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https://www.readbyqxmd.com/read/29148534/genetic-testing-of-complement-and-coagulation-pathways-in-patients-with-severe-hypertension-and-renal-microangiopathy
#1
Christopher P Larsen, Jon D Wilson, Alejandro Best-Rocha, Marjorie L Beggs, Randolph A Hennigar
A diagnosis of thrombotic microangiopathy on kidney biopsy in a patient presenting with hypertensive emergency has historically elicited the diagnosis of malignant hypertension-associated thrombotic microangiopathy. Recent studies, however, have raised awareness that a number of these patients may actually represent atypical hemolytic uremic syndrome. To further investigate this premise, we performed next-generation sequencing to interrogate the coding regions of 29 complement and coagulation cascade genes associated with atypical hemolytic uremic syndrome in 100 non-elderly patients presenting with severe hypertension, renal failure and a kidney biopsy showing microangiopathic changes limited to the classic accelerated hypertension-associated lesion of arterial intimal edema ('mucoid intimal hyperplasia') in isolation and without accompanying glomerular microthrombi...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29148397/evolutionary-context-of-non-sorbitol-fermenting-shiga-toxin-producing-escherichia-coli-o55-h7
#2
Kyle Schutz, Lauren A Cowley, Sharif Shaaban, Anne Carroll, Eleanor McNamara, David L Gally, Gauri Godbole, Claire Jenkins, Timothy J Dallman
In July 2014, an outbreak of Shiga toxin-producing Escherichia coli (STEC) O55:H7 in England involved 31 patients, 13 (42%) of whom had hemolytic uremic syndrome. Isolates were sequenced, and the sequences were compared with publicly available sequences of E. coli O55:H7 and O157:H7. A core-genome phylogeny of the evolutionary history of the STEC O55:H7 outbreak strain revealed that the most parsimonious model was a progenitor enteropathogenic O55:H7 sorbitol-fermenting strain, lysogenized by a Shiga toxin (Stx) 2a-encoding phage, followed by loss of the ability to ferment sorbitol because of a non-sense mutation in srlA...
December 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29142942/complement-activation-induces-neutrophil-adhesion-and-neutrophil-platelet-aggregate-formation-on-vascular-endothelial-cells
#3
Magdalena Riedl, Damien G Noone, Meraj A Khan, Fred G Pluthero, Walter H A Kahr, Nades Palaniyar, Christoph Licht
Introduction: Atypical hemolytic uremic syndrome is a thrombotic microangiopathy, which is linked to hereditary or autoimmune defects in complement activators or regulators present in blood and on vascular endothelial cells. Acute thrombotic microangiopathy episodes are typically preceded by infections, which by themselves would not be expected to manifest HUS. Thus, it is possible that the host immune response contributes to the precipitation of aHUS. However, the mechanisms involved are not fully understood...
January 2017: KI Reports
https://www.readbyqxmd.com/read/29136640/long-term-outcomes-of-the-atypical-hemolytic-uremic-syndrome-after-kidney-transplantation-treated-with-eculizumab-as-first-choice
#4
Luis Gustavo Modelli de Andrade, Mariana Moraes Contti, Hong Si Nga, Ariane Moyses Bravin, Henrique Mochida Takase, Rosa Marlene Viero, Trycia Nunes da Silva, Kelem De Nardi Chagas, Lilian Monteiro Pereira Palma
INTRODUCTION: The treatment of choice for Atypical Hemolytic Uremic Syndrome (aHUS) is the monoclonal antibody eculizumab. The objective of this study was to assess the efficacy and safety of eculizumab in a cohort of kidney transplant patients suffering from aHUS. METHODS: Description of the prospective cohort of all the patients primarily treated with eculizumab after transplantation and divided into the therapeutic (onset of aHUS after transplantation) and prophylactic use (patients with previous diagnosis of aHUS undergoing kidney transplantation)...
2017: PloS One
https://www.readbyqxmd.com/read/29121863/multiplex-real-time-pcr-assay-for-detection-of-escherichia-coli-o157-h7-and-screening-for-non-o157-shiga-toxin-producing-e-coli
#5
Baoguang Li, Huanli Liu, Weimin Wang
BACKGROUND: Shiga toxin-producing Escherichia coli (STEC), including E. coli O157:H7, are responsible for numerous foodborne outbreaks annually worldwide. E. coli O157:H7, as well as pathogenic non-O157:H7 STECs, can cause life-threating complications, such as bloody diarrhea (hemolytic colitis) and hemolytic-uremic syndrome (HUS). Previously, we developed a real-time PCR assay to detect E. coli O157:H7 in foods by targeting a unique putative fimbriae protein Z3276. To extend the detection spectrum of the assay, we report a multiplex real-time PCR assay to specifically detect E...
