Acquired Heart Disease In Children Research Articles

Identification of key ferroptosis‑related biomarkers in Kawasaki disease by clinical and experimental validation.

Kawasaki disease (KD) is an acute febrile rash that is primarily characterized by systemic vasculitis and is the leading cause of childhood-acquired heart disease. At present, a KD diagnosis is solely dependent on clinical symptoms and effective diagnostic markers are unavailable. Ferroptosis, a novel form of programmed cell death, contributes to the pathophysiology of infectious diseases. The present study aimed to identify key ferroptosis-related genes (FRGs) involved in the pathological process of KD and thus potential diagnostic biomarkers for this disease. For this purpose, differentially expressed-FRGs (DE-FRGs) between patients with KD and healthy controls were screened. The least absolute shrinkage and selection operator (LASSO) algorithm and a logistic regression model combined with receiver operating characteristic analysis were then used to identify and assess ferroptosis-related markers. Additionally, immune cell infiltration landscapes in the KD and control groups were evaluated using CIBERSORT. Moreover, the predictive value of the identified markers was validated in the clinical samples as well as vascular endothelial cells. A total of 10 DE-FRGs were screened from the KD and control samples. These 10 DE-FRGs were then applied to the LASSO model and 6 key ferroptosis-related markers were obtained. The subsequent Gene Set Variation Analysis results suggested that high expression levels of these markers were closely associated with innate immune activation and metabolism, while low expression was mainly linked to adaptive immune-related pathways. In addition to validating each gene in the training and validation sets, the diagnostic potential of these markers was assessed utilizing KD samples obtained from Shenzhen Baoan Women's and Children's Hospital. As a result, MAPK14, SLC2A3 and PGD were selected as potential diagnostic markers for KD. Additionally, changes in the expression of marker genes during inflammatory activation of vascular endothelial cells were measured by reverse transcription-quantitative PCR. The results of the present study will help to understand the role of FRGs in the pathogenesis of KD. Moreover, the identified FRGs may serve as diagnostic biomarkers, providing new strategies for KD prediction and treatment.

Challenges of Congenital Heart Surgery in Brazil: It is Time to Designate Pediatric Congenital Heart Surgery Subspecialty.

Congenital heart disease (CHD) affects eight to ten out of every 1,000 births, resulting in approximately 23,057 new cases in Brazil in 2022. About one in four children with CHD requires surgery or other procedures in the first year of life, and it is expected that approximately 81% of these children with CHD will survive until at least 35 years of age. Professionals choosing to specialize in CHD surgery face numerous challenges, not only related to mastering surgical techniques and the complexity of the diseases but also to the lack of recognition by medical societies as a separate subspecialty. Furthermore, families face difficulties when access to services capable of providing treatment for these children. To address these challenges, it is essential to have specialized hospitals, qualified professionals, updated technologies, sustainable industry, appropriate financing, quality assessment systems, and knowledge generation. The path to excellence involves specialization across all involved parties. As we reflect on the importance of Pediatric Cardiovascular Surgery and Congenital Heart Diseases establishing themselves as a subspecialty of Cardiovascular Surgery, it is essential to look beyond our borders to countries like the United States of America and United Kingdom, where this evolution is already a reality. This autonomy has led to significant advancements in research, education, and patient care outcomes, establishing a care model. By following this path in Brazil, we not only align our practice with the highest international standards but also demonstrate our maturity and the ability to meet the specific needs of patients with CHD and those with acquired childhood heart disease.

Maternal Obesity and Kawasaki Disease-like Vasculitis: A New Perspective on Cardiovascular Injury and Inflammatory Response in Offspring Male Mice.

Maternal obesity affects the risk of cardiovascular disease and inflammatory response in offspring. However, the impact of maternal obesity on offspring with Kawasaki disease (KD), the leading cause of childhood acquired heart disease, is still an understudied area. This study aimed to elucidate the impact of maternal obesity on offspring in KD-like vasculitis and the underlying mechanisms. Offspring of obese female mice and normal diet dams were randomly divided into two subgroups. The pups were injected intraperitoneally with either Candida albicans water-soluble fraction (CAWS) or phosphate buffered saline (PBS) to establish the obesity (OB)-CAWS group, OB group, wild type (WT)-CAWS group, and WT group. Their weight was monitored during the study. After four weeks, echocardiography was applied to obtain the alternation of cardiac structures. Mouse cytokine panel, Hematoxylin-Eosin (HE) staining, western blot, and real-time qPCR were used to study the pathological changes and protein and RNA expression alternations. Based on the study of pathology, serology and molecular biology, maternal obesity lead to more severe vasculitis and induced altered cardiac structure in the offspring mice and promoted the expression of pro-inflammatory cytokines through activating the NF-κB signaling pathway. Maternal obesity aggravated the inflammatory response of offspring mice in KD-like vasculitis.

