Incidence Of Coronary Artery Abnormalities Research Articles

Different dose aspirin plus immunoglobulin (DAPI) for prevention of coronary artery abnormalities in Kawasaki disease: Study protocol for a multi-center, prospective, randomized, open-label, blinded end-point, non-inferiority trial

BackgroundKawasaki disease is a pediatric acute systemic vasculitis that specifically involves the coronary arteries. Timely initiation of immunoglobulin plus aspirin is necessary for diminishing the incidence of coronary artery abnormalities (CAAs). The optimal dose of aspirin, however, remains controversial. The trial aims to evaluate if low-dose aspirin is noninferior to moderate-dose in reducing the risk of CAAs during the initial treatment of Kawasaki disease. MethodsThis is a multi-center, prospective, randomized, open-label, blinded endpoint, noninferiority trial to be conducted in China. The planned study duration is from 2023 to 2026. Data will be analyzed according to intention-to-treat principles. Participants are children and adolescents under the age of 18 with Kawasaki disease, recruited from the inpatient units. A sample size of 1,346 participants will provide 80% power with a one-sided significance level of 0.025. Qualifying children will be randomized (1:1) to receive either intravenous immunoglobulin (2 g/kg) plus oral moderate-dose aspirin (30-50 mg·kg−1·d−1) until the patient is afebrile for at least 48 hours, or immunoglobulin plus low-dose aspirin (3-5 mg·kg−1·d−1) as initial treatment. The primary outcome will be the occurrence of CAAs at 8 weeks after immunoglobulin infusion. Independent blinded pediatric cardiologists will assess the primary endpoint using echocardiography. ConclusionsThere is a shortage of consensus on the dose of aspirin therapy for Kawasaki disease due to the lack of evidence. The results of our randomized trial will provide more concrete evidence for the efficacy and adverse events of low- or moderate-dose aspirin in the acute phase of Kawasaki disease. Trial Registrationwww.chictr.org.cn: ChiCTR2300072686.

Corticosteroids for the treatment of Kawasaki disease in children.

Kawasaki disease (KD), or mucocutaneous syndrome, is the leading cause of childhood-acquired heart disease in high-income countries. There is much controversy on how best to treat children with KD and in particular who may benefit from additional treatment beyond the standard intravenous immunoglobulin (IVIG) and aspirin, such as the addition of corticosteroids. This is an update of the review first published in 2017. To assess the impact of corticosteroid use on the incidence of coronary artery abnormalities in KD as either first-line or second-line treatment. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and two trials registers to 8 February 2021. We searched the reference lists of relevant articles for additional studies. We selected randomised controlled trials involving children with all severities of KD who were treated with corticosteroids, including different types of corticosteroids, different durations of treatment, and where corticosteroids were used alone or in conjunction with other accepted KD treatments. We included trials using corticosteroids for both first- and second-line treatment. Two review authors independently selected studies, assessed study quality and extracted data using standard Cochrane methods. We performed fixed-effect model meta-analyses with odds ratios (ORs) or mean difference (MD) with 95% confidence intervals (CIs). We used a random-effects model when there was heterogeneity. We assessed the certainty of the evidence using GRADE. The outcomes of interest were incidence of coronary artery abnormalities, serious adverse events, mortality, duration of acute symptoms (such as fever), time for laboratory parameters to normalise, length of hospital stay and longer-term coronary morbidity. This update identified one new study, therefore the analysis included eight trials consisting of 1877 participants. Seven trials investigated the use of corticosteroids in first-line treatment and one investigated second-line treatment. The trials were all of good methodological quality. On pooled analysis, corticosteroid treatment reduced the subsequent occurrence of coronary artery abnormalities (OR 0.32, 95% CI 0.14 to 0.75; 8 studies, 986 participants; moderate-certainty evidence), without resultant serious adverse events (0 events; 6 studies, 737 participants; moderate-certainty) and mortality (0 events; 8 studies, 1075 participants; moderate-certainty evidence). In addition, corticosteroids reduced the duration of fever (MD -1.34 days, 95% CI -2.24 to -0.45; 3 studies, 290 participants; low-certainty evidence), time for laboratory parameters (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) to normalise (MD -2.80 days, 95% CI -4.38 to -1.22; 1 study, 178 participants; moderate-certainty evidence), and length of hospital stay (MD -1.01 days, 95% CI -1.72 to -0.30; 2 studies, 119 participants; moderate-certainty evidence). None of the included studies reported long-term (greater than one year after disease onset) coronary morbidity. Moderate-certainty evidence shows that use of steroids in the acute phase of KD can be associated with reduced coronary artery abnormalities, reduced inflammatory markers and shorter duration of hospital stay when compared to no corticosteroids. There were no serious adverse events or deaths reported with or without corticosteroid use. Low-certainty evidence shows use of corticosteroids can reduce duration of clinical symptoms (fever and rash). None of the included studies reported on long-term (greater than one year after disease onset) coronary morbidity. Evidence presented in this systematic review agrees with current clinical guidelines on the use of corticosteroids in the first-line treatment in KD.