November 9, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/29114374/prevention-of-chemotherapy-induced-nephrotoxicity-in-children-with-cancer
#6
REVIEW
Fatemeh Ghane Sharbaf, Hamid Farhangi, Farahnak Assadi
Children with cancer treated with cytotoxic drugs are frequently at risk of developing renal dysfunction. The cytotoxic drugs that are widely used for cancer treatment in children are cisplatin (CPL), ifosfamide (IFO), carboplatin, and methotrexate (MTX). Mechanisms of anticancer drug-induced renal disorders are different and include acute kidney injury (AKI), tubulointerstitial disease, vascular damage, hemolytic uremic syndrome (HUS), and intrarenal obstruction. CPL nephrotoxicity is dose-related and is often demonstrated with hypomagnesemia, hypokalemia, and impaired renal function with rising serum creatinine and blood urea nitrogen levels...
2017: International Journal of Preventive Medicine
https://www.readbyqxmd.com/read/29111613/management-of-shiga-toxin-producing-escherichia-coli-infected-children-a-multi-national-multi-specialty-survey
#7
Stephen B Freedman, Silviu Grisaru, Jianling Xie, Susan Samuel, Andrew Dixon, Amy C Plint, David Schnadower
AIM: Research has highlighted the potential role that hydration status may play in predicting outcomes in Shiga toxin-producing Escherichia coli (STEC)-infected children. Because little is known about the management of STEC-infected children in the pre-haemolytic uremic syndrome phase, we compared paediatric emergency medicine and nephrologist-stated management approaches to STEC-infected children. METHODS: Members of the Pediatric Emergency Research Canada (PERC; n = 228), the Pediatric Emergency Medicine Collaborative Research Committee (PEM CRC; n = 221) and the Canadian Association of Pediatric Nephrologists (CAPN; n = 66) were surveyed...
November 7, 2017: Journal of Paediatrics and Child Health
https://www.readbyqxmd.com/read/29107962/apoptosis-signal-regulating-kinase-1-inhibition-attenuates-cardiac-hypertrophy-and-cardiorenal-fibrosis-induced-by-uremic-toxins-implications-for-cardiorenal-syndrome
#8
Feby Savira, Longxing Cao, Ian Wang, Wendi Yang, Kevin Huang, Yue Hua, Beat M Jucker, Robert N Willette, Li Huang, Henry Krum, Zhiliang Li, Qiang Fu, Bing Hui Wang
Intracellular accumulation of protein-bound uremic toxins in the setting of cardiorenal syndrome leads to adverse effects on cardiorenal cellular functions, where cardiac hypertrophy and cardiorenal fibrosis are the hallmarks. In this study, we sought to determine if Apoptosis Signal-Regulated Kinase 1 (ASK1), an upstream regulator of cellular stress response, mediates cardiac hypertrophy and cardiorenal fibrosis induced by indoxyl sulfate (IS) and p-cresol sulfate (PCS) in vitro, and whether ASK1 inhibition is beneficial to ameliorate these cellular effects...
2017: PloS One
https://www.readbyqxmd.com/read/29106598/safety-and-effectiveness-of-restrictive-eculizumab-treatment-in-atypical-haemolytic-uremic-syndrome
#9
Kioa L Wijnsma, Caroline Duineveld, Elena B Volokhina, Lambertus P van den Heuvel, Nicole C A J van de Kar, Jack F M Wetzels
Background: Atypical haemolytic uremic syndrome (aHUS) is a rare but severe form of thrombotic microangiopathy as a consequence of complement dysregulation. aHUS has a poor outcome with high mortality and >50% of patients developing end-stage renal disease. Since the end of 2012, these outcomes have greatly improved with the introduction of eculizumab. Currently the duration of treatment is debated. Most guidelines advise lifelong treatment. However, there is no hard evidence to support this advice...
