tbuckley/cabot-search huggingface dataset:
Improving Heart Failure Therapeutics Development in the United States
Authors: Christopher M. O’Connor, Mitchell A. Psotka, Mona Fiuzat, JoAnn Lindenfeld, William T. Abraham, Michael R. Bristow, Daniel Canos, Robert A. Harrington, Matt Hillebrenner, Mariell Jessup, Fady I. Malik, Scott D. Solomon, Norman Stockbridge, James E. Tcheng, Ellis F. Unger, David J. Whellan, Bram Zuckerman, Robert M. Califf
Journal: Journal of the American College of Cardiology (2018)

The current heart failure clinical trial environment is strained by increasing complexity and cost, regulatory requirements, competing demands on stakeholders, implementation challenges, and decreasing patient and investigator participation. To begin the process of developing potentially effective strategies and tactics, stakeholders including patients; investigators; academic leaders; pharmaceutical and device industry representatives; society representatives; third-party payers; and government representatives from the U.S. Food and Drug Administration, National Institutes of Health, and Centers for Medicare and Medicaid Services convened in March of 2017. This paper summarizes the discussions, outlines current challenges and actionable opportunities, and makes targeted recommendations to achieve the goals of improving efficiency in clinical trials and speeding the development of effective heart failure therapies, including the formation of an organized Heart Failure Collaboratory.
IgG4-related disease of the mitral valve demonstrated by immunohistochemistry
Authors: Benedict K Tiong, Gregory A Fishbein, Ernest Brahn
Journal: Annals of the Rheumatic Diseases (2018)

IgG4-related disease (IgG4-RD) is known to involve the cardiovascular system as aortitis or periaortitis1; however, the number of reported valvulopathies are exceptionally rare. This case is the first with immunohistochemistry proven mitral valve involvement.

A 72-year-old Korean woman with paroxysmal atrial fibrillation and end-stage renal disease due to long-standing diabetes and hypertension presented to the emergency department with near-syncope and dyspnoea with exertion. Further evaluation revealed three-vessel coronary artery disease and severe mitral valve stenosis due to suspected rheumatic mitral valve disease with a mitral valve area of 0.62 cm2, peak gradient of 15.5 mm Hg and mean velocity of 136 cm/s. The patient underwent three-vessel coronary artery bypass graft surgery and mitral valve replacement with a 27 mm pericardial bioprosthesis. Both the anterior and posterior chordae tendineae were …
Newly found arsons ignite the fire of gut GVHD
Authors: Defu Zeng
Journal: Journal of Clinical Investigation (2018)

Acute graft-versus-host disease (GVHD) in the gut is common following hematopoetic cell transplantation (HCT) and is associated with high mortality. However, it remains unclear whether Th1 or Th17 CD4+ T cells can initiate acute gut GVHD. In this issue of the JCI, Ullrich and colleagues identified a subset of CD4+ T cells that express high levels of IL-7Rα and granulocyte-macrophage CSF (IL-7RαhiGM-CSF+) cells that are involved in the induction of acute gut GVHD in murine models. The IL-7RαhiGM-CSF+ effector memory cells were BATF dependent, RORγt independent, produced large amounts of GM-CSF and IFN-γ, and released little IL-17. CD4+IL-7RαhiGM-CSF+ cells were not classical Th17 cells but had more of a Th1-like phenotype, despite their dependence on BATF. This work suggests that targeting the IL-7R/BATF/GM-CSF axis has therapeutic potential for treating acute gut GVHD.
Abstract 19776: 3 to 5 Years Outcomes of TAVR vs SAVR for High Surgical Risk Patients, a Systematic Review and Metanalysis
Authors: Garly Rushler Saint Croix, Michel Ibrahim, Carlos Alfonso
Journal: Circulation (2017)

