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https://www.readbyqxmd.com/read/29447987/escmid-study-group-for-infections-in-compromised-hosts-esgich-consensus-document-on-the-safety-of-targeted-and-biological-therapies-an-infectious-diseases-perspective-soluble-immune-effector-molecules-ii-agents-targeting-interleukins-immunoglobulins-and-complement
#1
REVIEW
Kevin L Winthrop, Xavier Mariette, Jose T Silva, Esther Benamu, Leonard H Calabrese, Alexandre Dumusc, Josef S Smolen, José María Aguado, Mario Fernández-Ruiz
BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting interleukins, immunoglobulins and complement factors and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family...
February 12, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29440240/atypical-presentation-of-atypical-haemolytic-uraemic-syndrome
#2
Ratna Basak, Xiaotong Wang, Caitlin Keane, Robert Woroniecki
A 17-year-old girl presented with fever, myalgia, vomiting for 1 month and oliguria and dyspnoea for 4 days. She was tachycardic,hypertensive, with pedal oedema and decreased breath sounds. She had high serum creatinine (3 mg/dL), anaemia, thrombocytopenia, leucocytosis and eosinophilia with schistocytes. Lactate dehydrogenase, transaminases were high , with low haptoglobin and high ferritin (5269 ng/mL). Complement C3/C4 and fibrinogen were normal. Urinalysis showed large blood and protein and stool studies were negative...
February 11, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29437288/staphylococcus-aureus-induced-complement-activation-promotes-tissue-factor-mediated-coagulation
#3
E W Skjeflo, D Christiansen, H Fure, J K Ludviksen, T M Woodruff, Terje Espevik, E W Nielsen, O L Brekke, T E Mollnes
BACKGROUND: There is extensive cross-talk between the complement system, the Toll-like receptors (TLR) and hemostasis. Consumptive coagulopathy is a hallmark of sepsis and often mediated through increased tissue factor (TF) expression. OBJECTIVES: To study the relative roles of complement, TLRs and TF in Staphylococcus aureus (S. aureus)-induced coagulation. METHODS: Lepirudin-anticoagulated human whole blood was incubated with the three S...
February 13, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29435915/eculizumab-a-review-in-generalized-myasthenia-gravis
#4
Sohita Dhillon
The humanized monoclonal antibody eculizumab (Soliris ® ) is a complement inhibitor indicated for use in anti-acetylcholine receptor (AChR) antibody-positive adults with generalized myasthenia gravis (gMG) in the USA, refractory gMG in the EU, or gMG with symptoms that are difficult to control with high-dose IVIg therapy or PLEX in Japan. It is the first complement inhibitor to be approved for use in these patients. In the well-designed, 26-week REGAIN study in patients with anti-AChR-positive refractory gMG, although a statistically significant benefit of eculizumab over placebo in the prespecified primary endpoint analysis (change from baseline in MG-activities of daily living (ADL) score assessed by worst-rank ANCOVA) was not formally demonstrated, preplanned and post hoc sensitivity analyses of this outcome, as well as other secondary outcomes supported the efficacy of eculizumab...
February 12, 2018: Drugs
https://www.readbyqxmd.com/read/29434134/a-rare-case-of-lupus-nephritis-presenting-as-thrombotic-microangiopathy-with-diffuse-pseudotubulization-possibly-caused-by-atypical-hemolytic-uremic-syndrome
#5
Masafumi Ono, Naro Ohashi, Akio Namikawa, Naoko Katahashi, Sayaka Ishigaki, Naoko Tsuji, Shinsuke Isobe, Takamasa Iwakura, Yukitoshi Sakao, Takayuki Tsuji, Akihiko Kato, Yoshihide Fujigaki, Akira Shimizu, Hideo Yasuda
A 31-year-old woman was admitted to our hospital for thrombotic microangiopathy (TMA). She was diagnosed with systemic lupus erythematosus (SLE) and class V lupus nephritis. She had no aggravated SLE activity, Shiga toxin positivity, ADAMTS13 abnormality, or other causes of secondary TMA. Plasma exchange partially improved TMA, and eculizumab was introduced for suspected atypical hemolytic uremic syndrome (aHUS), as eculizumab was effective in suppressing the TMA activity. A kidney biopsy revealed diffusely organized crescents (pseudotubulization) with glomerular and arteriolar endothelial injury and subepithelial immune deposits...