Frequency of Coronary Artery Anomalies Undergoing Coronary Interventions Patients at Tertiary Hospital

Aims: This study aims to identify the frequency of Coronary Artery Anomalies (CAA) in coronary intervention receiving patients at tertiary care hospital.
 Sample: To obtain the sample size of the study i.e., 228 were selected at a Confidence level of 95%.
 Study Design: Cross-sectional study.
 Place and Duration of Study: This Descriptive cross-sectional study was conducted at Tertiary care hospital - National Institute of Cardiovascular Disease, Sindh-Karachi. Six months after the approval from IRB-NICVD (April 2018 – October 2018).
 Methodology: Nonprobability consecutive sampling was used to collect the study data. All Patients of either gender from age 18 to 60 years of age undergoing Primary Coronary Intervention (PCI)/ coronary artery angiography because of substernal chest pain were included.
 Results: Total 228 sample population was enrolled in the study, among which 88 (38.6%) were females and 140 (61.4%) were males. CAA was found in the coronary arteries of patients with abnormal aortic valves with a frequency of 1.3 percent. The most often occurring anomaly in our analysis is the separation of the origins of Left Anterior Descending Artery (LAD) and Left Circumflex Artery (LCx) from the Left Coronary Artery (LCA). The Circumflex Artery resulting from Right Coronary Sinus (RCS)/ Right Coronary Artery (RCA) was the second most often seen anomaly in our analysis, accounting for 22.78 percent of all anomalies. The RCA caused by LCS was the next abnormality, with a 7.59 percent frequency. In three cases, the left major coronary artery was derived from RCS, accounting for 3.8 percent of abnormalities.
 Conclusion: Among patients receiving diagnostic coronary angiography, we discovered a 0.9 percent incidence of coronary artery abnormalities. In our research, the prevalence of coronary artery abnormalities was 7% among patients who had coronary procedures. The drawback of our research is that we only included individuals who had had coronary angiograms rather than a random sample of the different cardiac tertiary care hospitals.

A 2-Month-Old with Kawasaki Disease with Coronary Artery Dilation in the Pre-COVID-19 Era

Patient: Male, 2-month-old Final Diagnosis: Kawasaki disease Symptoms: Bleeding and peeling lips • conjunctival injection • erythema of the palms and soles • erythematous (polymorphous) maculopapular rash • fever • nasal congestion Medication: — Clinical Procedure: Echocardiography • electrocardiogram Specialty: Pediatrics and Neonatology Objective: Rare disease Background:Kawasaki disease (KD) is an acute inflammatory vasculitis, which occurs mostly in childhood, predominantly between the ages of 6 months and 5 years. The incidence of coronary artery abnormalities associated with KD has decreased from 25% to 4% as a result of timely diagnosis and treatment with intravenous immunoglobulin (IVIG). Infants ≤6 months of age are the most likely to develop prolonged fever without the other clinical criteria for KD, and diagnosis can sometimes be challenging or delayed. They are therefore at particularly high risk of developing coronary artery abnormalities.Case Report:A 2-month-old male infant with no significant medical history initially presented with a history of nasal congestion, right conjunctivitis, red lips, and 1 loose stool in the pre-COVID-19 era. He was diagnosed with otitis media and was started on oral amoxicillin. By day 7 of fever, he had developed symptoms and signs and laboratory findings consistent with Kawasaki disease, which is rare in this age group. His echocardiogram showed dilated proximal left anterior descending and right coronary arteries. He was successfully treated, and his most recent echocardiogram, performed 17 months after his treatment, showed remarkable improvement in the coronary arteries.Conclusions:Kawasaki disease in children less than 6 months of age is still rare, and the presentation can sometimes make the diagnosis somewhat challenging. Increased clinical suspicion is required for recognition in the youngest patients, as they are more likely to present with few features of KD. Early diagnosis and treatment are needed to prevent or minimize the risk of significant coronary artery abnormalities.

Kawasaki disease associated pulmonary involvement in infants.

Kawasaki disease (KD) is an acute, self-limited multisystemic vasculitis of unknown cause. Pulmonary involvement has been reported in case reports and limited small case series, which is not commonly recognized, especially in younger patients <1 year. Here, we describe clinical and radiological features of infants with KD-associated pulmonary involvement (KD-PI). Infants with KD were retrospectively enrolled during the period January 2017 to December 2020 in Shenzhen Children's hospital. Patients with KD-PI were matched 1:1 based on current age and sex with KD patients without clinically apparent PI. Clinical data were collected from inpatient or outpatient medical records, including clinical manifestations, laboratory parameters, radiological findings, management, and prognosis. Of 248 infant patients with KD, 34 presented with KD-PI. Of these, 22 had only subtle respiratory symptoms. Compared to KD controls, patients with KD-PI had significantly higher mean Kobayashi score (mean ± SD: 2.85 ± 1.94; p = .004), more had extremely high C-reactive protein (≥10 mg/dl: 11/34, 32.3%; p = .0115) and procalcitonin levels (˃1 ng/ml: 16/34, 47%; p = .039), and more were administered with adjuvant corticosteroids as initial therapy (38.2% vs. 2.9%; p = .0005). Abnormal chest radiological findings included peripheral consolidation (97.0%), localized pleural thickening (73.0%), lobular septal thickening (70.6%), ground-glass opacities (55.9%), linear opacities (35.3%), and pleural effusion (20.6%). No statistical difference was observed in the incidence of coronary artery abnormalities (CAAs) between two groups either in the acute phase or follow-up phase. Higher use of adjuvant corticosteroids during initial therapy in our population may result in no difference in CAAs between the two groups despite higher levels of inflammation in KD-PI. Those results suggest that use of adjuvant corticosteroids may be beneficial in this population.

