini Mahanti, Erin Morris, Adele Brudnicki, Deborah Friedman, Simon Li, Oya Levendoglu-Tugal, Mitchell S Cairo
Journal: Blood (2019)
“Painless” Bone Marrow Aspiration by Slow Suctioning Does Not Affect Peripheral Blood Contamination of the Specimen: Randomized Prospective Crossover Trials
Authors: Yuki Asano-Mori, Shin-ichiro Mori, Toshimitsu Ueki, Miwa Sakai, Takuya Yamashita, Kazuteru Ohashi, Hideki Akiyama, Hisashi Sakamaki
Journal: Blood (2008)
Pomalidomide + Bortezomib + Low-Dose Dexamethasone after 1 Prior Line of Therapy in Patients with Lenalidomide-Pretreated Multiple Myeloma: Subanalysis of the Phase 3 Optimismm Trial By Patient Age and Prior Stem Cell Transplant
Authors: Meletios A. Dimopoulos, Katja C. Weisel, Philippe Moreau, Larry D. Anderson, Darrell J White, Jesús San-Miguel, Pieter Sonneveld, Monika Engelhardt, Matthew Jenner, Alessandro Corso, Jan Dürig, Michel Pavic, Morten Salomo, Eva Casal, Ruiyun Jiang, Shankar Srinivasan, Tuong Vi Nguyen, Tsvetan Biyukov, Teresa Peluso, Paul G. Richardson
Journal: Blood (2019)
TMOD-01. CHARACTERIZATION OF PATIENT-DERIVED PRIMARY CELL LINES AND XENOGRAFTS FOR GLIOBLASTOMA
Authors: Noriyuki Kijima, Daisuke Kanematsu, Tomoko Shofuda, Masahiro Nonaka, Ryoichi Iwata, Junya Fukai, Akihiro Inoue, Takashi Sasayama, Naohiro Tsuyuguchi, Toshiyuki Kawashima, Yuichiro Higuchi, Hiroshi Suemizu, Kanji Mori, Haruhiko Kishima, Yonehiro Kanemura
Journal: Neuro-Oncology (2019)

Abstract Patient-derived primary cell culture and xenograft are essential tools for translational research for glioblastoma. However, characteristics of each patient derived cell line and xenograft is not extensively studied. In this study, we aim to analyze the characteristics of our glioblastoma patient-derived cell lines and xenografts based on cell surface markers and their differentiation patterns. We have established 20 glioblastoma primary cell culture lines by serum free medium containing EGF and bFGF and found that primary cell culture lines could be classified based on the expression of CD133 and CD44. Four cell lines had high expression of both CD133 and CD44. Eleven cell lines had high expression of only CD44, three cell lines had high expression of only CD133, two cell lines had low expression of both CD133 and CD44. In addition when we induce differentiation, these cell lines showed differentiation to both glial and neuronal differentiation, but differentiation patterns were different depending on each cell line. Four cell lines showed predominant neuronal differentiation and others showed predominant glial differentiation. We next investigated in vivo characteristics of glioblastoma patient derived xenografts from these established cell lines. We have injected these cell lines into NOD/Shi-scid IL2Rγ KO mouse and histopathologically analyzed characteristics of xenografts. Each xenograft well recapitulated histological features of original patients’ tumors and tumor cells remarkably invade through subventricular zone. These results suggest that glioblastoma patient derived primary cell lines and xenografts have different characteristics of cell surface marker expressions and differentiation patterns, thus can classify these cell lines depending on cell surface marker expressions and differentiation patterns. Further analysis is needed to examine the biological importance of the differences in cell surface marker expressions and differentiation patterns.