tbuckley/cabot-search huggingface dataset:
Abstract 19694: Reduction in Non-hemorrhagic Stroke With Ezetimibe/Simvastatin Compared With Simvastatin Alone in the IMPROVE-IT Trial
Authors: Stephen D Wiviott, Robert P Giugliano, Michael A Blazing, Christopher P Cannon, Jing Zhou, Sabina A Murphy, Andrew M Tershakovec, Thomas A Musliner, Braunwald Eugene
Journal: Circulation (2015)

Background: Statins have been demonstrated to reduce ischemic stroke. Intensive therapy with ezetimibe/simvastatin (E/S) in IMPROVE-IT significantly reduced the occurrence of cardiovascular events in patients post ACS compared to placebo/simvastatin (S). We evaluated the effect of E/S vs S on stroke outcomes. Methods: We determined the KM-rate of stroke, by type,during the median 6 year follow-up in 18,144 patients treated with E/S vs S in the IMPROVE-IT trial. Stroke was adjudicated and divided into non-hemorrhagic (NH), hemorrhagic (H), or unknown (U) by a blinded clinical event committee. Stroke reductions were adjusted to absolute change in LDL-C for comparison to prior studies. Results: There were 641 (3.5%) subjects with stroke during follow up, including 533 non-hemorrhagic, 102 hemorrhagic, and 14 unknown strokes. Overall, stroke tended to be reduced with E/S (4.2 vs 4.8%; HR 0.86, CI 0.73-1.00, p=0.052), with a significant reduction of NH stroke (3.4 vs 4.1%; HR 0.79, CI 0.67-0.94, p=0.008, Figure), but a numerical increase in H stroke (0.8 vs 0.6%; HR 1.38, CI 0.93-2.04, p=0.11, Figure). Results were similar when NH/U strokes were combined. When adjusted for LDL reduction, the NH stroke reduction appears to be similar to greater than the extent previously reported with statin therapy alone (figure). Reductions in NH strokes were consistent across major demographic and lipid subgroups. Of note, in 1071 patients with prior stroke or TIA, a known high-risk group, the absolute benefit of E/S was particularly marked for NH strokes; 9.9vs 14.7% (HR 0.61 (0.41-0.91, NNT 21), though benefit remained in those without prior stroke 3.1 vs 3.5% (HR 0.84, CI 0.70-1.01, NNT 250, Pint=0.16). No difference in hemorrhagic stroke was noted in either group. Conclusions: Lipid lowering therapy with E/S was superior to S in the incidence of non-hemorrhagic stroke through a median of 6 years; there was a large absolute benefit in patients with prior stroke or TIA.
Low-dose computed tomography in elderly pneumonia patients: a need to individualise
Authors: Deepak Aggarwal, Varinder Saini, Hitesh Gour
Journal: European Respiratory Journal (2018)

<b>Low-dose computed tomography is an important diagnostic tool in elderly patients with pneumonia; however, its use should be individualised based on patient- and disease-related factors</b>http://ow.ly/sqZs30kuLEX
Analytical Validity and Clinical Utility of Tumor Biomarkers
Authors: Steven Sorscher
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
In IBS with constipation, plecanatide reduced abdominal pain and increased bowel movements at 12 wk
Authors: Sander Veldhuyzen van Zanten
Journal: Annals of Internal Medicine (2018)

Source Citation Brenner DM, Fogel R, Dorn SD, et al. Efficacy, safety, and tolerability of plecanatide in patients with irritable bowel syndrome with constipation: results of two phase 3 randomized clinical trials. Am J Gastroenterol. 2018;113:735-45. 29545635
A Dead Gene Walking: Convergent Degeneration of a Clade of MADS-Box Genes in Crucifers
Authors: Andrea Hoffmeier, Lydia Gramzow, Amey S Bhide, Nina Kottenhagen, Andreas Greifenstein, Olesia Schubert, Klaus Mummenhoff, Annette Becker, Günter Theißen
Journal: Molecular Biology and Evolution (2018)

