tbuckley/cabot-search huggingface dataset:
Association Between Cirrhosis and Stroke in a Nationally Representative Cohort
Authors: Neal S. Parikh, Babak B. Navi, Yecheskel Schneider, Arun Jesudian, Hooman Kamel
Journal: JAMA Neurology (2017)

Cirrhosis is associated with hemorrhagic and thrombotic extrahepatic complications. The risk of cerebrovascular complications is less well understood.To investigate the association between cirrhosis and various stroke types.We performed a retrospective cohort study using inpatient and outpatient Medicare claims data from January 1, 2008, through December 31, 2014, for a random 5% sample of 1 618 059 Medicare beneficiaries older than 66 years.Cirrhosis, as defined by a validated diagnosis code algorithm.The primary outcome was stroke, and secondary outcomes were ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage as defined by validated diagnosis code algorithms.Among 1 618 059 beneficiaries, 15 586 patients (1.0%) had cirrhosis (mean [SD] age, 74.1 [6.9] years; 7263 [46.6%] female). During a mean (SD) of 4.3 (1.9) years of follow-up, 77 268 patients were hospitalized with a stroke. The incidence of stroke was 2.17% (95% CI, 1.99%-2.36%) per year in patients with cirrhosis and 1.11% (95% CI, 1.10%-1.11%) per year in patients without cirrhosis. After adjustment for demographic characteristics and stroke risk factors, patients with cirrhosis had a higher risk of stroke (hazard ratio [HR], 1.4; 95% CI, 1.3-1.5). The magnitude of association appeared to be higher for intracerebral hemorrhage (HR, 1.9; 95% CI, 1.5-2.4) and subarachnoid hemorrhage (HR, 2.4; 95% CI, 1.7-3.5) than for ischemic stroke (HR, 1.3; 95% CI, 1.2-1.5).In a nationally representative sample of Medicare beneficiaries, cirrhosis was associated with an increased risk of stroke, particularly hemorrhagic stroke. A potential explanation of these findings implicates the mixed coagulopathy observed in cirrhosis.
Postmastectomy radiotherapy.
Authors: L R Prosnitz, L B Marks
Journal: Journal of Clinical Oncology (1994)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1994.12.7.1525 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8021745 Postmastectomy radiotherapy. L R ProsnitzxL R ProsnitzSearch for articles by this author , L B MarksxL B MarksSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.7.1525 PDF "Postmastectomy radiotherapy.." Journal of Clinical Oncology, 12(7), p. 1525© 1994 by American Society of Clinical Oncology
Abstract 243: The E3 Ubiquitin Ligase Parkin Mediates Clearance of Damaged Mitochondria via Two Distinct Pathways
Authors: Babette C Hammerling, Melissa Q Cortez, Rita A Hanna, Eileen R Gonzalez, Åsa B Gustafsson
Journal: Circulation Research (2015)

Damaged mitochondria release reactive oxygen species and pro-death factors which can lead to loss of cardiac myocytes. To protect against such damage, myocytes have developed several mechanisms of quality control that act both on the protein and organelle levels. We have previously identified the E3 ubiquitin ligase Parkin as an important regulator of mitochondrial clearance via autophagy in the myocardium. Here, we report that Parkin can also mediate clearance of mitochondria via the endosomal-lysosomal pathway. We found that Parkin promotes clearance of damaged mitochondria in both wild type (WT) and autophagy-deficient Atg5 knockout mouse embryonic fibroblasts (MEFs) treated with the mitochondria uncoupler FCCP. Mitochondrial damage leads to rapid activation of the endosomal-lysosomal pathway in both WT and Atg5-/- MEFs. We further observed increased activation of Rab5, a protein involved in early endosome formation, in both WT and Atg5-/- MEFs after treatment with FCCP. In addition, we observed sequestration of damaged mitochondria in Rab5+ and Rab7+ early and late endosomes, respectively. Mitochondria also colocalized with Lamp2+ vesicles in Atg5-/- MEFs indicating that the mitochondria are ultimately being delivered to the lysosomes for degradation. Overexpression of Rab5S34N, a dominant negative of Rab5, reduces FCCP-mediated clearance and increases cell death in Atg5-/- MEFs. Pharmacological inhibition of the endosomal-lysosomal pathway also results in increased FCCP-mediated cell death. Furthermore, we confirmed that FCCP treatment or simulated ischemia reperfusion exposure induces Rab5 activation with subsequent mitochondrial sequestration in early endosomes in neonatal myocytes. Interestingly, the activation of Rab5 is abrogated in the presence of the mitochondrial targeted antioxidant Mito-Tempo, suggesting that mitochondrial ROS is involved in the activation the endosomal pathway. Mitochondrial clearance via this pathway is also dependent on Parkin, as FCCP treatment fails to activate Rab5 and induce mitochondrial clearance in both WT and Atg5-/- MEFS in the absence of Parkin. Thus, our data suggest that Parkin can mediate clearance of damaged mitochondria via two distinct pathways in cells.