July 4, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29092674/autoantibodies-against-complement-components-in-systemic-lupus-erythematosus-role-in-the-pathogenesis-and-clinical-manifestations
#10
M H Hristova, V S Stoyanova
Many complement structures and a number of additional factors, i.e. autoantibodies, receptors, hormones and cytokines, are implicated in the complex pathogenesis of systemic lupus erythematosus. Genetic defects in the complement as well as functional deficiency due to antibodies against its components lead to different pathological conditions, usually clinically presented. Among them hypocomplementemic urticarial vasculitis, different types of glomerulonephritis as dense deposit disease, IgA nephropathy, atypical haemolytic uremic syndrome and lupus nephritis are very common...
December 2017: Lupus
https://www.readbyqxmd.com/read/29080423/prevalence-and-characteristics-of-shiga-toxin-producing-escherichia-coli-in-finishing-pigs-implications-on-public-health
#11
Wonhee Cha, Pina M Fratamico, Leah E Ruth, Andrew S Bowman, Jacqueline M Nolting, Shannon D Manning, Julie A Funk
Shiga toxin-producing Escherichia coli (STEC) are important food-borne pathogens, which can cause serious illnesses, including hemorrhagic colitis and hemolytic uremic syndrome. To study the epidemiology of STEC in finishing pigs and examine the potential risks they pose for human STEC infections, we conducted a longitudinal cohort study in three finishing sites. Six cohorts of pigs (2 cohorts/site, 20 pigs/cohort) were randomly selected, and fecal samples (n=898) were collected every two weeks through their finishing period...
October 21, 2017: International Journal of Food Microbiology
https://www.readbyqxmd.com/read/29078927/acquired-bleeding-disorders
#12
REVIEW
Alisheba Hurwitz, Richard Massone, Bernard L Lopez
Emergency medicine practitioners treat bleeding patients on a regular basis. Disorders of hemostasis are an additional challenge in these patients but can be assessed and managed in a systematic fashion. Of particular importance to the emergency clinician are the iatrogenic causes of abnormal hemostasis. Other acquired causes of abnormal hemostasis include renal disease, immune thrombocytopenia, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, acquired coagulation factor inhibitors, acute traumatic coagulopathy, liver disease, and disseminated intravascular coagulopathy...
December 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/29078925/thrombotic-microangiopathies-ttp-hus-hellp
#13
REVIEW
Shane Kappler, Sarah Ronan-Bentle, Autumn Graham
Thrombocytopenia, strictly defined as a platelet count less than 150,000, is common in the emergency department. Recognition, diagnostic investigation, and proper disposition of a thrombocytopenic patient are imperative. One group of disorders leading to thrombocytopenia is the thrombotic microangiopathies, hallmarked by platelet destruction. These thrombotic microangiopathies include thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) and hemolysis, elevated liver enzyme levels, low platelet count (HELLP), which should be distinguished from similar disease processes such as immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC) and heparin induced thrombocytopenia (HIT)...
December 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/29071054/enterococcus-raffinosus-infection-with-atypical-hemolytic-uremic-syndrome-in-a-multiple-myeloma-patient-after-autologous-stem-cell-transplant
#14
Pankaj Mathur, Blake Hollowoa, Nupur Lala, Sharmilan Thanendrarajan, Aasiya Matin, Atul Kothari, Carolina Schinke
No abstract text is available yet for this article.
September 26, 2017: Hematology Reports
https://www.readbyqxmd.com/read/29068997/atypical-hemolytic-uremic-syndrome-induced-by-cblc-subtype-of-methylmalonic-academia-a-case-report-and-literature-review
#15
REVIEW
Minguang Chen, Jieqiu Zhuang, JianHuan Yang, Dexuan Wang, Qing Yang
RATIONALE: Methylmalonic acidemia (MMA) is a common organic acidemia, mainly due to methylmalonyl-CoA mutase (MCM) or its coenzyme cobalamin (VitB12) metabolic disorders. Cobalamin C (CblC) type is the most frequent inborn error of cobalamin metabolism; it can develop symptoms in childhood and often combine multisystem damage, which leads to methylmalonic acid, propionic acid, methyl citrate, and other metabolites abnormal accumulation, causing nerve, liver, kidney, bone marrow, and other organ damage...
