Abstract

BACKGROUND Standard first-step therapy for Kawasaki disease consists of Intravenous immunoglobulin and high dose Aspirin (80-100 mg/kg/day). The standard dose of Intravenous immunoglobulin (2gr/kg) is strongly effective in reducing the risk of coronary arteries abnormalities. So, the proper dose and efficacy of Aspirin to decrease the risk of coronary arteries abnormalities is a controversial issue. In this study, it is tried to assess the result of eliminating high-dose Aspirin in the treatment of the acute phase of Kawasaki and observe the incidence rate of coronary arteries abnormalities when only Intravenous immunoglobulin was administered. METHODS This study is a prospective randomized, open-label, blinded end-points clinical trial performed in Afzalipour hospital in Kerman University of Medical Sciences from September 2017 to September 2018 in 62 patients with typical and atypical Kawasaki disease. The study group received Intravenous immunoglobulin (2 g/kg) and the control group get the same dose of Intravenous immunoglobulin plus Aspirin with the dose of 80-100 mg/Kg/day until they were afebrile for 48 hours. Afterward, both groups received a daily single dose (3-5 mg/kg) of Aspirin for six weeks. Echocardiography was done after two weeks, six weeks, and six months. Internal diameter of the left and right main coronary arteries was measured and then the corresponding Z-score was calculated. RESULTS In the study group, coronary arteries abnormalities decreased from 38.7% in the 2nd week to 16.1% in the 6th month. In the control group, it declined from 54.8% to 22.6%. There was no statistically significant difference between the groups in term of frequency of abnormal coronary arteries at the study period (P=0.151). CONCLUSIONS We concluded that high dose Aspirin does not have a significant role in preventing coronary arteries abnormalities in Kawasaki disease and giving standard 2 gr/kg/day Intravenous immunoglobulin without high-dose Aspirin in acute-phases therapy does not increase the risk of coronary arteries abnormality.

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.

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.

Abstract

BACKGROUND Coronary artery lesion (CAL) caused by Kawasaki disease (KD) is a leading cause of acquired heart disease in children. Initial treatment of intravenous immunoglobulin (IVIG) can reduce the incidence of CAL. Although most of the current studies have shown a certain correlation between CAL and IVIG resistance, the conclusions are not completely consistent. Thus, we performed this meta-analysis to evaluate the association between IVIG resistance and CAL in KD. METHODS PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure through April 21, 2020 were searched to detect relevant studies. Data analysis was performed with STATA 15.1. RESULTS A total of 53 relevant studies were eligible to this analysis, including 30312 KD patients, of which 4750 were IVIG resistance and 25562 were responders. There was a significant difference found between IVIG resistance and IVIG response groups in the incidence of CAL (P < 0.001, odds ratio (OR), 3.89; 95% confidence interval (CI) (3.18, 4.75)). The heterogeneity test results showed that the I2 value was 74.8%. The meta-regression analysis showed that the study regions might be the sources of heterogeneity. The subgroup analysis suggested that the incidence of CAL in the IVIG resistance group was still higher than that in the IVIG response group under different regions, IVIG resistance diagnostic criteria, CAL diagnostic criteria, and study types. Meanwhile, the sensitivity analysis did not find any significant impact from every single study. CONCLUSIONS This is the first meta-analysis to reveal the incidence of CAL was associated with IVIG resistance in KD patients. Further well-designed studies with uniform criteria are needed to evaluate the incidence of CAL in IVIG resistant patients.

Abstract

The present study aimed to review the relevant studies in order to determine the efficacy of infliximab (IFX) in the treatment of Kawasaki disease (KD). The relevant studies were retrieved using the PubMed, Cochrane and Embase databases. Key sources in the literature were reviewed; all articles published by July 2019 were considered for inclusion. For each study, odds ratios, mean difference and 95% confidence interval (95% CI) were assessed to evaluate study outcomes. A total of 16 studies involving 429 patients were relevant to the questions of interest of the current meta-analysis. Compared with intravenous immunoglobulin (IVIG), IFX or IFX plus IVIG significantly reduced the incidence of adverse events, including the number of patients with fever, changes in lip and oral cavity and/or cervical lymphadenopathy. The white blood cell (WBC), neutrophil and C-reactive protein (CRP) levels were also reduced in the IFX or IFX plus IVIG group compared with those in the IVIG or polyethylene glycol-treated human immunoglobulin (VGIH) groups. The platelet counts, alanine aminotransferase (ALT) levels and Z-scores were increased in the IFX or IFX plus IVIG groups compared with those in the IVIG or VGIH groups. In the single-arm studies, the incidence of coronary artery aneurysm was 0.150 (95% CI: 0.024, 0.277), the non-response rate was 0.097 (95% CI: 0.056, 0.138), and the incidence of adverse events was 0.156 (95% CI: 0.122, 0.190). IFX not only effectively reduced the incidence of fever, conjunctival injection, changes in lip and oral cavity and cervical lymphadenopathy polymorphous exanthema, but also the WBC, neutrophil, ALT and CRP levels. The platelet levels were increased in patients after the IFX therapy compared with patients in the IVIG or VGIH groups. IFX or IFX plus IVIG exhibited improved clinical efficacy in the treatment of KD compared with that of IVIG or VGIH. However, as a limited number of studies was included in the current study, the findings should be verified further.