Whole-Exome Sequencing for Identification of Potential Sex-Biased Variants in Kawasaki Disease Patients.

Kawasaki disease (KD) is an autoimmune disease of unknown etiology and has become a main cause of childhood acquired heart disease. KD is more prevalent in males than in females. The reason for this sex bias is unknown. Here, we used whole-exome sequencing (WES) to identify significantly different variants between male and female KD patients. From WES result, a total of 19,500 shared genetic variants in 8421 genes were captured via a series of filters. Further comparisons based on sex were performed to obtain 34 potential sex-biased variants in 34 genes for GO and Reactome Gene Sets enrichment analyses. Moreover, we selected 6 variants associated with immune, cells adhesion, platelet function, homeostasis, and ion channel signaling and expanded the sample size (1247 KD patients containing 713 males and 534 females, 803 healthy population containing 481 males and 322 females) for genotyping validation. From the results, USH2A/rs148135241, LMO7/rs142687160, CEMIP/rs12441101, and EFCC1/rs142391828 presented significant differences of alleles/genotypes frequency distributions between male and female only in KD patients (which were consistent with the result of WES analysis) but not in healthy population. In addition, the result also found that only EFCC1/rs142391828 polymorphism was associated with KD susceptibility. This result suggested that those four variants might play critical roles in sex bias in KD. The study would be in favor of a sex-specific genome atlas establishing and novel sex-specific precision therapies development for KD.

Coronary Artery Involvement in Kawasaki Disease-Echocardiographic Evaluation of Cases in a Tertiary Care Hospital

Background: Kawasaki disease (KD) is the leading cause of childhood acquired heart disease. Cardiovascular manifestations can be prominent in the acute phase of the illness. Echocardiography is useful in recognizing these cardiac manifestations. We carried out a retrospective study by analyzing the data of Kawasaki disease patients in a tertiary care hospital. Methods: The prevalence of coronary artery dilatation and clinical outcome were documented. Clinical, laboratory, and echocardiographic findings were obtained at baseline and 1 week, 6 weeks after initial therapy with intravenous immunoglobulin in addition to high doses of Aspirin which reduces the risk of coronary artery aneurysm. Results: One hundred and forty-nine patients with mean age 3± 2 years old, 60% males with Kawasaki disease were included. One hundred and thirty-two patients had coronary involvement (left main coronary artery 36.37 %, left anterior descending artery 28.03%, right main coronary artery 24.25%, circumflex branch in 11.37%). Administration of intravenous immunoglobulin (IVIG) and aspirin has greatly reduced the incidence of coronary lesions in affected children. The initial cardiac findings developed over first few weeks of illness resolved in most of the cases in the subsequent echocardiogram studies after IVIG. The mean duration to normalization of abnormal echocardiography findings is 6±3 months. Conclusion: Coronary artery involvement is seen in most of children with Kawasaki disease. Intravenous gamma globulin and aspirin has been reported to reduce the likelihood of development of giant coronary artery aneurysms and appears to have a direct beneficial effect on abnormalities in cardiac function associated with the acute phase of Kawasaki disease. Cardiovasc j 2023; 15(2): 144-150

Presence of coronary aneurysms during Kawasaki Disease (KD) correlates with lower levels of autoantibodies to both full form and spliced variant of immune regulator Del-1

Kawasaki disease (KD), a rare multisystem inflammatory condition that predominantly affects children under six years of age, is the leading cause of childhood-acquired heart disease in developed countries. The pathogenesis is unknown, but studies support that an infectious stimulus triggers an autoimmune reaction in a genetically susceptible child. Recent studies demonstrated an association with autoantibody response to Del-1 (also known as EDIL3) in children with KD. Del-1 is an extracellular matrix protein that is expressed both in macrophages and vascular endothelium. Del-1 has an anti-inflammatory role by preventing leucocyte migration to inflammatory sites. Del-1 has two expression variants and genetic variants of Del-1 have been associated with the risk of intracranial aneurysms. Due to the physiologic plausibility for a role during KD, we chose to assess if autoantibodies against DEL-1 are seen in a larger cohort of children with KD and to assess if responses correlated to aneurysm formation. Contrary to prior findings, in comparison to febrile controls, autoantibodies were not overall higher in children with KD. Elevation in Post-IVIG samples in comparison to pre-IVIG and convalescent samples supports the commonality of anti-Del-1 antibodies. Autoantibodies were notably lower in children with KD who had coronary Z score elevations in comparison to those who did not.