Efficacy and safety associated with the infusion speed of intravenous immunoglobulin for the treatment of Kawasaki disease: a randomized controlled trial

BackgroundHigh-dose intravenous immunoglobulin (IVIG) is the mainstay of treatment for Kawasaki disease (KD). Usually, 2 g/kg of IVIG is administered over 10–24 h, depending on the institution or physician, but the association between infusion speed and effectiveness has not been reported. In this study, we evaluated the differences in efficacy and safety between two different IVIG administration speeds.MethodsThis was a multicenter, unblinded, randomized controlled study. Patients newly diagnosed with KD were randomized into two groups: one who received IVIG over 12 h (12H group, double speed), and one that received IVIG over 24 h (24H group, reference speed). The endpoints included the duration of fever, incidence of coronary artery abnormalities (CAAs) and of adverse events. Laboratory data were evaluated before and after IVIG administration.ResultsA total of 39 patients were enrolled. There was no difference between groups in fever duration after the initiation of IVIG (21 h vs. 21.5 h, p = 0.325), and no patient experienced CAAs. Two adverse events were observed in the 12H group (elevation of aspartate aminotransferase and vomiting), however no severe adverse events requiring treatments or extension of hospital stay were observed in either group. After initial IVIG administration, the change ratio of inflammatory markers, such as white blood cell counts, neutrophils, C-reactive protein, and albumin, did not show significant differences between the two groups. On the other hand, a greater increase of serum immunoglobulin G from its baseline level was observed in the 24H group compared to the 12H group (3037 ± 648 mg/dl vs. 2414 ± 248 mg/dl, p < 0.01).ConclusionThe efficacy and safety of IVIG administered over 12 h (double speed) were similar to those administered over 24 h (reference speed).Trial registrationUniversity Hospital Medical Information Network (UMIN000014665). Registered 27 July 2014 – Prospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000017058

A Retrospective Cohort Study of Intravenous Immunoglobulin Therapy in the Acute Phase of Kawasaki Disease: The Earlier, the Better?

Background Although intravenous immunoglobulin (IVIG) is expected to prevent coronary artery abnormalities of Kawasaki disease (KD) in the acute phase, the timing and effectiveness of IVIG remain to be determined. The association of timing of IVIG administration in KD patients with coronary artery abnormalities is evaluated in this cohort study. Methods We systematically studied KD patients from two participating institutions between 2015 and 2017. To reveal the effectiveness of IVIG treatment, these patients were classified into four groups regarding the time of IVIG treatment. Primary outcome was coronary artery abnormalities by echo at diagnosis and 12 months follow-up; secondary outcomes included inflammatory markers. Results A total of 1281 patients were included in this study. The best time of IVIG treatment cut-off values in 12 months follow-up for predicting coronary artery abnormalities was days 7.5 of illness onset. According to the best time of IVIG treatment cut-off values, all patients were classified into 4 groups. Group 1 was defined as earlier IVIG treatment administration on days ≤4 of the illness (n = 77). Group 2 was defined with days 5-7 (n = 817), group 3 with days 8-10 (n = 249), group 4 with days >10 (n = 138). A greater proportion of IVIG-resistant KD patients were group 4 than the other three groups, and there were significant differences (p < 0.05). The incidence of coronary artery lesions (CALs) and coronary artery aneurysms (CAAs) in group 3 and group 4 was higher than that in group 1 (p < 0.05) and group 2 (p < 0.05) during a 12-month follow-up. Additionally, the incidence of CALs in group 1 was higher than that in group 2 but without statistical significance (p > 0.05). The OR was significantly higher for those who started IVIG administration more than 7 days from the onset was positively associated with the occurrence of CALs (OR, 5.3; 95% CI, 2.0-13.9) and CAAs (OR, 13.5; 95% CI, 2.9-14.1) 12 months after initial onset. Multivariate regression revealed that the timing of IVIG treatment and IVIG-resistance was independent risk factors of CALs. Conclusions IVIG treatment less than 7 days after illness onset are found to be sufficient for preventing developing coronary artery abnormalities in KD patients. Earlier IVIG treatment administration within 4 days may not increase the higher incidence of coronary artery abnormalities and IVIG resistance (Chinese Clinical Trial Registry:ChiCTR1800015800).

