Steady-State Therapy with Azithromycin or Low-Dose Prednisolone in Paediatric Cystic Fibrosis Patients: Inflammatory Markers and Disease Progression

2017 ◽  
Vol 172 (1) ◽  
pp. 45-54 ◽  
Author(s):  
Galina Shmarina ◽  
Alexander Pukhalsky ◽  
Lucine Avakian ◽  
Sergey Semykin ◽  
Daria Pukhalskaya ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Steady State ◽  
Disease Progression ◽  
Inflammatory Markers ◽  
Low Dose

scholarly journals Age and Infectious Dose Significantly Affect Disease Progression after RHDV2 Infection in Naïve Domestic Rabbits

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1184
Author(s):  
Robyn N. Hall ◽  
Tegan King ◽  
Tiffany O’Connor ◽  
Andrew J. Read ◽  
Jane Arrow ◽  
...  
Keyword(s):  
New Zealand ◽  
Disease Progression ◽  
Case Fatality Rate ◽  
Low Dose ◽  
Case Fatality ◽  
Wild Rabbit ◽  
Fatality Rate ◽  
Infectious Dose ◽  
Welfare Impacts ◽  
Rabbit Haemorrhagic Disease

Rabbit haemorrhagic disease virus 2 (RHDV2 or GI.2, referring to any virus with lagovirus GI.2 structural genes) is a recently emerged calicivirus that causes generalised hepatic necrosis and disseminated intravascular coagulation leading to death in susceptible lagomorphs (rabbits and hares). Previous studies investigating the virulence of RHDV2 have reported conflicting results, with case fatality rates ranging from 0% to 100% even within a single study. Lagoviruses are of particular importance in Australia and New Zealand where they are used as biocontrol agents to manage wild rabbit populations, which threaten over 300 native species and result in economic impacts in excess of $200 million AUD annually to Australian agricultural industries. It is critically important that any pest control method is both highly effective (i.e., virulent, in the context of viral biocontrols) and has minimal animal welfare impacts. To determine whether RHDV2 might be a suitable candidate biocontrol agent, we investigated the virulence and disease progression of a naturally occurring Australian recombinant RHDV2 in both 5-week-old and 11-week-old New Zealand White laboratory rabbits after either high or low dose oral infection. Objective measures of disease progression were recorded through continuous body temperature monitoring collars, continuous activity monitors, and twice daily observations. We observed a 100% case fatality rate in both infected kittens and adult rabbits after either high dose or low dose infection. Clinical signs of disease, such as pyrexia, weight loss, and reduced activity, were evident in the late stages of infection. Clinical disease, i.e., welfare impacts, were limited to the period after the onset of pyrexia, lasting on average 12 h and increasing in severity as disease progressed. These findings confirm the high virulence of this RHDV2 variant in naïve rabbits. While age and infectious dose significantly affected disease progression, the case fatality rate was consistently 100% under all conditions tested.

scholarly journals 213 Study evaluating the effect of weekends on activity and inflammatory markers in adult patients with cystic fibrosis

2012 ◽  
Vol 11 ◽  
pp. S111
Author(s):  
C. O'Connor ◽  
C. Reilly ◽  
S. Kelly ◽  
A. Leeney ◽  
C. O'Farrell ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Inflammatory Markers ◽  
Adult Patients

Shunt resistance and ion permeabilities in normal and cystic fibrosis airway epithelia

1989 ◽  
Vol 256 (5) ◽  
pp. C1054-C1063 ◽  
Author(s):  
N. J. Willumsen ◽  
R. C. Boucher
Keyword(s):  
Cystic Fibrosis ◽  
Steady State ◽  
Apical Membrane ◽  
Short Circuit ◽  
Strongly Correlated ◽  
Shunt Resistance ◽  
Human Nasal Epithelium ◽  
Cystic Fibrosis Airway ◽  
Intracellular Ion Activities ◽  
Ion Activities

A method for determination of shunt resistance (Rs) and absolute conductive ion permeabilities of the apical membrane in epithelia from steady-state data is described. The method assumes that the currents are satisfactorily described by the Goldman-Hodgkin-Katz regime. Its application requires measurements of standard transepithelial electrophysiological parameters and of one or more intracellular ion activities. It is applicable under both open- and short-circuit conditions. The method was tested in an electrophysiological analysis of cultured normal and cystic fibrosis (CF) human nasal epithelium. In 15 normal and 10 CF preparations with mean transepithelial resistances of 338 and 427 omega.cm2, Rs was 412 and 623 omega.cm2, respectively. The Rs values determined with the present method were strongly correlated (r = 0.94) with those obtained with another method available in the electrophysiological literature but were as a mean 20% lower. Amiloride increased Rs by 25% in CF and by 8% in normal preparations. In normal preparations, the apical Cl permeability (PCla) was 3.6 x 10(-6) cm/s, and the apical Na permeability (PNaa) was 1.6 x 10(-6) cm/s. In CF preparations, PCla was reduced to a maximum of 2.3 x 10(-7) cm/s, whereas PNaa was increased to 6.2 x 10(-6) cm/s. The apical membrane electromotive force was -1 mV in normal and 43 mV in CF preparations. It is concluded that the method can be used to calculate Rs, apical membrane ion permeabilities, and electromotive forces from steady-state electrophysiological data.

scholarly journals High CD169 Monocyte/Lymphocyte Ratio Reflects the Immunophenotyping Disruption and Predicts Oxygen Need in COVID-19 Patients

2021 ◽  
Author(s):  
Antonella Minutolo ◽  
Vita Petrone ◽  
Marialaura Fanelli ◽  
Marco Iannetta ◽  
Martina Giudice ◽  
...  
Keyword(s):  
Disease Progression ◽  
Inflammatory Markers ◽  
Predictive Marker ◽  
Pulmonary Involvement ◽  
Mrna Levels ◽  
Healthy Donors ◽  
Respiratory Outcome ◽  
Early Biomarker