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.

276 Management of Giant Coronary Artery Aneurysms as a Coronary Sequelae of Kawasaki Disease – Surgical or Conservative Management?

Abstract Introduction Kawasaki Disease (KD) is the commonest childhood acquired heart disease in developed countries, predominantly affecting children younger than 5 years of age. These patients are at high risks of developing coronary arterial aneurysms (CAA) and CAA with absolute internal luminal diameters measuring ≥8mm or Z-score ≥10 is classified as giant coronary aneurysms (GCA). Case Report A 19-year-old girl with previous history of Kawasaki disease was diagnosed with giant coronary aneurysms on echocardiograms. Her subsequent CT coronary angiography showed large aneurysms in the right coronary artery (29mm x 25mm) and left anterior descending artery (10mm x 10mm) with signs of calcification. However, surprisingly, despite the evidence of large coronary aneurysms, she was completely asymptomatic and was physically active. Her cardiac MRI scan showed right coronary perfusion deficit in the distal right coronary territory but with no evidence of myocardial infarction. After having a detailed discussion in the MDT and with colleagues from San Diego, USA, a conservative approach was decided to be in the patient’s best interest. She has been advised to avoid competitive or strenuous exercise due to the associated risks. She is fit-and-well and is currently on Warfarin variable dose and Aspirin 75mg OD, with annual cardiac MRI surveillance.

P76 Management of Giant Coronary Artery Aneurysms as a Coronary Sequelae of Kawasaki Disease – Surgical or Conservative Management?

Abstract Introduction Kawasaki Disease (KD) is the commonest childhood acquired heart disease in developed countries, predominantly affecting children younger than 5 years’ of age. These patients are at high risks of developing coronary arterial aneurysms (CAA) and CAA with absolute internal luminal diameters measuring ≥8mm or Z-score ≥10 are classified as giant coronary aneurysms (GCA). Case Report A 19-year-old girl with previous history of Kawasaki disease was diagnosed with giant coronary aneurysms on echocardiograms. Her subsequent CT coronary angiography showed large aneurysms in the right coronary artery (29mm x 25mm) and left anterior descending artery (10mm x 10mm) with signs of calcification. However, surprisingly, despite the evidence of large coronary aneurysms, she was completely asymptomatic and was physically active, participating in competitive sports. Her cardiac MRI scan 17 years after KD onset showed right coronary perfusion deficit in the distal right coronary territory but with no evidence of myocardial infarction. A repeated cardiac CT was performed and showed delayed filling of the distal right coronary artery. However, it was uncertain at this point if the aneurysm was causing true ischaemia or simply delayed perfusion. An ECG stress test was subsequently performed for further investigation which showed no significant abnormality. After having a detailed discussion in the MDT and with colleagues from San Diego, USA, a conservative approach was decided to be in the patient’s best interest. She has been advised to avoid competitive or strenuous exercise due to the associated risks. She is fit-and-well, and is currently on Warfarin variable dose and Aspirin 75mg OD, with annual cardiac MRI surveillance. Discussion 20% of KD patients develop CAA and approximately 5% of KD patients have evidence of GCA. Unlike small and medium CAA, GCA regress in a much slower and more constant rate, and they never achieve complete resolution. A Japanese retrospective study showed the 10-year coronary event-free survival rates in small, medium and giant CAA as 100%, 96% and 61% respectively (p<.001). Patients with GCA are at significantly increased risks of coronary complications and major cardiac events (48%). Despite maximal medical treatment, patients with GCA have high risks of aneurysm rupture which is associated with high mortality rates. These patients are also at lifelong risks of atherosclerosis and stenosis which may lead to myocardial ischaemia and even death. Therefore, it is absolutely essential to control for cardiovascular risk factors and adhere to strict treatment regime. These patients also require lifelong, uninterrupted cardiology follow-up in a specialist KD clinic. Catheter and surgical interventions may be indicated in some patients. There have been recent attempts in combining CABG with downsizing reconstruction for GCA in an attempt to decrease GCA diameter and improve the coronary flow rate to prevent thrombosis which has shown quite promising results. However, the decisions whether to undergo a surgical intervention should be tailored to each individual, taking into consideration all aspects of a patient, including their disease status and social life. Conclusion With an increasing prevalence of KD in UK, it is essential to always consider the diagnosis of KD in a febrile child with raised inflammatory markers, especially in patients presenting with prolonged fever (longer than 4-5 days) as a delay in commencing treatment poses a significantly increased risk of developing coronary complications which are associated with high morbidity and mortality rates.

