scholarly journals Monitoring of Unfractionated Heparin in Severe COVID-19: An Observational Study of Patients on CRRT and ECMO

TH Open ◽  
2020 ◽  
Vol 04 (04) ◽  
pp. e365-e375
Author(s):  
Alexander S. Streng ◽  
Thijs S.R. Delnoij ◽  
Mark M.G. Mulder ◽  
Jan Willem E.M. Sels ◽  
Rick J.H. Wetzels ◽  
...  

Abstract Objective Severe cases of coronavirus disease 2019 (COVID-19) can require continuous renal replacement therapy (CRRT) and/or extracorporeal membrane oxygenation (ECMO). Unfractionated heparin (UFH) to prevent circuit clotting is mandatory but monitoring is complicated by (pseudo)-heparin resistance. In this observational study, we compared two different activated partial thromboplastin time (aPTT) assays and a chromogenic anti-Xa assay in COVID-19 patients on CRRT or ECMO in relation to their UFH dosages and acute phase reactants. Materials and Methods The aPTT (optical [aPTT-CS] and/or mechanical [aPTT-STA] clot detection methods were used), anti-Xa, factor VIII (FVIII), antithrombin III (ATIII), and fibrinogen were measured in 342 samples from 7 COVID-19 patients on CRRT or ECMO during their UFH treatment. Dosage of UFH was primarily based on the aPTT-CS with a heparin therapeutic range (HTR) of 50–80s. Associations between different variables were made using linear regression and Bland–Altman analysis. Results Dosage of UFH was above 35,000IU/24 hours in all patients. aPTT-CS and aPTT-STA were predominantly within the HTR. Anti-Xa was predominantly above the HTR (0.3–0.7 IU/mL) and ATIII concentration was >70% for all patients; mean FVIII and fibrinogen were 606% and 7.5 g/L, respectively. aPTT-CS correlated with aPTT-STA (r 2 = 0.68) with a bias of 39.3%. Correlation between aPTT and anti-Xa was better for aPTT-CS (0.78 ≤ r 2 ≤ 0.94) than for aPTT-STA (0.34 ≤ r 2 ≤ 0.81). There was no general correlation between the aPTT-CS and ATIII, FVIII, fibrinogen, thrombocytes, C-reactive protein, or ferritin. Conclusion All included COVID-19 patients on CRRT or ECMO conformed to the definition of heparin resistance. A patient-specific association was found between aPTT and anti-Xa. This association could not be explained by FVIII or fibrinogen.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1790.2-1790
Author(s):  
R. M. Alcobendas ◽  
C. Quintana ◽  
J. Arostegui ◽  
C. Udaondo ◽  
S. Murias Loza ◽  
...  

Background:Few patients have been described in the literature with mutations in the Lacasa Domain containing one (LACC1) gene. Its clinical presentation usually associates sustained systemic inflammation associated with chronic polyarticular erosive arthritis. Until now, there have been multiple treatments described to try to control the disease, however, they are generally unsuccessful in the long term.Objectives:Describe the clinical course of a patient as well as the different treatments usedMethods:Clinical chart reviewResults:Female 18-year-old born from a consanguineous Moroccan couple. Mother, brother and sister with similar conditions. She started at 3 years with fever, anemia, intense elevation of acute phase reactants and symmetric polyarthritis (knees, elbows, carps, shoulders, hands and ankles). Subsequent whole exome sequencing identified c.128_129delGT mutation in the LACC1/FAMIN gene. During the course of her illness, she has received treatment with oral, intravenous and infiltrated corticosteroid, methotrexate and etanercept, without getting adequate control of the disease. In 2016, she started treatment with tocilizumab (8 mg / kg every two weeks), obtaining an acceptable control of the disease (requiring periodic infiltrations every 2-3 months due to persistent arthritis). Nonetheless, in April 2019, she consulted for clinical worsening of the arthritis and laboratory test (C reactive protein 99.7 mg / L, erythrosedimentation rate 53 mm / h, leukocytes 13,500/µL and neutrophils 10,930/µL). At that time, she discontinued therapy with tocilizumab and started tofacitinib 5 mg every 12 hours with good evolution. Since its introduction, it has not required joint infiltration again and the inflammatory parameters (persistently elevated previously) have normalized.Conclusion:The jak kinasa inhibitors may be a treatment option in those patients with bad response to conventional therapy.References:[1]Rabionet R, Remesal A, Mensa-Vilaró A, Murías S, Alcobendas R, González-Roca E, Ruiz-Ortiz E, Antón J, Iglesias E, Modesto C, Comas D, Puig A, Drechsel O, Ossowski S, Yagüe J, Merino R, Estivill X, Arostegui JI. Biallelic loss-of-function LACC1/FAMIN Mutations Presenting as Rheumatoid Factor-Negative Polyarticular Juvenile Idiopathic Arthritis. Sci Rep. 2019 Mar 14;9(1):4579Disclosure of Interests:None declared


Author(s):  
Rohit S Loomba ◽  
Enrique G Villarreal ◽  
Juan S Farias ◽  
Gaurav Aggarwal ◽  
Saurabh Aggarwal ◽  
...  