Background: The comparative benefits and harms of transcatheter aortic valve intervention and surgical aortic valve replacement for high surgical risk patients with aortic stenosis haven’t shown an...
Farm dust reduces viral load in human bronchial epithelial cells by increasing barrier function and antiviral responses
Authors: Luciën E.P.M. van der Vlugt, Katrien Eger, Christoph Müller, Dennis K. Ninaber, Maria C. Zarcone, Gimano D. Amatngalim, Franz Bracher, Erika von Mutius, Hermelijn H. Smits, Pieter S. Hiemstra
Journal: Journal of Allergy and Clinical Immunology (2018)
Eltrombopag (EPAG) Treatment Improved Platelet Counts in Patients with Persistent or Chronic Immune Thrombocytopenia during a 2-Year, Phase IV, Open-Label Study
Authors: Raymond Sm Wong, Russell K Brynes, Attilio Orazi, Zeba Aziz, Anait L. Melikyan, Abdulgabar Salama, Ozlem Ocak Arikan, Joan Maier, Tahir Shamsi
Journal: Blood (2017)
Regulation of serum cytokines following IL-4 and IL-10 therapy in patients with acute myelogenous leukemia
Authors: M. Tao, Biaoru Li, J. Nayini, S. Sivaraman, S. Song, A. Larson, M. Toofanfard, H. Chen, P. Venugopal, H. D. Preisler
Journal: Blood (2000)
Eradication of Triple-Negative Breast Cancer Cells by Targeting Glycosylated PD-L1
Authors: Chia-Wei Li, Seung-Oe Lim, Ezra M. Chung, Yong-Soo Kim, Andrew H. Park, Jun Yao, Jong-Ho Cha, Weiya Xia, Li-Chuan Chan, Taewan Kim, Shih-Shin Chang, Heng-Huan Lee, Chao-Kai Chou, Yen-Liang Liu, Hsin-Chih Yeh, Evan P. Perillo, Andrew K. Dunn, Chu-Wei Kuo, Kay-Hooi Khoo, Jennifer L. Hsu, Yun Wu, Jung-Mao Hsu, Hirohito Yamaguchi, Tzu-Hsuan Huang, Aysegul A. Sahin, Gabriel N. Hortobagyi, Stephen S. Yoo, Mien-Chie Hung
Journal: Cancer Cell (2018)
The roles of leukocyte cell-derived chemotaxin 2 (LECT2) in hepatocellular carcinoma invasion and angiogenesis
Authors: Yu-Ling Wu, Ching-Yao Yang, Wan-Chin Chung, King-Jen Chang, Po-Huang Lee, Min-Liang Kuo
Journal: Cancer Research (2008)

1080   Hepatocellular carcinoma (HCC) is the fifth commonest cancer worldwide and the second leading fatal cancer in Southeast Asia. The five year survival rate for HCC patients is only about 40% to 50%, and the major poor prognostic factors include vascular invasion and large tumor size. Using high throughput technology suppression subtractive hybridization (SSH) and oligonucleotide microarray of human membrane/secreted proteins (TMSEC microarray), we found that LECT2, is a 16-kDa protein that consists of 133 amino acids and three intramolecular disulfide bonds, was associated with less vascular invasion in HCC patients. Univariate analysis of  LECT2  mRNA level and various risk factors in 127 HCC patients showed that LECT2 was highly correlated with overall survival and smaller tumor size. LECT2 overexpression did not influence hepatoma cells growth property, but strongly reduced tumorigenesis in subcutaneous xenograft model  in vivo . Immunohistochemical staining revealed that tumors from LECT2-transfectant displayed less vascualrization as compared to vector control tumors. In addition, we purified LECT2-Fc recombinant proteins, and found that rhLECT2 could strongly and directly inhibit migration, invasion, and angiogenesis  in vitro  and  in vivo . In conclusion, we first established that LECT2 is a promising prognostic molecular marker and could be a potential therapeutic protein drug for HCC invasion and angiogenesis.
Erythropoietin induces bone marrow and plasma fibroblast growth factor 23 during acute kidney injury
Authors: Luis Toro, Víctor Barrientos, Pablo León, Macarena Rojas, Magdalena Gonzalez, Alvaro González-Ibáñez, Sebastián Illanes, Keigo Sugikawa, Néstor Abarzúa, César Bascuñán, Katherine Arcos, Carlos Fuentealba, Ana María Tong, Alvaro A. Elorza, María Eugenia Pinto, Rodrigo Alzamora, Carlos Romero, Luis Michea
Journal: Kidney International (2018)
Abstract 19867: Pai-1 Regulates Cardiac Tgf-β Expression And Fibrosis
Authors: Panagiotis Flevaris, Mesut Eren, Alexander Mackie, Sadiya Khan, Douglas Vaughan
Journal: Circulation (2016)

