tbuckley/cabot-search huggingface dataset:
Differentiation of cytomegalovirus infection from acute rejection using renal allograft fine needle aspirates.
Authors: C C Nast, A Wilkinson, J T Rosenthal, L Barba, P N Bretan, P Beaumont, G M Danovitch
Journal: Journal of the American Society of Nephrology (1991)

Cytomegalovirus (CMV) infection is an important cause of renal allograft dysfunction and may be difficult to distinguish from acute transplant rejection both clinically and histologically. To establish the early diagnosis of CMV infection, we used immunohistochemical staining with antibodies against CMV early nuclear protein (CMV-A) and histocompatibility leukocyte class II antigen (DR) in renal transplant fine needle aspirates. Fifty-eight aspirates from 27 patients were assessed, 53 for CMV-A and 53 for DR. Positive staining was defined as greater than or equal to 35% stained tubular cells for CMV-A and greater than or equal to 30% stained tubular cells for DR. Clinical diagnoses were made retrospectively without using the information obtained from aspirate diagnoses. CMV-A staining was negative in 44 aspirates, none at the time of CMV infection. CMV-A was positive in nine aspirates, seven during CMV infection (78%, P less than 0.00001 versus CMV-A negative). DR staining was never present in the absence of acute rejection. All aspirates performed during acute rejection had positive DR staining (P less than 0.00001 versus DR negative). Aspirates with acute rejection comprised 80% of all DR-positive aspirates, whereas those with CMV infection included only 13%. The percent CMV-A staining increased with CMV disease progression; DR staining decreased after successful treatment of acute rejection. These data demonstrate that CMV-A staining is associated with CMV infection whereas DR staining is not. DR staining is specifically related to acute rejection. CMV-A and DR staining of fine needle aspirates is a potentially valuable diagnostic tool to distinguish rapidly between CMV infection and acute transplant rejection as the etiology of renal allograft dysfunction.
Human PCSK9 promotes hepatic lipogenesis and atherosclerosis development via apoE- and LDLR-mediated mechanisms
Authors: Hagai Tavori, Ilaria Giunzioni, Irene M. Predazzi, Deanna Plubell, Anna Shivinsky, Joshua Miles, Rachel M. Devay, Hong Liang, Shirya Rashid, MacRae F. Linton, Sergio Fazio
Journal: Cardiovascular Research (2016)

Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of hepatic low-density lipoprotein (LDL) receptors (LDLR), thereby, decreasing hepatocyte LDL-cholesterol (LDL-C) uptake. However, it is unknown whether PCSK9 has effects on atherogenesis that are independent of lipid changes. The present study investigated the effect of human (h) PCSK9 on plasma lipids, hepatic lipogenesis, and atherosclerotic lesion size and composition in transgenic mice expressing hPCSK9 (hPCSK9tg) on wild-type (WT), LDLR−/−, or apoE−/− background. hPCSK9 expression significantly increased plasma cholesterol (+91%), triglycerides (+18%), and apoB (+57%) levels only in WT mice. The increase in plasma lipids was a consequence of both decreased hepatic LDLR and increased hepatic lipid production, mediated transcriptionally and post-transcriptionally by PCSK9 and dependent on both LDLR and apoE. Despite the lack of changes in plasma lipids in mice expressing hPCSK9 and lacking LDLR (the main target for PCSK9) or apoE (a canonical ligand for the LDLR), hPCSK9 expression increased aortic lesion size in the absence of apoE (268 655 ± 97 972 µm2 in hPCSK9tg/apoE−/− vs. 189 423 ± 65 700 µm2 in apoE−/−) but not in the absence of LDLR. Additionally, hPCSK9 accumulated in the atheroma and increased lesion Ly6Chi monocytes (by 21%) in apoE−/− mice, but not in LDLR−/− mice. PCSK9 increases hepatic lipid and lipoprotein production via apoE- and LDLR-dependent mechanisms. However, hPCSK9 also accumulate in the artery wall and directly affects atherosclerosis lesion size and composition independently of such plasma lipid and lipoprotein changes. These effects of hPCSK9 are dependent on LDLR but are independent of apoE.
Zika virus infection in a traveller returning to Europe from Brazil, March 2015
Authors: L Zammarchi, D Tappe, C Fortuna, M E Remoli, S Günther, G Venturi, A Bartoloni, J Schmidt-Chanasit
Journal: Eurosurveillance (2015)