Intensive Versus Non-Intensive Induction Therapy for Patients (Pts) with Newly Diagnosed Acute Myeloid Leukemia (AML) Using Two Different Novel Prognostic Models
Authors: Mohamed L. Sorror, Barry E. Storer, Mahmoud Elsawy, Amir T. Fathi, Andrew M. Brunner, Aaron T. Gerds, Mikkael A. Sekeres, Sudipto Mukherjee, Bruno C. Medeiros, Eunice S. Wang, Pankit Vachhani, Paul J Shami, Esteban Peña, Shylo Wardyn, Jenny Whitten, Rachelle Moore, Pamela S. Becker, Jeannine McCune, Stephanie J. Lee, Brenda M. Sandmaier, Frederick R. Appelbaum, Elihu H. Estey
Journal: Blood (2016)
Ongoing haemolytic uraemic syndrome (HUS) outbreak caused by sorbitol-fermenting (SF) Shiga toxin-producing Escherichia coli (STEC) O157, Germany, December 2016 to May 2017
Authors: Sabine Vygen-Bonnet, Bettina Rosner, Hendrik Wilking, Angelika Fruth, Rita Prager, Annelene Kossow, Christina Lang, Sandra Simon, Juliane Seidel, Mirko Faber, Anika Schielke, Kai Michaelis, Alexandra Holzer, Rolf Kamphausen, Daniela Kalhöfer, Sebastian Thole, Alexander Mellmann, Antje Flieger, Klaus Stark
Journal: Eurosurveillance (2017)

We report an ongoing, protracted and geographically dispersed outbreak of haemolytic uraemic syndrome (HUS) and gastroenteritis in Germany, involving 30 cases since December 2016. The outbreak was caused by the sorbitol-fermenting immotile variant of Shiga toxin-producing (STEC) Escherichia coli O157. Molecular typing revealed close relatedness between isolates from 14 cases. One HUS patient died. Results of a case–control study suggest packaged minced meat as the most likely food vehicle. Food safety investigations are ongoing.
