tbuckley/cabot-search huggingface dataset:
Quality and Safety in Health Care, Part XLIV
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2018)

Abstract This article discusses 2 specialized implantable cardioverter defibrillator (ICD) devices. A special type of implantable device is available for cardiac resynchronization therapy, which can also have a defibrillator, in which case it is called a CRT-D device. In patients who meet guidelines for eligibility, a CRT-D will diminish the number of significant cardiac events including death. A subcutaneous ICD device does not need any leads placed in the vascular system and therefore does not have some of the complications that may be seen with transvenous ICDs. Also, there are patients who are not candidates for a typical ICD implantation. On the other hand, there are important disadvantages to the subcutaneous ICD.
Re: Ryan Swearingen, Akshay Sood, Rabii Madi, et al. Zero-fragment Nephrolithotomy: A Multi-center Evaluation of Robotic Pyelolithotomy and Nephrolithotomy for Treating Renal Stones. Eur Urol 2017;72:1014–21
Authors: Yuqi Xia, Weimin Yu, Fan Cheng
Journal: European Urology (2018)
Management of acute HCV infection in the era of direct-acting antiviral therapy
Authors: Marianne Martinello, Behzad Hajarizadeh, Jason Grebely, Gregory J. Dore, Gail V. Matthews
Journal: Nature Reviews Gastroenterology & Hepatology (2018)

The management of acute HCV infection has not been standardized following the availability of direct-acting antiviral agents (DAAs) for chronic HCV infection, and substantial uncertainty exists regarding the optimal treatment regimen and duration. Despite the lack of direct evidence, the 2016 American Association for the Study of Liver Diseases (AASLD)-Infectious Diseases Society of America (IDSA) guidelines supported "the same regimens for acute HCV as recommended for chronic HCV infection … owing to high efficacy and safety", whereas the 2016 European Association for the Study of the Liver (EASL) guidelines recommended sofosbuvir-ledipasvir, sofosbuvir-velpatasvir or sofosbuvir plus daclatasvir for 8 weeks in acute HCV infection, with a longer duration of 12 weeks recommended for those infected with HIV and/or baseline HCV RNA levels >1,000,000 IU/ml. This Review outlines the epidemiology, natural history and diagnosis of acute HCV infection and provides contemporary information on DAAs for acute and recent HCV infection. The Review also discusses the 2016 AASLD-IDSA and EASL recommendations for acute HCV infection management in light of available evidence and highlights key differences in study populations and design that influence interpretation. We focus on populations at high risk of HCV transmission and acquisition, including people who inject drugs and HIV-positive men who have sex with men, and highlight the potential effects of diagnosis and treatment of acute HCV infection in contributing to HCV elimination.
YAP Controls Endothelial Activation and Vascular Inflammation Through TRAF6
Authors: Yang Lv, Kyungho Kim, Yue Sheng, Jaehyung Cho, Zhijian Qian, You-Yang Zhao, Gang Hu, Duojia Pan, Asrar B. Malik, Guochang Hu
Journal: Circulation Research (2018)

Rationale: Microvascular inflammation and endothelial dysfunction secondary to unchecked activation of endothelium play a critical role in the pathophysiology of sepsis and organ failure. The intrinsic signaling mechanisms responsible for dampening excessive activation of endothelial cells are not completely understood. Objective: To determine the central role of YAP (Yes-associated protein), the major transcriptional coactivator of the Hippo pathway, in modulating the strength and magnitude of endothelial activation and vascular inflammation. Methods and Results: Endothelial-specific YAP knockout mice showed increased basal expression of E-selectin and ICAM (intercellular adhesion molecule)-1 in endothelial cells, a greater number of adherent neutrophils in postcapillary venules and increased neutrophil counts in bronchoalveolar lavage fluid. Lipopolysaccharide challenge of these mice augmented NF-κB (nuclear factor-κB) activation, expression of endothelial adhesion proteins, neutrophil and monocyte adhesion to cremaster muscle venules, transendothelial neutrophil migration, and lung inflammatory injury. Deletion of YAP in endothelial cells also markedly augmented the inflammatory response and cardiovascular dysfunction in a polymicrobial sepsis model induced by cecal ligation and puncture. YAP functioned by interacting with the E3 ubiquitin-protein ligase TLR (Toll-like receptor) signaling adaptor TRAF6 (tumor necrosis factor receptor-associated factor 6) to ubiquitinate TRAF6, and thus promoted TRAF6 degradation and modification resulting in inhibition of NF-κB activation. TRAF6 depletion in endothelial cells rescued the augmented inflammatory phenotype in mice with endothelial cell–specific deletion of YAP. Conclusions: YAP modulates the activation of endothelial cells and suppresses vascular inflammation through preventing TRAF6-mediated NF-κB activation and is hence essential for limiting the severity of sepsis-induced inflammation and organ failure.
Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma
Authors: Mario Castro, Jonathan Corren, Ian D Pavord, Jorge Maspero, Sally Wenzel, Klaus F Rabe, William W Busse, Linda Ford, Lawrence Sher, J Mark FitzGerald, Constance Katelaris, Yuji Tohda, Bingzhi Zhang, Heribert Staudinger, Gianluca Pirozzi, Nikhil Amin, Marcella Ruddy, Bolanle Akinlade, Asif Khan, Jingdong Chao, Renata Martincova, Neil M H Graham, Jennifer D Hamilton, Brian N Swanson, Neil Stahl, George D Yancopoulos, Ariel Teper
Journal: New England Journal of Medicine (2018)

Dupilumab is a fully human anti–interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma.
Systematic Review of the Impact of Cancer Survivorship Care Plans on Health Outcomes and Health Care Delivery
Authors: Paul B. Jacobsen, Antonio P. DeRosa, Tara O. Henderson, Deborah K. Mayer, Chaya S. Moskowitz, Electra D. Paskett, Julia H. Rowland
Journal: Journal of Clinical Oncology (2018)

Purpose Numerous organizations recommend that patients with cancer receive a survivorship care plan (SCP) comprising a treatment summary and follow-up care plans. Among current barriers to implementation are providers' concerns about the strength of evidence that SCPs improve outcomes. This systematic review evaluates whether delivery of SCPs has a positive impact on health outcomes and health care delivery for cancer survivors. Methods Randomized and nonrandomized studies evaluating patient-reported outcomes, health care use, and disease outcomes after delivery of SCPs were identified by searching MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library. Data extracted by independent raters were summarized on the basis of qualitative synthesis. Results Eleven nonrandomized and 13 randomized studies met inclusion criteria. Variability was evident across studies in cancer types, SCP delivery timing and method, SCP recipients and content, SCP-related counseling, and outcomes assessed. Nonrandomized study findings yielded descriptive information on satisfaction with care and reactions to SCPs. Randomized study findings were generally negative for the most commonly assessed outcomes (ie, physical, functional, and psychological well-being); findings were positive in single studies for other outcomes, including amount of information received, satisfaction with care, and physician implementation of recommended care. Conclusion Existing research provides little evidence that SCPs improve health outcomes and health care delivery. Possible explanations include heterogeneity in study designs and the low likelihood that SCP delivery alone would influence distal outcomes. Findings are limited but more positive for proximal outcomes (eg, information received) and for care delivery, particularly when SCPs are accompanied by counseling to prepare survivors for future clinical encounters. Recommendations for future research include focusing to a greater extent on evaluating ways to ensure SCP recommendations are subsequently acted on as part of ongoing care.
Diagnostic Performance of 18F-Fluciclovine in Detection of Prostate Cancer Bone Metastases
Authors: Albert Chau, Peter Gardiner, Patrick M. Colletti, Hossein Jadvar
Journal: Clinical Nuclear Medicine (2018)

F-fluciclovine is a synthetic amino acid radiotracer that has recently been approved in Europe and the United States for PET imaging in men with biochemical recurrence (BCR) of prostate cancer after prior definitive treatment. Accurate identification of the sites of disease in patients presenting with BCR of prostate cancer is important in determining the appropriate treatment. Bone is the most frequent site of metastatic disease in patients with prostate cancer.We conducted a comprehensive review of the available preclinical and clinical data on the diagnostic performance of F-fluciclovine PET/CT in an attempt to draw practical and general conclusions on the utility and limitations of F-fluciclovine PET/CT in localization of osseous metastatic disease in prostate cancer.The cumulative preclinical data and results of some retrospective and 2 prospective clinical studies suggest that F-fluciclovine can detect early bone marrow involvement in patients with BCR of prostate cancer and negative prior bone-specific imaging findings.F-fluciclovine PET/CT seems to offer useful information for early detection of bone metastases in men with BCR of prostate cancer. Additional investigations will be needed to compare the diagnostic performance of F-fluciclovine PET/CT to other standard and novel imaging methods in initial staging, BCR, and castrate-resistant phases of disease.
Abstract 14589: Characterization and High-Throughput Drug Screening of a Cardiomyopathy Using Cardiomyocytes From Patient-Derived Induced Pluripotent Stem Cells
Authors: Teisha J Rowland, Sherin I Hashem, Kenneth L Jones, Eric D Adler, Daniel V LaBarbera, Luisa Mestroni, Matthew R Taylor
Journal: Circulation (2016)

Danon disease is an untreatable and severe X-linked form of cardiomyopathy that leads to profound cardiac hypertrophy, causing death or a need for cardiac transplantation in males by the third decade. Danon disease is known to be caused by loss of the lysosome-associated membrane protein-2 (LAMP-2) protein, which is a membrane glycoprotein likely involved in lysosome-autophagosome fusion and vesicle trafficking during autophagy. However, it is unknown how LAMP-2 protein deficiency leads to the development of Danon disease. To better characterize the molecular and cellular pathogenic mechanisms involved and enable high-throughput screening (HTS) of compound libraries, human induced pluripotent stem cells (iPSCs) were generated from patients with Danon disease and differentiated into cardiomyocytes. RNA transcription levels from the Danon iPSC-derived cardiomyocytes (iPSC-CMs) were analyzed using RNA-Sequencing (RNA-Seq) and expression of key genes confirmed via quantitative real-time PCR (qRT-PCR). The data show significant upregulation of genes involved in cellular respiration and sarcomere expression in Danon iPSC-CMs compared to unaffected control iPSC-CMs. The upregulation of cellular respiration transcripts in our data align with published data suggesting mitochondrial function is affected in these cells, including increased levels of mitochondrial oxidative stress. Our RNA-Seq findings of potentially impacted molecular pathways in the Danon iPSC-CM model have been used to identify biomarkers, such as the sarcomeric protein troponin T type 2, for conducting HTS drug discovery. Following development and validation of a primary HTS assay, a pilot HTS using a library of 355 kinase inhibitors and then a HTS drug discovery using a custom designed diversity library of 20,000 compounds will be performed and hits confirmed using secondary and tertiary assays. These confirmed hits may offer novel potential therapeutic treatments for individuals with this currently devastating and untreatable cardiomyopathy.
Antibiotic treatment–induced secondary IgA deficiency enhances susceptibility to Pseudomonas aeruginosa pneumonia
Authors: Oliver H. Robak, Markus M. Heimesaat, Andrey A. Kruglov, Sandra Prepens, Justus Ninnemann, Birgitt Gutbier, Katrin Reppe, Hubertus Hochrein, Mark Suter, Carsten J. Kirschning, Veena Marathe, Jan Buer, Mathias W. Hornef, Markus Schnare, Pascal Schneider, Martin Witzenrath, Stefan Bereswill, Ulrich Steinhoff, Norbert Suttorp, Leif E. Sander, Catherine Chaput, Bastian Opitz
Journal: Journal of Clinical Investigation (2018)

Broad-spectrum antibiotics are widely used with patients in intensive care units (ICUs), many of whom develop hospital-acquired infections with Pseudomonas aeruginosa. Although preceding antimicrobial therapy is known as a major risk factor for P. aeruginosa–induced pneumonia, the underlying mechanisms remain incompletely understood. Here we demonstrate that depletion of the resident microbiota by broad-spectrum antibiotic treatment inhibited TLR-dependent production of a proliferation-inducing ligand (APRIL), resulting in a secondary IgA deficiency in the lung in mice and human ICU patients. Microbiota-dependent local IgA contributed to early antibacterial defense against P. aeruginosa. Consequently, P. aeruginosa–binding IgA purified from lamina propria culture or IgA hybridomas enhanced resistance of antibiotic-treated mice to P. aeruginosa infection after transnasal substitute. Our study provides a mechanistic explanation for the well-documented risk of P. aeruginosa infection following antimicrobial therapy, and we propose local administration of IgA as a novel prophylactic strategy.
Linear Keratotic Lesions in a Young Woman
Authors: Yuan Li, Yuhan Wang, Zhimiao Lin
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Head and Neck Cancers: Advantages of Advanced Radiation Therapy and Importance of Supportive Care
Authors: Sharon Spencer
Journal: Journal of the National Comprehensive Cancer Network (2018)

For more than a decade, the incidence of head and neck cancers has been increasing in the United States. Worldwide, they are the ninth most common cancer. Today, newer advances in radiotherapy (RT), such as fractionation, 4-dimensional cone-beam CT, and intensity-modulated RT, have provided clinicians with the opportunity for improved patient outcomes. At the NCCN 23rd Annual Conference, Sharon Spencer, MD, described the advantages of advances in RT and the means to mitigate untoward side effects.
Abstract 1626: Selective Mineralocorticoid Receptor Blocker Eplerenone Reduces Inflammatory Biomarkers in Hypertensive Patients
Authors: Carmine Savoia, Rhian M Touyz, Farhad Amiri, Ernesto L Schiffrin
Journal: Circulation (2007)

High blood pressure (BP) may stimulate an inflammatory reaction, which in turn might induce the changes in the arterial wall that are characteristic of hypertension. We have recently reported that BP control with the selective mineralocorticoid receptor (MR) blocker eplerenone is associated with reduced stiffness of resistance arteries of hypertensive patients. Here we questioned whether in hypertensive patients BP reduction after one year (1yr) of therapy with either eplerenone or the beta-blocker atenolol is associated with a decreased inflammatory response. Sixteen hypertensive patients (age 30 to 70 yrs) were randomized to double-blind treatment for 1yr with eplerenone (50–100 mg) or atenolol (50–100 mg) once daily. Seven normal subjects were studied as a control group. Serum levels of cytokines (IL-1β, IL-6, IL-8, IL-10, IL-1Ra), chemokines (MCP-1), and fibroblast growth factor (FGF) were measured by Bio-plex assay, and osteopontin by ELISA, as indices of systemic and vascular inflammation, before and 1yr after treatment. After 1yr of treatment, systolic and diastolic BP were well controlled in both the atenolol and eplerenone groups (144.3±3.7/95.4±1.8mmHg reduced to 121.4±3.1/79.2±2.6 mmHg, p
Evolving role of diet in the pathogenesis and treatment of inflammatory bowel diseases
Authors: Arie Levine, Rotem Sigall Boneh, Eytan Wine
Journal: Gut (2018)

Recent advances in basic and clinical science over the last 3 years have dramatically altered our appreciation of the role of diet in inflammatory bowel diseases (IBD). The marked increase in incidence of these diseases along with the important role of non-genetic susceptibility among patients with IBD has highlighted that these diseases have a strong environmental component. Progress in the field of microbiome and IBD has demonstrated that microbiome appears to play an important role in pathogenesis, and that diet may in turn impact the composition and functionality of the microbiome. Uncontrolled clinical studies have demonstrated that various dietary therapies such as exclusive enteral nutrition and newly developed exclusion diets might be potent tools for induction of remission at disease onset, for patients failing biologic therapy, as a treatment for disease complications and in reducing the need for surgery. We review these advances from bench to bedside, along with the need for better clinical trials to support these interventions.
Functional Relevance of the Anaphylatoxin Receptor C3aR for Platelet Function and Arterial Thrombus Formation Marks an Intersection Point Between Innate Immunity and Thrombosis
Authors: Reinhard J. Sauter, Manuela Sauter, Edimara S. Reis, Frederic N. Emschermann, Henry Nording, Sonja Ebenhöch, Peter Kraft, Patrick Münzer, Maximilian Mauler, Johannes Rheinlaender, Johannes Madlung, Frank Edlich, Tilman E. Schäffer, Sven G. Meuth, Daniel Duerschmied, Tobias Geisler, Oliver Borst, Meinrad Gawaz, Christoph Kleinschnitz, John D. Lambris, Harald F. Langer
Journal: Circulation (2018)