We report a case of laboratory-confirmed Zika virus infection imported into Europe from the Americas. The patient developed fever, rash, and oedema of hands and feet after returning to Italy from Brazil in late March 2015. The case highlights that, together with chikungunya virus and dengue virus, three major arboviruses are now co-circulating in Brazil. These arboviruses represent a burden for the healthcare systems in Brazil and other countries where competent mosquito vectors are present.
Abstract 2866: Defining epigenetic vulnerabilities in synovial sarcoma
Authors: Ana Banito, Nilgun Tasdemir, Marc Ladanyi, Scott W. Lowe
Journal: Cancer Research (2015)

Abstract Synovial sarcoma constitutes 10% of all soft-tissue sarcomas and arises most frequently in adolescents and young adults. The defining genetic event of synovial sarcoma and main driver of the disease is the translocation of the SS18 gene on chromosome 18q11 to either the SSX1 and SSX2 genes located on chromosome Xp11. The resulting SS18-SSX fusion oncogene lacks a DNA binding domain, but is thought to exert its function via interaction with transcription factors and chromatin remodelers such as polycomb-group chromatin remodeling factors, and components of the SWI/SNF complex. The fact that the fusion oncogene is the defining event in this disease suggests that, on its own, it is able to generate an epigenetic profile that drives tumorigenesis. In this study we expressed SS18-SSX2 in C2C12 myoblasts to recreate the epigenetic events driving synovial sarcoma. C2C12 myoblasts expressing SS18-SSX1/2 did not show significant differences in cell growth however became completely refractory to differentiation to myotubes. In addition, knockdown of SS18-SSX2 in a mouse synovial sarcoma cell line (derived from a mouse model in which the human SS18-SSX2 fusion oncogene is expressed in the myogenic progenitor compartment) led to strong growth arrest and induction of induction of p16 and p21 cell cycle regulators. This results support the notion that the SS18-SSX oncogene drives tumorigenesis by blocking differentiation programs and by repressing tumor suppressor genes to maintain self-renewal of synovial sarcoma cells. To identify epigenetic vulnerabilities that are specifically generated by the SS18-SSX fusion protein we screened two cell lines using an shRNA library targeting epigenetic modulators: the synovial sarcoma cell line mentioned above and C2C12 myoblasts. Three control shRNAs targeting the SS18-SSX2 oncogene were within the top depletion hits in the synovial sarcoma cell line but were neutral in the C2C12 myoblasts, validating the screen performance. To uncover SS18-SSX specific hits we concentrated in genes within this list that specifically depleted in the synovial sarcoma cell line but not in myoblasts. Genes within this list and to which at least two independent shRNAs scored were subjected to extensive one-by one validation. Our results may uncover epigenetic mechanisms required to maintain self-renewal in synovial sarcoma. Citation Format: Ana Banito, Nilgun Tasdemir, Marc Ladanyi, Scott W. Lowe. Defining epigenetic vulnerabilities in synovial sarcoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2866. doi:10.1158/1538-7445.AM2015-2866
Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation
Authors: Pontus Ørning, Kine Samset Hoem, Abba Elizabeth Coron, Gudmund Skjåk-Bræk, Tom Eirik Mollnes, Ole-Lars Brekke, Terje Espevik, Anne Mari Rokstad
Journal: Journal of Controlled Release (2016)
Early outpatient follow‐up and 30‐day outcomes in patients hospitalized with cirrhosis
Authors: Fasiha Kanwal, Steven M. Asch, Jennifer R. Kramer, Yumei Cao, Sumeet Asrani, Hashem B. El‐Serag
Journal: Hepatology (2016)