Phase II non-randomized trial using pegfilgrastim for hematopoietic recovery after autologous peripheral stem cell transplantation
Authors: S. A. Patel, S. Sethi, J. Holter, G. Selby
Journal: Journal of Clinical Oncology (2007)

7101 Background: Filgrastim (FIL), granulocyte-colony stimulating factor(G-CSF) reduces time to neutrophil engraftment, hospital stay and antibiotic therapy but requires uncomfortable and inconvenient daily subcutaneous (SC) injections.Pegfilgrastim (PFIL), while more expensive, requires a single SC injection.Before changing our practice and for internal validation, we initiated phase II nonrandomized trial using PFIL instead of FIL for hematopoietic recovery after autologous peripheral stem cell transplantation(autoPBSCT).An interim analysis of this study was presented (Poster No: - 417) at 2006 BMT Tandem Meetings.Here we present a complete analysis of our study. Method: A Phase II nonrandomized trial compares a single injection PFIL 6mg SC on Day +1 to historical controls using FIL 5mcg/kg SC daily starting Day+7 and continued until ANC=500/mm 3 for three consecutive days.Twenty-two patients prospectively(05/2005–06/2006) accrued (MM=2; NHL=13; HD=7, MM=Multiple Myeloma, NHL= Nonhodgkin's lymphoma, HD= Hodgkin's lymphoma).Sixty-six consecutive patients retrospectively (MM=21; NHL=25; HD=20) were analyzed as historical controls(04/1999–04/2005).This study has been completed and closed. The primary endpoint of this study was to determine the days needed to engraft neutrophils &amp; platelet following PFIL administration after autoPBSCT. Wilcoxon Rank Sums test performed for all comparisons except gender comparison was done by chi-square test. Results: Use of a single convenient injection of PFIL resulted in earlier neutrophilic recovery, less packed red blood cell(PRBC) transfusion &amp; shorter hospital stay. No PFIL patients required additional G-CSF. One patient had prolonged fever probably PFIL- related. Conclusion: Our phase II study indicates the equivalency of PFIL and FIL related to hematopoietic recovery after autoPBSCT. No significant financial relationships to disclose. [Table: see text]
The role of high-dose chemotherapy (CT) and stem-cell support in high-risk stage II, locally advanced, and responding stage IV breast cancer (BC): The Israeli experience with 20 years median follow-up.
Authors: Idit Peretz, Shulamith Rizel, Izhar Hardan, Salomon M. Stemmer
Journal: Journal of Clinical Oncology (2017)

1077 Background: Lately, updated data led the medical community to reconsider the use of intensive CT with stem-cell support for selected groups of BC patients (pts). Herein, we provide an update on a study investigating the efficacy, feasibility, and toxicity of high-dose CT with stem-cell support in pts with high-risk stage II, chemosensitive stage III and IV BC. Methods: The protocol offered adjuvant/neoadjuvant/induction doxorubicin-based CT, 75-90 mg/m 2 X 4 courses followed by high-dose CT (cyclophosphamide 6000 mg/m 2 , carboplatin 800 mg/m 2 , and thiotepa 500 mg/m 2 ) and autologous stem cell support with growth factors. Post-transplant local radiotherapy was delivered. Pts who were hormone receptor (HR) positive received Tamoxifen. Results: From 2/1994 to 11/1998, 292 BC pts were referred to the study from all Israeli oncology centers. Median follow-up from transplant was 20 (range, 18-22) years; 119 had stage 2 disease (42 with 4-9 positive nodes, 77 with ≥10 positive nodes); 87 had stage 3 disease, of whom 50 had locally advanced/inflammatory BC treated with neoadjuvant CT; and 86 had chemosensitive stage IV BC. Two acute transplant-related deaths and one death due to late transplant-related toxicity were reported. Median age at transplant was 45 (range, 24-63) years. Overall survival (OS) by HR status is presented in the table. In total, 167 of the 292 pts died (based on death status data retrieved from the Registry of the Ministry of the Interior), representing OS of 42%. The OS rates for stage II, III, and IV were 55%, 45%, and 23%, respectively. Conclusions: Long-term accurate follow-up of pts receiving well-defined treatments remains an important tool in cancer research. High-dose CT with stem-cell support could represent a therapeutic/curative option in select BC patients in all disease stages. Reintroduction of this approach should be re-examined. [Table: see text]
NCI Breast Cancer Steering Committee Working Group (WG) report on meaningful and appropriate endpoints for clinical trials (CT) in metastatic breast cancer (MBC).