February 9, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29429752/patterns-of-clinical-response-to-eculizumab-in-patients-with-c3-glomerulopathy
#6
Moglie Le Quintrec, Anne-Laure Lapeyraque, Arnaud Lionet, Anne-Laure Sellier-Leclerc, Yahsou Delmas, Véronique Baudouin, Eric Daugas, Stéphane Decramer, Leila Tricot, Mathilde Cailliez, Philippe Dubot, Aude Servais, Catherine Mourey-Epron, Franck Pourcine, Chantal Loirat, Véronique Frémeaux-Bacchi, Fadi Fakhouri
BACKGROUND: Cases reports and small series of patients with C3 glomerulopathy have reported variable efficacy of eculizumab. STUDY DESIGN: Case series of C3 glomerulopathy. SETTING & PARTICIPANTS: Pediatric and adult patients with C3 glomerulopathy treated with eculizumab between 2010 and 2016 were identified through the C3 glomerulopathy French registry database, and a questionnaire was sent to participating French pediatric and adult nephrology centers, as well as one pediatric referral center in Québec, Canada...
February 8, 2018: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/29419916/consensus-opinion-on-diagnosis-and-management-of-thrombotic-microangiopathy-in-australia-and-new-zealand
#7
REVIEW
Lucy Fox, Solomon J Cohney, Joshua Y Kausman, Jake Shortt, Peter D Hughes, Erica M Wood, Nicole M Isbel, Theo de Malmanche, Anne Durkan, Pravin Hissaria, Piers Blombery, Thomas D Barbour
Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. Whilst TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal...
February 8, 2018: Nephrology
https://www.readbyqxmd.com/read/29417722/is-there-a-case-for-eculizumab-for-pediatric-renal-transplantation
#8
EDITORIAL
Guido Filler, Christoph Licht, Shih-Han Susan Huang
No abstract text is available yet for this article.
February 7, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29407333/eculizumab-for-prevention-of-antibody-mediated-rejection-in-blood-group-incompatible-renal-transplantation
#9
P West-Thielke, K Progar, M Campara, N Jasiak, L Gallon, I Tang, M Spaggiari, I Tzvetanov, E Benedetti
Antibody-mediated rejection (AMR) is one of the leading causes of allograft failure especially in patients undergoing ABO-incompatible (ABOi) renal transplantation. We hypothesized that complement inhibition with eculizumab, a C5 inhibitor, would protect against AMR and maintain graft function in ABOi renal transplant recipients. Four patients undergoing living donor kidney transplant from ABOi donors were treated with a 9-week eculizumab course without therapeutic plasma exchange, intravenous immunoglobulin, or splenectomy...