Background: CD169 has been found overexpressed in the blood of COVID-19 patients and identified as a biomarker in the early disease. We have analysed CD169 in blood cells of COVID-19 patients to assess its role as predictive marker of the disease. Methods : The ratio of the CD169 Median median Fluorescence fluorescence Intensity intensity of CD169 between monocytes and lymphocytes (CD169 RMFI ) was analysed by flow cytometry in blood samples of COVID-19 patients (COV) and healthy donors (HD ) and correlated with immunophenotyping, inflammatory markers, cytokines mRNA expression, pulmonary involvement and disease progression. Results: CD169 RMFI increased in COV but not in HD. CD169 RMFI correlated with T-cell differentiation and exhaustion markers as well as with B cells maturation and differentiation. In vitro stimulation of PBMCs of HD with SARS-CoV-2 Spike spike protein induced CD169 RMFI together with IL-6 and IL-10 gene expression. Likewise, CD169 RMFI correlated with blood cytokine mRNA levels, inflammatory markers, and pneumonia severity in patients which that had not received any treatment at sampling. Notably, in untreated patients, CD169 RMFI reflected the respiratory outcome during hospitalization. Conclusion : Considering the immunological role of CD169 and its involvement during the infection and the progression of COVID-19, it could be considered as an early biomarker to evaluate disease progression and clinical outcome.

scholarly journals The alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Rafael Bayarri-Olmos ◽  
Laust Bruun Johnsen ◽  
Manja Idorn ◽  
Line S Reinert ◽  
Anne Rosbjerg ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
United Kingdom ◽  
Disease Progression ◽  
Low Dose ◽  
Transmission Rate ◽  
Functional Characterization ◽  
Fitness Advantage ◽  
The United Kingdom ◽  
A Minor

The alpha/B.1.1.7 SARS-CoV-2 lineage emerged in autumn 2020 in the United Kingdom and transmitted rapidly until winter 2021 when it was responsible for most new COVID-19 cases in many European countries. The incidence domination was likely due to a fitness advantage that could be driven by the RBD residue change (N501Y), which also emerged independently in other Variants of Concern such as the beta/B.1.351 and gamma/P.1 strains. Here we present a functional characterization of the alpha/B.1.1.7 variant and show an eight-fold affinity increase towards human ACE-2. In accordance with this, transgenic hACE-2 mice showed a faster disease progression and severity after infection with a low dose of B.1.1.7, compared to an early 2020 SARS-CoV-2 isolate. When challenged with sera from convalescent individuals or anti-RBD monoclonal antibodies, the N501Y variant showed a minor, but significant elevated evasion potential of ACE-2/RBD antibody neutralization. The data suggest that the single asparagine to tyrosine substitution remarkable rise in affinity may be responsible for the higher transmission rate and severity of the B.1.1.7 variant.

scholarly journals Racial/ethnic Disparities on Inflammation and Response to Methylprednisolone in Severe Covid-19 Pneumonia

2021 ◽  
Author(s):  
Ronaldo C. Go ◽  
Themba Nyirenda ◽  
Maryam Bojarian ◽  
Davood Karimi Hosseini ◽  
Kevin Kim ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Asian Indians ◽  
Low Dose ◽  
Ethnic Disparities ◽  
Prolonged Survival ◽  
High Dose ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
High Dose Methylprednisolone ◽  
Racial Ethnic

Abstract BACKGROUNDRacial/Ethnic minorities are at higher risk for Severe COVID-19. This may be related to social determinants that lead to chronic inflammatory states. The aims of the study were to determine if there are racial/ethnic differences between the inflammatory markers of survivors and non-survivors and if there was a dose dependent association of methylprednisolone to in hospital survival. METHODSThis was a secondary analysis of a retrospective cohort. Patients were older than 18 years of age and admitted for severe COVID-19 Pneumonia Between March to June 2020 in 13 Hospitals in New Jersey, United States. Comparison of inflammatory markers used Kruskal-Wallis followed by pairwise comparison using two-sided Wilcoxon rank sum test. A Youden Index Method was used to determine the cut-off between low dose and high dose methylprednisolone. For each racial/ethnic group, cox regression was used to determine the association to survival between no methylprednisolone and methylprednisolone (high dose versus low dose). RESULTSPropensity matched sample (n=759) between no methylprednisolone (n=380) and methylprednisolone (n=379) had 338 Whites, 102 Blacks, 61 Asian/Indians, and 251 Non-Black Non-White Hispanics. Interleukin-6, C-reactive protein, ferritin, and d-dimer values were higher in non-survivors compared to survivors except in Asian/Indian survivors who had higher ferritin values compared to non-survivors (median: 1,265 vs 418 ug/L, P=0.0211). Black and Hispanic survivors had persistently elevated C-reactive protein, (10.2 mg/mL) and (13.70 mg/mL) respectively. Low dose methylprednisolone was associated with prolonged 60 days in hospital survival over no methylprednisolone in Whites (P<0.0001), Asian/Indians (P=0.0180), and Hispanics (P=0.0004). Regardless of dose, methylprednisolone was not associated with prolonged survival in Blacks. High dose methylprednisolone was associated with worse survival in Hispanics. (P=0.0181). CONCLUSIONRacial/Ethnic disparities with inflammatory markers in survivors and non-survivors preclude the use of one marker as predictor of survival. Low dose methylprednisolone is associated with prolonged survival in Asian/Indians, Hispanics, and Whites. Methylprednisolone, regardless of dose, was not associated with prolonged survival in Blacks.

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