Research priorities for therapeutic plasma exchange in critically ill patients

Intensive Care Medicine Experimental, Journal Year: 2023, Volume and Issue: 11(1)

Published: May 7, 2023

Therapeutic plasma exchange (TPE) is a therapeutic intervention that separates from blood cells to remove pathological factors or replenish deficient factors. The use of TPE increasing over the last decades. However, despite good theoretical rationale and biological plausibility for as therapy numerous diseases syndromes associated with critical illness, in intensive care unit (ICU) setting has not been studied extensively. A group eighteen experts around globe different clinical backgrounds used modified Delphi method phrase key research questions related "TPE critically ill patient". These focused on: (1) pathophysiological role removal replacement process, (2) optimal timing treatment, (3) dosing treatment regimes, (4) risk-benefit assumptions (5) novel indications need exploration. For all five topics, current understanding well gaps knowledge future directions were assessed. content should stimulate field applications.

Language: Английский

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Whole transcriptome profiling of placental pathobiology in SARS‐CoV‐2 pregnancies identifies placental dysfunction signatures

Clinical & Translational Immunology, Journal Year: 2024, Volume and Issue: 13(2)

Published: Jan. 1, 2024

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus infection in pregnancy is associated with higher incidence of placental dysfunction, referred to by a few studies as 'preeclampsia-like syndrome'. However, the mechanisms underpinning SARS-CoV-2-induced malfunction are still unclear. Here, we investigated whether transcriptional architecture placenta altered response SARS-CoV-2 infection.

Language: Английский

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Pregnancy-specific responses to COVID-19 revealed by high-throughput proteomics of human plasma

Communications Medicine, Journal Year: 2023, Volume and Issue: 3(1)

Published: April 4, 2023

Pregnant women are at greater risk of adverse outcomes, including mortality, as well obstetrical complications resulting from COVID-19. However, pregnancy-specific changes that underlie such worsened outcomes remain unclear.Plasma samples were collected pregnant and non-pregnant individuals (male female) with (n = 72 pregnant, 52 non-pregnant) without 29 41 COVID-19 patients grouped asymptomatic, mild, moderate, severe, or critically ill according to NIH classifications. Proteomic profiling 7,288 analytes corresponding 6,596 unique protein targets was performed using the SOMAmer platform.Herein, we profile plasma proteome controls show alterations display a dose-response relationship disease severity; yet, proteomic perturbations dampened during pregnancy. In both state, response induced by shows enrichment mediators implicated in cytokine storm, endothelial dysfunction, angiogenesis. Shared identified: tailored may protect conceptus heightened inflammation, while stronger repel infection. Furthermore, can accurately identify patients, even when asymptomatic mild symptoms.This study represents most comprehensive characterization patients. Our findings emphasize distinct immune modulation between states, providing insight into pathogenesis potential explanation for more severe observed women.Pregnant increased experiencing compared general population. reasons this still unclear. We measured proteins present blood these healthy individuals. found some COVID-19-associated lower levels women, which could help fetus harmful body’s natural While affected shared others distinctly only group.

Language: Английский

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The placental transcriptomic profile determined by maternal COVID-19 disease encompasses alterations reminiscent of preeclampsia

Placenta, Journal Year: 2025, Volume and Issue: 165, P. 127 - 135

Published: Feb. 28, 2025

Language: Английский

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Single-nucleus transcriptional profiling of the placenta reveals the syncytiotrophoblast stress response to COVID-19

American Journal of Obstetrics and Gynecology, Journal Year: 2025, Volume and Issue: 232(4), P. S160 - S175.e7

Published: April 1, 2025

COVID-19 in pregnancy is associated with placental immune activation, inflammation, and vascular malperfusion, but its impact on syncytiotrophoblast biology function unclear. This study aimed to determine the effects of maternal syncytiotrophoblasts using single-nucleus transcriptional profiling compare stress responses preeclampsia. For characterization syncytiotrophoblasts, we used RNA sequencing platform, single-cell combinatorial indexing (sci-RNA-seq3), profile villi fetal membranes from unvaccinated patients symptomatic at birth (n = 4), gestational age-matched controls a case critical second trimester delivery term 1). Clustering nuclei differential gene expression analysis was performed Seurat. Gene ontology conducted Enrichr. High-confidence target identify key transcription factor nodes governing response SARS-CoV-2 infection. Bioinformatic approaches were further dataset published preeclampsia signatures. Tissue analysis, including immunofluorescence, validate data histology for an expanded cohort placentas: 6), asymptomatic 3), 5), severe features 7). The analyzed comprised 15 cell clusters 47,889 nuclei. We identified 3 representing fusing mature overlapping distinct COVID-19. analyses indicated that following alterations syncytiotrophoblasts: (1) endoplasmic reticulum activation signaling pathways, unfolded protein integrated response; (2) regulation by CCAAT/enhancer-binding beta (CEBPB), master lineage; (3) upregulation preeclampsia-associated genes. Using complementary methods, confirmed increased levels proteins (eg, BiP, G3BP1) (spliced XBP1 mRNA), CEBPB (phosphorylation) Increased cytotrophoblast proliferation (Ki-67) also detected COVID-19, consistent trophoblast injury. Markers demonstrated similarities phenotype Maternal lineage factor, CEBPB. Similarities between provide insights into their clinical association.