Authors: Andrew David Seidman, Meredith M. Regan, Dawn L. Hershman, Larissa A. Korde, Jane Perlmutter, William E. Barlow, Larry Rubinstein, Louis Fehrenbacher, Julia A. Beaver, Laleh Amiri-Kordestani, Suparna B. Wedam, Mary Lou Smith, Priya Rastogi, Louise Bordeleau, Lynn Pearson Butler, Jennifer Fallas Hayes, Jo Anne Zujewski
Journal: Journal of Clinical Oncology (2017)

1073 Background: There is significant heterogeneity in the natural history of MBC. Several recent randomized CT have yielded statistically significant advantages for the experimental arm, but neither led to regulatory approval nor practice change. Formal guidance for industry on CT endpoints provided by the US FDA in 2007 was not disease-specific. Patient-focused drug development is mandated by Prescription Drug User Fee Act V. Our WG sought to create specific consensus on endpoints for MBC CT focusing on subtype and line of therapy, with sensitivity to various stakeholders. Methods: A WG composed of medical oncologists, statisticians, advocates, FDA and NCI liaisons performed a systematic literature review of MBC natural history, CT endpoints by subtype (HR+/HER2-, HR+/HER+, HR-/HER2-, HR-/HER2+), and line of therapy (n = 146 papers). External expertise was obtained on industry perspectives, big data and real world evidence (RWE), and patient reported outcomes (PROs). WG members voted anonymously on statements and positions generated from deliberation. Results: The WG reached consensus on definitions relevant to contemporary CT endpoints. WG recommendations on the appropriate choice of OS or PFS are sensitive to expected post progression survival (PPS), and proportional and absolute gains. Currently, for HR-/HER2- MBC, OS is preferred as the optimal primary endpoint regardless of line of therapy; PFS is preferred in settings where expected PPS is longer. Toxicity can outweigh modest gains in PFS; scant data exist to gauge how patients value PFS gain vs toxicity. Where new agents may prolong PFS without impacting OS, exploring/validating graphic approaches that capture grade and timing of toxicity and PROs is warranted. An overview of WG Consensus Statements will be presented in detail. Conclusions: CT design for MBC should be sensitive to natural history (PPS), availability of other effective agents, PROs and toxicity burden. As unique subtypes (e.g. AR+) and novel therapies (e.g. immunotherapy) emerge, reassessment of relevant benchmarks is indicated. Rigorous big data approaches providing insights from RWE may inform CT endpoints in the future.
Differential requirements for myeloid leukemia IFN-γ conditioning determine graft-versus-leukemia resistance and sensitivity
Authors: Catherine Matte-Martone, Jinling Liu, Meng Zhou, Maria Chikina, Douglas R. Green, John T. Harty, Warren D. Shlomchik
Journal: Journal of Clinical Investigation (2017)

The graft-versus-leukemia (GVL) effect in allogeneic hematopoietic stem cell transplantation (alloSCT) is potent against chronic phase chronic myelogenous leukemia (CP-CML), but blast crisis CML (BC-CML) and acute myeloid leukemias (AML) are GVL resistant. To understand GVL resistance, we studied GVL against mouse models of CP-CML, BC-CML, and AML generated by the transduction of mouse BM with fusion cDNAs derived from human leukemias. Prior work has shown that CD4+ T cell-mediated GVL against CP-CML and BC-CML required intact leukemia MHCII; however, stem cells from both leukemias were MHCII negative. Here, we show that CP-CML, BC-CML, and AML stem cells upregulate MHCII in alloSCT recipients. Using gene-deficient leukemias, we determined that BC-CML and AML MHC upregulation required IFN-γ stimulation, whereas CP-CML MHC upregulation was independent of both the IFN-γ receptor (IFN-γR) and the IFN-α/β receptor IFNAR1. Importantly, IFN-γR-deficient BC-CML and AML were completely resistant to CD4- and CD8-mediated GVL, whereas IFN-γR/IFNAR1 double-deficient CP-CML was fully GVL sensitive. Mouse AML and BC-CML stem cells were MHCI+ without IFN-γ stimulation, suggesting that IFN-γ sensitizes these leukemias to T cell killing by mechanisms other than MHC upregulation. Our studies identify the requirement of IFN-γ stimulation as a mechanism for BC-CML and AML GVL resistance, whereas independence from IFN-γ renders CP-CML more GVL sensitive, even with a lower-level alloimmune response.
