Compartmentalisation of immune responses in critical illness: does it matter?
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ABSTRACT:
SUBMITTER: Conway Morris A
PROVIDER: S-EPMC9436168 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
Publications
Compartmentalisation of immune responses in critical illness: does it matter?
Conway Morris Andrew A Rynne Jennifer J Shankar-Hari Manu M
Intensive care medicine 20220901 11
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2016-07-01 | E-GEOD-64346 | biostudies-arrayexpress
Project description:To investigate the nasal transcriptional response and peripheral plasmablast response in acute influenza infection
2016-07-01 | GSE64346 | GEO
Project description:This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2022. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2022 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .
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| S-EPMC7390458 | biostudies-literature
Project description:BackgroundICU survivors suffer from impaired physical function and reduced exercise capacity, yet the underlying mechanisms are poorly understood. The goal of this exploratory pilot study was to investigate potential mechanisms of exercise limitation using cardiopulmonary exercise testing (CPET) and 6-min walk testing (6MWT).MethodsWe enrolled adults aged 18 years or older who were treated for respiratory failure or shock in medical, surgical, or trauma ICUs at Vanderbilt University Medical Center (Nashville, TN, United States). We excluded patients with pre-existing cardiac dysfunction, a contraindication to CPET, or the need for supplemental oxygen at rest. We performed CPET and 6MWT 6 months after ICU discharge. We measured standard CPET parameters in addition to two measures of oxygen utilization during exercise (VO2-work rate slope and VO2 recovery half-time).ResultsWe recruited 14 participants. Low exercise capacity (i.e., VO2Peak < 80% predicted) was present in 11 out of 14 (79%) with a median VO2Peak of 12.6 ml/kg/min [9.6-15.1] and 6MWT distance of 294 m [240-433]. In addition to low VO2Peak, CPET findings in survivors included low oxygen uptake efficiency slope, low oxygen pulse, elevated chronotropic index, low VO2-work rate slope, and prolonged VO2 recovery half-time, indicating impaired oxygen utilization with a hyperdynamic heart rate and ventilatory response, a pattern seen in non-critically ill patients with mitochondrial myopathies. Worse VO2-work rate slope and VO2 recovery half-time were strongly correlated with worse VO2Peak and 6MWT distance, suggesting that exercise capacity was potentially limited by impaired muscle oxygen utilization.ConclusionsThese exploratory data suggest ICU survivors may suffer from impaired muscular oxygen metabolism due to mitochondrial dysfunction that impairs exercise capacity long-term. These findings should be further characterized in future studies that include direct assessments of muscle mitochondrial function in ICU survivors.
| S-EPMC9410741 | biostudies-literature
Project description:In a nationwide randomized controlled trial, white matter microstructure was assessed before and immediately after Cogmed Working-Memory Training (CWMT) in school-age neonatal critical illness survivors. Eligible participants were survivors (8-12 years) with an IQ ≥ 80 and a z-score of ≤ -1.5 on (working)memory test at first assessment. Diffusion Tensor Imaging was used to assess white matter microstructure. Associations between any training-induced changes and improved neuropsychological outcome immediately and one year post-CWMT were evaluated as well. The trial was conducted between October 2014-June 2017 at Erasmus MC-Sophia, Rotterdam, Netherlands. Researchers involved were blinded to group allocation. Participants were randomized to CWMT(n = 14) or no-intervention(n = 20). All children completed the CWMT. Global fractional anisotropy(FA) increased significantly post-CWMT compared to no-intervention(estimated-coefficient = .007, p = .015). Increased FA(estimated coefficient = .009, p = .033) and decreased mean diffusivity(estimated-coefficient = -.010, p = .018) were found in the left superior longitudinal fasciculus(SFL) post-CWMT compared no-intervention. Children after CWMT who improved with >1SD on verbal working-memory had significantly higher FA in the left SLF post-CWMT(n = 6; improvement = .408 ± .01) than children without this improvement post-CWMT(n = 6; no-improvement = .384 ± .02), F(1,12) = 6.22, p = .041, ηp2 = .47. No other structure-function relationships were found post-CWMT. Our findings demonstrate that white matter microstructure and associated cognitive outcomes are malleable by CWMT in survivors of neonatal critical illness.
| S-EPMC6969347 | biostudies-literature
Project description:ObjectivesNosocomial infection/sepsis occurs in up to 40% of children requiring long-term intensive care. Zinc, selenium, glutamine, metoclopramide (a prolactin secretalogue), and/or whey protein supplementation have been effective in reducing infection and sepsis in other populations. We evaluated whether daily nutriceutical supplementation with zinc, selenium, glutamine, and metoclopramide, compared to whey protein, would reduce the occurrence of nosocomial infection/sepsis in this at-risk population.DesignRandomized, double-blinded, comparative effectiveness trial.SettingEight pediatric intensive care units in the National Institutes of Child Health and Human Development Collaborative Pediatric Critical Care Research Network.PatientsTwo hundred ninety-three long-term intensive care patients (age 1-17 yrs) expected to require >72 hrs of invasive care.InterventionsPatients were stratified according to immunocompromised status and center and then were randomly assigned to receive daily enteral zinc, selenium, glutamine, and intravenous metoclopramide (n = 149), or daily enteral whey protein (n = 144) and intravenous saline for up to 28 days of intensive care unit stay. The primary end point was time to development of nosocomial sepsis/infection. The analysis was intention to treat.Measurements and main resultsThere were no differences by assigned treatment in the overall population with respect to time until the first episode of nosocomial infection/sepsis (median whey protein 13.2 days vs. zinc, selenium, glutamine, and intravenous metoclopramide 12.1 days; p = .29 by log-rank test) or the rate of nosocomial infection/sepsis (4.83/100 days whey protein vs. 4.99/100 days zinc, selenium, glutamine, and intravenous metoclopramide; p = .81). Only 9% of the 293 subjects were immunocompromised and there was a reduction in rate of nosocomial infection/sepsis with zinc, selenium, glutamine, and intravenous metoclopramide in this immunocompromised group (6.09/100 days whey protein vs. 1.57/100 days zinc, selenium, glutamine, and intravenous metoclopramide; p = .011).ConclusionCompared with whey protein supplementation, zinc, selenium, glutamine, and intravenous metoclopramide conferred no advantage in the immune-competent population. Further evaluation of zinc, selenium, glutamine, and intravenous metoclopramide supplementation is warranted in the immunocompromised long-term pediatric intensive care unit patient.
| S-EPMC3302948 | biostudies-literature
Project description:BackgroundDecreased TNF-α production in whole blood after ex vivo LPS stimulation indicates suppression of the Toll-like receptor (TLR)4 pathway. This is associated with increased mortality in pediatric influenza critical illness. Whether antiviral immune signaling pathways are also suppressed in these patients is unclear.ObjectivesWe sought to evaluate suppression of the TLR4 and the antiviral retinoic acid-inducible gene-I (RIG-I) pathways with clinical outcomes in children with severe influenza infection.MethodsIn this 24-center, prospective, observational cohort study of children with confirmed influenza infection, blood was collected within 72 hours of intensive care unit admission. Ex vivo whole blood stimulations were performed with matched controls using the viral ligand polyinosinic-polycytidylic acid-low-molecular-weight/LyoVec and LPS to evaluate IFN-α and TNF-α production capacities (RIG-I and TLR4 pathways, respectively).ResultsSuppression of either IFN-α or TNF-α production capacity was associated with longer duration of mechanical ventilation and hospitalization, and increased organ dysfunction. Children with suppression of both RIG-I and TLR4 pathways (n = 33 of 103 [32%]) were more likely to have prolonged (≥7 days) multiple-organ dysfunction syndrome (30.3% vs 8.6%; P = .004) or prolonged hypoxemic respiratory failure (39.4% vs 11.4%; P = .001) compared with those with single- or no pathway suppression.ConclusionsSuppression of both RIG-I and TLR4 signaling pathways, essential for respective antiviral and antibacterial responses, is common in previously immunocompetent children with influenza-related critical illness and is associated with bacterial coinfection and adverse outcomes. Prospective testing of both pathways may aid in risk-stratification and in immune monitoring.
| S-EPMC7323584 | biostudies-literature
Project description:Critical care practitioners must frequently make decisions about their patients' ability to swallow food, liquids, and pills. These decisions can be particularly difficult given the incompletely defined epidemiology, diagnostic criteria, and prognostic features of swallowing disorders in critically ill patients. Furthermore, the consequences of improper decisions-namely, aspiration, malnutrition, hunger, and thirst-can be devastating to patients and their families. This review outlines the problem of swallowing dysfunction in critically ill patients and then addresses the most clinically relevant questions that critical care practitioners face today. First, we review the epidemiology of swallowing dysfunction in critically ill patients. Next, we describe the different diagnostic tests for swallowing dysfunction and describe a general approach to the initial assessment for swallowing disorders. Finally, we explore the existing treatments for swallowing dysfunction. Given the burden of swallowing dysfunction in patients recovering from critical illness, enabling critical care practitioners to manage these disorders, while stimulating new investigation into their pathophysiology, diagnosis, and management, will enhance our care of critically ill patients.
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Project description:Oligodeoxynucleotides (ODNs) containing a CpG or certain synthetic dinucleotides, referred to as immune-stimulatory dinucleotides, induce Toll-like receptor 9 (TLR9)-mediated immune responses. Chemical modifications such as 2'-O-methylribonucleotides incorporated adjacent to the immune-stimulatory dinucleotide on the 5'-side abrogate TLR9-mediated immune responses. In this study, we evaluated the effect of the location of immune-stimulatory dinucleotides in ODNs on TLR9-mediated immune responses. We designed and synthesized ODNs with two immune-stimulatory dinucleotides, one placed toward the 5'-end region and the other toward the 3'-end region, incorporated 2'-O-methylribonucleotides selectively preceding the 5'- or 3'-immune-stimulatory dinucleotide or both, and studied TLR9-mediated immune responses of these compounds in cell-based assays and in vivo in mice. These studies showed that an immune-stimulatory dinucleotide located closer to the 5'-end is critical for and dictates TLR9-mediated immune responses. These studies provide insights for the use of ODNs when employed as TLR9 agonists and antagonists or antisense agents.
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