Language: Английский

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Endothelial damage and complement dysregulation in fetuses from pregnancies complicated by preeclampsia

Acta Obstetricia Et Gynecologica Scandinavica, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Abstract Introduction Our objective was to evaluate the endothelial function profile and complement system in fetuses from preeclamptic pregnancies using ex vivo vitro approaches. Material Methods A total of 66 singleton were prospectively recruited comprising 34 cases preeclampsia 32 normotensive matched for baseline characteristics. In approach, soluble tumor necrosis factor‐a receptor 1 (sTNFR1), vascular cell adhesion molecule‐1 (sVCAM‐1), intercellular (sICAM‐1), Von Willebrand factor (sVWF), terminal complex (sC5b‐9), Factor H, component C3a Bb analyzed fetal cord blood samples. model, (VCAM‐1), (ICAM‐1), (VWF), cadherin (VE‐Cadherin), nitric oxide synthase (eNOS), reactive oxygen species (ROS) C5b‐9 deposits evaluated on cells culture exposed sera or plasma. Results Increased sVCAM‐1, sICAM‐ l decreased H concentrations detected as compared mothers (509.4 ± 28 vs. 378.4 34.3 ng/mL, 161.1 11.9 114.8 6.8, 199.6 18.3 267.1 15.4 ng/mL 6.6 0.7 10.3 1.4 μg/mL respectively, p < 0.05) with similar results sTNFR1, sVWF, sC5b‐9 C3a. Endothelial showed incremented expression VCAM‐1(38.1 1.4% 28.3 1.6%, 0.01), ICAM‐1 (12 0.9% 8.6 0.6%, 0.05), VWF (43.5 2.9% 3.7 0.3%, ROS (5 × 10 13 12 3.5 , 0.01) VE‐Cadherin eNOS those control fetuses. While between study groups (851.4 177.5 751.4 132.81 > significantly less induced by plasma (fold change 0.08 0.02 0.48 0.13, 0.01). Conclusions High levels molecules oxidative stress products suggest damage reduced deposition indicates dysregulation More research is necessary impact health innate immunity.

Language: Английский

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Maternal Serum Heparan Sulfate in Preeclampsia Pathophysiology: Insights from a Systematic Review and Meta-Analysis.

Placenta, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

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Functional consequences of SARS-CoV-2 infection in pregnant women, fetoplacental unit, and neonate

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2022, Volume and Issue: 1869(1), P. 166582 - 166582

Published: Oct. 20, 2022

Language: Английский

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The sFlt-1/PlGF Ratio in Pregnant Patients Affected by COVID-19

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(3), P. 1059 - 1059

Published: Jan. 29, 2023

COVID-19 in pregnant women increases the risk of adverse pregnancy outcomes, including preeclampsia. This meta-analysis aimed to examine effect SARS-CoV-2 infection on sFlt-1/PIGF ratio during pregnancy. The study was designed as a systematic review and meta-analysis. PubMed, Web Science, Embase Cochrane Library were searched for relevant studies reporting sFlt-1/PlGF with COVID-19. Results compared using by Mantel-Haenszel method. A total 7 included analysis. ratios between positive vs. negative 45.8 ± 50.3 37.4 22.5, respectively (SMD = 1.76; 95% CI: 0.43 3.09; p 0.01). asymptomatic symptomatic patients 49.3 35.7 37.1 25.6 0.30; -0.35 0.95; 0.36). non-severe group 30.7 56.5, 64.7 53.5 severe -1.88; -3.77 0.01; 0.05). patients, without hypertensive disease pregnancy, 187.0 121.8 21.6 8.6, 2.46; 0.99 3.93; 0.001). Conclusions: Patients COVID-19, characterized higher ratio. Moreover, related significantly

Language: Английский

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Endothelial activation and damage as a common pathological substrate in different pathologies and cell therapy complications

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: Nov. 14, 2023

The endothelium is a biologically active interface with multiple functions, some of them common throughout the vascular tree, and others that depend on its anatomical location. Endothelial cells are continually exposed to cellular humoral factors, all those elements (biological, chemical, or hemodynamic) circulate in blood at certain time. It can adapt different stimuli but this capability may be lost if strong enough and/or persistent If loses adaptability it become dysfunctional, becoming potential real danger host. dysfunction present clinical conditions, such as chronic kidney disease, obesity, major depression, pregnancy-related complications, septic syndromes, COVID-19, thrombotic microangiopathies, among other pathologies, also association cell therapies, hematopoietic stem transplantation treatment chimeric antigen receptor T cells. In these diverse evidence suggests presence severity endothelial correlate associated disease. More importantly, has diagnostic prognostic value for development critical complications that, although differ according underlying have background common. Our multidisciplinary team women devoted many years exploring role mentioned diseases conditions. research group characterized mechanisms proposed biomarkers damage. A better knowledge would provide therapeutic strategies either prevent treat dysfunction.

Language: Английский

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