Introduction:  Cardiac fibrosis is the pathologic consequence of stress-induced myocardial remodeling and matrix accumulation. Our group and others have previously reported that genetic deficiency of the serine protease inhibitor, plasminogen activator inhibitor type I (PAI-1), leads to age-dependent spontaneous cardiac-selective fibrosis.   Hypothesis:  We hypothesized that PAI-1 knockout mice (PAI-1 -/-) would exhibit accelerated fibrosis following myocardial stress, and that PAI-1 serves as a molecular switch that regulates TGF-β, extracellular matrix, and integrin expression following cardiac injury.   Results:  Following infusion of Angiotensin II (AngII) via osmotic minipump (1000 ng/kg/min) PAI-1 -/- mice exhibit augmented cardiac fibrosis (16.4% vs 3.4% fibrotic area, p 3 -integrin expression occurs both during aging as well as AngII-induced interstitial fibrosis in PAI-1 -/- mice. Whole heart RNA sequencing analysis after only 1 week of AngII treatment reveals that PAI-1 -/- mice had marked elevation in transcripts for multiple forms of collagen, as well as other matrix components including matricellular proteins compared to WT mice. Cardiac integrin transcripts were also significantly altered, with the most pronounced elevation observed in integrin β 3 . Finally, absence of PAI-1 led to dramatic increases in cardiac TGF-β and TGF-β-receptor RNA in response to AngII. Interestingly, immunostaining also demonstrates that ventricular myocytes are a major source of TGF-β in the PAI-1 -/- heart.   Conclusions:  PAI-1 is a key negative regulator of cardiomyocyte TGF-β expression and fibrosis in response to AngII. Together, these results define an upstream role of PAI-1 in matrix homeostasis and TGF-β-mediated fibrogenesis in multiple forms of cardiac stress.
History of Childhood Kidney Disease and Risk of Adult End-Stage Renal Disease
Authors: Ronit Calderon-Margalit, Eliezer Golan, Gilad Twig, Adi Leiba, Dorit Tzur, Arnon Afek, Karl Skorecki, Asaf Vivante
Journal: New England Journal of Medicine (2018)

The long-term risk associated with childhood kidney disease that had not progressed to chronic kidney disease in childhood is unclear. We aimed to estimate the risk of future end-stage renal disease (ESRD) among adolescents who had normal renal function and a history of childhood kidney disease.We conducted a nationwide, population-based, historical cohort study of 1,521,501 Israeli adolescents who were examined before compulsory military service in 1967 through 1997; data were linked to the Israeli ESRD registry. Kidney diseases in childhood included congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease; all participants included in the primary analysis had normal renal function and no hypertension in adolescence. Cox proportional-hazards models were used to estimate the hazard ratio for ESRD associated with a history of childhood kidney disease.During 30 years of follow-up, ESRD developed in 2490 persons. A history of any childhood kidney disease was associated with a hazard ratio for ESRD of 4.19 (95% confidence interval [CI], 3.52 to 4.99). The associations between each diagnosis of kidney disease in childhood (congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease) and the risk of ESRD in adulthood were similar in magnitude (multivariable-adjusted hazard ratios of 5.19 [95% CI, 3.41 to 7.90], 4.03 [95% CI, 3.16 to 5.14], and 3.85 [95% CI, 2.77 to 5.36], respectively). A history of kidney disease in childhood was associated with younger age at the onset of ESRD (hazard ratio for ESRD among adults <40 years of age, 10.40 [95% CI, 7.96 to 13.59]).A history of clinically evident kidney disease in childhood, even if renal function was apparently normal in adolescence, was associated with a significantly increased risk of ESRD, which suggests that kidney injury or structural abnormality in childhood has long-term consequences.
Abstract 12688: Abdominal Aortic Aneurysm in Marfan Syndrome: Time for Screening Guidelines?
Authors: Tracy Hagerty, Patrick Geraghty, Alan C Braverman
Journal: Circulation (2015)

Background: Marfan syndrome (MFS) leads to aortic root aneurysm, while descending thoracic aortic aneurysm (TAA) occurs less commonly. With imaging surveillance and prophylactic surgery, lifespan in MFS has increased to near normal. Abdominal aortic aneurysm (AAA) complicating Marfan syndrome is rarely reported in the literature. There are no guidelines for routine screening for AAA in MFS. We sought to characterize AAA disease in our MFS cohort. Methods: The records of 11 adults from our MFS Clinic with MFS (by Ghent or revised Ghent Criteria) and AAA disease were reviewed. Clinical features, imaging, operative reports, and outcomes were analyzed. Results: Eleven adults (9 male) with MFS and AAA, age at AAA diagnosis 43 + 15 yrs (range 18-63 yrs), were studied. Five patients smoked cigarettes. Nine of eleven patients were being treated with beta-blockers and angiotensin receptor blockers or ACE-inhibitors at the time of AAA diagnosis. Ten underwent prior aortic root replacement at age 31 + 15 yrs (range 8-62 yrs). The AAA was diagnosed 1-21 years after aortic root repair. The AAA was suprarenal in 5 patients, juxtarenal in 2, and infrarenal in 4. The size of the AAA ranged from 3.5 to 9.7 cm at time of diagnosis. Three patients had descending TAA. One patient had a prior type B dissection, not involving the abdominal aorta. Branch vessel aneurysms present in these patients included popliteal, intercostal, hepatic, subclavian and axillary. Four patients underwent open surgical repair (AAA size from 5.5 to 9.7 cm); one underwent endovascular repair; and five are being treated medically (aortic size 4.1 + 0.6 cm). One patient died suddenly with AAA size 5.7 cm at last measurement. Conclusions: Adults with MFS are at risk for developing AAA. Our cohort is the largest to date characterizing AAA in MFS. The AAAs were often very large at the time of initial diagnosis. MFS patients with AAA have a relatively high frequency of branch vessel aneurysms. Imaging to evaluate for AAA is recommended early after the diagnosis of MFS in adults and periodically thereafter to improve outcomes in this population.
Abstract 20586: Comparison of Inpatient Initiation of Sotalol vs Dofetilide in Patients With Atrial Fibrillation
Authors: Vidhya Gunasekaran, Sandia Iskandar, Madhu Reddy, Sudharani Bommana, Donita Atkins, Dhanunjaya Lakkireddy
Journal: Circulation (2016)

