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Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2351
Author(s):  
Ji-Soo Kwon ◽  
Sol Jin ◽  
Ji-Yeun Kim ◽  
Sang-Hyun Ra ◽  
Taeeun Kim ◽  
...  

Significant progress has been made on the molecular biology of the severe fever with thrombopenia virus (SFTSV); however, many parts of the pathophysiological mechanisms of mortality in SFTS remain unclear. In this study, we investigated virologic and immunologic factors for fatal outcomes of patients with SFTS. We prospectively enrolled SFTS patients admitted from July 2015 to October 2020. Plasma samples were subjected to SFTSV RNA RT-PCR, multiplex microbead immunoassay for 17 cytokines, and IFA assay. A total of 44 SFTS patients were enrolled, including 37 (84.1%) survivors and 7 (15.9%) non-survivors. Non-survivors had a 2.5 times higher plasma SFTSV load than survivors at admission (p < 0.001), and the viral load in non-survivors increased progressively during hospitalization. In addition, non-survivors did not develop adequate anti-SFTSV IgG, whereas survivors exhibited anti-SFTSV IgG during hospitalization. IFN-α, IL-10, IP-10, IFN-γ, IL-6, IL-8, MCP-1, MIP-1α, and G-CSF were significantly elevated in non-survivors compared to survivors and did not revert to normal ranges during hospitalization (p < 0.05). Severe signs of inflammation such as a high plasma concentration of IFN-α, IL-10, IP-10, IFN-γ, IL-6, IL-8, MCP-1, MIP-1α, and G-CSF, poor viral control, and inadequate antibody response during the disease course were associated with mortality in SFTS patients.


2020 ◽  
Vol 80 ◽  
pp. 52-55 ◽  
Author(s):  
Stéphane Jaisson ◽  
Aurore Desmons ◽  
Antoine Braconnier ◽  
Alain Wynckel ◽  
Philippe Rieu ◽  
...  

2020 ◽  
Author(s):  
Laurent Chouchana ◽  
Sana Boujaafar ◽  
Ines Gana ◽  
Laure-Hélène ◽  
Lucile Regard ◽  
...  

ABSTRACTBackgroundLopinavir/ritonavir has been proposed as off-label treatment for Covid-19, although efficacy have not been proven. It has previously been shown that lopinavir plasma concentration is dramatically increased in inflammatory settings. As Covid-19 may be associated with major inflammation, assessing lopinavir plasma concentration and its safety in Covid-19 patients is essential.MethodsReal-world Covid-19 experience based on a retrospective study.ResultsOf 31 patients treated by lopinavir/ritonavir for Covid-19, we observed very high lopinavir plasma concentrations, increased of 4.6-fold (IQR, 3.6-6.2) with regards to average plasma concentrations in HIV. All except one patient were above the upper limit of the concentration ranges of HIV treatment. About one over four to five patients prematurely stopped treatment mainly secondary an adverse drug reaction related to hepatic or gastrointestinal disorders.ConclusionLopinavir plasma concentrations in patients with moderate to severe Covid-19 were higher than expected, associated with the occurrence of hepatic or gastrointestinal adverse drug reactions. However, owing that high plasma concentration may be required for in vivo antiviral activity against SARS-CoV-2 as suggested by previous studies, it appears that, in the absence of adverse drug reaction, lopinavir dosage should not be reduced. Cautious is necessary as off-label use can be associated with a new drug safety profile.


2020 ◽  
Author(s):  
Maxime Nguyen ◽  
Abderrahmane Bourredjem ◽  
Lionel Piroth ◽  
Bélaïd Bouhemad ◽  
Antoine Jalil ◽  
...  

2017 ◽  
Vol 94 (8) ◽  
pp. 562-564 ◽  
Author(s):  
Caiying Wang ◽  
Shuxin He ◽  
Hongling Yang ◽  
Yuhuan Liu ◽  
Yang Zhao ◽  
...  

ObjectivesThe objective of this retrospective study was to summarise the clinical manifestations of, and to analyse the incidence and risk factors of, Jarisch–Herxheimer reaction (JHR) during the treatment of children with symptomatic congenital syphilis.MethodsClinical data of 60 children with clinically and laboratory diagnosed congenital syphilis, hospitalised in Beijing Ditan Hospital between January 2010 and November 2015, were collected and analysed.ResultsA total of 11 patients with congenital syphilis (11/60, 18.3%) developed JHR. JHR occurred in 1–6 hour after the first dose of penicillin. Common clinical manifestations included fever (11/11, 100%), irritability (11/11, 100%), rapid pulse and breathing (11/11, 100%), exacerbation of existing rash (5/11, 45.6%) and chills (3/11, 27.3%). Of the 11 patients who developed JHR, 9 patients (9/11, 81.8%) had bone syphilis, 10 (10/11, 90.9%) had more than three organs affected by syphilis and 10 (10/11, 90.9%) had a high plasma concentration of rapid plasma reagin (RPR) (≥1:256); these percentages were significantly higher than in patients who had not developed JHR (p<0.05), suggesting that the occurrence of JHR was related to bone syphilis, having more than three organs affected by syphilis and a high plasma concentration of RPR.ConclusionsClinicians should be familiar with the risk factors for this reaction and its common clinical manifestations.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3751-3751
Author(s):  
Masayoshi Masuko ◽  
Tatsuo Furukawa ◽  
Toyoyuki Tanaka ◽  
Syukuko Miyakoshi ◽  
Takashi Kozakai ◽  
...  