Correlation of Coronary Artery Abnormalities with Fever Pattern in Patients with Kawasaki Disease

To investigate the incidence of coronary artery abnormalities (CAAs) by fever pattern after intravenous immunoglobulin (IVIG) therapy in patients with Kawasaki disease. This retrospective cohort study included 172 patients with Kawasaki disease aged ≤12years who underwent IVIG therapy and had no CAAs before treatment. Resistance to initial IVIG was defined as persistent fever ≥37.5 °C for ≥24hours after therapy or the recurrence of Kawasaki disease after initial defervescence. The patients were divided into 3 groups: IVIG responders, nonresponders with persistent fever, and nonresponders with recurrent fever. CAAs were evaluated 2 or 4weeks and 12months after onset and were defined by a coronary artery z-score ≥2.5. The incidence of CAAs within 12months after onset was significantly higher in nonresponders with persistent fever (27%) compared with the other 2 groups. On multivariate logistic regression analysis, being a nonresponder with persistent fever was an independent risk factor for having CAAs within 12months after the onset of Kawasaki disease (OR, 6.48; P=.007). In patients with Kawasaki disease resistant to IVIG therapy, persistent fever, but not recurrent fever, was found to be a risk factor for the incidence of CAAs. Aggressive additional therapy may be beneficial to prevent CAA formation in patients with Kawasaki disease with persistent fever.

Indian Academy of Pediatrics Position Paper on Kawasaki Disease

To formulate practice guidelines on diagnosis and management of Kawasaki disease (KD) for Indian children. KD is a systemic vasculitis that predominantly affects infants and children less than 5 years of age. Coronary artery abnormalities (CAA) develop in around 15-25% of untreated children with KD. Coronary artery involvement can lead to long-term cardiovascular implications such as development of premature coronary artery disease. Diagnosis of KD is essentially clinical based on recognition of a constellation of characteristic symptoms and signs. Timely diagnosis and initiation of intravenous immunoglobulin (IVIG) therapy is known to produce five-fold reduction in the incidence of CAA. As there is no confirmatory laboratory test for KD, the diagnosis may be missed if one is not familiar with the nuances of clinical diagnosis. A committee was formed under the auspices of Indian Academy of Pediatrics in early 2018 for preparing guidelines on KD in Indian children. A meeting of the consultative committee was held in Mumbai, and a draft protocol was devised. All members scrutinized the recent publications on the subject and an attempt was made to arrive at a broad consensus. Published guidelines on the subject were also reviewed. The diagnosis is clinical and is aided by laboratory and 2D echocardiography. First line of therapy is IVIG, and should be started expeditiously once the diagnosis is made.

Treatment change and coronary artery abnormality in incomplete Kawasaki disease.

Incomplete Kawasaki disease (iKD) showed a higher incidence of coronary artery abnormalities (CAAs) than complete KD. However, the incidence of CAAs among iKD patients may have changed recently. We examined KD patients from recent nationwide surveys conducted between 2013 and 2016 and compared them with the results of a previous survey (2001-2002). Of 63270 KD patients, 13770 patients (22%) had iKD. They showed a higher incidence of convalescent-phase CAAs (cCAAs, 2.8%) than complete KD (2.1%). The incidence of cCAAs in patients with one or two symptoms (6.7%) was significantly higher than those with three or four symptoms (2.6%) (P < 0.0001). Intravenous immunoglobulin (IVIG) treatment was administered to 80% of iKD patients; 30% of them received IVIG before the fifth illness day (early treatment) and 12% of patients received IVIG after the seventh illness day (late treatment). In the previous survey, the incidence of cCAAs was higher in both iKD (5.9%) and cKD (4.4%). Intravenous immunoglobulin was administered to 62% of iKD patients; 26% of them received early treatment, and 16% received late treatment. The incidence of cCAAs remained higher among iKD patients than cKD patients but this difference was reduced by the increased proportion of iKD patients treated with IVIG and those at an earlier time point. It is important to recognize the possibility that patients may have iKD and perform echocardiography even if they present with a few principal symptoms.

Aspirin Dose and Treatment Outcomes in Kawasaki Disease: A Historical Control Study in Japan.

Aspirin has been used as a concomitant drug in the treatment of Kawasaki disease (KD). In recent years, there has been discussion concerning whether high-dose aspirin is appropriate for treatment in the acute phase of KD. We retrospectively investigated the incidence of coronary artery abnormalities (CAAs) and the antipyretic effect of 30 to 50 mg/kg/day aspirin, the minimum and the maximum approved doses in Japan. This was a single-center, non-randomized, retrospective, historical cohort study. Patients were routinely treated with 50 mg/kg/day aspirin (50-mg Group) between 2007 and April 2014, and with 30 mg/kg/day aspirin (30-mg Group) between May 2014 and 2016. All patients were given initial and, if necessary, subsequent intravenous immunoglobulin (IVIG) 2.0 g/kg. The primary endpoint was incidence of CAAs defined as a CA diameter with a Z score ≥2.5 at treatment week 4. The secondary endpoint was incidence of further treatment. Incidences were compared using inverse probability weighting analysis adjusting for age, sex, and risk scores. In 587 patients, there was no significant difference in incidence of CAAs (odds ratio in 30-mg Group 0.769, 95% confidence interval (CI): 0.537–1.101, p = 0.151). Risk of further treatment after the first IVIG in the 30-mg Group was significantly higher than that in the 50-mg Group (odds ratio 1.379, 95% CI: 1.051–1.811, p = 0.021). Although this study has some limitations, the findings suggest that aspirin 50 mg/kg/day may have no significant effect on improving incidence of CAAs compared with 30 mg/kg/day but may have a lower rate of further treatment.