Introduction: There is limited data comparing the safety and efficacy of dofetilide and sotalol in the management of atrial fibrillation. Hypothesis: Both dofetilide and sotalol have similar effica...
Differences in Longitudinal Health Utility between Stereotactic Body Radiation Therapy and Surgery in Stage I Non–Small Cell Lung Cancer
Authors: Henri B. Wolff, Leonie Alberts, Elisabeth A. Kastelijn, Birgit I. Lissenberg-Witte, Jos W. Twisk, Frank J. Lagerwaard, Suresh Senan, Sherif Y. El Sharouni, Franz M.N.H. Schramel, Veerle M.H. Coupé
Journal: Journal of Thoracic Oncology (2018)
Oncolytic Virotherapy for Malignant Gliomas
Authors: Peter A. Forsyth, Daniel Abate-Daga
Journal: Journal of Clinical Oncology (2018)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma. February 12, 2018 ARTICLE CITATION DOI: 10.1200/JCO.2017.77.3192 Journal of Clinical Oncology - published online before print February 13, 2018 PMID: 29437534 Oncolytic Virotherapy for Malignant Gliomas Peter A. ForsythxPeter A. ForsythSearch for articles by this author and Daniel Abate-DagaxDaniel Abate-DagaSearch for articles by this author Show More Peter A. Forsyth and Daniel Abate-Daga, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL https://doi.org/10.1200/JCO.2017.77.3192 First Page Full Text PDF Figures and Tables © 2018 by American Society of Clinical Oncology Companion Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma
Disruption of staphylococcal aggregation protects against lethal lung injury
Authors: Jaime L. Hook, Mohammad N. Islam, Dane Parker, Alice S. Prince, Sunita Bhattacharya, Jahar Bhattacharya
Journal: Journal of Clinical Investigation (2018)

Infection by Staphylococcus aureus strain USA300 causes tissue injury, multiorgan failure, and high mortality. However, the mechanisms by which the bacteria adhere to, then stabilize on, mucosal surfaces before causing injury remain unclear. We addressed these issues through the first real-time determinations of USA300-alveolar interactions in live lungs. We found that within minutes, inhaled USA300 established stable, self-associated microaggregates in niches at curved, but not at flat, regions of the alveolar wall. The microaggregates released α-hemolysin toxin, causing localized alveolar injury, as indicated by epithelial dye loss, mitochondrial depolarization, and cytosolic Ca2+ increase. Spread of cytosolic Ca2+ through intercellular gap junctions to adjoining, uninfected alveoli caused pulmonary edema. Systemic pretreatment with vancomycin, a USA300-cidal antibiotic, failed to protect mice infected with inhaled WT USA300. However, vancomycin pretreatment markedly abrogated mortality in mice infected with mutant USA300 that lacked the aggregation-promoting factor PhnD. We interpret USA300-induced mortality as having resulted from rapid bacterial aggregation in alveolar niches. These findings indicate, for the first time to our knowledge, that alveolar microanatomy is critical in promoting the aggregation and, hence, in causing USA300-induced alveolar injury. We propose that in addition to antibiotics, strategies for bacterial disaggregation may constitute novel therapy against USA300-induced lung injury.
Phase II Clinical Trial of Personalized-VCD-VTD Sequential Therapy Using VES-13 for Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma
Authors: Tomonori Nakazato, Masao Hagihara, Seiji Irie, Naohi Sahara, Eri Tanaka, Yotaro Tamai, Ryuji Ishii, Shigehisa Tamaki, Atsushi Wake, Kenji Tajika, Rika Sakai, Takeshi Kobayashi, Fumiya Sano, Takayuki Abe, Rachel Roberts, Shin Fujisawa, Koji Miyazaki, Masaaki Higashihara
Journal: Blood (2017)
Smartphone application for the general public (mobile app review)
Authors: Clare Killingback, Emily Dore-Smith, Naomi Wakeman, Lauren Searles, Osman Ahmed
Journal: British Journal of Sports Medicine (2018)

Sportsinjuryclinic.