Preventing readmission has been the focus of numerous quality improvement efforts across many conditions. Early outpatient follow-up has been proposed as the best mechanism for reducing readmissions. The extent to which early outpatient follow-up averts readmission or improves outcomes in cirrhosis is not known. We evaluated the relationship between early outpatient follow-up and short-term readmission and mortality in patients with cirrhosis. We conducted a retrospective cohort study of patients with cirrhosis who were hospitalized with a liver-related diagnosis and discharged to home from 122 Veterans Administration hospitals between 2010 and 2013. We defined early follow-up as an outpatient visit with a clinician within 7 days after discharge. We propensity matched patients who received early visit with those who did not have any visit and examined the associations between early follow-up and all-cause readmission and mortality within 8-30 days after discharge. Of 25,217 patients hospitalized with cirrhosis, 8,123 (32.2%) had an early follow-up visit within 7 days of discharge. A total of 3,492 (13.8%) patients were readmitted and 1,185 (4.6%) died between 8 and 30 days after discharge. In the propensity-matched sample (N = 16,238), patients with early outpatient follow-up visit had a slightly higher risk of readmission (15.3% vs. 13.8%; hazard ratio [HR] =1.10; 95% confidence interval [CI] = 1.02-1.19), but significantly lower risk of mortality (3.2% vs. 5.2%; HR = 0.60; 95% CI = 0.51-0.70) than those without early visit. The findings persisted in several subgroup and sensitivity analyses.Early outpatient follow-up after discharge was associated with a small increase in readmissions but lower overall mortality in patients with cirrhosis. Transitional care may be effective in improving short-term outcomes in patients with cirrhosis, but readmission performance measures would miss this effect. (Hepatology 2016;64:569-581).
Skeletal related events (SREs) in metastatic androgen independent prostate cancer (AIPC) treated with docetaxel-based chemotherapy: Results from ASCENT
Authors: J. S. Chan, C. W. Ryan, P. M. Venner, D. P. Petrylak, G. S. Chatta, J. Ruether, K. N. Chi, J. Young, C. Shen, T. M. Beer
Journal: Journal of Clinical Oncology (2006)

4614 Background: Docetaxel prolongs survival in AIPC patients and zoledronic acid (ZA) reduces the incidence of SREs. The SRE incidence of patients treated with docetaxel-based chemotherapy has not previously been reported. Methods: ASCENT was a randomized clinical trial that compared weekly DN-101 (calcitriol, 45 μg p.o. on day 1) plus docetaxel (36 mg/m 2 iv on day 2 for 3 weeks of a 4-week cycle) to placebo plus docetaxel in patients with chemotherapy-naïve metastatic AIPC. ZA use was not restricted. SRE-free survival was described for the entire group and then compared for patients randomly assigned to DN-101 or placebo and stratified by ZA use. Statistical comparisons were conducted using Cochran-Mantel-Haenszel for incidence and log-rank for SRE-free survival. Results: With a median follow-up of 18.3 months, 33% of subjects experienced at least one SRE and the overall median SRE-free survival was 13 (95% CI 10.5–14.3) months. The incidence of SRE by type was: radiation to bone (18.8%), fracture (10%), spinal cord compression (4%), surgery to bone (0.4%). Eighty-five (34%) patients received ZA. The study was not adequately powered to measure the impact of DN-101 or ZA on SRE endpoints. Exploratory analyses showed a trend for an increase in SRE-free survival (HR 0.78, p = 0.13) of DN-101-treated patients. SRE-free survival and incidence for subgroups were examined ( Table ). Conclusions: This is the first report of SRE incidence in a large, prospective study of docetaxel-based therapy. Improved therapies for reducing SREs in AIPC are needed because the risk of SREs remains high despite the use of modern chemotherapy and ZA. [Table: see text] [Table: see text]
Side Effects of Chemotherapy
Authors: Harold J. Burstein
Journal: Journal of Clinical Oncology (2000)