Abstract Abstract 3751 Background and Purpose: The introduction of imatinib to the treatment regimen of chronic myeloid leukemia (CML) has markedly changed its outcome. Several reports have shown that the efficacy of imatinib correlates with the trough plasma concentration in CML patients. However, little is known about the correlation between plasma concentration and long-term outcomes, including adverse effects. We analyzed the correlation between long term tolerability and plasma concentration in Japanese patients. Patients: Forty-three patients with chronic phase CML who had good adherence with daily 300mg (n=8) or 400mg (n=35) imatinib administration at hospitals in our study group were enrolled in this study. The median age of patients starting imatinib was 57 years (range 15–82). Imatinib was started between Dec. 2001 and May 2007. Plasma trough concentration was examined on a day between Nov. 2007 and Aug. 2008. Median time from the start of imatinib until the plasma assay was 1548 days (range 91–2390). Results: Clinical data were reviewed in Sep 2011. We excluded patients who had been switched from imatinib to a second tyrosine kinase inhibitor (TKI) despite major molecular response (MMR). Median plasma concentration was 925 ng/ml (range 200–3280). Median follow-up was 2632 days (range 884–3496) and median follow-up after the plasma assay was 1216 days (range 361–1323). We divided the patients into two groups: the low plasma concentration group (<925ng/ml n=22) and high plasma concentration group (>925ng/ml n=21). Overall survival and achievement of complete molecular response (negative by RT-PCR) did not differ between the two groups. We defined all death, progression, switch to a second TKI and imatinib dose reduction as events. Also we defined death by adverse effect, imatinib dose reduction or switch to a second TKI due to adverse effects as intolerance-related events and progression, switch to a second TKI due to failure of achieve MMR or loss of MMR as efficacy-related events. Event-free survival (EFS) showed no difference between the two groups. However cumulative incidence of intolerance-related event was significantly higher in the high plasma concentration group than in the low plasma concentration group (whole observation period, p=0.02 by log-rank test; observation period after the plasma assay, p=0.01 by log-rank test). Grade 3 or 4 anemia occurred in 4 patients only in the high plasma concentration group. Cumulative incidence of efficacy-related event was slightly higher in the low plasma concentration group than the high plasma concentration group (whole observation period, p=0.06 by log-rank test; observation period after the plasma assay p=0.05 by log-rank test). Conclusion: Trough imatinib plasma concentration at steady-state after initiation of therapy has been demonstrated to have correlation with the early efficacy of imatinib. Our findings suggest that imatinib plasma concentration also correlates with intolerance or adverse effect in long-term clinical observation. Although further studies are required to confirm the current data prospectively, imatinib plasma level testing seems to be helpful to optimize clinical outcomes for patients with CML. Disclosures: No relevant conflicts of interest to declare.


2011 ◽  
Vol 57 (6) ◽  
pp. 883-890 ◽  
Author(s):  
Alexander G Semenov ◽  
Karina R Seferian ◽  
Natalia N Tamm ◽  
Marina M Artem'eva ◽  
Alexander B Postnikov ◽  
...  

BACKGROUND The appearance of B-type natriuretic peptide (BNP) in the blood is ultimately caused by proteolytic processing of its precursor, proBNP. The mechanisms leading to the high plasma concentration of unprocessed proBNP are still poorly understood. The goals of the present study were to examine whether processing of proBNP takes place in the circulation and to evaluate the clearance rate of proBNP and proBNP-derived peptides. METHODS We studied the processing of human proBNP in the circulation and the clearance rate of proBNP and proBNP-derived peptides (BNP and N-terminal fragment of proBNP, NT-proBNP) in rats by injecting the corresponding peptides and analyzing immunoreactivity at specific time points. Glycosylated and nonglycosylated proBNP and NT-proBNP were used in the experiments. We applied immunoassays, gel filtration, and mass spectrometry (MS) techniques to analyze the circulation-mediated processing of proBNP. RESULTS ProBNP was effectively processed in the circulation into BNP (1–32) and various truncated BNP forms as confirmed by gel filtration and MS analysis. Glycosylation of proBNP close to the cleavage-site region suppressed its processing in the circulation. The terminal half-life for human glycosylated proBNP was 9.0 (0.5) min compared with 6.4 (0.5) min for BNP. For NT-proBNP, the terminal half-lives were 15.7 (1.4) min and 15.5 (1.3) min for glycosylated and nonglycosylated forms, respectively. CONCLUSIONS In rats, processing of human proBNP to active BNP occurs in the circulation. The clearance rate of proBNP is quite similar to that of BNP. These observations suggest that peripheral proBNP processing may be an important regulatory step rather than mere degradation.


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