January 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29403543/when-myasthenia-gravis-is-deemed-refractory-clinical-signposts-and-treatment-strategies
#10
REVIEW
Renato Mantegazza, Carlo Antozzi
The prognosis for patients with myasthenia gravis (MG) has improved significantly over the past half century, including substantial reductions in mortality and morbidity. However, approximately 10% of patients fails to respond adequately to current therapies and are considered treatment refractory, or treatment intolerant, and up to 80% have disease that fails to achieve complete stable remission. Although patients with autoantibodies to muscle-specific tyrosine kinase (anti-MuSK positive) are more likely to become treatment refractory than those with autoantibodies to the acetylcholine receptor (anti-AChR positive), each of these serotypes is substantially represented in the refractory MG population...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29390523/efficacy-of-eculizumab-in-an-adult-patient-with-hiv-associated-hemolytic-uremic-syndrome-a-case-report
#11
Marine Freist, Cyril Garrouste, Nora Szlavik, Paul Coppo, Alexandre Lautrette, Anne Elisabeth Heng
INTRODUCTION: Hemolytic uremic syndrome (HUS) in Human Immunodeficiency Virus (HIV)-positive patients has become a rare cause of kidney injury since the era of highly active antiretroviral therapy (HAART). Plasma exchange and antiretroviral therapy were previously recommended but often failed to achieve remission. We report a case of HUS in a HIV-positive patient treated successfully with eculizumab. CASE SUMMARY: A 52-year-old woman presented to hospital with acute renal failure, thrombocytopenia, anemia, and hypoxemia...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29383624/effects-of-eculizumab-treatment-on-quality-of-life-in-patients-with-paroxysmal-nocturnal-hemoglobinuria-in-japan
#12
Yasutaka Ueda, Naoshi Obara, Yuji Yonemura, Hideyoshi Noji, Masayoshi Masuko, Yoshinobu Seki, Katsuya Wada, Takahisa Matsuda, Hirozumi Akiyama, Takayuki Ikezoe, Shigeru Chiba, Yoshinobu Kanda, Tatsuya Kawaguchi, Tsutomu Shichishima, Hideki Nakakuma, Shinichiro Okamoto, Jun-Ichi Nishimura, Yuzuru Kanakura, Haruhiko Ninomiya
In paroxysmal nocturnal hemoglobinuria (PNH), various symptoms due to intravascular hemolysis exert a negative impact on patients' quality of life (QOL). To determine clinical factors related with improvements in QOL in PNH patients treated, we analyzed changes in QOL scales in PNH patients treated with eculizumab based on data collected from post-marketing surveillance in Japan. Summary statistics were obtained using figures from QOL scoring systems and laboratory values, and evaluated by t test. One-year administration of eculizumab improved the most QOL items in comparison with the baseline...
January 30, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29377474/a-prospective-randomized-controlled-trial-of-eculizumab-to-prevent-ischemia-reperfusion-injury-in-pediatric-kidney-transplantation
#13
Michael Kaabak, Nadeen Babenko, Ron Shapiro, Allan Zokoyev, Olga Dymova, Edward Kim
Ischemia-reperfusion injury has multiple effects on a transplanted allograft, including delayed or impaired graft function, compromised long-term survival, and an association with an increased incidence of rejection. Eculizumab, a monoclonal antibody blocking terminal complement activation, has been postulated to be an effective agent in the prevention or amelioration of IRI. We performed a single-center prospective, randomized controlled trial involving 57 pediatric kidney transplant recipients between 2012 and 2016...
January 29, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29370420/c3-glomerulonephritis-secondary-to-mutations-in-factors-h-and-i-rapid-recurrence-in-deceased-donor-kidney-transplant-effectively-treated-with-eculizumab
#14
Neetika Garg, Yuzhou Zhang, Anne Nicholson-Weller, Eliyahu V Khankin, Nicolò Ghiringhelli Borsa, Nicole C Meyer, Susan McDermott, Isaac E Stillman, Helmut G Rennke, Richard J Smith, Martha Pavlakis
Background: C3 glomerulonephritis (C3GN) is caused by alternate complement pathway over-activation. It frequently progresses to end-stage renal disease, recurs in two-thirds of transplants and in half of these cases progresses to allograft loss. There is currently no proven treatment for C3GN. Case Presentation: We describe a family segregating pathogenic alleles of complement factor H and I (CFH and CFI). The only member carrying both mutations developed C3GN. Prolonged delayed graft function after deceased donor transplantation, heavy proteinuria and isolated C3 hypocomplementemia prompted an allograft biopsy confirming diagnosis of recurrent C3GN...
January 23, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29363392/evaluation-of-health-related-quality-of-life-in-hemolytic-uraemic-syndrome-patients-treated-with-eculizumab-a-systematic-evaluation-on-basis-of-empro
#15
Anwesha A Mukherjee, Amit D Kandhare, Subhash L Bodhankar
BACKGROUND: Hemolytic uraemic syndrome (HUS) is progressive renal failure disease and determination of their quality of life (QoL) on the basis of patient-reported outcomes (PROs) are becoming increasingly important in the economic evaluations for its treatment with eculizumab (ECU). AIM: To perform the systematic evaluation of QoL in HUS patients treated with ECU on the basis of Evaluating Measures of Patient Reported Outcomes (EMPRO) tool. MATERIALS AND METHODS: A systematic review was conducted in PubMed, EMBASE, the Cochrane Library, CINAHL and Google Scholar till September 2016 by two independent researchers...