Article Tools Side Effects of Chemotherapy Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.3.693 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10653885 Side Effects of Chemotherapy Harold J. BursteinxHarold J. BursteinSearch for articles by this author Show More Dana-Farber Cancer Institute and Brigham & Women's Hospital, Harvard Medical School, Boston, MA https://doi.org/10.1200/JCO.2000.18.3.693 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: a systematic review and meta-analysis
Authors: Jason H Y Wu, Celine Foote, Juuso Blomster, Tadashi Toyama, Vlado Perkovic, Johan Sundström, Bruce Neal
Journal: The Lancet Diabetes & Endocrinology (2016)
An autoimmune bullous dermatosis with clinical, histopathological and immunological features of bullous pemphigoid and epidermolysis bullosa acquisita in an adult
Authors: A. Yamase, T. Kono, N. Ishii, T. Hashimoto, H. Saeki
Journal: British Journal of Dermatology (2016)

Abstract Bullous pemphigoid (BP) and epidermolysis bullosa acquisita (EBA) are both acquired autoimmune blistering diseases (AIBD) of the skin and mucous membranes. BP is characterized by IgG autoantibodies to two hemidesmosomal components, BP180 and BP230, at the cutaneous basement membrane zone (BMZ).(1) EBA is characterized by IgG autoantibodies to type VII collagen at the cutaneous BMZ.(2) Clinically BP and EBA may be difficult to distinguish from each other and from other AIBDs like mucous membrane pemphigoid (MMP). Here, we report the second case of BP associated with EBA. This article is protected by copyright. All rights reserved.
Identification of TET1⊣miR-22⊣CREB-MYC Signaling Reveals Potent Tumor-Suppressor Role of Mir-22 in Acute Myeloid Leukemia
Authors: Xi Jiang, Ping Chen, Stephen Arnovitz, Hao Huang, Jason Bugno, Zhixiang Zuo, Hengyou Weng, Bryan Ulrich, Chao Hu, Sandeep Gurbuxani, Yuanyuan Li, Justin Salat, Shenglai Li, Yang Yang, Yungui Wang, Mary Elizabeth Neilly, Richard A. Larson, Michelle M. Le Beau, Tobias Herold, Stefan K. Bohlander, Jiwang Zhang, Jie Jin, Seungpyo Hong, Zejuan Li, Jianjun Chen
Journal: Blood (2014)
Central Nervous System Involvement in Chronic Lymphocytic Leukemia: Diagnosis and Treatment in a Retrospective Cohort of Thirty Patients
Authors: Anne Wanquet, Rudy Birsen, Sylvain Choquet, Vincent Levy, Jehan Dupuis, Stephane Lepretre, Daniel Re, Jonathan Fahri, Mathilde Hunault, Charlotte Bonnet, Anne-Sophie Michallet, Loic Ysebaert, Richard Lemal, Thierry Lamy, Richard Delarue, Atchroue Johnson Ansah, Sylvain P Chantepie, Xavier Troussard, Frederic Davi, Florence Cymbalista, Pierre-Yves Dietrich, Veronique Leblond, Therese Aurran-Schleinitz
Journal: Blood (2015)
Sorafenib (S) in combination with irinotecan (I) as a treatment in metastatic colorectal cancer (mCRC) patients (pts) with KRAS mutation (mt) as second line or later: Interim analysis results of multicenter phase II part trial (NEXIRI).
Authors: M. Ychou, E. François, S. Thézenas, P. Laurent-Puig, O. Bouche, A. Adenis, J. Bennouna, E. Assenat, F. Portales, E. Samalin
Journal: Journal of Clinical Oncology (2010)