Effect of neoadjuvant pertuzumab-containing regimens on pathologic complete response rates in stage II-III HER2-neu positive breast cancer: A retrospective, single institutional experience.
Authors: Rashmi Krishna Murthy, Takeo Fujii, Kenneth R. Hess, Akshara Singareeka Raghavendra, Bora Lim, Carlos Hernando Barcenas, Hong Amy Zhang, Mariana Chavez-Mac Gregor, Elizabeth Ann Mittendorf, Jennifer Keating Litton, Sharon Hermes Giordano, Alastair Mark Thompson, Vicente Valero, Debu Tripathy, Naoto T. Ueno
Journal: Journal of Clinical Oncology (2017)

580 Background: Pertuzumab (P) in combination with trastuzumab (H) based chemotherapy is currently FDA- approved as a standard neoadjuvant treatment for patients with clinical stage II-III HER2-positive (HER2+) breast cancer (BC). The chemotherapy backbone of HER2-targeted therapy varies and may include taxane (T) and/or anthracycline (A), or carboplatin (C). The goal of this study was to retrospectively evaluate the pathologic complete response (pCR) rate for HP-containing regimens compared to H containing regimens for stage II-III HER2+ BC. Methods: We identified all patients (n = 1150) with stage II-III HER2+ BC who received neoadjuvant HER2-targeted therapy from 2005 to 2016 through an institutional database. All patients underwent primary breast and lymph node surgery. pCR was defined as ypT0/is, ypN0. Univariate/multivariate logistic regression and chi-squared test for comparing proportions was used for the statistical analysis. Results: pCR was significantly higher for the HP group (n = 200) compared to the H group (n = 950): 44% vs. 41%, odds ratio = 1.8 (95% CI = 1.3, 2.5; P = 0.0002). Even with adjustment for all clinically significant factors (age, stage, tumor grade, hormone receptor (HR) status, A or C exposure), the improvement was statistically significant (adjusted OR = 2.1 (95% CI = 1.5, 2.9; P &lt; 0.0001). The pCR rate by stage and HR status for the HP group is 62% vs. 55% (stage II vs. III) and 71% vs. 51% (HR- vs. HR+). The effect of P was not modified by HR status (HR-, OR = 2.3; HR+, OR = 1.7, P = 0.39) or by A (A-yes, OR = 1.8; A-no, OR = 2.6) (P = 0.28 for interaction) or C (C-yes, OR 2.6; C-no, OR = 1.8) (P = 0.30 for interaction). P was significantly more likely to be given to patients without A (36% vs. 10%, P &lt; 0.0001) and more likely to be given to patients with C (30% vs. 14%, P &lt; 0.001). In both groups, significant predictors of pCR were found to be stage, HR status, and C exposure. Conclusions: Pertuzumab containing regimens yield higher pCR rates compared to non-Pertuzumab containing regimens in stage II- III HER-2 positive breast cancer. The effect of Pertuzumab is not modified by anthracycline or carboplatin use.