What dose of aspirin should be used in the initial treatment of Kawasaki disease? A meta-analysis.

The use of IVIG plus high- or low-dose aspirin for the initial treatment of Kawasaki disease remains controversial. The aim of this study was to evaluate the efficacy of IVIG plus high-dose aspirin compared with IVIG plus low-dose aspirin in the treatment of Kawasaki disease. Studies related to aspirin therapy for Kawasaki disease were selected by searching the databases of Medline (PubMed), Embase and the Cochrane Library before March 2019. Statistical analyses were performed by using a Review Manager Software package and STATA v.15.1. Eight retrospective cohort studies, characterizing 12176 patients, were analysed. Overall, no significant difference was found in the incidence of coronary artery abnormalities between the high- and low-dose aspirin groups [relative risk (RR) 1.15; 95% CI: 0.93, 1.43; P = 0.19; random-effects model]. The patients treated with high-dose aspirin had slightly faster resolution of fever [mean difference (MD) -0.30; 95% CI: -0.58, -0.02; P = 0.04; random-effects model]. but the rates of IVIG resistance (RR, 1.26; 95% CI: 0.55, 2.92; P = 0.59; random-effects model) and days in hospital (MD, 0.22; 95% CI: -0.93, 1.37; P = 0.71; random-effects model) were similar between the two groups. Low-dose aspirin plus IVIG might be as effective as high-dose aspirin plus IVIG for the initial treatment of Kawasaki disease. Considering that high-dose aspirin may cause more adverse reactions than low-dose aspirin, low-dose aspirin plus IVIG should be recommended as the first-line therapy in the initial treatment of Kawasaki disease.

TNF-α blockers for the treatment of Kawasaki disease in children

Kawasaki disease (KD) is an acute inflammatory vasculitis (inflammation of the blood vessels) that mainly affects children between six months and five years of age. The vasculitis primarily impacts medium-sized blood vessels, especially in the coronary arteries. In most children, intravenous immunoglobulin (IVIG) and aspirin therapy rapidly reduce inflammatory markers, fever, and other clinical symptoms. However, approximately 15% to 20% of children receiving the initial IVIG infusion show persistent or recurrent fever and are classified as IVIG-resistant. Tumor necrosis factor-alpha (TNF-α) is an inflammatory cytokine that plays an important role in host defence against infections and in immune responses. Several studies have established that blocking TNF-α is critical for obtaining anti-inflammatory effects in children with KD, thus, there is a need to identify benefits and risks of TNF-α blockers for the treatment of KD. To evaluate the efficacy and safety of using TNF-α blockers (i.e. infliximab and etanercept) to treat children with Kawasaki disease. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 19 September 2018. We also undertook reference checking of grey literature. We included randomised controlled trials (RCTs) that compared TNF-α blockers (i.e. infliximab and etanercept) to placebo or other drugs (including retreatment with IVIG) in children with KD, reported in abstract or full-text. Two review authors independently applied the study selection criteria, assessed risk of bias and extracted data. When necessary, we contacted study authors for additional information. We used GRADE to assess the certainty of the evidence. We included five trials from 14 reports, with a total of 494 participants. All included trials were individual RCTs that examined the effect of TNF-α blockers for KD.Five trials (with 494 participants) reported the incidence of treatment resistance. TNF-α blockers reduced the incidence of treatment resistance (TNF-α blocker intervention group 30/237, control group 58/257; risk ratio (RR) 0.57, 95% confidence interval (CI) 0.38 to 0.86; low-certainty evidence).Four trials reported the incidence of coronary artery abnormalities (CAAs). Three trials (with 270 participants) contributed data to the meta-analysis, since we could not get the data needed for the analysis from the fourth trial. There was no clear difference between groups in the incidence of CAAs (TNF-α blocker intervention group 8/125, control group 9/145; RR 1.18, 95% CI 0.45 to 3.12; low-certainty evidence).Three trials with 250 participants reported the adverse effect 'infusion reactions' after treatment initiation. The TNF-α blocker intervention decreased infusion reactions (TNF-α blocker intervention group 0/126, control group 15/124; RR 0.06, 95% CI 0.01 to 0.45; low-certainty evidence).Two trials with 227 participants reported the adverse effect 'infections' after treatment initiation. There was no clear difference between groups (TNF-α blocker intervention group 7/114, control group 10/113; RR 0.68, 95% CI 0.33 to 1.37; low-certainty evidence).One trial (with 31 participants) reported the adverse effect 'cutaneous reactions' (rash and contact dermatitis). There was no clear difference between the groups for incidence of rash (TNF-α blocker intervention group 2/16, control group 0/15; RR 4.71, 95% CI 0.24 to 90.69; very low-certainty evidence) or for incidence of contact dermatitis (TNF-α blocker intervention group 1/16, control group 3/15; RR 0.31, 95% CI 0.04 to 2.68; very low-certainty evidence).No trials reported other adverse effects such as injection site reactions, neutropenia, infections, demyelinating disease, heart failure, malignancy, and induction of autoimmunity. We found a limited number of RCTs examining the effect of TNF-α blockers for KD. In summary, low-certainty evidence indicates that TNF-α blockers have beneficial effects on treatment resistance and the adverse effect 'infusion reaction' after treatment initiation for KD when compared with no treatment or additional treatment with IVIG. Further research will add to the evidence base. Due to the small number of underpowered trials contributing to the analyses, the results presented should be treated with caution. Further large high quality trials with timing and type of TNF-α blockers used are needed to determine the effects of TNF-α blockers for KD.