Background There is limited information regarding the role of biomarker levels at predicting mortality in patients with the novel coronavirus pandemic (Covid-19). The purpose of this study is to determine the differences in serum biomarker levels in adults with Covid-19 who survived hospitalization from those who did not. Methods A comprehensive search was completed on PubMed, EMBASE, and Cochrane libraries to identify studies of interest. Endpoints of interest were blood counts, hepatic function test, acute phase reactants, cytokines and cardiac biomarkers. Results A total of 10 studies with 1,584 patients were included in the pooled analyses. Biomarkers that were noted to be significantly higher in those who died from Covid-19 (coronavirus disease 2019) included: white blood cell count, neutrophil count, C-reactive protein, high sensitivity C-reactive protein, procalcitonin, ferritin, D-dimer, interleukins 6, lactate dehydrogenase, creatine kinase, prothrombin time, aspartate aminotransferase, alanine aminotransferase, total bilirubin, and creatinine. Lymphocyte count, platelet count, and albumin were significantly lower in patients who died. Conclusion This pooled analysis of 10 studies including 1,584 patients identified significant differences in biomarkers on admission in patients who survived from those who did not. Further research is needed to develop risk stratification models to help with judicious use of limited healthcare resources.


Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1862-1872 ◽  
Author(s):  
M Introna ◽  
VV Alles ◽  
M Castellano ◽  
G Picardi ◽  
L De Gioia ◽  
...  

Abstract Pentraxins, which include C reactive protein (CRP) and serum amyloid P component (SAP), are prototypic acute phase reactants that serve as indicators of inflammatory reactions. Here we report genomic and cDNA cloning of mouse ptx3 (mptx3), a member of the pentraxin gene family and characterize its extrahepatic expression in vitro and in vivo. mptx3 is organized into three exons on chromosome 3: the first (43 aa) and second exon (175 aa) code for the signal peptide and for a protein portion with no high similarity to known sequences the third (203 aa) for a domain related to classical pentraxins, which contains the “pentraxin family signature.” Analysis of the N terminal portion predicts a predominantly alpha helical structure, while the pentraxin domain of ptx3 is accommodated comfortably in the tertiary structure fold of SAP. Normal and transformed fibroblasts, undifferentiated and differentiated myoblasts, normal endothelial cells, and mononuclear phagocytes express mptx3 mRNA and release the protein in vitro on exposure to interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF)alpha. mptx3 was induced by bacterial lipopolysaccharide in vivo in a variety of organs and, most strongly, in the vascular endothelium of skeletal muscle and heart. Thus, mptx3 shows a distinct pattern of in vivo expression indicative of a significant role in cardiovascular and inflammatory pathology.


Buildings ◽  
2018 ◽  
Vol 8 (8) ◽  
pp. 94 ◽  
Author(s):  
Clotilde Pierson ◽  
Jan Wienold ◽  
Magali Bodart

Nowadays, discomfort glare indices are frequently calculated by using evalglare. Due to the lack of knowledge on the implications of the methods and parameters of evalglare, the default settings are often used. But wrong parameter settings can lead to inappropriate glare source detection and therefore to invalid glare indices calculations and erroneous glare classifications. For that reason, this study aims to assess the influence of several glare source detection methods and parameters on the accuracy of discomfort glare prediction for daylight. This analysis uses two datasets, representative of the two types of discomfort glare: saturation and contrast glare. By computing three different statistical indicators to describe the accuracy of discomfort glare prediction, 63 different settings are compared. The results suggest that the choice of an evalglare method should be done when considering the type of glare that is most likely to occur in the visual scene: the task area method should be preferred for contrast glare scenes, and the threshold method for saturation glare scenes. The parameters that should be favored or avoided are also discussed, although a deeper understanding of the discomfort glare mechanism and a clear definition of a glare source would be necessary to reliably interpret these results.


2011 ◽  
Vol 3 (3) ◽  
pp. 361-374
Author(s):  
Marcos Livato ◽  
Gideon Carvalho de Benedicto

The new "molds" of competitiveness have suggested that the attentions should be focused on an efficient management of the supply chain in the supermarket departments, starting from the producer until the end user of the products, reducing the operational costs. It's known that the elimination of some of these stages of intermediation of the ways of distribution can represent to the small and mediums retailers an important competitive advantage, with the elimination of the additional costs charged by the intermediaries. The objective of this work is to propose a model of restructuring  of the ways of distribution in the brazilian retail of  food through of the strategy, inducing the elimination of the intermediaries. The search of the bibliography was used like basement to the definition of the methodology of this search, that was realized through of an observational study realized with nineteen Central Business Supermarket s in the state of São Paulo. To do the collection of the datas was prepared a questionary with specific questions. After the collection of the datas and tab, were used techniques quantitive  of analysis of datas through of SAS system. The study intends to discuss the proposal of the cooperation's networks like a strategic alternative, with the possibility of elimination of some phases of intermediation of the distribuition's ways.


