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Stem Cell Research & Therapy Jan 2022Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory coronavirus 2 is currently spreading throughout the world with a high rate of infection... (Review)
Review
Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory coronavirus 2 is currently spreading throughout the world with a high rate of infection and mortality and poses a huge threat to global public health. COVID-19 primarily manifests as hypoxic respiratory failure and acute respiratory distress syndrome, which can lead to multiple organ failure. Despite advances in the supportive care approaches, there is still a lack of clinically effective therapies, and there is an urgent need to develop novel strategies to fight this disease. Currently, stem cell therapy and stem cell-derived organoid models have received extensive attention as a new treatment and research method for COVID-19. Here, we discuss how stem cells play a role in the battle against COVID-19 and present a systematic review and prospective of the study on stem cell treatment and organoid models of COVID-19, which provides a reference for the effective control of the COVID-19 pandemic worldwide.
Topics: COVID-19; Humans; Pandemics; Prospective Studies; SARS-CoV-2; Stem Cells
PubMed: 35012650
DOI: 10.1186/s13287-021-02683-1 -
Pediatrics Jan 2022Develop evidence-based criteria for individual organ dysfunction.
CONTEXT
Develop evidence-based criteria for individual organ dysfunction.
OBJECTIVES
Evaluate current evidence and develop contemporary consensus criteria for acute liver dysfunction with associated outcomes in critically ill children.
DATA SOURCES
Electronic searches of PubMed and Embase conducted from January 1992 to January 2020, used medical subject heading terms and text words to characterize acute liver dysfunction and outcomes.
STUDY SELECTION
Studies evaluating critically ill children with acute liver dysfunction, assessed screening tools, and outcomes were included. Studies evaluating adults, infants ≤36 weeks gestational age, or animals or were reviews/commentaries, case series with sample size ≤10, or non-English language studies were excluded.
DATA EXTRACTION
Data were abstracted from each eligible study into a data extraction form along with risk of bias assessment by a task force member.
RESULTS
The systematic review supports criteria for acute liver dysfunction, in the absence of known chronic liver disease, as having onset of symptoms <8 weeks, combined with biochemical evidence of acute liver injury, and liver-based coagulopathy, with hepatic encephalopathy required for an international normalized ratio between 1.5 and 2.0.
LIMITATIONS
Unable to assess acute-on-chronic liver dysfunction, subjective nature of hepatic encephalopathy, relevant articles missed by reviewers.
CONCLUSIONS
Proposed criteria identify an infant, child, or adolescent who has reached a clinical threshold where any of the 3 outcomes (alive with native liver, death, or liver transplant) are possible and should prompt an urgent liaison with a recognized pediatric liver transplant center if liver failure is the principal driver of multiple organ dysfunction.
Topics: Adolescent; Child; Critical Illness; Humans; Infant; Liver Diseases; Multiple Organ Failure; Organ Dysfunction Scores
PubMed: 34970684
DOI: 10.1542/peds.2021-052888I -
Pediatrics Jan 2022Multiple scores exist to characterize organ dysfunction in children.
CONTEXT
Multiple scores exist to characterize organ dysfunction in children.
OBJECTIVE
To review the literature on multiple organ dysfunction (MOD) scoring systems to estimate severity of illness and to characterize the performance characteristics of currently used scoring tools and clinical assessments for organ dysfunction in critically ill children.
DATA SOURCES
Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020.
STUDY SELECTION
Studies were included if they evaluated critically ill children with MOD, evaluated the performance characteristics of scoring tools for MOD, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes.
DATA EXTRACTION
Data were abstracted into a standard data extraction form by a task force member.
RESULTS
Of 1152 unique abstracts screened, 156 full text studies were assessed including a total of 54 eligible studies. The most commonly reported scores were the Pediatric Logistic Organ Dysfunction Score (PELOD), pediatric Sequential Organ Failure Assessment score (pSOFA), Pediatric Index of Mortality (PIM), PRISM, and counts of organ dysfunction using the International Pediatric Sepsis Definition Consensus Conference. Cut-offs for specific organ dysfunction criteria, diagnostic elements included, and use of counts versus weighting varied substantially.
LIMITATIONS
While scores demonstrated an increase in mortality associated with the severity and number of organ dysfunctions, the performance ranged widely.
CONCLUSIONS
The multitude of scores on organ dysfunction to assess severity of illness indicates a need for unified and data-driven organ dysfunction criteria, derived and validated in large, heterogenous international databases of critically ill children.
Topics: Child; Critical Illness; Humans; Multiple Organ Failure; Organ Dysfunction Scores; Prognosis
PubMed: 34970683
DOI: 10.1542/peds.2021-052888D -
Pediatrics Jan 2022Renal dysfunction is associated with poor outcomes in critically ill children.
CONTEXT
Renal dysfunction is associated with poor outcomes in critically ill children.
OBJECTIVE
To evaluate the current evidence for criteria defining renal dysfunction in critically ill children and association with adverse outcomes. To develop contemporary consensus criteria for renal dysfunction in critically ill children.
DATA SOURCES
PubMed and Embase were searched from January 1992 to January 2020.
STUDY SELECTION
Included studies evaluated critically ill children with renal dysfunction, performance characteristics of assessment tools for renal dysfunction, and outcomes related to mortality, functional status, or organ-specific or other patient-centered outcomes. Studies with adults or premature infants (≤36 weeks' gestational age), animal studies, reviews, case series, and studies not published in English with inability to determine eligibility criteria were excluded.
DATA EXTRACTION
Data were extracted from included studies into a standard data extraction form by task force members.
RESULTS
The systematic review supported the following criteria for renal dysfunction: (1) urine output <0.5 mL/kg per hour for ≥6 hours and serum creatinine increase of 1.5 to 1.9 times baseline or ≥0.3 mg/dL, or (2) urine output <0.5 mL/kg per hour for ≥12 hours, or (3) serum creatinine increase ≥2 times baseline, or (4) estimated glomerular filtration rate <35 mL/minute/1.73 m2, or (5) initiation of renal replacement therapy, or (6) fluid overload ≥20%. Data also support criteria for persistent renal dysfunction and for high risk of renal dysfunction.
LIMITATIONS
All included studies were observational and many were retrospective.
CONCLUSIONS
We present consensus criteria for renal dysfunction in critically ill children.
Topics: Biomarkers; Critical Illness; Glomerular Filtration Rate; Humans; Kidney Diseases; Multiple Organ Failure; Organ Dysfunction Scores; Renal Replacement Therapy
PubMed: 34970682
DOI: 10.1542/peds.2021-052888J -
Pediatrics Jan 2022Acute neurologic dysfunction is common in critically ill children and contributes to outcomes and end of life decision-making.
CONTEXT
Acute neurologic dysfunction is common in critically ill children and contributes to outcomes and end of life decision-making.
OBJECTIVE
To develop consensus criteria for neurologic dysfunction in critically ill children by evaluating the evidence supporting such criteria and their association with outcomes.
DATA SOURCES
Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020, by using a combination of medical subject heading terms and text words to define concepts of neurologic dysfunction, pediatric critical illness, and outcomes of interest.
STUDY SELECTION
Studies were included if the researchers evaluated critically ill children with neurologic injury, evaluated the performance characteristics of assessment and scoring tools to screen for neurologic dysfunction, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes. Studies with an adult population or premature infants (≤36 weeks' gestational age), animal studies, reviews or commentaries, case series with sample size ≤10, and studies not published in English with an inability to determine eligibility criteria were excluded.
DATA EXTRACTION
Data were abstracted from each study meeting inclusion criteria into a standard data extraction form by task force members.
DATA SYNTHESIS
The systematic review supported the following criteria for neurologic dysfunction as any 1 of the following: (1) Glasgow Coma Scale score ≤8; (2) Glasgow Coma Scale motor score ≤4; (3) Cornell Assessment of Pediatric Delirium score ≥9; or (4) electroencephalography revealing attenuation, suppression, or electrographic seizures.
CONCLUSIONS
We present consensus criteria for neurologic dysfunction in critically ill children.
Topics: Child; Clinical Decision-Making; Critical Illness; Electroencephalography; Glasgow Coma Scale; Humans; Multiple Organ Failure; Nervous System Diseases; Neurologic Examination; Prognosis; Severity of Illness Index
PubMed: 34970681
DOI: 10.1542/peds.2021-052888E -
Pediatrics Jan 2022Prior criteria to define pediatric multiple organ dysfunction syndrome (MODS) did not include gastrointestinal dysfunction.
CONTEXT
Prior criteria to define pediatric multiple organ dysfunction syndrome (MODS) did not include gastrointestinal dysfunction.
OBJECTIVES
Our objective was to evaluate current evidence and to develop consensus criteria for gastrointestinal dysfunction in critically ill children.
DATA SOURCES
Electronic searches of PubMed and EMBASE were conducted from January 1992 to January 2020, using medical subject heading terms and text words to define gastrointestinal dysfunction, pediatric critical illness, and outcomes.
STUDY SELECTION
Studies were included if they evaluated critically ill children with gastrointestinal dysfunction, performance characteristics of assessment/scoring tools to screen for gastrointestinal dysfunction, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes. Studies of adults or premature infants, animal studies, reviews/commentaries, case series with sample size ≤10, and non-English language studies with inability to determine eligibility criteria were excluded.
