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Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review
Wang Z, Zhao S, Tang Y, Wang Z, Shi Q, Dang X, Gan L, Peng S, Li W, Zhou Q, et al
European journal of pediatrics. 2022;:1-12
Abstract
The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that after the treatment, 54.7% (95%CI, 10.3 to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2 to 10.1%) died, and 27.0% (95%CI, 0 to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone.Conclusions: Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines. What is Known: • The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19/MIS-C are unclear. What is New: • Overall, the current evidence cannot adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C. • We are calling for the publication of high-quality clinical trials and provide substantial evidence for the development of guidelines.
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Efficacy of human immunoglobulin injection and effects on serum inflammatory cytokines in neonates with acute lung injury
Wang S, Tang Z, Zheng X, Deng J, Wang Z
Experimental and therapeutic medicine. 2021;22(3):931
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Abstract
The present study aimed to explore the efficacy of intravenous immunoglobulin (IVIG) injection in neonates with acute lung injury (ALI) and assess its effects on serum inflammatory cytokine levels. The research subjects were 140 neonates with ALI who were evenly distributed into a control group (COG) and a study group (STG). The COG patients were treated routinely, whereas patients in the STG were administered IVIG in addition to the standard treatment received by the COG. The arterial partial pressure of oxygen (PaO(2)), PaO(2)/fraction of inspired oxygen (FIO(2)), mechanical ventilation time and hospitalization time were compared between the two groups. ELISA was used to determine the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the patients before treatment and at 12, 24 and 36 h after treatment. The Kaplan-Meier method was used to analyze the survival of the patients, including their survival for 30 days after treatment. The patients were divided into high and low cytokine expression groups based on their mean expression levels of serum IL-6 and TNF-α before treatment. After treatment, PaO(2) and PaO(2)/FiO2 were significantly higher and mechanical ventilation and hospitalization time were reduced in the STG in comparison with the COG (all P<0.001). At 12, 24 and 36 h after treatment, serum IL-6 and TNF-α levels in the STG were lower than those in the COG (both P<0.05). The 30-day survival rate after treatment was not significantly different between the two groups (P>0.05). The 30-day survival rate in the high IL-6 and high TNF-α expression COG was lower than that in the low IL-6 and low TNF-α expression COG (both P<0.05). The results of the present study indicate that IVIG may improve pulmonary gas exchange, shorten the course of disease and reduce the inflammatory response in neonates with ALI.
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Clinical Features in Children With Kawasaki Disease Shock Syndrome: A Systematic Review and Meta-Analysis
Zheng Z, Huang Y, Wang Z, Tang J, Chen X, Li Y, Li M, Zang C, Wang Y, Wang L, et al
Frontiers in cardiovascular medicine. 2021;8:736352
Abstract
Objective: This study aimed to identify the clinical features of Kawasaki disease shock syndrome (KDSS) in children. Methods: The case-control studies of KDSS and KD children up until April 30, 2021 were searched in multiple databases. The qualified research were retrieved by manually reviewing the references. Review Manager 5.3 software was used for statistical analysis. Results: The results showed that there was no significant difference in the incidence of male and female in children with KDSS. Children with KDSS compared with non-shocked KD, there were significant difference in age, duration of fever, white blood cell (WBC) count, percentage of neutrophils (NEUT%), platelet count (PLT), c-reactive protein level (CRP), alanine transaminase concentration (ALT), aspartate transaminase concentration (AST), albumin concentration (ALB), sodium concentration (Na), ejection fraction, and length of hospitalization as well as the incidence of coronary artery dilation, coronary artery aneurysm, left ventricular dysfunction, mitral regurgitation, pericardial effusion, initial diagnosis of KD, intravenous immunoglobulin (IVIG) resistance and receiving second dose of IVIG, vasoactive drugs, hormones, and albumin. In contrast, there was no difference in the hemoglobin concentration, erythrocyte sedimentation rate, and the incidence of conjunctival injection, oropharyngeal change, polymorphous rash, extremity change, and incomplete KD. Conclusion: Current evidence suggested that the children with KDSS had more severe indicators of inflammation and more cardiac abnormalities. These patients were resistant to immunoglobulin treatment and required extra anti-inflammatory treatment. Systematic Review Registration: PROSPERO registration number CRD42021241207.
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Coronary artery complication in Kawasaki disease and the importance of early intervention: a systematic review and meta-analysis
Chen S, Dong Y, Kiuchi MG, Wang J, Li R, Ling Z, Zhou T, Wang Z, Martinek M, Purerfellner H, et al
Jama Pediatrics. 2016;170((12):):1156-1163
Abstract
Importance: The timing and selection of patients with Kawasaki disease for corticosteroid use to prevent coronary artery complications remain controversial. Objective: To evaluate the effect of corticosteroid therapy in KD. Data Sources: Databases of Medline, The Cochrane Library, and the Clinicaltrials.gov website until July 2015. We used the key words ["Kawasaki disease"] and ["steroid" OR "corticosteroid"] to retrieve potentially relevant studies in the databases of Medline, the Cochrane Library, and the Clinicaltrials.gov website until July 2015. Both English and non-English literature was identified. Titles and abstracts were reviewed by 2 authors (S.C. and Y.D.) to determine suitability for inclusion. Relevant articles were reassessed by reviewing the full text. Discrepancies in study inclusion were resolved by consensus (M.G.K.). Study Selection: Clinical studies that compared corticosteroids plus intravenous immunoglobulin (IVIG) therapy with IVIG therapy alone in treating patients with KD. Studies either using corticosteroids as initial therapy or as rescue therapy were included. Data Extraction and Synthesis: Investigators independently extracted the data information. Data were quantitatively synthesized using random-effects analysis. Main Outcomes and Measures: Rate of coronary artery abnormalities. Results: Sixteen comparative studies characterizing 2746 patients were analyzed. The duration of illness before corticosteroids therapy was significantly shorter in the initial corticosteroids subset than in the rescue corticosteroids subset. The rate of coronary artery abnormalities was significantly lower in adjunctive corticosteroids therapy than in IVIG therapy (odds ratio [OR], 0.424; 95% CI, 0.270-0.665). Meta-regression based on known variables demonstrated that the overall efficacy was negatively correlated with the duration of illness before corticosteroid therapy (P < .001). Subgroup analysis, including studies using corticosteroids plus IVIG as initial therapy, showed a more advantageous effect than IVIG alone regarding coronary artery abnormality prevention (OR, 0.320; 95% CI, 0.183-0.560), whereas this benefit was not found in a subgroup of studies using corticosteroids as rescue therapy. Further analysis found that patients predicted at baseline to be at high risk of IVIG resistance seemed to obtain the greatest benefit from adjunctive corticosteroid therapy regarding coronary artery abnormality prevention (OR, 0.240; 95% CI, 0.123-0.467). The fever duration was significantly reduced in the corticosteroids group. The favorable effects of corticosteroids were conferred without an increased risk of adverse events. Conclusions and Relevance: This study highlights the importance of timing to prevent coronary artery complication in treating KD. High-risk patients with KD benefit greatly from a timely and potent adjunctive corticosteroid therapy strategy.