2021 ◽  
Vol 12 ◽  
Author(s):  
Pedro Rosa-Guerrero ◽  
Antonio Trujillo-Aguilera ◽  
Juan Molina ◽  
Ana Navas ◽  
Cristina López-Martín ◽  
...  

The impact of Covid-19 pneumonia caused by SARS-CoV-2 on transplanted populations under chronic immunosuppression seems to be greater than in normal population. Clinical management of the disease, particularly in those patients worsening after a cytokine storm, with or without allograft impairment and using available therapeutic approaches in the absence of specific drugs to fight against the virus, involves a major challenge for physicians. We herein provide evidence of the usefulness of high-dose intravenous immunoglobulin (IVIG) combined with steroid pulses to successfully treat a case of Covid-19 pneumonia in a single-kidney transplanted patient with mechanical ventilation and hemodialysis requirements in the setting of a cytokine storm. A rapid decrease in the serum level of inflammatory cytokines, particularly IL-6, IL-8, TNF-α, MCP-1 and IL-10, as well as of acute-phase reactants such as ferritin, D-dimer and C-reactive protein was observed after the IVIG infusion and methylprednisolone bolus administration with a parallel clinical improvement and progressive allograft function recovery, allowing the patient’s final discharge 40 days after the treatment onset. The immunomodulatory effect of IVIG together with the anti-inflammatory and immunosuppressive potential of steroids could be an alternative strategy to treat severe cases of Covid-19 pneumonia associated with an uncontrolled inflammatory response in transplanted populations.


2020 ◽  
Author(s):  
Gabriela Balderrama-Gutierrez ◽  
Ana Milovic ◽  
Vanessa J. Cook ◽  
M. Nurul Islam ◽  
Youwen Zhang ◽  
...  

ABSTRACTAnimals that are competent natural reservoirs of zoonotic diseases commonly suffer little morbidity from the pathogens they persistently harbor. The mechanisms of this infection tolerance and the trade-off costs are poorly understood. We used exposure to a single dose of lipopolysaccharide (LPS) endotoxin as an experimental model of inflammation to compare the responses of the cricentine rodent Peromyscus leucopus, the white-footed deermouse, to that of Mus musculus, the standard laboratory model for pathogenesis studies. Four hours after injection with either LPS or saline, blood and spleen and liver tissues were collected postmortem and subjected to RNA-seq, untargeted metabolomics, and specific RT-qPCR. This was followed by analysis of differential expression at the gene, pathway, and empirical network levels. The deermice showed the same signs of sickness as the mice with LPS exposure, and in addition demonstrated comparable increases in levels of corticosterone and expression of interleukin (IL)-6, tumor necrosis factor, IL-1β, and acute phase reactants, including C-reactive protein. But whereas the M. musculus response to LPS was best-characterized by network analysis as cytokine-associated, the P. leucopus response was dominated by pathway terms associated with neutrophil activity. Dichotomies between the species in expression profiles of arginase 1 and nitric oxide synthase 2, as well as the ratios of IL-10 to IL-12, were consistent with a type M1 polarized macrophage response in the mice and a type M2 or alternatively-activated response in the deermice. Analysis of metabolites in the plasma and RNA in the tissues revealed differences between the two species in tryptophan metabolism during response to LPS. Two up-regulated genes in particular signified the difference between the species: Slpi (secretory leukocyte proteinase inhibitor) and Ibsp (integrin-binding protein sialoprotein). The latter was previously unrecognized in the context of inflammation or infection. Key RNA-seq findings in P. leucopus were replicated in a second LPS experiment with older animals, in a systemic bacterial infection model, and with cultivated fibroblasts. Taken together, the results indicate that the deermouse possesses several adaptive traits to moderate effects of inflammation and oxidative stress ensuing from infection. This seems to be at the cost of infection persistence and that is to the benefit of the pathogen.


2018 ◽  
Vol 25 (4) ◽  
pp. 895-906 ◽  
Author(s):  
F. Leaman ◽  
C. Niedringhaus ◽  
S. Hinderer ◽  
K. Nienhaus

In account of its abilities to follow the damage progression, also at early stages, the acoustic emission (AE) analysis has become an attractive technique for machine condition monitoring. An AE analysis involves the detection of transients within the signals, which are called AE bursts. Traditional methods for AE burst detection are based on the definition of threshold values. When the machine under analysis works under variable operating conditions, threshold-based methods could lead to poor results due to the influence of these conditions on the AE generation. The present work compares the ability of three AE burst detection methods in a planetary gearbox working under different rotational speeds and loads. The results showed that performance could be significantly improved by using factors of the root mean square value as threshold values instead of fixed values. Among the evaluated methods, the method that includes demodulation and differentiation as a signal processing technique had the best performance overall.


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