Genes are "born," and eventually they "die." These processes shape the phenotypic evolution of organisms and are hence of great biological interest. If genes die in plants, they generally do so quite rapidly. Here, we describe the fate of GOA-like genes that evolve in a dramatically different manner. GOA-like genes belong to the subfamily of Bsister genes of MIKC-type MADS-box genes. Typical MIKC-type genes encode conserved transcription factors controlling plant development. We show that ABS-like genes, a clade of Bsister genes, are indeed highly conserved in crucifers (Brassicaceae) maintaining the ancestral function of Bsister genes in ovule and seed development. In contrast, their closest paralogs, the GOA-like genes, have been undergoing convergent gene death in Brassicaceae. Intriguingly, erosion of GOA-like genes occurred after millions of years of coexistence with ABS-like genes. We thus describe Delayed Convergent Asymmetric Degeneration, a so far neglected but possibly frequent pattern of duplicate gene evolution that does not fit classical scenarios. Delayed Convergent Asymmetric Degeneration of GOA-like genes may have been initiated by a reduction in the expression of an ancestral GOA-like gene in the stem group of Brassicaceae and driven by dosage subfunctionalization. Our findings have profound implications for gene annotations in genomics, interpreting patterns of gene evolution and using genes in phylogeny reconstructions of species.
Nodular Regenerative Hyperplasia Associated With Immune Checkpoint Blockade
Authors: Jaclyn LoPiccolo, Michael I. Brener, Kiyoko Oshima, Evan J. Lipson, James P. Hamilton
Journal: Hepatology (2018)

LoPiccolo, Jaclyn; Brener, Michael I.; Oshima, Kiyoko; Lipson, Evan J.; Hamilton, James P. Author Information
Biobank-driven genomic discovery yields new insight into atrial fibrillation biology
Authors: Jonas B. Nielsen, Rosa B. Thorolfsdottir, Lars G. Fritsche, Wei Zhou, Morten W. Skov, Sarah E. Graham, Todd J. Herron, Shane McCarthy, Ellen M. Schmidt, Gardar Sveinbjornsson, Ida Surakka, Michael R. Mathis, Masatoshi Yamazaki, Ryan D. Crawford, Maiken E. Gabrielsen, Anne Heidi Skogholt, Oddgeir L. Holmen, Maoxuan Lin, Brooke N. Wolford, Rounak Dey, Håvard Dalen, Patrick Sulem, Jonathan H. Chung, Joshua D. Backman, David O. Arnar, Unnur Thorsteinsdottir, Aris Baras, Colm O’Dushlaine, Anders G. Holst, Xiaoquan Wen, Whitney Hornsby, Frederick E. Dewey, Michael Boehnke, Sachin Kheterpal, Bhramar Mukherjee, Seunggeun Lee, Hyun M. Kang, Hilma Holm, Jacob Kitzman, Jordan A. Shavit, José Jalife, Chad M. Brummett, Tanya M. Teslovich, David J. Carey, Daniel F. Gudbjartsson, Kari Stefansson, Gonçalo R. Abecasis, Kristian Hveem, Cristen J. Willer
Journal: Nature Genetics (2018)
Osteopontin Plays an Important Role in the Development of Medial Thickening and Neointimal Formation
Authors: KikuoIsoda, KenichirouNishikawa, YashuhiroKamezawa, MikotoYoshida, MasatoshiKusuhara, MasaoMoroi, NorihiroTada, FumitakaOhsuzu
Journal: Circulation Research (2002)

Osteopontin (OPN) is a soluble secreted phosphoprotein that binds with high affinity to several integrins and it has been found at the site of atherosclerotic lesions. However, the role of OPN expression in vivo is still poorly understood. To investigate the physiological role of OPN in detail, we generated transgenic mice (Tg) overexpressing the OPN gene under control of the cytomegalovirus enhancer/chicken β-actin promoter. We detected OPN mRNAs in almost all tissues of 3 lines of Tg mice by Northern blotting. The serum levels of OPN were significantly higher in Tg than in non-Tg mice (782±107 versus 182±44 ng/mL; P<0.001). Compared with non-Tg mice, a 73% (88±6 versus 51±7 μm; P<0.001) and 94% (126±15 versus 73±11 μm; P<0.0001) increase in the medial thickness of the aorta was determined in Tg mice at 16 and 32 weeks after birth. However, we found no evidence of inflammatory cells adhering to endothelial cells, intimal hyperplasia, or calcification in any region of Tg mice without artery injury. We the...
Thiotepa, busulfan and fludarabine compared to busulfan and cyclophosphamide as conditioning regimen for allogeneic stem cell transplant from matched siblings and unrelated donors for acute myeloid leukemia
Authors: Francesco Saraceni, Eric Beohou, Myriam Labopin, William Arcese, Francesca Bonifazi, Polina Stepensky, Mahmoud Aljurf, Benedetto Bruno, Pietro Pioltelli, Jakob Passweg, Gerard Sociè, Stella Santarone, Ibrahim Yakoub‐Agha, Francesco Lanza, Bipin N. Savani, Mohamad Mohty, Arnon Nagler
Journal: American Journal of Hematology (2018)