Efficacy of primary treatment with immunoglobulin plus ciclosporin for prevention of coronary artery abnormalities in patients with Kawasaki disease predicted to be at increased risk of non-response to intravenous immunoglobulin (KAICA): a randomised controlled, open-label, blinded-endpoints, phase 3 trial

Genetic studies have indicated possible involvement of the upregulated calcium-nuclear factor of activated T cells pathway in the pathogenesis of Kawasaki disease. We aimed to assess safety and efficacy of ciclosporin, an immunosuppressant targeting this pathway, for protection of patients with Kawasaki disease against coronary artery abnormalities. We did a randomised, open-label, blinded endpoints trial involving 22 hospitals in Japan between May 29, 2014, and Dec 27, 2016. Eligible patients predicted to be at higher risk for intravenous immunoglobulin (IVIG) resistance were randomly assigned to IVIG plus ciclosporin (5 mg/kg per day for 5 days; study treatment) or IVIG (conventional treatment) groups, stratified by risk score, age, and sex. The primary endpoint was incidence of coronary artery abnormalities using Japanese criteria during the 12-week trial, assessed in participants who received at least one dose of study drug and who visited the study institution at least once during treatment. This trial is registered to Center for Clinical Trials, Japan Medical Association, number JMA-IIA00174. We enrolled 175 participants. One patient withdrew consent after enrolment and was excluded and one patient (in the study treatment group) was excluded from analysis because of lost echocardiography data. Incidence of coronary artery abnormalities was lower in the study treatment group than in the conventional treatment group (12 [14%] of 86 patients vs 27 [31%] of 87 patients; risk ratio 0·46; 95% CI 0·25-0·86; p=0·010). No difference was found in the incidence of adverse events between the groups (9% vs 7%; p=0·78). Combined primary therapy with IVIG and ciclosporin was safe and effective for favourable coronary artery outcomes in Kawasaki disease patients who were predicted to be unresponsive to IVIG. Japan Agency for Medical Research and Development (grant CCT-B-2503).

Kawasaki disease in Turkish children: a single center experience with emphasis on intravenous immunoglobulin resistance and giant coronary aneurysms.

Yılmazer MM, Özdemir R, Meşe T, Küçük M, Öner T, Devrim İ, Bayram N, Güven B, Tavlı V. Kawasaki disease in Turkish children: a single center experience with emphasis on intravenous immunoglobulin resistance and giant coronary aneurysms. Turk J Pediatr 2019; 61: 648-656. Prompt diagnosis and the administration of intravenous immunoglobulin (IVIG) has reduced the incidence of coronary artery abnormalities (CAA) in Kawasaki Disease (KD). The resistance to treatment and development of the coronary sequelae remain the most important problems in KD. We aimed to determine the predicting factors of nonresponse to initial IVIG therapy and to analyze the cases who had giant coronary aneurysms. A total of 120 KD cases, including 61 children fulfilling the criteria for KD and 59 with incomplete KD were enrolled into this study. Demographic, laboratory, clinical, echocardiographic characteristics, and treatment regimens were reviewed, retrospectively. The median age of the patients was 33.5 months (range: 3-168 months). Coronary artery aneurysms were detected in 35 patients (29%) at the time of diagnosis. Twenty-eight patients had coronary aneurysms small or medium in size, one had a large, and seven had giant coronary aneurysms. CAA persisted in 8 cases in the follow-up, all of which were large or giant aneurysms. A ten month-old girl with a giant coronary aneurysm was referred to coronary bypass surgery in the subacute phase of follow-up, due to myocardial ischemia. Eighteen patients were unresponsive to the initial IVIG therapy (%15), of whom 10 were diagnosed as cKD and 8 were iKD. Patients who did not respond to initial IVIG therapy, had higher white blood cell (WBC) count, higher C-reactive protein (CRP) and lower albumin levels than those who did (P < 0.05). In univarite analysis; CRP, WBC and albumin were found to be significant predictors of nonresponse to initial IVIG therapy, while a stepwise multiple linear regression analysis showed that WBC count and albumin levels were significantly correlated with nonresponse to initial treatment with IVIG. Our study showed that WBC count and albumin levels might be used as predictors of nonresponse to the IVIG therapy in Turkish children with KD.

