Clinical effect of reduning combined with gamma globulin treatment on symptom improvement serum levels of IL-6, 25-(OH)D and LDH in children with severe mycoplasma pneumonia
Pakistan journal of medical sciences. 2022;38(4Part-II):826-832
OBJECTIVES To investigate the effects of Reduning combined with gamma globulin on symptom improvement and serum levels of interleukin-6 (IL-6), 25-hydroxyvitamin D[25-(OH)D] and lactate dehydrogenase (LDH) in children with severe mycoplasma pneumonia (MP). METHODS A total of 123 children with severe MP admitted to the Changzhou Cancer Hospital affiliated to Soochow University from May 2018 to April 2020 were selected as subjects and randomly divided into three groups: control Group-A, control Group-B and the observation group, with 41 cases in each group. Control Group-A was given with Reduning, control Group-B was treated with gamma globulin, while the observation group was treated with Reduning injection combined with gamma globulin. The clinical efficacy, symptom improvement, incidence of adverse reactions, serum levels of IL-6, 25-(OH)D, LDH, Toll-like receptor 4/myeloid differentiation factor 88 (TLR4/MyD88) signaling pathway and T lymphocyte subsets before and after treatment were statistically compared between the three groups. RESULTS The total effective rate of treatment in the observation group was higher than that in control Group-A and control Group-B (p<0.05); The time for body temperature, lung rales, and cough to return to normal in the observation group was shorter than that in control Group-A and control Group-B (p<0.05). After treatment, the observation group had lower serum levels of IL-6, LDH, and higher levels of 25-(OH)D compared with control Group-A and control Group-B (p<0.05). Moreover, the observation group had lower serum expressions of TLR4 and MyD88 (p<0.05), higher serum levels of CD4(+), CD4(+)/CD8(+), and lower CD8(+) compared with control Group-A and control Group-B (p<0.05). No significant difference can be seen in the comparison of the incidence of adverse reactions between the three groups (p>0.05). CONCLUSIONS Reduning combined with gamma globulin in the treatment of severe MP is worthy of clinical promotion and application. With such a treatment regimen, the immune function of children with severe MP can be significantly enhanced, the inflammatory response can be suppressed, and symptom improvement can be promoted, further improving the treatment outcome.
Pharmacologic interventions for Kawasaki disease in children: A network meta-analysis of 56 randomized controlled trials
BACKGROUND Although the current consensus recommends a standard treatment of high-dose intravenous immunoglobulin with high-dose aspirin to manage Kawasaki disease (KD), the use of different adjunctive therapies remains controversial. The aim of the current network meta-analysis (NMA) was to compare the efficacy and tolerability of different existing interventions for the initial and refractory stages of KD. METHODS An NMA of randomised controlled trials (RCTs) was conducted using the frequentist model applied after electronic searches in PubMed, Embase, ScienceDirect, ProQuest, ClinicalTrials.gov, ClinicalKey, Cochrane CENTRAL, and Web of Science. The main outcomes were reduced fever duration/diminished severity of fever subsided. The initial stage of KD was defined as the first stage to treat patients with KD; the refractory stage of KD represents KD patients who failed to respond to standard KD treatment. The cut-off points for intravenous immunoglobulin (IVIG) were low (100-400 mg), medium (1 g), and high (at least 2 g). FINDINGS A total of fifty-six RCTs with 6486 participants were included. NMA demonstrated that the medium-dosage IVIG + aspirin + infliximab [mean difference=-1.76 days (95% confidence intervals (95% CIs): -3.65 to 0.13 days) compared to high-dosage IVIG + aspirin] exhibited the shortest fever duration; likewise, the medium-dosage IVIG + aspirin + infliximab [odds ratio (OR)=0.50, 95% CIs: 0.18-1.37 compared to high-dosage IVIG + aspirin] exhibited the smallest incidence of coronary artery lesion (CAL) in the initial-stage KD. In the refractory-stage KD, the high-dosage IVIG + pulse steroid therapy (OR=0.04, 95% CIs: 0.00-0.43 compared to the high-dosage IVIG only) had the best rate of decline of fever; likewise, the high-dosage IVIG + ciclosporin [OR=0.05 (95% CIs: 0.00-1.21) compared to the high-dosage IVIG only] exhibited the smallest incidence of CAL. Infliximab significantly improved resolution compared to the high-dosage IVIG only group (OR=0.20, 95%CIs: 0.07-0.62) in refractory-stage KD. INTERPRETATION The NMA demonstrated that the combination therapy with the standard therapy of IVIG and aspirin might have an additional effect on shortening the duration of fever and lowering the CAL incidence rate in patients with acute KD. Moreover, the combination therapy with high-dose IVIG and pulse steroid therapy or cyclosporine therapy might have an additional effect on improving the rate of decline of fever and lowering the incidence rate of CAL in children with refractory KD. Because some of the findings of this NMA should be considered hypothesis-generating rather than confirmatory, further evidence from de novo randomised trials is needed to support our results. FUNDING None.
Characteristics and conflicting recommendations of clinical practice guidelines for COVID-19 management in children: A scoping review
Travel medicine and infectious disease. 2022;48:102354
BACKGROUND Clinical practice guidelines (CPGs) are statements that should be rigorously developed to guide clinicians' decision-making. However, given the scarce evidence for certain vulnerable groups like children, CPGs' recommendations formulation could be challenging. METHODS We conducted a scoping review of CPGs for COVID-19 management in children. Documents were included if they claimed to be a "clinical practice guideline", published between January and October 2021, and described the process followed to issue their recommendations. We assessed the quality using the "Appraisal of Guidelines for Research and Evaluation II" (AGREE-II) and described how the recommendations were reached. RESULTS We found five CPGs that fulfilled our inclusion criteria. The median score on the overall AGREE-II evaluation was 61% (range: 49%-72%), and the score on the third domain referred to the rigor of methodological development was 52% (range: 25%-88%). Recommendations for remdesivir, tocilizumab, and intravenous immunoglobulin were heterogeneous across CPGs (in favor, against, no recommendation), as well as the methodologies used to present the evidence, perform the benefits/harms balance, and issue the recommendation. CONCLUSIONS Heterogeneous recommendations and justifications across CPGs were found in the three assessed topics. Future CPGs should describe in detail their evidence-to-decision process to issue reliable and transparent recommendations.
Tranexamic acid reduces postoperative blood loss in Chinese pediatric patients undergoing cardiac surgery: A PRISMA-compliant systematic review and meta-analysis
BACKGROUND Tranexamic acid has been increasingly used for blood conservation in cardiac surgery. However, the evidence supporting the routine use of tranexamic acid in Chinese pediatric patients undergoing cardiac surgery remains weak. This meta-analysis aimed to systematically review the efficacy of tranexamic acid when applying to Chinese pediatric patients undergoing cardiac surgery. PARTICIPANTS Chinese pediatric patients undergoing cardiac surgery. INTERVENTIONS Tranexamic acid or control drugs (saline/blank). METHODS PUBMED, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Data till May 4, 2021, database search was updated on August 1. Primary outcomes of interest included postoperative bleeding, allogeneic transfusion, and reoperation for bleeding. Secondary outcomes of interest included postoperative recovery. For continuous/dichotomous variables, treatment effects were calculated as weighted mean difference (WMD)/odds ratio and 95% confidence interval. RESULTS A database search yielded 15 randomized controlled trials including 1641 patients, where 8 studies were allocated into non-cyanotic congenital group, 5 were allocated into cyanotic congenital group, and the other 2 were allocated into combined cyanotic/non-cyanotic group. This meta-analysis demonstrate that tranexamic acid administration can reduce the postoperative 24 hours blood loss in non-cyanotic, cyanotic, and combined cyanotic/non-cyanotic patients, the red blood cell transfusion in non-cyanotic and cyanotic patients, and the fresh frozen plasma transfusion in non-cyanotic and combined cyanotic/non-cyanotic patients. CONCLUSION This meta-analysis demonstrates that tranexamic acid is highly effective in reducing the blood loss in Chinese pediatric cardiac surgery, but it behaves poorly when it comes to the transfusion requirement. To further confirm this, more well-designed and adequately-powered randomized trials are needed.