Abstract Busulfan plus cyclophosphamide (BuCy) is the traditional conditioning regimen for allogeneic stem cell transplant (allo‐SCT) for young, fit patients with acute myeloid leukemia (AML). The thiotepa‐busulfan‐fludarabine (TBF) protocol has recently demonstrated promising outcome in cord blood and haploidentical SCT; however, there is limited evidence about this regimen in transplant from matched siblings (MSD) and unrelated donors (UD). We retrospectively compared outcomes of 2523 patients aged 18‐50 with AML in remission, undergoing transplant from MSD or UD prepared with either TBF or BuCy conditioning. A 1:3 pair‐matched analysis was performed: 146 patients receiving TBF were compared with 438 patients receiving BuCy. Relapse risk was significantly lower in the TBF when compared with BuCy group (HR 0.6, P = .02), while NRM did not differ. No significant difference was observed in LFS and OS between the two regimens. TBF was associated with a trend towards higher risk of grades III‐IV aGVHD (HR 1.8, P = .06) and inferior cGVHD (HR 0.7, P = .04) when compared with BuCy. In patients undergoing transplant in first remission, the advantage for TBF in terms of relapse was more evident (HR 0.4, P = .02), leading to a trend for better LFS in favor of TBF (HR 0.7, P = .10), while OS did not differ between the two cohorts. In conclusion, TBF represents a valid myeloablative conditioning regimen providing significantly lower relapse and similar survival when compared with BuCy. Patients in first remission appear to gain the most from this protocol, as in this subgroup a tendency for better LFS was observed when compared with BuCy.
Double-Strand DNA Sensing Aim2 Inflammasome Regulates Atherosclerotic Plaque Vulnerability
Authors: Nicole Paulin, Joana R. Viola, Sanne L. Maas, Renske de Jong, Teresa Fernandes-Alnemri, Christian Weber, Maik Drechsler, Yvonne Döring, Oliver Soehnlein
Journal: Circulation (2018)
Epigenetic regulation of brain region-specific microglia clearance activity
Authors: Pinar Ayata, Ana Badimon, Hayley J. Strasburger, Mary Kaye Duff, Sarah E. Montgomery, Yong-Hwee E. Loh, Anja Ebert, Anna A. Pimenova, Brianna R. Ramirez, Andrew T. Chan, Josefa M. Sullivan, Immanuel Purushothaman, Joseph R. Scarpa, Alison M. Goate, Meinrad Busslinger, Li Shen, Bojan Losic, Anne Schaefer
Journal: Nature Neuroscience (2018)
Association of Circulating Tumor Cells With Late Recurrence of Estrogen Receptor–Positive Breast Cancer
Authors: Joseph Sparano, Anne O’Neill, Katherine Alpaugh, Antonio C. Wolff, Donald W. Northfelt, Chau T. Dang, George W. Sledge, Kathy D. Miller
Journal: JAMA Oncology (2018)