Platelets have distinct roles in the vascular system in that they are the major mediator of thrombosis, critical for restoration of tissue integrity, and players in vascular inflammatory conditions. In close spatiotemporal proximity, the complement system acts as the first line of defense against invading microorganisms and is a key mediator of inflammation. Whereas the fluid phase cross-talk between the complement and coagulation systems is well appreciated, the understanding of the pathophysiological implications of such interactions is still scant.We analyzed coexpression of the anaphylatoxin receptor C3aR with activated glycoprotein IIb/IIIa on platelets of 501 patients with coronary artery disease using flow cytometry; detected C3aR expression in human or murine specimen by polymerase chain reaction, immunofluorescence, Western blotting, or flow cytometry; and examined the importance of platelet C3aR by various in vitro platelet function tests, in vivo bleeding time, and intravital microscopy. The pathophysiological relevance of C3aR was scrutinized with the use of disease models of myocardial infarction and stroke. To approach underlying molecular mechanisms, we identified the platelet small GTPase Rap1b using nanoscale liquid chromatography coupled to tandem mass spectrometry.We found a strong positive correlation of platelet complement C3aR expression with activated glycoprotein IIb/IIIa in patients with coronary artery disease and coexpression of C3aR with glycoprotein IIb/IIIa in thrombi obtained from patients with myocardial infarction. Our results demonstrate that the C3a/C3aR axis on platelets regulates distinct steps of thrombus formation such as platelet adhesion, spreading, and Ca2+ influx. Using C3aR-/- mice or C3-/- mice with reinjection of C3a, we uncovered that the complement activation fragment C3a regulates bleeding time after tail injury and thrombosis. Notably, C3aR-/- mice were less prone to experimental stroke and myocardial infarction. Furthermore, reconstitution of C3aR-/- mice with C3aR+/+ platelets and platelet depletion experiments demonstrated that the observed effects on thrombosis, myocardial infarction, and stroke were specifically caused by platelet C3aR. Mechanistically, C3aR-mediated signaling regulates the activation of Rap1b and thereby bleeding arrest after injury and in vivo thrombus formation.Overall, our findings uncover a novel function of the anaphylatoxin C3a for platelet function and thrombus formation, highlighting a detrimental role of imbalanced complement activation in cardiovascular diseases.
Glutaminolysis is a metabolic dependency in FLT3ITD acute myeloid leukemia unmasked by FLT3 tyrosine kinase inhibition
Authors: Paolo Gallipoli, George Giotopoulos, Konstantinos Tzelepis, Ana S. H. Costa, Shabana Vohra, Paula Medina-Perez, Faisal Basheer, Ludovica Marando, Lorena Di Lisio, Joao M. L. Dias, Haiyang Yun, Daniel Sasca, Sarah J. Horton, George Vassiliou, Christian Frezza, Brian J. P. Huntly
Journal: Blood (2018)
Evolution of “Nightmare Bacteria”
Authors: Bridget Kuehn
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
A traditional Chinese remedy points to a natural skin habitat: indirubin (indigo naturalis) for psoriasis and the <i>Malassezia</i> metabolome
Authors: G. Gaitanis, P. Magiatis, A. Velegraki, I.D. Bassukas
Journal: British Journal of Dermatology (2018)

Linked Article:Lin et al. Br J Dermatol 2018; 178:124–31.