November 2018: Renal Failure
https://www.readbyqxmd.com/read/29337452/-neurology
#16
Isabelle Chopard, David Benninger, Jean-François Demonet, Renaud Du Pasquier, Lorenz Hirt, Thierry Kuntzer, Patrik Michel, Bernard Nater, Jan Novy, Andrea Rossetti, Olivier Rouaud, Philippe Ryvlin, Myriam Schluep, Marie Theaudin
Ocrelizumab (Ocrevus), an anti-CD20 monoclonal antibody, has been approved for the treatment of multiple sclerosis. Eculizumab (Soliris) has been approved in several countries for refractory forms of generalized seropositive severe myasthenia gravis. A form of gene therapy, patisiran, has shown positive results in transthyretin familial amyloidosis. In the treatment of headaches, particularly migraines, non-pharmacological approaches have shown some interesting results. The criteria for Lewy body dementia have been revised...
January 10, 2018: Revue Médicale Suisse
https://www.readbyqxmd.com/read/29333418/low-dose-prednisolone-in-patients-with-paroxysmal-nocturnal-hemoglobinuria-and-inadequate-response-to-eculizumab
#17
Ji Young Moon, Deog-Yeon Jo, So Yeon Lee, Deok Yeong Kim, Seung-Woo Baek, Ik-Chan Song
No abstract text is available yet for this article.
December 2017: Blood Research
https://www.readbyqxmd.com/read/29331477/atypical-presentation-of-pregnancy-related-hemolytic-uremic-syndrome
#18
Salim Baghli, Catherine Abendroth, Umar Farooq, Jennifer A Schaub
The cause of acute kidney injury during pregnancy and in the postpartum period can be particularly challenging to diagnose, especially when it is necessary to differentiate among preeclampsia; eclampsia; hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome; and thrombotic microangiopathies (TMAs). All these disease entities can present with kidney failure, microangiopathic hemolytic anemia, and thrombocytopenia. We present a teaching case of atypical hemolytic uremic syndrome in the postpartum period in a young woman who was found to have mutations of uncertain clinical significance in the complement cascade, including in C3, CFH, and CFI...
January 10, 2018: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/29329521/treating-c3-glomerulopathy-with-eculizumab
#19
Thomas Welte, Frederic Arnold, Julia Kappes, Maximilian Seidl, Karsten Häffner, Carsten Bergmann, Gerd Walz, Elke Neumann-Haefelin
BACKGROUND: C3 glomerulopathy (C3G) is a rare, but severe glomerular disease with grim prognosis. The complex pathogenesis is just unfolding, and involves acquired as well as inherited dysregulation of the alternative pathway of the complement cascade. Currently, there is no established therapy. Treatment with the C5 complement inhibitor eculizumab may be a therapeutic option. However, due to rarity of the disease, parameters predicting treatment response remain largely unknown. METHODS: Seven patients with C3G (five with C3 glomerulonephritis and two with dense deposit disease) were treated with eculizumab...
January 12, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29329518/the-use-of-eculizumab-in-gemcitabine-induced-thrombotic-microangiopathy
#20
Vinod Krishnappa, Mohit Gupta, Haikoo Shah, Abhijit Das, Natthavat Tanphaichitr, Robert Novak, Rupesh Raina
BACKGROUND: Thrombotic microangiopathy (TMA) secondary to gemcitabine therapy (GiTMA) is a very rare pathology that carries a poor prognosis, with nearly half of the cases progressing to end stage renal disease. GiTMA is most commonly associated with adenocarcinomas, most notably pancreatic cancers. The mainstay of management is withdrawal of the offending drug and supportive care. Plasmapheresis has a limited role and hemodialysis may help in the management of fluid overload secondary to renal failure...
January 12, 2018: BMC Nephrology
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