Late recurrence 5 or more years after diagnosis accounts for at least one-half of all cases of recurrent hormone receptor-positive breast cancer.To determine whether the presence of circulating tumor cells (CTCs) in a peripheral blood sample obtained approximately 5 years after diagnosis was associated with late clinical recurrence of operable human epidermal growth factor receptor 2-negative breast cancer.This per-protocol secondary analysis of the Double-Blind Phase III Trial of Doxorubicin and Cyclophosphamide Followed by Paclitaxel With Bevacizumab or Placebo in Patients With Lymph Node Positive and High Risk Lymph Node Negative Breast Cancer enrolled patients from 2007 to 2011 who were without clinical evidence of recurrence between 4.5 and 7.5 years after primary surgical treatment of human epidermal growth factor receptor 2-negative stage II-III breast cancer followed by adjuvant systemic therapy. Patients were enrolled in a subprotocol for secondary analysis from February 25, 2013, to July 29, 2016, after signing consent for the subprotocol. The analysis was performed in April 2018.A blood sample was obtained for identification and enumeration of CTCs.The association between a positive CTC assay result (at least 1 CTC per 7.5 mL of blood) and clinical recurrence.Among 547 women included in this analysis, the results of the CTC assay were positive for 18 of 353 with hormone receptor-positive disease (5.1% [95% CI, 3.0%-7.9%]); 23 of 353 patients (6.5% [95% CI, 4.2%-9.6%]) had a clinical recurrence. The recurrence rates per person-year of follow-up in the CTC-positive and CTC-negative groups were 21.4% (7 recurrences per 32.7 person-years) and 2.0% (16 recurrences per 796.3 person-years), respectively. In multivariate models including clinical covariates, a positive CTC assay result was associated with a 13.1-fold higher risk of recurrence (hazard ratio point estimate, 13.1; 95% CI, 4.7-36.3). Seven of 23 patients (30.4% [95% CI, 13.2%-52.9%]) with recurrence had a positive CTC assay result at a median of 2.8 years (range, 0.1-2.8 years) before clinical recurrence. The CTC assay result was also positive for 8 of 193 patients (4.1% [95% CI, 1.8%-8.0%]) with hormone receptor-negative disease, although only 1 patient (0.5% [95% CI, 0%-2.9%]) experienced disease recurrence (this patient was CTC negative).A single positive CTC assay result 5 years after diagnosis of hormone receptor-positive breast cancer provided independent prognostic information for late clinical recurrence, which provides proof of concept that liquid-based biomarkers may be used to risk stratify for late recurrence and guide therapy.ClinicalTrials.gov identifier: NCT00433511.
Heat Shock Protein 90α–Dependent B‐Cell‐2–Associated Transcription Factor 1 Promotes Hepatocellular Carcinoma Proliferation by Regulating MYC Proto‐Oncogene c‐MYC mRNA Stability
Authors: Xueqiong Zhou, Ying Wen, Ye Tian, Meiling He, Xiangyu Ke, Zhizhou Huang, Yangfan He, Lixia Liu, Annette Scharf, Meiting Lu, Guowei Zhang, Yaotang Deng, Yuxia Yan, Matthias P. Mayer, Xuemei Chen, Fei Zou
Journal: Hepatology (2018)

B‐cell lymphoma 2 (Bcl‐2)‐associated transcription factor 1 (Bclaf1) is known to be involved in diverse biological processes, but, to date, there has been no evidence for any functional role of Bclaf1 in hepatocellular carcinoma (HCC) progression. Here, we demonstrate that Bclaf1 is frequently up‐regulated in HCC and that Bclaf1 up‐regulation is associated with Edmondson grade, lower overall survival rates, and poor prognosis. Overexpression of Bclaf1 in HCC cell lines HepG2 and Huh7 promoted proliferation considerably, whereas Bclaf1 knockdown had the opposite effect. Xenograft tumors grown from Bclaf1 knockdown Huh7 cells had smaller tumor volumes than tumors grown from control cells. Furthermore, our study describes MYC proto‐oncogene (c‐Myc) as a downstream target of Bclaf1, given that Bclaf1 regulates c‐MYC expression posttranscriptionally by its RS domain. To exert this function, Bclaf1 must interact with the molecular chaperone, heat shock protein 90 alpha (Hsp90α). In HCC tissue samples, Hsp90α levels were also increased significantly and Hsp90α‐Bclaf1 interaction was enhanced. Bclaf1 interacts with the C‐terminal domain of Hsp90α, and this interaction is disrupted by the C‐terminal domain inhibitor, novobiocin (NB), resulting in proteasome‐dependent degradation of Bclaf1. Moreover, NB‐induced disruption of Hsp90α‐Bclaf1 interaction dampened the production of mature c‐MYC mRNA and attenuated tumor cell growth in vitro and in vivo . Conclusion: Our findings suggest that Bclaf1 affects HCC progression by manipulating c‐MYC mRNA stability and that the Hsp90α/Bclaf1/c‐Myc axis might be a potential target for therapeutic intervention in HCC.
Phase 1/2 trial of ixazomib, cyclophosphamide and dexamethasone in patients with previously untreated symptomatic multiple myeloma
Authors: Shaji K. Kumar, Francis K. Buadi, Betsy LaPlant, Alese Halvorson, Nelson Leung, Prashant Kapoor, David Dingli, Morie A. Gertz, Ronald S. Go, P. Leif Bergsagel, Yi Lin, Angela Dispenzieri, Yi Lisa Hwa, Amie Fonder, Miriam Hobbs, Rafael Fonseca, Suzanne R. Hayman, A. Keith Stewart, John A. Lust, Joseph Mikhael, Wilson Gonsalves, Craig Reeder, Tomas Skacel, S. Vincent Rajkumar, Martha Q. Lacy
Journal: Blood Cancer Journal (2018)