October 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29068360/soluble-cd40-ligand-and-oxidative-response-are-reciprocally-stimulated-during-shiga-toxin-associated-hemolytic-uremic-syndrome
#16
Maria J Abrey Recalde, Romina S Alvarez, Fabiana Alberto, Maria P Mejias, Maria V Ramos, Romina J Fernandez Brando, Andrea C Bruballa, Ramon A Exeni, Laura Alconcher, Cristina A Ibarra, María M Amaral, Marina S Palermo
Shiga toxin (Stx), produced by Escherichia coli, is the main pathogenic factor of diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by the obstruction of renal microvasculature by platelet-fibrin thrombi. It is well known that the oxidative imbalance generated by Stx induces platelet activation, contributing to thrombus formation. Moreover, activated platelets release soluble CD40 ligand (sCD40L), which in turn contributes to oxidative imbalance, triggering the release of reactive oxidative species (ROS) on various cellular types...
October 25, 2017: Toxins
https://www.readbyqxmd.com/read/29063990/identification-and-biochemical-characterization-of-wbwb-a-novel-udp-gal-neu5ac-r-%C3%AE-1-4-galactosyltransferase-from-the-intestinal-pathogen-escherichia-coli-serotype-o104
#17
Diana Czuchry, Walter A Szarek, Inka Brockhausen
The intestinal pathogen Escherichia coli serotype O104:H4 (ECO104) can cause bloody diarrhea and haemolytic uremic syndrome. The ECO104 O antigen has the unique repeating unit structure [4Galα1-4Neu5,7,9Ac3α2-3Galβ1-3GalNAcβ1-], which includes the mammalian sialyl-T antigen as an internal structure. Previously, we identified WbwC from ECO104 as the β3Gal-transferase that synthesizes the T antigen, and showed that α3-sialyl-transferase WbwA transfers sialic acid to the T antigen. Here we identify the wbwB gene product as a unique α1,4-Gal-transferase WbwB that transfers Gal from UDP-Gal to the terminal sialic acid residue of Neu5Acα2-3Galβ1-3GalNAcα-diphosphate-lipid acceptor...
October 24, 2017: Glycoconjugate Journal
https://www.readbyqxmd.com/read/29058539/belgian-consensus-statement-on-the-diagnosis-and-management-of-patients-with-atypical-hemolytic-uremic-syndrome
#18
Kathleen J Claes, Annick Massart, Laure Collard, Laurent Weekers, Eric Goffin, Jean-Michel Pochet, Karin Dahan, Johann Morelle, Brigitte Adams, Nilufer Broeders, Patrick Stordeur, Daniel Abramowicz, Jean-Louis Bosmans, Koen Van Hoeck, Peter Janssens, Lissa Pipeleers, Patrick Peeters, Steven Van Laecke, Elena Levtchenko, Ben Sprangers, Lambertus van den Heuvel, Nathalie Godefroid, Johan Van de Walle
No abstract text is available yet for this article.
October 23, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/29054297/hemolytic-uremic-syndrome-due-to-shiga-toxin-producing-escherichia-coli-infection
#19
REVIEW
M Bruyand, P Mariani-Kurkdjian, M Gouali, H de Valk, L A King, S Le Hello, S Bonacorsi, C Loirat
The leading cause of hemolytic uremic syndrome (HUS) in children is Shiga toxin-producing Escherichia coli (STEC) infection, which has a major outbreak potential. Since the early 2010s, STEC epidemiology is characterized by a decline of the historically predominant O157 serogroup and the emergence of non-O157 STEC, especially O26 and O80 in France. STEC contamination occurs through the ingestion of contaminated food or water, person-to-person transmission, or contact with ruminants or their contaminated environment...
October 17, 2017: Médecine et Maladies Infectieuses
https://www.readbyqxmd.com/read/29046944/complement-functional-tests-for-monitoring-eculizumab-treatment-in-patients-with-atypical-hemolytic-uremic-syndrome-an-update
#20
Gianluigi Ardissino, Francesca Tel, Martina Sgarbanti, Donata Cresseri, Antenore Giussani, Samantha Griffini, Elena Grovetto, Ilaria Possenti, Michela Perrone, Sara Testa, Fabio Paglialonga, Piergiorgio Messa, Massimo Cugno
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) characterized by platelet consumption, hemolysis, and organ damage. Eculizumab (ECU), a humanized antibody that blocks complement activity, has been successfully used in aHUS, but the best treatment schedule is not yet clear. METHODS: Here, we report our experience with ECU maintenance treatment and the interval between subsequent doses being extended based on global classical complement pathway (CCP) activity aimed at <30% for maintaining aHUS into remission...
October 18, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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