e14022 Background: A KRAS mt is significantly associated with the absence of response to anti-EGFR antibodies. S (BAY 43-9006)–Bayer, is the lead compound in a serie of raf signalling pathway inhibitors with raf kinase inhibitor activity and could inhibit cell growth and proliferation of pts with KRAS mt. The main objective of this phase II trial was to evaluate the disease control (DC) of I combined with S as second- or later-line treatment (tt) in mCRC pts KRAS mt. Methods: In the previous phase I, the recommended dose of I was 180 mg/m2 in a biweekly regimen combined to a fixed dose of S (400 mg twice daily). In the phase II, pts received this combination until progression or toxicity. Eligibility criteria included: measurable and not resectable mCRC, age > 18 years, PS ≤ 2, progression after I-based chemotherapy, one or more previous lines, centralized analysis confirmation of KRAS mt on 12 or 13 codons on the primary tumour (pt) or metastases. Primary endpoint was the DC according to RECIST criteria. Secondary were toxicity, PFS and OS. A two-stage Simon design considered the tt inactive if DC was observed in 3 pts or less among the first 21 pts, otherwise the trial was planned to continue accrual up to 51 pts. Pharmacokinetic, pharmacogenetics, pathologic studies were also undertaken. Results: The first 21 pts were included between 2009-06 and 09 from 5 centres. Median age was 54 (range: 43-78) years, 67% were male, 55% PS 0, 62% pt in the colon. The tt schedule was administered as second line for 2 pts, third for 5 and later for 14. At least 4 courses were completed in 17 pts. No DLTs were seen. After C4, the toxicities Gr 3/4 per pt were: cutaneous 20% (hand-foot syndrome), diarrhea 38% (Gr 4 0%), neutropenia 29%. After 2 courses, 8 pts (38%) have reduced S until to 400 mg daily because of toxicities. After C4 13/20 evaluable pts had stable disease (DC 62% CI95% [38-82]) with no objective response. Conclusions: The combination of S and biweekly I as second- or later-line tt for mCRC pts KRAS mt shows an interesting DC in this preliminary analysis. According to the statistical design, the trial recruited total of 51 pts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Amgen, Bayer, Novartis, Pfizer Amgen, Bayer, Merck, Novartis Amgen, Bayer, Merck
Radiofrequency ablation in hepatocellular carcinoma: Effect on survival
Authors: S. M. Henderson, K. Suleman, S. Bidyasar, A. Gill
Journal: Journal of Clinical Oncology (2008)

15649 Background: The use of radiofrequency ablation (RFA) is a reasonable option for patients who do not meet the criteria for surgical resection of hepatocellular carcinoma (HCC), but who are candidates for a liver-directed procedure based upon the presence of disease limited to liver. A review of the literature suggests an increasing use of RFA as a treatment modality because it is usually well tolerated and has possible survival benefits. Current literature reports median survival of patients with untreated cirrhosis and HCC as 2–4 months. This retrospective study aims to provide institutional data for the survival rates in these patients. Methods: Twenty patients with unresectable HCC and cirrhosis have been treated in our institution between 2001 and 2006 with RFA. Data was obtained from the cancer registry database and the interventional radiology RFA database. Variables that are included in the study are age, sex, Child-Pugh class, etiology of cirrhosis, AFP level, approach of RFA, and survival in years. Results: The main endpoint of the data is overall survival. Fifteen (75%) patients were male and five (25%) patients were female. Thirteen (65%) patients had hepatitis C, 4 (20%) patients had hepatitis B, and 3 (15%) patients had alcoholic induced cirrhosis. Twelve (60%) patients were Child-Pugh class A, 8(40%) were class B, and no patients were treated with class C. Fifteen (75%) patients underwent RFA performed by ultrasound guidance and 5 (25%) laparoscopically. Tumor sizes ranged from 1 -5 cm. One year survival was 75%; 3 year 65%, and 5 year 60%. Of the patients who survived 5 years, 10 (83%) were Child's class A with average AFP of 28 ng/ml; 2(17%) were Child's class B with average AFP of 2060 ng/ml. Conclusions: RFA treatment in patients with unresectable HCC, well compensated cirrhosis, and lower AFP levels has shown to possibly have survival benefit over those patients with worse liver function and higher AFP levels. No significant financial relationships to disclose.
Matricellular protein CCN3 mitigates abdominal aortic aneurysm
Authors: Chao Zhang, Dustin van der Voort, Hong Shi, Rongli Zhang, Yulan Qing, Shuichi Hiraoka, Minoru Takemoto, Koutaro Yokote, Joseph V. Moxon, Paul Norman, Laure Rittié, Helena Kuivaniemi, G. Brandon Atkins, Stanton L. Gerson, Guo-Ping Shi, Jonathan Golledge, Nianguo Dong, Bernard Perbal, Domenick A. Prosdocimo, Zhiyong Lin
Journal: Journal of Clinical Investigation (2016)