Abstract

BACKGROUND Kawasaki disease (KD) is a self-limited illness that results in coronary artery aneurysms (CAAs) and threatens children's health and lives. The therapeutic effects of single intravenous immunoglobulin gamma (IVIG) vs. infliximab (IFX) (with or without IVIG) in young children with KD remain unclear. Thus, we made a meta-analysis and systematic review, including all of the studies which have evaluated the effectiveness and safety of IFX and IVIG KD patients. METHODS The databases of the Cochrane Library, PubMed and Embase websites were searched for articles appearing from inception until December 31, 2020. Clinical studies that compared IFX either as initial therapy plus IVIG or rescue therapy after IVIG (IFX group) failure compared with IVIG treatment alone (IVIG group) in treating KD patients were included. RESULTS The meta-analysis included nine studies characterizing 712 patients. The treatment response was significantly higher in the adjunctive IFX therapy group than in the IVIG therapy group [odds ratio (OR) 2.64; 95% CI: 1.52-4.59; P=0.0005]. Subgroup analysis, the effect of IFX therapy on treatment response is more effectiveness in the group of the high-risk KD patients than IVIG therapy (OR 6.07; 95% CI: 2.30-16.04; P=0.0003; random-effects model). Further analysis showed no difference in the improvement of CAAs in short-term follow-up between the two groups. However, adding IFX either as initial therapy or as additional therapy all showed an advantageous effect regarding the ∆Z score of the left anterior descending (LAD) (MD =0.29; 95% CI: 0.27-0.31; P<0.00001) and right coronary artery (RCA) (MD =0.24; 95% CI: 0.22-0.26; P<0.00001). Further, IFX exhibited significant effect on the treatment response compared with IVIG therapy in the Asian group (OR, 2.84; 95% CI: 1.51-5.36; P=0.001; random-effects model), and the beneficial effects of IFX were given without increasing the risk of AEs. CONCLUSIONS This meta-analysis emphasizes the importance of IFX on the treatment response in the high-risk KD patients. IFX may play a role in the Asian KD patients and prevention of progressive CAA, and does not increase the risk of AEs in KD patients.

Abstract

BACKGROUND In childhood immune thrombocytopenia (ITP), an autoimmune bleeding disorder, there is a need for better prediction of individual disease courses and treatment outcomes. OBJECTIVE To predict the response to intravenous Immunoglobulins (IVIg) and ITP disease course using genetic and immune markers. METHODS Children aged below seven years with newly diagnosed ITP (N = 147) from the TIKI study were included, which randomized children to an IVIg or observation group. A total of 46 variables were available: clinical characteristics, targeted genotyping, lymphocyte immune phenotyping, and platelet autoantibodies. RESULTS In the treatment arm, 48/80 children (60%) showed a complete response (platelets ≥100 x 10(9) /L) that lasted for at least one month (complete sustained response; CSR) and 32 exhibited no or a temporary response (absence of a sustained response; ASR). For a biological risk score, five variables were selected by regularized logistic regression that predicted ASR vs CSR: 1) hemoglobin; 2) platelet count; 3) genetic polymorphisms of FcγRIIc; 4) the presence of IgG anti-platelet antibodies; and 5) preceding vaccination. The ASR sensitivity was 0.91 (95% CI, 0.80 - 1.00) and specificity was 0.67 (95% CI, 0.53 - 0.80). In the 67 patients of the observation arm, this biological score was also associated with recovery during one-year follow-up. The addition of the biological score to a predefined clinical score further improved the discrimination of favorable ITP disease courses. CONCLUSIONS The prediction of disease courses and IVIg treatment responses in ITP is improved by using both clinical and biological stratification.