Dorsal Dartos Flap Prepared Before Urethroplasty, Less Bleeding of Operation: A New Perspective on Hypospadias
Turkish journal of urology. 2022;48(2):150-154
BACKGROUND The benefits of preparing the dorsal dartos flap before urethroplasty were investigated. MATERIALS AND METHODS Patients with coronal, subcoronal, and distal penile hypopadias without severe cordee who underwent surgical repair between October 2016 and September 2020 were included in the study. Tubularized incised plate urethroplasty technique was applied to all patients. The patients were divided into two groups: In Group 1, the dorsal dartos flap was prepared after urethroplasty, which is the commonly used technique today, and sutured on the neourethra. In Group 2, the dorsal dartos flap was prepared before the post-degloving urethroplasty. The amount of bleeding, the duration of the surgery, and the complications between the two groups were recorded and compared. RESULTS Twenty-two patients who could be followed up for at least 3 months were examined. There were 10 patients in Group 1 and 12 patients in Group 2. A statistically significant difference was found between the amount of bleeding of the operation in the two groups. Duration of operation, hematoma, infection, skin necrosis, or glanular dehiscence were not observed in any patient. CONCLUSIONS Preparing the dorsal dartos flap, before urethroplasty significantly reduces the amount of bleeding. This may be a new modification alternative in hypospadias surgery.
Safety and efficacy of aprotinin versus tranexamic acid for reducing absolute blood loss and transfusion in pediatric patients undergoing craniosynostosis surgery: a randomized, double-blind, three-arm controlled trial
Journal of neurosurgery. Pediatrics. 2022;:1-9
OBJECTIVE Craniosynostosis surgery is associated with considerable blood loss and need for transfusion. Considering the lower estimated blood volume (EBV) of children compared to adults, excessive blood loss may quickly lead to hypovolemic shock. Therefore, reducing blood loss is important in craniosynostosis surgery. This study was conducted to evaluate the efficacy of aprotinin or tranexamic acid (TXA) in blood loss reduction in these patients. METHODS In the current randomized controlled trial, 90 eligible pediatric patients with craniosynostosis were randomly divided into three groups to receive either aprotinin, TXA, or no intervention. The absolute blood loss and transfusion amount were assessed for all patients both intraoperatively and 2 and 8 hours postoperatively. RESULTS Although crude values of estimated blood loss were not significantly different between groups (p = 0.162), when adjusted to the patient's weight or EBV, the values reached the significance level (p = 0.018), particularly when the aprotinin group was compared to the control group (p = 0.0154). The EBV losses 2 hours and 8 hours postoperatively significantly dropped in the TXA and aprotinin groups compared to the control group (p = 0.001 and p < 0.001, respectively). Rates of postoperative blood transfusion were significantly higher in the control group (p = 0.024). Hemoglobin and hematocrit 8 hours postoperatively were lower in the control group than in the TXA or aprotinin treatment groups (p < 0.002 and p < 0.001, respectively). There were no serious adverse events associated with the interventions in this study. CONCLUSIONS Aprotinin and TXA can reduce blood loss and blood transfusion without serious complications and adverse events in pediatric patients undergoing craniosynostosis surgery.
Paediatric patients undergoing craniosynostosis surgery (n= 90).
Aprotinin (n= 30).
Tranexamic acid (TXA, n= 30). No intervention (n= 30).
The estimated blood volume losses 2 hours and 8 hours postoperatively significantly dropped in the TXA and aprotinin groups compared to no intervention. Rates of postoperative blood transfusion were significantly higher in the no intervention group. Haemoglobin and haematocrit 8 hours postoperatively were lower in the no intervention group than in the TXA or aprotinin treatment groups.
Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review
European journal of pediatrics. 2022;:1-12
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.