Ixazomib is the first oral proteasome inhibitor to enter the clinic. Given the efficacy of bortezomib in combination with cyclophosphamide and dexamethasone, we studied the combination of ixazomib, cyclophosphamide and dexamethasone (ICd) in newly diagnosed multiple myeloma (NDMM) and patients with measurable disease, irrespective of transplant eligibility, were enrolled. The phase 1 was to determine the maximum tolerated dose (MTD) of cyclophosphamide in the combination. Patients received ixazomib 4 mg (days 1, 8, 15), dexamethasone 40 mg (days 1, 8, 15, 22), and cyclophosphamide 300 or 400 mg/m2 days 1, 8, 15, 22; cycles were 28 days. We enrolled 51 patients, 10 in phase 1 and 41 patients in phase 2. The median age was 64.5 years (range: 41-88); 29% had high or intermediate risk FISH. The MTD was 400 mg/m2 of cyclophosphamide weekly. The best confirmed response in all 48 patients included ≥ partial response in 77%, including ≥ VGPR in 35%; 3 patients had a sCR. The response rate for all 48 evaluable patients at 4-cycles was 71%; the median time to response was 1.9 months. Common adverse events included cytopenias, fatigue and GI intolerance. ICd is a convenient, all oral combination that is well tolerated and effective in NDMM.
An urgent dacryocele
Authors: Marina Syrimi, Sean Blaney, Lance Tooke, Danny Morrison
Journal: BMJ (2018)

Congenital nasolacrimal duct obstruction is manifest in about 5% of newborns. Dacryocele (or dacryocystocele), resulting from accumulation of fluid trapped within the lacrimal sac, complicates <1% of the infants affected.12 It is …
Nearly 1700 requests for knee and hip surgery were rejected in England last year
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Increasing numbers of patients seeking knee or hip surgery are finding they can’t have operations on the NHS, an investigation by The BMJ has found. In 2017-18 a total of 1675 exceptional funding requests (1188 for knee surgery and 487 for hip surgery) were turned down by clinical commissioning groups (CCGs), show the data obtained under a freedom of information request. This was a 45% increase from 2016-17, when 1155 requests were rejected (766 for knee and 389 for hip surgery). Exceptional funding requests have been used since the 2000s to limit cosmetic procedures and fertility treatment. But as NHS finances have been squeezed, some CCG areas have started to use them for a wider range of treatments. GPs refer patients to specialists as normal, but there is no guarantee that if they recommend a treatment it will be funded. Instead the patient’s GP then has to submit an exceptional funding request to the CCG, and a panel decides whether to fund it. As The BMJ first revealed last year,12 these types of requests have surged in recent years as CCGs try to keep down costs. The BMJ ’s latest analysis shows stark variation across the country in how CCGs are applying restrictions on surgery (box 1). For example, Buckinghamshire CCG had 1298 exceptional funding requests for knee surgery last year and rejected 18% (fig 1), while Doncaster had far fewer requests through this route (24) but rejected all but one. Box 1 ### How access to hip and knee surgery varies across England #### CCGs with highest numbers of exceptional funding or prior approval rejections in 2017-18 Knee surgery 1. Buckinghamshire: 230 rejections, from 1298 requests (18%) 2. East and North Hertfordshire: 198 , from 1575 (13%) 3. Wiltshire: 62 , from 194 (32%) 4. Basildon and Brentwood: 52 , from 280 (19%) 5. East Berkshire: 46 , from 280 (16%) Hip surgery 1. Basildon and Brentwood: 99 , from 216 (46%) 2. Buckinghamshire: 91 , from 907 (10%) 3. East and … RETURN TO TEXT
Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial
Authors: Hunter B Moore, Ernest E Moore, Michael P Chapman, Kevin McVaney, Gary Bryskiewicz, Robert Blechar, Theresa Chin, Clay Cothren Burlew, Fredric Pieracci, F Bernadette West, Courtney D Fleming, Arsen Ghasabyan, James Chandler, Christopher C Silliman, Anirban Banerjee, Angela Sauaia
Journal: The Lancet (2018)
Prevalence of and Risk Factors for Colorectal Neoplasia in Asymptomatic Young Adults (20–39 Years Old)
Authors: Nam Hee Kim, Yoon Suk Jung, Hyo-Joon Yang, Soo-Kyung Park, Jung Ho Park, Dong Il Park, Chong Il Sohn
Journal: Clinical Gastroenterology and Hepatology (2018)
Optimal Treatment for High-Risk Prostate Cancer
Authors: Wee Loon Ong, Tze Lui Koh, Jeremy Millar
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal