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https://www.readbyqxmd.com/read/29353350/clinical-pharmacokinetics-and-pharmacodynamics-of-evolocumab-a-pcsk9-inhibitor
#1
REVIEW
Sreeneeranj Kasichayanula, Anita Grover, Maurice G Emery, Megan A Gibbs, Ransi Somaratne, Scott M Wasserman, John P Gibbs
Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases plasma low-density lipoprotein cholesterol (LDL-C) by decreasing expression of the LDL receptor on hepatic cells. Evolocumab is a human monoclonal immunoglobulin G2 that binds specifically to human PCSK9 to reduce LDL-C. Evolocumab exhibits nonlinear kinetics as a result of binding to PCSK9. Elimination is predominantly through saturable binding to PCSK9 at lower concentrations and a nonsaturable proteolytic pathway at higher concentrations. The effective half-life of evolocumab is 11-17 days...
January 20, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29353318/diagnostic-value-of-vascular-endothelial-growth-factor-transforming-growth-factor-%C3%AE-interleukin-8-and-the-ratio-of-lactate-dehydrogenase-to-adenosine-deaminase-in-pleural-effusion
#2
Takeshi Saraya, Kosuke Ohkuma, Takayasu Watanabe, Sunao Mikura, Fumi Kobayashi, Junpei Aso, Hiroki Nunokawa, Kojiro Honda, Yukari Ogawa, Masaki Tamura, Mitsuru Sada, Miku Oda, Manami Inoue, Takuma Yokoyama, Daisuke Kurai, Haruyuki Ishii, Hirokazu Kimura, Hajime Takizawa
PURPOSE: We studied the diagnostic value of cytokines, including vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and interleukin-8 (IL-8), and the ratio of lactate dehydrogenase (LDH) to adenosine deaminase (ADA) in pleural fluid. METHODS: Prospective analysis of 44 inpatients or outpatients with pleural fluid, from December 2016 to March 2017 was conducted. RESULTS: We enrolled patients with malignant pleural effusion (MPE, N = 15), empyema (N = 11), parapneumonic effusion (PPE, N = 7), chronic renal failure (CRF)/chronic heart failure (CHF) (N = 7), and tuberculous pleural effusion (TBPE, N = 4)...
January 20, 2018: Lung
https://www.readbyqxmd.com/read/29353233/cardiovascular-safety-long-term-noncardiovascular-safety-and-efficacy-of-sodium-glucose-cotransporter-2-inhibitors-in-patients-with-type-2-diabetes-mellitus-a-systemic-review-and-meta-analysis-with-trial-sequential-analysis
#3
REVIEW
Xin-Lin Zhang, Qing-Qing Zhu, Yu-Han Chen, Xue-Ling Li, Fu Chen, Jian-An Huang, Biao Xu
BACKGROUND: The cardiovascular and long-term noncardiovascular safety and efficacy of SGLT2 (sodium-glucose cotransporter 2) inhibitors have not been well documented. METHODS AND RESULTS: For cardiovascular outcomes, we performed a meta-analysis with trial sequential analysis of randomized controlled trials and adjusted observational studies, each with a minimum of 26 weeks and 2000 patient-years of follow-up. For long-term noncardiovascular safety and efficacy outcome analyses, we included only randomized controlled trials with at least 2 years and 1000 patient-years of follow-up...
January 20, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29352596/thirty-day-readmissions-following-parathyroidectomy-evidence-from-the-national-readmissions-database-2013-2014
#4
Adam M Kravietz, Jessica L Buicko, Joshua P Parreco, Michael A Lopez, Robert A Kozol
PURPOSE: Parathyroidectomy is one of the most common procedures performed in the United States, and are increasingly being performed safely in the outpatient setting. However, complications from surgery can be life-threatening, and thus an understanding of who may be at risk is essential. We analyzed and compared the risk factors for patients readmitted within 30 days following inpatient parathyroidectomy for primary or secondary hyperparathyroidism. MATERIALS AND METHODS: We reviewed the National Readmissions Database from 2013 to 2014 for patients who received inpatient parathyroidectomy for primary or secondary hyperparathyroidism...