Medical.

Requires iOS 7.0 or later and Android 2.1 or later.

iOS: £0.99; Android: free.

Sportsinjuryclinic.net, developed by Virtual Sports Injury Clinic, claims to be an ‘instant sport injury expert’. The app aims to provide athletes with an easily accessible tool to seek expert information on various common sporting injuries.1 Although the app is available on both Apple and Android devices, the format differs considerably. This review focuses on the Apple version of the app as at the time of writing this had been updated most recently.

Sportsinjuryclinic has three main sections: ‘Symptom Check’, ‘Sports Injuries’ and ‘Find a Clinic’ (figure 1). The ‘Symptom Check’ feature encourages the user to touch ‘where it hurts’ on a body …
Proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1) controls immune synapse stability in human T cells
Authors: Willemijn J.M. Janssen, Valeria Grobarova, Jardin Leleux, Lieneke Jongeneel, Marielle van Gijn, Joris M. van Montfrans, Marianne Boes
Journal: Journal of Allergy and Clinical Immunology (2018)
Criminal and professional sanctions impede honesty and improvement
Authors: Richard N Rees
Journal: BMJ (2018)

I’m astounded that the concept of a single person being the cause of medical error is still so pervasive. We have learnt from industrial processes (from airlines to atomic energy) that tragedy occurs only when enough small things have aligned to provide the momentum. One person does not have the capacity to make all of these changes, so the last person holding …
Left Atrial Appendage Occlusion During Cardiac Operations for Prevention of Thromboembolic Events
Authors: Victor A. Ferraris
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
Use of Appropriate Surveillance for Patients With Nondysplastic Barrett’s Esophagus
Authors: Anna Tavakkoli, Henry D. Appelman, David G. Beer, Chaitra Madiyal, Maryam Khodadost, Kimberly Nofz, Val Metko, Grace Elta, Thomas Wang, Joel H. Rubenstein
Journal: Clinical Gastroenterology and Hepatology (2018)
HLA-E molecule expression in the liver is associated with severity of liver disease in chronic hepatitis C
Authors: Roberta Araújo, Fernanda Souza, Andreza C Teixeira, Patrícia Almeida, Marcia G. Villanova, Fabrício C. Dias, Leandra Naíra Zambelli Ramalho, Eduardo Antônio Donadi, Ana Lourdes Candolo Martinelli
Journal: Hepatology (2016)
Donor intravascular monocyte trafficking: a potential therapeutic target for primary graft dysfunction following lung transplantation?
Authors: Christopher Andrew Lamb, John Andrew Kirby
Journal: Thorax (2018)

Ischaemia reperfusion injury at the time of lung transplantation may lead to primary graft dysfunction (PGD).1 Occurring within the first 72 hours following allograft reperfusion, PGD is characterised by hypoxaemia and alveolar infiltrates in the transplanted organ and occurs in up to 30% of patients.2 The development of PGD carries significant early mortality of up to 50% in 30 days.3 Those who survive the early postoperative period have a higher propensity to develop bronchiolitis obliterans syndrome,4 and long-term mortality is also higher at 1, 5 and 10 years.5 

Several risk factors have been identified for the development of PGD, including a donor history of smoking, higher FiO2 at the time of reperfusion, elevated pulmonary arterial pressures, large volume blood transfusion and raised recipient body mass index.6 This observation has led to the development of ex vivo lung perfusion. Here. lungs are ventilated and perfused with an acellular buffer. The use of this technique has allowed longer total ischaemic time prior to transplantation without an increase in incidence of PGD.7 However, incomplete understanding of the immune mechanisms leading to ischaemia reperfusion injury is a major limitation to preventing disease onset. There are no disease-specific therapeutics available for the condition, nor to prevent progression to PGD. Improved understanding of the immune responses underlying ischaemia reperfusion injury may allow development of new therapeutic strategies.

Dysregulation of the innate immune response is central to ischaemia reperfusion pathobiology. Neutrophils …