Efficacy of combined immunosuppression with or without eltrombopag in children with newly diagnosed aplastic anemia
Blood advances. 2022
We compared the efficacy and safety of eltrombopag (ELTR) combined with immunosuppressive therapy (IST) and IST alone in treatment-naïve children with severe (SAA) and very severe (vSAA) aplastic anemia. Ninety-eight pediatric patients were randomized to receive horse antithymocyte globulin and cyclosporin A with (n=49) or without (n=49) ELTR. The primary endpoint was the overall response rate (ORR) at 4 months. After 4 months, nonresponders were crossed over to the alternative group. In all patients, the ORR in ELTR+IST and IST groups was similar (65% vs. 53%, p=0.218); however, the complete response (CR) rate was significantly higher in ELTR+IST group (31% vs. 12%, p=0.027). In severity subgroups, the ORR was 89% vs. 57% (p=0.028) in favor of IST+ELTR in SAA, but it did not differ in patients with vSAA (52% vs. 50%, p=0.902). At 6 months after the crossover, 61% of initial ELTR(-) patients achieved a response compared to 17% of initial ELTR(+) patients (p=0.016). No significant difference in ELTR+IST and IST groups was observed in the 3-year OS (89% vs. 91%, p=0.673) or the 3-year EFS (53% vs. 41%, p=0.326). There was no unexpected toxicity related to ELTR. Adding ELTR to standard IST was well tolerated and increased the CR rate. The greatest benefit from ELTR combined with IST was observed in patients with SAA, but not in those with vSAA. The second course of IST resulted in a high ORR in initial ELTR(-) patients who added ELTR and had limited efficacy among patients who received ELTR upfront. Clinicaltrials.gov #NCT03413306.
Clinical effect of combination of octreotide and omeprazole in children with acute upper gastrointestinal bleeding and the levels of serum creatinine and serum urea nitrogen
Pakistan journal of pharmaceutical sciences. 2022;35(1(Special)):343-347
Pediatric upper gastrointestinal bleeding refers to an acute massive hemorrhage of the upper digestive tract and biliary tract, which is a common clinical emergency in pediatrics. This study aimed to evaluate the clinical effect of octreotide combined with omeprazole in pediatric upper gastrointestinal bleeding. Totally 84 cases of pediatric upper gastrointestinal bleeding admitted to Ningbo Women and Children's Hospital from November 2019 to April 2021 were divided into groups according to the admission order. The control group received omeprazole treatment and the observation group received octreotide plus. The total clinical effective rate of children in the observation group was higher than that of the control group. The observation group was superior to the control group with respect to the average hemostasis time, hemostasis rate, rebleeding rate and length of stay after treatment. The observation group witnessed a significantly better quality of life than the control group. For children with acute upper gastrointestinal bleeding, the combination of omeprazole and octreotide yields a promising effect in the adjustment of blood creatinine and serum urea nitrogen levels and hemostasis, which is worthy of clinical application.
Multisystemic Inflammatory Syndrome in Neonates: A Systematic Review
INTRODUCTION Multisystem inflammatory syndrome in neonates (MIS-N) related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has increasingly been reported worldwide amid the spread of the SARS-CoV-2 pandemic. METHODS We searched PubMed, EMBASE, and CINAHL and preprint servers (BioRxiv.org and MedRxiv.org) using a specified strategy integrating Medical Subject Headings terms and keywords until October 20, 2021. Our aim was to systematically review demographic profiles, clinical features, laboratory parameters, complications, treatments, and outcomes of neonates with MIS-N. Studies were selected when fulfilling the inclusion criteria. Articles were included if they fulfilled the World Health Organization (WHO), Centers for Disease Control (CDC) definitions of MIS-C, or our proposed definition. RESULTS Sixteen reports of MIS-N including 47 neonates meeting MIS-N criteria were identified. Presentation included cardiovascular compromise (77%), respiratory involvement (55%), and fever in (36%). Eighty-three percent of patients received steroids, and 76% received immunoglobulin. Respiratory support was provided to 60% of patients and inotropes to 45% of patients. Five (11%) neonates died. CONCLUSION The common presentation of MIS-N included cardiorespiratory compromise with the possibility of high mortality. Neonates with MIS-N related to SARS-CoV-2 may be at higher risk of adverse outcomes.