Serum Biomarkers of Regeneration and Plasticity are Associated with Functional Outcome in Pediatric Neurocritical Illness: An Exploratory Study

Madurski, Catherine; Jarvis, Jessica; Wagner, Amy K.; Fabio, Anthony; Wang, Chunyan; Janesko‐Feldman, Keri; Rubin, P.; Strohm, Sharon; Stanger, Meg; Orringer, Maxine; Fink, Ericka L.; Beers, Sue R.; Ortiz-Aguayo, Roberto; Houtrow, Amy J.; Burns, Clare L.; Valenta, Cynthia; Chrisman, Maddie; Golightly, Lynn; Treble‐Barna, Amery; Kochanek, Patrick M.; Smith, Craig; Zhou, Amy; Patrick, Cheryl; Sisung, Charles E.; Hojnacki, Katie; Lacci, Christina; Hill, Jeanette R.; Hinkes-Molinaro, Laura; Walsh, Katie; Johnson, Tyler; Borrowman, Julie; Russo, Laura; Doughty, Lesley; Kiger, Michelle; Howard, Kelli; Benken, Laura; Peariso, Katrina; Broomall, Eileen; Frank, Erin; Clonan, Ann; Capizzi, Lindsey; Miller, Claire; Phillips, J. D.; Ruffing, Marin; Evanson, Nate; Kurowski, Brad G.; Taylor, Jordan M.; Yunger, Toni; Music, Rebekah W.; Betz, Emily; Wainwright, Mark S.; Marshal, Linda; Pollon, Dorothy; Braksick, Leslie; LaPorte, Matthew G.; Docimo, Steve; Brown, Brenda Eagan; Rieker, James P.; Budin, Lee; Sanders, Maurita; Klepac, Dahlia

doi:10.1007/s12028-021-01199-z

Cited by 7 publications

(6 citation statements)

References 69 publications

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“…In children with traumatic brain injury or cardiac arrest, diagnostic and prognostic biomarkers, such as NSE and S100b, have been evaluated [ 141 , 142 ]. Recently, low blood levels of brain-derived neurotrophic factor and vascular endothelial growth factor, which are biomarkers of regeneration, have identified children at risk for new cognitive impairment among survivors of pediatric neurocritical care [ 143 ]. Ultimately, the cognitive impairments will evolve afterward and the PCPC score at PICU discharge may worsen or improve [ 120 ].…”

Section: Introductionmentioning

confidence: 99%

Chronic critical illness and post-intensive care syndrome: from pathophysiology to clinical challenges

Voiriot

Oualha²,

Pierre³

et al. 2022

Ann. Intensive Care

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Background Post‐intensive care syndrome (PICS) encompasses physical, cognition, and mental impairments persisting after intensive care unit (ICU) discharge. Ultimately it significantly impacts the long‐term prognosis, both in functional outcomes and survival. Thus, survivors often develop permanent disabilities, consume a lot of healthcare resources, and may experience prolonged suffering. This review aims to present the multiple facets of the PICS, decipher its underlying mechanisms, and highlight future research directions. Main text This review abridges the translational data underlying the multiple facets of chronic critical illness (CCI) and PICS. We focus first on ICU-acquired weakness, a syndrome characterized by impaired contractility, muscle wasting, and persisting muscle atrophy during the recovery phase, which involves anabolic resistance, impaired capacity of regeneration, mitochondrial dysfunction, and abnormalities in calcium homeostasis. Second, we discuss the clinical relevance of post-ICU cognitive impairment and neuropsychological disability, its association with delirium during the ICU stay, and the putative role of low-grade long-lasting inflammation. Third, we describe the profound and persistent qualitative and quantitative alteration of the innate and adaptive response. Fourth, we discuss the biological mechanisms of the progression from acute to chronic kidney injury, opening the field for renoprotective strategies. Fifth, we report long-lasting pulmonary consequences of ARDS and prolonged mechanical ventilation. Finally, we discuss several specificities in children, including the influence of the child’s pre-ICU condition, development, and maturation. Conclusions Recent understandings of the biological substratum of the PICS’ distinct features highlight the need to rethink our patient trajectories in the long term. A better knowledge of this syndrome and precipitating factors is necessary to develop protocols and strategies to alleviate the CCI and PICS and ultimately improve patient recovery.

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Section: Introductionmentioning

confidence: 99%

Chronic critical illness and post-intensive care syndrome: from pathophysiology to clinical challenges

Voiriot

Oualha²,

Pierre³

et al. 2022

Ann. Intensive Care

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“…The impairments rates in a general PICU population ranged from 0.02 to 10.3% at discharge to 38% at 6 months (19,20,26). However, the rates of impairments in acquired brain injury patients ranged from 28.9 to 70% (23,27,30,32,35), 2 to 69% among those with sepsis (19,21,24), and 20 to 34.3% among those needing MV (25,28,29). Overall, physical function impairments in the included studies ranged from 0.02 to 85.1% during hospitalization/at discharge (15,19), 20 to 55.7% at 6 months (15,28), and 2 to 70% at more than 1 year (19,27).…”

Section: Discussionmentioning

confidence: 98%

“…In addition, more The physical instruments used in the selected studies varied, and the POPC and FSS were the most frequently used global physical function instruments. The FSS was primarily used during the PICU stay (31)(32)(33), and the POPC was used during the PICU stay or post-PICU discharge (19,20,22,24,28), particularly as a longitudinal measurement. In addition, assessment of muscle wasting and atrophy via ultrasound or muscle strength via dynamometry were conducted longitudinally during the PICU/hospital stay (25,29).…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Physical Function Impairments in Postintensive Care Syndrome: A Scoping Review

Ding

Yang

2022

Front. Pediatr.

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ObjectiveSurvivors of critical illness may experience short- and long-term physical function impairments. This review aimed to identify the risk factors for physical function impairments from the current literature.Data SourcesA systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases following the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews guideline was performed.Study SelectionThe risk factors reported in all human studies reporting physical function impairments in children admitted to the pediatric intensive care unit (PICU) were reviewed and categorized. Two investigators independently screened, evaluated, and selected studies for inclusion. Data from eligible studies were extracted by one investigator, and another investigator reviewed and verified the data. A systematic narrative approach was employed to review and summarize the data.ResultsA total of 264 studies were found to be eligible, with 19 studies meeting the inclusion criteria. Children admitted to the PICU experienced physical function impairments during their stay, which can last for years. The studies varied primarily in the measurement timing and tools used. The most frequently reported risk factors for physical function impairments were age, race or ethnicity, a pre-admission chronic condition, sex, disease severity, duration or the presence of mechanical ventilation, and admission diagnosis.ConclusionsPhysical function impairments may be persistent in PICU survivors. To prevent these impairments in critically ill patients, pediatricians should pay attention to modifiable risk factors, such as the duration of mechanical ventilation. Future studies need to promote a combination of standardized measures for the detection and prevention of physical function impairments.

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“…It has been implicated in providing neuroplasticity and neuroprotection through reduction in secondary brain injury. BDNF has been associated with pediatric traumatic brain injury (TBI) 35 , favorable outcomes in neonatal hypoxic-ischemic encephalopathy (HIE) 36 , 37 , and decreased functional impairment in pediatric neurocritical illness 38 . Next, to address markers of astrocytic injury, GFAP is a cytoskeletal filament protein found in mature astrocytes, and its expression is increased during reactive astrogliosis after neurologic injury 39 .…”

Section: Discussionmentioning

confidence: 99%

Exploratory factor analysis yields grouping of brain injury biomarkers significantly associated with outcomes in neonatal and pediatric ECMO

Huang,

Roem,

et al. 2024

Sci Rep

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In this two-center prospective cohort study of children on ECMO, we assessed a panel of plasma brain injury biomarkers using exploratory factor analysis (EFA) to evaluate their interplay and association with outcomes. Biomarker concentrations were measured daily for the first 3 days of ECMO support in 95 participants. Unfavorable composite outcome was defined as in-hospital mortality or discharge Pediatric Cerebral Performance Category > 2 with decline ≥ 1 point from baseline. EFA grouped 11 biomarkers into three factors. Factor 1 comprised markers of cellular brain injury (NSE, BDNF, GFAP, S100β, MCP1, VILIP-1, neurogranin); Factor 2 comprised markers related to vascular processes (vWF, PDGFRβ, NPTX1); and Factor 3 comprised the BDNF/MMP-9 cellular pathway. Multivariable logistic models demonstrated that higher Factor 1 and 2 scores were associated with higher odds of unfavorable outcome (adjusted OR 2.88 [1.61, 5.66] and 1.89 [1.12, 3.43], respectively). Conversely, higher Factor 3 scores were associated with lower odds of unfavorable outcome (adjusted OR 0.54 [0.31, 0.88]), which is biologically plausible given the role of BDNF in neuroplasticity. Application of EFA on plasma brain injury biomarkers in children on ECMO yielded grouping of biomarkers into three factors that were significantly associated with unfavorable outcome, suggesting future potential as prognostic instruments.

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Serum Biomarkers of Regeneration and Plasticity are Associated with Functional Outcome in Pediatric Neurocritical Illness: An Exploratory Study

Cited by 7 publications

References 69 publications

Chronic critical illness and post-intensive care syndrome: from pathophysiology to clinical challenges

Chronic critical illness and post-intensive care syndrome: from pathophysiology to clinical challenges

Risk Factors for Physical Function Impairments in Postintensive Care Syndrome: A Scoping Review

Exploratory factor analysis yields grouping of brain injury biomarkers significantly associated with outcomes in neonatal and pediatric ECMO

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