Abdominal aortic aneurysm (AAA) is a major cause of morbidity and mortality; however, the mechanisms that are involved in disease initiation and progression are incompletely understood. Extracellular matrix proteins play an integral role in modulating vascular homeostasis in health and disease. Here, we determined that the expression of the matricellular protein CCN3 is strongly reduced in rodent AAA models, including angiotensin II–induced AAA and elastase perfusion–stimulated AAA. CCN3 levels were also reduced in human AAA biopsies compared with those in controls. In murine models of induced AAA, germline deletion of Ccn3 resulted in severe phenotypes characterized by elastin fragmentation, vessel dilation, vascular inflammation, dissection, heightened ROS generation, and smooth muscle cell loss. Conversely, overexpression of CCN3 mitigated both elastase- and angiotensin II–induced AAA formation in mice. BM transplantation experiments suggested that the AAA phenotype of CCN3-deficient mice is intrinsic to the vasculature, as AAA was not exacerbated in WT animals that received CCN3-deficient BM and WT BM did not reduce AAA severity in CCN3-deficient mice. Genetic and pharmacological approaches implicated the ERK1/2 pathway as a critical regulator of CCN3-dependent AAA development. Together, these results demonstrate that CCN3 is a nodal regulator in AAA biology and identify CCN3 as a potential therapeutic target for vascular disease.
Incremental Value of Gait Speed in Predicting Prognosis of Older Adults With Heart Failure
Authors: Giovanni Pulignano, Donatella Del Sindaco, Andrea Di Lenarda, Gianfranco Alunni, Michele Senni, Luigi Tarantini, Giovanni Cioffi, Maria Denitza Tinti, Giulia Barbati, Giovanni Minardi, Massimo Uguccioni, Giovanni Gaschino, Luigi Tarantini, Giovanni Cioffi, Andrea Di Lenarda, Giulia Russo, Donatella Radini, Kira Stellato, Michele Senni, Gianfranco Alunni, Adriano Murrone, Cinzia Zuchi, Giovanni Pulignano, Donatella Del Sindaco, Stefano Tolone, Maria Denitza Tinti, Luca Monzo, Giovanni Minardi, Massimo Uguccioni
Journal: JACC Heart Failure (2016)
Two in five consultant posts were unfilled last year
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

Jane Dacre, the president of the Royal College of Physicians, asked the health secretary, Jeremy Hunt, how he proposes to provide a safe seven day NHS without adequate numbers of doctors, at the college’s annual conference on 15 March.

Dacre said that trusts have found themselves unable to fill new posts that were created to meet demands in patient care. She said, “Over the last year, our census data shows that 40% of consultant physician posts remain unfilled, nearly always due to a lack of candidates.

“If 40% of teaching or policing posts were unfilled, …
Abstract 12651: C-jun N-terminal Kinase is a Novel Therapeutic Target for Controlling the Development of Kawasaki Disease-related Arterial Aneurysm
Authors: Yukako Yoshikane, Mitsuhisa Koga, Tamaki Cho, Kyoko Imanaka-Yoshida, Junichi Hashimoto, Hiroki Aoki, Koichi Yoshimura, Shinichi Hirose
Journal: Circulation (2013)

Introduction: Kawasaki disease (KD), which is the most common multisystem vasculitis with unknown origin in childhood, and causes inflammation of coronary arteries leading to aneurysms, the most se...