January 10, 2018: American Journal of Otolaryngology
https://www.readbyqxmd.com/read/29352071/worsening-renal-function-in-acute-heart-failure-patients-undergoing-aggressive-diuresis-is-not-associated-with-tubular-injury
#5
Tariq Ahmad, Keyanna Jackson, Veena S Rao, W H Wilson Tang, Meredith A Brisco-Bacik, Horng H Chen, G Michael Felker, Adrian F Hernandez, Christopher M O'Connor, Venkata S Sabbisetti, Joseph V Bonventre, F Perry Wilson, Steven G Coca, Jeffrey M Testani
Background -Worsening renal function (WRF) in the setting of aggressive diuresis for acute heart failure (AHF) treatment may reflect renal tubular injury or simply indicate a hemodynamic or functional change in glomerular filtration. Well-validated tubular injury biomarkers-NAG, NGAL, and KIM-1- are now available that can quantify the degree of renal tubularinjury. The ROSE-AHF trial provides an experimental platform for the study of mechanisms of WRF during aggressive diuresis for AHF, as the ROSE-AHF protocol dictated high dose loop diuretic therapy in all patients...
January 19, 2018: Circulation
https://www.readbyqxmd.com/read/29351744/risk-factors-for-first-time-acute-myocardial-infarction-patients-in-trinidad
#6
M Bahall, T Seemungal, G Legall
BACKGROUND: The relative importance of coronary artery disease (CAD) risk varies globally. The aim of this study was to determine CAD risk factors for acute myocardial infarction (AMI) among patients in public health care institutions in Trinidad using a case-control type study design. METHODS: The sample comprised 251 AMI patients hospitalized between March 1, 2011 and April 30, 2012 and 464 age- and sex-matched non-AMI patients with no terminal or life-threatening illness and who did not undergo treatment for CAD...
January 19, 2018: BMC Public Health
https://www.readbyqxmd.com/read/29350569/practice-pearl-liraglutide-and-cardiovascular-and-renal-events-in-type-2-diabetes
#7
Robert Guthrie
Review of: Marso S, Daniels G, Brown-Frandsen K, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016; 375: 311-322. Mann J, Orsted D, Brown-Frandsen K, et al. Liraglutide and Renal Outcomes in Type 2 Diabetes. N Engl J Med 2017; 377: 839-848. This comprehensive research project, LEADER, led to two reports, one focusing on the effect of liraglutide on cardiovascular events, and the second one reporting on the renal effects on the same study population. The study group included 9340 patients with type 2 diabetes...
January 19, 2018: Postgraduate Medicine
https://www.readbyqxmd.com/read/29350254/sacubitril-valsartan-for-heart-failure-with-reduced-left-ventricular-ejection-fraction-a%C3%A2-retrospective-cohort-study
#8
R De Vecchis, C Ariano, G Di Biase, M Noutsias
BACKGROUND: The combination drug sacubitril/valsartan was reported to be superior to enalapril in reducing all-cause death, cardiovascular mortality, and heart failure (HF) hospitalizations in patients with cardiac insufficiency and reduced left ventricular ejection fraction (HFREF) with NYHA class II-IV. METHODS: Our retrospective cohort study aimed to assess the effects of sacubitril/valsartan in addition to a beta-blocker and mineral receptor antagonist (MRA) in a group of HFREF patients with NYHA class II-III HF vs...
January 19, 2018: Herz
https://www.readbyqxmd.com/read/29350173/membranoproliferative-glomerulonephritis-and-interstitial-nephritis-in-the-setting-of-epstein-barr-virus-related-hemophagocytic-syndrome%C3%A2
#9
Iolanda Godinho, Estela Nogueira, Sofia Jorge, António Teixeira Alves, António Gomes da Costa
BACKGROUND: Hemophagocytic syndrome (HPS) is a rare, aggressive disorder characterized by dysregulation of lymphocyte and macrophage activity, which culminates in tissue infiltration with hemophagocytosis and ultimately organ failure. Renal involvement frequently ensues and usually results in acute tubular necrosis with associated interstitial inflammation. Less frequently, glomerulopathy can also be found. CASE: We report a case of a 24-year-old Caucasian woman with previous asymptomatic hematuria, mild proteinuria, and normal renal function who presented to us with fever...
January 19, 2018: Clinical Nephrology
https://www.readbyqxmd.com/read/29348194/health-care-costs-associated-with-incident-complications-in-patients-with-type-2-diabetes-in-germany
#10
Katharina Kähm, Michael Laxy, Udo Schneider, Wolf H Rogowski, Stefan K Lhachimi, Rolf Holle
OBJECTIVE: The aim of this study is to provide reliable regression-based estimates of costs associated with different type 2 diabetes complications. RESEARCH DESIGN AND METHODS: We used nationwide statutory health insurance (SHI) data from 316,220 patients with type 2 diabetes. Costs for inpatient and outpatient care, pharmaceuticals, rehabilitation, and nonmedical aids and appliances were assessed in the years 2013-2015. Quarterly observations are available for each year...
January 18, 2018: Diabetes Care
https://www.readbyqxmd.com/read/29348008/impact-of-pre-existing-prosthesis-patient-mismatch-on-survival-following-aortic%C3%A2-valve-in-valve%C3%A2-procedures
#11
Philippe Pibarot, Matheus Simonato, Marco Barbanti, Axel Linke, Ran Kornowski, Tanja Rudolph, Mark Spence, Neil Moat, Gabriel Aldea, Marco Mennuni, Alessandro Iadanza, Hafid Amrane, Diego Gaia, Won-Keun Kim, Massimo Napodano, Hardy Baumbach, Ariel Finkelstein, Junjiro Kobayashi, Stephen Brecker, Creighton Don, Alfredo Cerillo, Axel Unbehaun, David Attias, Mohammed Nejjari, Noah Jones, Claudia Fiorina, Didier Tchetche, Raphael Philippart, Konstantinos Spargias, Jose-Maria Hernandez, Azeem Latib, Danny Dvir
OBJECTIVES: The aim of this study was to determine whether the association of small label size of the surgical valve with increased mortality after transcatheter valve-in-valve (ViV) implantation is, at least in part, related to pre-existing prosthesis-patient mismatch (PPM) (i.e., a bioprosthesis that is too small in relation to body size). BACKGROUND: Transcatheter ViV implantation is an alternative for the treatment of patients with degenerated bioprostheses...
January 22, 2018: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/29346507/activity-and-safety-of-afatinib-in-a-window-pre-operative-eortc-study-in-patients-with-squamous-cell-carcinoma-of-the-head-and-neck-scchn
#12
J P Machiels, P Bossi, J Menis, M Lia, C Fortpied, Y Liu, R Lhommel, M Lemort, S Schmitz, S Canevari, L De Cecco, M Guzzo, R Bianchi, P Quattrone, F Crippa, T Duprez, Y Lalami, M Quiriny, N de Saint Aubain, P M Clement, R Coropciuc, E Hauben, L F Licitra
Background: To investigate the activity and safety of afatinib in the pre-operative treatment of squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5:1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were performed at diagnosis and just before surgery...
January 15, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29345092/-known-unknowns-examining-the-burden-of-neurocognitive-impairment-in-the-end-stage-renal-failure-population
#13
REVIEW
Scott Wilson, Arup Dhar, Peter Tregaskis, Gavin Lambert, David Barton, Rowan Walker
The burden of neurocognitive impairment (NCI) in patients receiving maintenance dialysis represents a spectrum of deficits across multiple cognitive domains which are associated with hospitalisation, reduced quality-of-life, mortality and forced decision-making around dialysis withdrawal. Point prevalence data suggests that dialysis patients manifest NCI at rates 3-5 fold higher than the general population with executive function the most commonly affected cognitive domain. The unique physiology of the renal failure state and maintenance dialysis appears to drive an excess of vascular dementia subtype compared to the general population where classical Alzheimer's disease predominates...
January 18, 2018: Nephrology
https://www.readbyqxmd.com/read/29344085/synthesis-secretion-function-metabolism-and-application-of-natriuretic-peptides-in-heart-failure
#14
REVIEW
Shihui Fu, Ping Ping, Fengqi Wang, Leiming Luo
As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically distinct, but structurally and functionally related for regulating circulatory homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A (NPPA) and NPPB genes on chromosome 1, whereas CNP is encoded by NPPC on chromosome 2...
2018: Journal of Biological Engineering
https://www.readbyqxmd.com/read/29344072/bilateral-compressive-optic-neuropathy-from-renal-osteodystrophy-caused-by-branchio-oto-renal-syndrome-stabilised-after-parathyroidectomy
#15
Arun N E Sundaram, Archana Abhayambika, Sunil Kumar
Renal osteodystrophy can cause calvarial hypertrophy and narrowing of the neural canals and foramina. Compressive optic neuropathy is extremely rare in renal osteodystrophy and was reported once only. The authors report bilateral, simultaneous compressive optic neuropathy secondary to renal osteodystrophy with features of uremic leontiasis ossea in chronic renal failure caused by branchio-oto-renal syndrome. Because of the extensive calvarial hypertrophy and the surgical difficulties envisaged with optic canal decompression, conservative approach was pursued...