DATA EXTRACTION
Data were abstracted from each eligible study into a standard data extraction form along with risk of bias assessment by a task force member.
RESULTS
The systematic review supports the following criteria for severe gastrointestinal dysfunction: 1a) bowel perforation, 1b) pneumatosis intestinalis, or 1c) bowel ischemia, present on plain abdominal radiograph, computed tomography (CT) scan, magnetic resonance imaging (MRI), or gross surgical inspection, or 2) rectal sloughing of gut mucosa.
LIMITATIONS
The validity of the consensus criteria for gastrointestinal dysfunction are limited by the quantity and quality of current evidence.
CONCLUSIONS
Understanding the role of gastrointestinal dysfunction in the pathophysiology and outcomes of MODS is important in pediatric critical illness.
Topics: Child; Critical Illness; Gastrointestinal Diseases; Gastrointestinal Tract; Humans; Multiple Organ Failure; Organ Dysfunction Scores
PubMed: 34970680
DOI: 10.1542/peds.2021-052888H -
Pediatrics Jan 2022Cardiovascular dysfunction is associated with poor outcomes in critically ill children.
CONTEXT
Cardiovascular dysfunction is associated with poor outcomes in critically ill children.
OBJECTIVE
We aim to derive an evidence-informed, consensus-based definition of cardiovascular dysfunction in critically ill children.
DATA SOURCES
Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020 using medical subject heading terms and text words to define concepts of cardiovascular dysfunction, pediatric critical illness, and outcomes of interest.
STUDY SELECTION
Studies were included if they evaluated critically ill children with cardiovascular dysfunction and assessment and/or scoring tools to screen for cardiovascular dysfunction and assessed mortality, functional status, organ-specific, or other patient-centered outcomes. Studies of adults, premature infants (≤36 weeks gestational age), animals, reviews and/or commentaries, case series (sample size ≤10), and non-English-language studies were excluded. Studies of children with cyanotic congenital heart disease or cardiovascular dysfunction after cardiopulmonary bypass were excluded.
DATA EXTRACTION
Data were abstracted from each eligible study into a standard data extraction form, along with risk-of-bias assessment by a task force member.
RESULTS
Cardiovascular dysfunction was defined by 9 elements, including 4 which indicate severe cardiovascular dysfunction. Cardiopulmonary arrest (>5 minutes) or mechanical circulatory support independently define severe cardiovascular dysfunction, whereas tachycardia, hypotension, vasoactive-inotropic score, lactate, troponin I, central venous oxygen saturation, and echocardiographic estimation of left ventricular ejection fraction were included in any combination. There was expert agreement (>80%) on the definition.
LIMITATIONS
All included studies were observational and many were retrospective.
CONCLUSIONS
The Pediatric Organ Dysfunction Information Update Mandate panel propose this evidence-informed definition of cardiovascular dysfunction.
Topics: Cardiovascular Diseases; Cardiovascular System; Child; Critical Illness; Humans; Multiple Organ Failure; Organ Dysfunction Scores
PubMed: 34970677
DOI: 10.1542/peds.2021-052888F -
Pediatrics Jan 2022To review, analyze, and synthesize the literature on endothelial dysfunction in critically ill children with multiple organ dysfunction syndrome and to develop a...
OBJECTIVES
To review, analyze, and synthesize the literature on endothelial dysfunction in critically ill children with multiple organ dysfunction syndrome and to develop a consensus biomarker-based definition and diagnostic criteria.
DATA SOURCES
Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020, using a combination of medical subject heading terms and key words to define concepts of endothelial dysfunction, pediatric critical illness, and outcomes.
STUDY SELECTION
Studies were included if they evaluated critically ill children with endothelial dysfunction, evaluated performance characteristics of assessment/scoring tools to screen for endothelial dysfunction, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes. Studies of adults or premature infants (≤36 weeks gestational age), animal studies, reviews or commentaries, case series with sample size ≤10, and non-English language studies with the inability to determine eligibility criteria were excluded.
DATA EXTRACTION
Data were abstracted from each eligible study into a standard data extraction form along with risk of bias assessment.
DATA SYNTHESIS
We identified 62 studies involving 84 assessments of endothelial derived biomarkers indirectly linked to endothelial functions including leukocyte recruitment, inflammation, coagulation, and permeability. Nearly all biomarkers studied lacked specificity for vascular segment and organ systems. Quality assessment scores for the collected literature were low.
CONCLUSIONS
The Endothelial Subgroup concludes that there exists no single or combination of biomarkers to diagnose endothelial dysfunction in pediatric multiple organ dysfunction syndrome. Future research should focus on biomarkers more directly linked to endothelial functions and with specificity for vascular segment and organ systems.