Abstract

INTRODUCTION This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of central disorders of hypersomnolence in adults and children. The review focuses on prescription medications with U.S. Food & Drug Administration approval and nonpharmacologic interventions studied for the treatment of symptoms caused by central disorders of hypersomnolence. METHODS The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine to perform a systematic review. Randomized controlled trials and observational studies addressing pharmacological and nonpharmacological interventions for central disorders of hypersomnolence were identified. Statistical analyses were performed to determine the clinical significance of all outcomes. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was used to assess the evidence for the purpose of making specific treatment recommendations. RESULTS The literature search identified 678 studies; 144 met the inclusion criteria and 108 provided data suitable for statistical analyses. Evidence for the following interventions is presented: armodafinil, clarithromycin, clomipramine, dextroamphetamine, flumazenil, intravenous immune globulin (IVIG), light therapy, lithium, l-carnitine, liraglutide, methylphenidate, methylprednisolone, modafinil, naps, pitolisant, selegiline, sodium oxybate, solriamfetol, and triazolam. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. CITATION Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2021;17(9):1895-1945.

Abstract

OBJECTIVES The purpose of this research was to determine the effectiveness of Pentaglobin® as adjuvant therapy in the treatment of sepsis in preterm newborns. MATERIALS AND METHODS It was a prospective, observational, randomized study for 272 premature neonates and very low birth weight (VLBW) that were diagnosed with sepsis carried at neonatal intensive care units. The patients randomized into control group who received standard sepsis antibiotic treatments, and an intervention group who received Pentaglobin® 5 ml/kg daily for 3 consecutive days as an adjunct therapy to a standard sepsis antibiotic treatment. RESULTS Multiple organisms that isolated from culture specimens were Gram-negative bacteria, Gram-positive, and candida (56.25%, 42.28%, and 1.47%, respectively). The disease duration was distinctively longer in patients who were treated by the standard antibiotic protocol (mean ± standard deviation [SD]: 30.76 ± 3.97, odds ratio [OR]: 30.76, 95% confidence interval [CI]: 30.051, 31.473) comparing to the patients who received Pentaglobin adjuvant therapy (mean ± SD: 26.48 ± 5.55, OR: 26.48, 95% CI: 25.489, 27.477) (P < 0.000). Patients treated by standard antibiotic protocol were associated to a substantially increased risk of death (11.76%, hazard ratio 4.400, 95% CI: 1.432, 13.529, P = 0.009). CONCLUSION Neonatal sepsis is more common in premature and VLBW newborns, and Pentaglobin® management of newborn nosocomial sepsis might be used in addition to other therapies.

Abstract

BACKGROUND Kawasaki disease (KD) is a form of self-limiting vasculitis that causes coronary artery abnormalities in children. Although clinical trials of monoclonal antibodies and anti-cytokine biologics that block cytokine cascades have been conducted, the studies have revealed contradictory results. To examine the effectiveness of treatment with monoclonal antibodies and anti-cytokine biologics for KD patients, we conducted this systematic review and meta-analysis. METHODS Relevant randomized controlled trials (RCTs) and observational studies (e.g., cohort studies, case-control studies, case-series, and case-reports) were included to summarize available evidence, both qualitatively and quantitatively. The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and ICUSHI were used for systematic research. Meta-analysis of the included studies was conducted using fixed-effect or random-effects models, depending on the degree of between-study heterogeneity. We assessed coronary artery and treatment outcomes of the interventions. The certainty of evidence and risk of bias were assessed using the GRADE and Cochrane risk of bias tool. The protocol of this review is registered with PROSPERO (CRD42016033079). RESULTS Results: Of all searched studies, 183 studies were qualitatively analyzed. We finally included four randomized controlled trials with 456 patients in quantitative syntheses. Monoclonal antibodies and anti-cytokine biologics did not reduce the frequency of CAA (risk ratio [RR], 0.93; 95% confidence interval [95%CI], 0.65 to 1.32, low certainty of evidence), compared with the conventional treatment with IVIG. However, the frequency of treatment resistance (RR, 0.60; 95%CI, 0.38 to 0.95, moderate certainty of evidence) was reduced by the antibodies. We found no statistical differences in either "any adverse event" (RR, 0.92; 95%CI, 0.80 to 1.06, low certainty of evidence) or "adverse events attributable to the administration of the medication" (RR, 1.10; 95%CI, 0.72 to 1.69, low certainty of evidence) between the two groups. CONCLUSION Conclusions: Although monoclonal antibodies and anti-cytokine biologics were not effective in reducing the frequency of CAA in KD patients, the frequency of treatment resistance might be reduced by those agents compared with conventional IVIG therapy alone.