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result(s) for
"Pilar-Orive, Francisco Javier"
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Treatments for multi-system inflammatory syndrome in children — discharge, fever, and second-line therapies
2023
Scarce evidence exists about the best treatment for multi-system inflammatory syndrome (MIS-C). We analyzed the effects of steroids, intravenous immunoglobulin (IVIG), and their combination on the probability of discharge over time, the probability of switching to second-line treatment over time, and the persistence of fever 2 days after treatment. We did a retrospective study to investigate the effect of different treatments on children with MIS-C from 1 March 2020 to 1 June 2021. We estimated the time-to-event probability using a Cox model weighted by propensity score to balance the baseline characteristics. Thirty of 132 (22.7%) patients were initially treated with steroids alone, 29/132 (21.9%) with IVIG alone, and 73/132 (55%) with IVIG plus steroids. The probability of early discharge was higher with IVIG than with IVIG plus steroids (hazard ratio [HR] 1.65, 95% CI 1.11–2.45,
p
= 0.013), but with a higher probability of needing second-line therapy compared to IVIG plus steroids (HR 3.05, 95% CI 1.12–8.25,
p
= 0.028). Patients on IVIG had a higher likelihood of persistent fever than patients on steroids (odds ratio [OR] 4.23, 95% CI 1.43–13.5,
p
= 0.011) or on IVIG plus steroids (OR 4.4, 95% CI 2.05–9.82,
p
< 0.001). No differences were found for this endpoint between steroids or steroids plus IVIG.
Conclusions
: The benefits of each approach may vary depending on the outcome assessed. IVIG seemed to increase the probability of earlier discharge over time but also of needing second-line treatment over time. Steroids seemed to reduce persistent fever, and combination therapy reduced the need for escalating treatment.
What is Known:
• Steroids plus intravenous immunoglobulin, compared with intravenous immunoglobulin alone for multi-system inflammatory syndrome (MIS-C) might reduce the need for hemodynamic support and the duration of fever, but the certainty of the evidence is low.
What is New:
• Intravenous immunoglobulin, steroids, and their combination for MIS-C may have different outcomes.
•
In this study, intravenous immunoglobulin increased the probability of discharge over time, steroids reduced persistent fever, while combination therapy reduced the need for second-line treatments.
Journal Article
Proteomics Reveals Differential Diagnosis Biomarkers Between Sepsis and Hemophagocytic Syndrome
by
Redondo, Silvia
,
Astigarraga, Itziar
,
Pilar-Orive, Francisco Javier
in
Bioinformatics
,
Biological markers
,
Biomarkers
2025
Background/Objectives: Hemophagocytic Lymphohistiocytosis (HLH) shares many clinical features with sepsis. To improve HLH diagnosis and its differential diagnosis with sepsis, serum proteomic analyses of healthy donors, HLH and septic patients were performed. Methods: Twenty-four individuals were enrolled in a label-free MS/MS spectrometry analysis. STRING was conducted to study the protein–protein interactions overrepresented within the proteins of each comparison. To integrate the functions of the proteins with their respective regulation patterns, Ingenuity Pathway Analysis software was used. Validation of selected proteins was carried out by ELISA. Results: Proteomic results revealed 537 differentially expressed proteins (DEPs) between HLH and sepsis, 471 DEPs between HLH and healthy donors, and 37 DEPs between sepsis and healthy donors. These results were subjected to functional analysis, which showed that apart from inflammation and lipid metabolism, the proteostasis network was deeply impaired in the HLH condition. Considering this information, protein fold changes and the functions of six proteins were validated by ELISA. Conclusions: sCD300a, sCD300b and sCD25 could be specific serum biomarkers for HLH diagnosis, and SAA-1 and LRG1 might be useful biomarkers for differential diagnosis between sepsis and HLH. PSMB1, a non-catalytic subunit of the 20S proteasome, showed promising results for HLH-specific and differential diagnosis. Its elevation in HLH patients may reflect an intensified demand for protein turnover, possibly driven by a higher activation of the immunoproteasome. These insights contribute to expanding our understanding of HLH pathophysiology regarding new pathways and highlight innovative therapeutic interventions, such as Bortezomib and other next-generation inhibitors, designed to modulate immunoproteasome activity.
Journal Article