December 2017: Neuro-ophthalmology
https://www.readbyqxmd.com/read/29344027/plasma-volume-and-renal-function-predict-six-month-survival-after-hospitalization-for-acute-decompensated-heart-failure
#16
Kenneth C Bilchick, Nathaniel Chishinga, Alex M Parker, David X Zhuo, Mitchell H Rosner, LaVone A Smith, Hunter Mwansa, Jacob N Blackwell, Peter A McCullough, Sula Mazimba
Background: Plasma volume (PV) is contracted in stable patients with heart failure (HF) due to decongestion strategies. On the other hand, increased PV can adversely affect the trajectory of HF. We therefore examined the effects of increased percentage change in PV (%ΔPV), blood urea nitrogen (BUN), and %ΔPV stratified by BUN and glomerular filtration rate (GFR) on survival after discharge in patients hospitalized for acute decompensated HF (ADHF). Methods: We used the Strauss-Davis-Rosenbaum formula to calculate the %ΔPV between baseline and hospital discharge in a cohort from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial (ESCAPE)...
December 2017: Cardiorenal Medicine
https://www.readbyqxmd.com/read/29343457/sphingolipid-signaling-in-renal-fibrosis
#17
REVIEW
Andrea Huwiler, Josef Pfeilschifter
Over the last decade, various sphingolipid subspecies have gained increasing attention as important signaling molecules that regulate a multitude of physiological and pathophysiological processes including inflammation and tissue remodeling. These mediators include ceramide, sphingosine 1-phosphate (S1P), the cerebroside glucosylceramide, lactosylceramide, and the gangliosides GM3 and Gb3. These lipids have been shown to accumulate in various chronic kidney diseases that typically end in renal fibrosis and ultimately renal failure...
January 14, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29341834/improvement-in-overall-survival-with-carfilzomib-lenalidomide-and-dexamethasone-in-patients-with-relapsed-or-refractory-multiple-myeloma
#18
David S Siegel, Meletios A Dimopoulos, Heinz Ludwig, Thierry Facon, Hartmut Goldschmidt, Andrzej Jakubowiak, Jesus San-Miguel, Mihaela Obreja, Julie Blaedel, A Keith Stewart
Purpose In the ASPIRE study of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide plus dexamethasone (Rd) in patients with relapsed or refractory multiple myeloma, progression-free survival was significantly improved in the carfilzomib group (hazard ratio, 0.69; two-sided P < .001). This prespecified analysis reports final overall survival (OS) data and updated safety results. Patients and Methods Adults with relapsed multiple myeloma (one to three prior lines of therapy) were eligible and randomly assigned at a one-to-one ratio to receive KRd or Rd in 28-day cycles until withdrawal of consent, disease progression, or occurrence of unacceptable toxicity...
January 17, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29341179/better-characterization-of-vinflunine-pharmacokinetics-variability-and-exposure-toxicity-relationship-to-improve-its-use-analyses-from-18-trials
#19
A Schmitt, L Nguyen, G Zorza, P Ferré, A Pétain
AIMS: Vinflunine is a novel tubulin-targeted inhibitor indicated as a single agent for the treatment of bladder cancers after failure of prior platinum-based therapy. Its pharmacokinetics (PK) and pharmacodynamics (PD) have been independently characterized through several phase I and phase II studies. However, no global pharmacometric analysis had been conducted yet. METHODS: Vinflunine concentrations and safety data from 18 phase I and phase II studies were used to conduct population PK and PK/PD analysis, using Nonmem...
January 17, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29341134/fatal-hemorrhage-from-an-arteriovenous-fistula
#20
Petr Handlos, Klára Marecová, Margita Smatanová, Igor Dvořáček, Martin Dobiáš
In this study, we present two cases of sudden deaths of people with end-stage kidney with arteriovenous fistulas for long-term hemodialysis treatment. This procedure is associated with a number of known complications. While stenosis, thrombosis, and infection are well known, lethal hemorrhage from arteriovenous fistula is much less commonly encountered. Inspection of the bodies at the scene of the death by a medical examiner suggested that the deaths were due to exsanguination. Autopsies revealed visible defects on the front wall of the arteriovenous fistulas...
January 16, 2018: Journal of Forensic Sciences
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