Screening for prostate cancer [2]
Authors: B. J. Miles, Michael W Kattan, R. B. Giesler, M. Cowen, W. J. Catalona, D. Leichtling, M. T. Ruffin, M. S. Klinkman, M. D. Fetters, L. A. Green, M. D. Krahn, J. E. Mahoney, A. S. Detsky, J. Trachtenberg, M. H. Eckman, S. G. Pauker, G. W. Chodak
Journal: JAMA (1995)
Japanese Encephalitis Surveillance and Immunization — Asia and Western Pacific Regions, 2016
Authors: James D. Heffelfinger, Xi Li, Nyambat Batmunkh, Varja Grabovac, Sergey Diorditsa, Jayantha B. Liyanage, Sirima Pattamadilok, Sunil Bahl, Kirsten S. Vannice, Terri B. Hyde, Susan Y. Chu, Kimberley K. Fox, Susan L. Hills, Anthony A. Marfin
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Japanese encephalitis (JE) virus is the most important vaccine-preventable cause of encephalitis in the Asia-Pacific region. The World Health Organization (WHO) recommends integration of JE vaccination into national immunization schedules in all areas where the disease is a public health priority (1). This report updates a previous summary of JE surveillance and immunization programs in Asia and the Western Pacific in 2012 (2). Since 2012, funding for JE immunization has become available through the GAVI Alliance, three JE vaccines have been WHO-prequalified,* and an updated WHO JE vaccine position paper providing guidance on JE vaccines and vaccination strategies has been published (1). Data for this report were obtained from a survey of JE surveillance and immunization practices administered to health officials in countries with JE virus transmission risk, the 2015 WHO/United Nations Children's Fund Joint Reporting Form on Immunization, notes and reports from JE meetings held during 2014-2016, published literature, and websites. In 2016, 22 (92%) of 24 countries with JE virus transmission risk conducted JE surveillance, an increase from 18 (75%) countries in 2012, and 12 (50%) countries had a JE immunization program, compared with 11 (46%) countries in 2012. Strengthened JE surveillance, continued commitment, and adequate resources for JE vaccination should help maintain progress toward prevention and control of JE.
Targeting of p32 in peritoneal carcinomatosis with intraperitoneal linTT1 peptide-guided pro-apoptotic nanoparticles
Authors: Hedi Hunt, Lorena Simón-Gracia, Allan Tobi, Venkata Ramana Kotamraju, Shweta Sharma, Mait Nigul, Kazuki N. Sugahara, Erkki Ruoslahti, Tambet Teesalu
Journal: Journal of Controlled Release (2017)
Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer in the randomised UK TACT2 trial (CRUK/05/19): a multicentre, phase 3, open-label, randomised, controlled trial
Authors: David Cameron, James P Morden, Peter Canney, Galina Velikova, Robert Coleman, John Bartlett, Rajiv Agrawal, Jane Banerji, Gianfilippo Bertelli, David Bloomfield, A Murray Brunt, Helena Earl, Paul Ellis, Claire Gaunt, Alexa Gillman, Nicholas Hearfield, Robert Laing, Nicholas Murray, Niki Couper, Robert C Stein, Mark Verrill, Andrew Wardley, Peter Barrett-Lee, Judith M Bliss
Journal: The Lancet Oncology (2017)

Adjuvant chemotherapy for early breast cancer has improved outcomes but causes toxicity. The UK TACT2 trial used a 2×2 factorial design to test two hypotheses: whether use of accelerated epirubicin would improve time to tumour recurrence (TTR); and whether use of oral capecitabine instead of cyclophosphamide would be non-inferior in terms of patients' outcomes and would improve toxicity, quality of life, or both.
Performance of a high-intensity 508-gene circulating-tumor DNA (ctDNA) assay in patients with metastatic breast, lung, and prostate cancer.
Authors: Pedram Razavi, Bob T. Li, Wassim Abida, Alex Aravanis, Byoungsok Jung, Ronglai Shen, Chenlu Hou, Ino De Bruijn, Sante Gnerre, Raymond S. Lim, Dalicia Reales, Tara Maddala, Michael F. Berger, Gregory J. Riely, Howard I. Scher, William F. Novotny, David B. Solit, Mark Lee, Jorge S. Reis-Filho, Jose Baselga
Journal: Journal of Clinical Oncology (2017)

LBA11516 The full, final text of this abstract will be available at abstracts.asco.org at 7:30 AM (EDT) on Saturday, June 3, 2017, and in the Annual Meeting Proceedings online supplement to the June 20, 2017, issue of the Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.