Topics: Biomarkers; Child; Critical Illness; Endothelium; Humans; Multiple Organ Failure; Organ Dysfunction Scores
PubMed: 34970676
DOI: 10.1542/peds.2021-052888O -
Pediatrics Jan 2022Immune system dysfunction is poorly represented in pediatric organ dysfunction definitions.
CONTEXT
Immune system dysfunction is poorly represented in pediatric organ dysfunction definitions.
OBJECTIVE
To evaluate evidence for criteria that define immune system dysfunction in critically ill children and associations with adverse outcomes and develop consensus criteria for the diagnosis of immune system dysfunction in critically ill children.
DATA SOURCES
We conducted electronic searches of PubMed and Embase from January 1992 to January 2020, using medical subject heading terms and text words to define immune system dysfunction and outcomes of interest.
STUDY SELECTION
Studies of critically ill children with an abnormality in leukocyte numbers or function that is currently measurable in the clinical laboratory in which researchers assessed patient-centered outcomes were included. Studies of adults or premature infants, animal studies, reviews and commentaries, case series (≤10 subjects), and studies not published in English with inability to determine eligibility criteria were excluded.
DATA EXTRACTION
Data were abstracted from eligible studies into a standard data extraction form along with risk of bias assessment by a task force member.
RESULTS
We identified the following criteria for immune system dysfunction: (1) peripheral absolute neutrophil count <500 cells/μL, (2) peripheral absolute lymphocyte count <1000 cells/μL, (3) reduction in CD4+ lymphocyte count or percentage of total lymphocytes below age-specific thresholds, (4) monocyte HLA-DR expression <30%, or (5) reduction in ex vivo whole blood lipopolysaccharide-induced TNFα production capacity below manufacturer-provided thresholds.
LIMITATIONS
Many measures of immune system function are currently limited to the research environment.
CONCLUSIONS
We present consensus criteria for the diagnosis of immune system dysfunction in critically ill children.
Topics: Child; Critical Illness; HLA-DR Antigens; Humans; Immune System; Immune System Diseases; Leukocyte Count; Lymphocyte Count; Lymphopenia; Multiple Organ Failure; Neutropenia; Neutrophils; Severity of Illness Index; Tumor Necrosis Factor-alpha
PubMed: 34970674
DOI: 10.1542/peds.2021-052888N -
Pediatrics Jan 2022Endocrine dysfunction is common in critically ill children and is manifested by abnormalities in glucose, thyroid hormone, and cortisol metabolism.
CONTEXT
Endocrine dysfunction is common in critically ill children and is manifested by abnormalities in glucose, thyroid hormone, and cortisol metabolism.
OBJECTIVE
To develop consensus criteria for endocrine dysfunction in critically ill children by assessing the association of various biomarkers with clinical and functional outcomes.
DATA SOURCES
PubMed and Embase were searched from January 1992 to January 2020.
STUDY SELECTION
We included studies in which researchers evaluated critically ill children with abnormalities in glucose homeostasis, thyroid function and adrenal function, performance characteristics of assessment and/or scoring tools to screen for endocrine dysfunction, and outcomes related to mortality, organ-specific status, and patient-centered outcomes. Studies of adults, premature infants or animals, reviews and/or commentaries, case series with sample size ≤10, and non-English-language studies were excluded.
DATA EXTRACTION
Data extraction and risk-of-bias assessment for each eligible study were performed by 2 independent reviewers.
RESULTS
The systematic review supports the following criteria for abnormal glucose homeostasis (blood glucose [BG] concentrations >150 mg/dL [>8.3 mmol/L] and BG concentrations <50 mg/dL [<2.8 mmol/L]), abnormal thyroid function (serum total thyroxine [T4] <4.2 μg/dL [<54 nmol/L]), and abnormal adrenal function (peak serum cortisol concentration <18 μg/dL [500 nmol/L]) and/or an increment in serum cortisol concentration of <9 μg/dL (250 nmol/L) after adrenocorticotropic hormone stimulation.
LIMITATIONS
These included variable sampling for BG measurements, limited reporting of free T4 levels, and inconsistent interpretation of adrenal axis testing.
CONCLUSIONS
We present consensus criteria for endocrine dysfunction in critically ill children that include specific measures of BG, T4, and adrenal axis testing.
Topics: Adrenal Cortex Function Tests; Blood Glucose; Child; Critical Illness; Endocrine System Diseases; Homeostasis; Humans; Hydrocortisone; Hyperglycemia; Hypoglycemia; Multiple Organ Failure; Organ Dysfunction Scores; Thyroid Function Tests
PubMed: 34970672
DOI: 10.1542/peds.2021-052888M