Efficacy and safety of intravenous immunoglobulin plus prednisolone therapy in patients with Kawasaki disease (Post RAISE): a multicentre, prospective cohort study

The RAISE study showed that additional prednisolone improved coronary artery outcomes in patients with Kawasaki disease at high risk of intravenous immunoglobulin (IVIG) resistance. However, no studies have been done to test the steroid regimen used in the RAISE study. We therefore aimed to verify the efficacy and safety of primary IVIG plus prednisolone. We did a multicentre, prospective cohort study at 34 hospitals in Japan. We included patients diagnosed with Kawasaki disease according to the Japanese diagnostic criteria, and excluded those who were treated at other hospitals before being transferred to a participating hospital. Patients who were febrile at diagnosis received primary IVIG (2 g/kg per 24 h) and oral aspirin (30 mg/kg per day) until the fever resolved, followed by oral aspirin (5 mg/kg per day) for 2 months after Kawasaki disease onset. We stratified patients using the Kobayashi score into predicted IVIG non-responders (Kobayashi score ≥5) or predicted IVIG responders (Kobayashi score <5). For predicted non-responders, each hospital independently decided whether to add prednisolone (intravenous injection of 2 mg/kg per day for 5 days) to the primary IVIG treatment, according to their respective treatment policy, and we further divided these patients based on the primary treatment received. The primary endpoint was the incidence of coronary artery abnormalities determined by two-dimensional echocardiography at 1 month after the primary treatment in predicted non-responders treated with primary IVIG plus prednisolone. Coronary artery abnormalities were defined according to the criteria of the Japanese Ministry of Health and Welfare and of the American Heart Association (AHA). This study is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000007133. From July 1, 2012, to June 30, 2015, we enrolled 2628 patients with Kawasaki disease, of whom 724 (27·6%) were predicted IVIG non-responders who received IVIG plus prednisolone as primary treatment. 132 (18·2%) of 724 patients did not respond to primary treatment. Among patients with complete data, coronary artery abnormalities were present in 40 (incidence rate 5·9%, 95% CI 4·3-8·0) of 676 patients according to the AHA criteria or in 26 (3·8%, 2·5-5·6) of 677 patients according to the Japanese criteria. Serious adverse events were reported in 12 (1·7%) of 724 patients treated with primary IVIG plus prednisolone; two of these patients had hypertension and bacteraemia that was probably related to prednisolone. One patient died possibly due to severe inflammation from the Kawasaki disease itself. Primary IVIG plus prednisolone therapy in this study had an effect similar to that seen in the RAISE study in reducing the non-response rate and decreasing the incidence of coronary artery abnormalities. A primary IVIG and prednisolone combination therapy might prevent coronary artery abnormalities and contribute to lowering medical costs. Tokyo Metropolitan Government Hospitals and the Japan Kawasaki Disease Research Center.

Kawasaki disease in infants 3 months of age and younger: a multicentre Spanish study

Kawasaki disease (KD) is a multisystem vasculitis of small and medium vessels typical of childhood. Timely treatment with intravenous immunoglobulin (IVIG) has reduced the incidence of coronary artery abnormalities (CAAs)...

Imaging and Clinical Data Distinguish Lymphadenopathy-First-Presenting Kawasaki Disease from Bacterial Cervical Lymphadenitis.

BACKGROUNDKawasaki disease (KD) sometimes presents with only fever and cervical lymphadenopathy before other clinical signs materialize. This lymphadenopathy-first-presenting Kawasaki disease (LKD) may be misdiagnosed as bacterial cervical lymphadenitis (BCL). We investigated characteristic imaging and clinical data for factors differentiating LKD from BCL.METHODSWe compared imaging, clinical, and laboratory data of patients with KD and BCL. We included patients admitted to a single tertiary center between January 2015 and July 2018.RESULTSWe evaluated data from 51 patients with LKD, 63 with BCL, and 218 with typical KD. Ultrasound imaging revealed multiple enlarged lymph nodes in both LKD and BCL patients. On the other hand, computed tomography (CT) showed more abscesses in patients with BCL. Patients with LKD were younger and showed higher systemic and hepatobiliary inflammatory markers and pyuria than BCL patients. In multivariable logistic regression, younger age and higher C-reactive protein (CRP) retained independent associations with LKD. A comparison of the echocardiographic findings in LKD and typical KD showed that patients with LKD did not have a higher incidence of coronary artery abnormalities (CAA).CONCLUSIONSLKD patients tend to have no abscesses on CT and more elevated systemic hepatobiliary inflammatory markers and pyuria compared to BCL patients. The absence of abscess on CT, younger age, and elevated CRP were the most significant variables differentiating LKD from BCL. There was no difference in CAA between LKD and typical KD.

Efficacy and prognostic factors of arterial switch operation in patients with complete transposition of great arteries

Objective To investigate the clinical efficacy and influencing factors of arterial switch operation (ASO) in the treatment of complete transposition of great arteries (TGA). Methods Totally 156 children with TGA who underwent ASO surgery from January 2005 to December 2011 were selected as the subjects. The clinical curative effect and prognosis of all patients were observed, and the relationship between clinical features and prognosis was analyzed. Results Totally 156 cases of TGA children were successfully completed the operation, and 29 patients died during the 5 year follow-up period, the mortality rate was 18.59%. Univariate analysis showed that the death in children with TGA after ASO was closely related to coronary artery abnormality, cardiopulmonary bypass time, aortic occlusion time, postoperative low cardiac output syndrome and reoperation (P<0.05). Multivariate logistic regression analysis showed that coronary artery abnormalities, and low cardiac output syndrome were independent outcome factors leading to postoperative death in patients. Conclusions The postoperative death of ASO in TGA children is closely related to the incidence of coronary artery abnormalities, the time of cardiopulmonary bypass, the time of occlusion of aorta and the occurrence of postoperative low cardiac output syndrome, which should be pay attention to and take relevant measures. Key words: Transposition of great vessels/SU; Prognosis

Corticosteroids for the treatment of Kawasaki disease in children.

Kawasaki disease (KD), or mucocutaneous syndrome, is the leading cause of childhood-acquired heart disease in the developed world. There is much controversy on how best to treat children with KD and in particular who may benefit from additional treatment beyond the standard intravenous immunoglobulin (IVIG) and aspirin, such as the addition of corticosteroids. To assess the impact of corticosteroid use on the incidence of coronary artery abnormalities in KD as either first-line or second-line treatment. Corticosteroids may be given alone or in conjunction with other accepted KD treatments. Secondary objectives include the effect of steroids on mortality, the time taken for laboratory parameters to normalise, the duration of acute symptoms (such as fever), the long-term impact of steroid use and evaluating their safety in KD and their efficacy in relevant population subgroups. The Cochrane Vascular Information Specialist searched Cochrane Vascular's Specialised Register (25 November 2016) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10) in the Cochrane Library (searched 25 November 2016). Trial registries were also searched for details of ongoing or unpublished studies. We selected randomised trials involving children with all severities of KD who were treated with corticosteroids, including different types of corticosteroid and different durations of treatment. MJS and GMC independently selected studies, assessed evidence quality and extracted data. This process was overseen by AJW. Seven trials consisting of 922 participants were included in this analysis. Trials ranged from 32 to 242 participants. On pooled analysis, corticosteroids reduced the subsequent occurrence of coronary artery abnormalities (odds ratio (OR) 0.29, 95% confidence interval (CI) 0.18 to 0.46; 907 participants; 7 studies; I² = 55%) without resultant serious adverse events (no events, 737 participants) and mortality (no events, 915 participants). In addition, corticosteroids reduced the duration of fever (mean difference (MD) -1.65 days, 95% CI -3.31 to 0.00; 210 participants; 2 studies; I² = 88%), time for laboratory parameters (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) to normalise (MD -2.80 days, 95% CI -4.38 to -1.22; 178 participants; 1 study) and length of hospital stay (MD -1.41 days, 95% CI -2.36 to -0.46; 39 participants; 1 study). No studies detailed outcomes beyond 24 weeks. Subgroup analysis showed some potential groups that may benefit more than others; however, further randomised controlled trials are required before this can be the basis for clinical action.Evidence quality was graded according to the GRADE system. Evidence was considered high quality for the incidence of serious adverse events, mortality and time for laboratory parameters to normalise. Evidence was considered moderate for the incidence of coronary artery abnormalities due to potential inconsistencies in data geography and patient benefits according to grouping. Evidence was moderate for duration of clinical symptoms (fever, rash) due to potential subjectivity in measurement. Evidence was moderate for length of hospital stay as only one study recorded this outcome. This means that we are reasonably confident that the true effect is close to that estimated in this work. Moderate-quality evidence shows that use of steroids in the acute phase of KD can be associated with improved coronary artery abnormalities, shorter duration of hospital stay and a decreased duration of clinical symptoms. High-quality evidence shows reduced inflammatory marker levels. There were insufficient data available regarding incidence of adverse effects attributable to steroids, mortality and long-term (> 1 year) coronary morbidity. Certain groups, including those based in Asia, those with higher risk scores, and those receiving longer steroid treatment may have greater benefit from steroid use, especially with decreasing rates of heart problems, but more tests are needed to answer these questions. Evidence presented in this study suggests that treatment with a long course of steroids should be considered for all children diagnosed with KD until further studies are performed.