Acquired heart diseases in children in Gadarif pediatrics teaching hospital, Gadarif state, Eastern Sudan

<p><strong>Background: </strong>Acquired heart diseases (AHD) are heterogeneous diseases including rheumatic heart disease (RHD) and other affecting the heart and blood vessels after birth but usually appear clinically after 5 years of age. AHD considered as major cause of morbidity and mortality. The present study was designed to document the spectrum, the affected age and clinical characteristics of AHDs in children of Gadarif state, eastern Sudan.</p><p><strong>Methods</strong>: This was a descriptive cross section study conducted in Gadarif pediatrics teaching hospital in period from June to Dec 2019.</p><p><strong>Results: </strong>A total of 46 children from Gadarif pediatrics teaching hospital with confirmed AHD were enrolled in this study. The females were 27 (58.7%), with a male-to-female ratio of 1.4:1. The mean age was 10.6±3.9 years (age’s ≤16 years old); the most common affected age group was 10-14 years accounted 18 (39.1) cases. RHD was the commonest AHD found in 38 (82.6%) patients, the commonest valvular lesion was mitral regurgitation 31 (73.9%).</p><p><strong>Conclusions: </strong>RHD was the most common AHD in the children in the present study, there is need to improve the scope of intervention facilities in the Sudan particularly in rural areas to prevent the growing and spread of these diseases.</p>

A Protein Epitope Targeted by the Antibody Response to Kawasaki Disease.

Kawasaki disease (KD) is the leading cause of childhood acquired heart disease in developed nations and can result in coronary artery aneurysms and death. Clinical and epidemiologic features implicate an infectious cause but specific antigenic targets of the disease are unknown. Peripheral blood plasmablasts are normally highly clonally diverse but the antibodies they encode are approximately 70% antigen-specific 1-2 weeks after infection. We isolated single peripheral blood plasmablasts from children with KD 1-3 weeks after onset and prepared 60 monoclonal antibodies (mAbs). We used the mAbs to identify their target antigens and assessed serologic response among KD patients and controls to specific antigen. Thirty-two mAbs from 9 of 11 patients recognize antigen within intracytoplasmic inclusion bodies in ciliated bronchial epithelial cells of fatal cases. Five of these mAbs, from 3 patients with coronary aneurysms, recognize a specific peptide, which blocks binding to inclusion bodies. Sera from 5/8 KD patients day ≥ 8 after illness onset, compared with 0/17 infant controls (P < .01), recognized the KD peptide antigen. These results identify a protein epitope targeted by the antibody response to KD and provide a means to elucidate the pathogenesis of this important worldwide pediatric problem.

P32 Kawasaki disease: learning points from 6 years of audit data from a large university teaching hospital

Abstract Background Kawasaki disease is the most common cause of acquired childhood heart disease in developed countries. If left untreated, 15 to 25% of children develop coronary artery aneurysms and more worryingly 2 to 3% will die from coronary vasculitis. Prompt recognition and management including referral to a cardiologist can ameliorate this. The clinical challenge however is the lack of any diagnostic tests and that many cases do not fit the typical diagnostic criteria. Here we present the results from an original audit assessing our practice against RCPCH guidelines. We show findings from audit cycles spanning six years from Leicester’s children’s hospital. We also take one step further to analyse this data looking for trends in presentation and lab findings. Methods Original audit data was collected from cases between 2008-2012 and 2015-2017 (audit standards are shown in figure 1). The data generated from these audits was re-analysed to assess for trends in presentation and laboratory findings. Results In six years we saw 41 cases: 23 were of atypical presentation and 18 were typical (figure 2); 27 patients were male and 14 were female. The age range was 1 month to 13 years. All patients received IVIG, aspirin and were referred to cardiology. No patients required biological therapies. Cardiological events: Data incomplete – patients disseminated across several tertiary units; acutely - 6 patients had a borderline/abnormal echocardiogram; long-term - 1 patient has persistent but resolving coronary artery aneurysms. Mortalities A 4-month old in 2008 died as a result of untreated atypical Kawasaki disease. This patient was diagnosed only at autopsy. Conclusion Over the 2 audit periods we noted a higher than expected caseload of atypical KD. At presentation: 88% had no desquamation, 30% had only mildly raised CRP, and 2% did not have fever for more than 5 days. Conflicts of Interest The authors declare no conflicts of interest.

Early childhood exposure to maternal smoking and Kawasaki Disease: A longitudinal survey in Japan

Kawasaki disease is the leading cause of acquired childhood heart disease in most developed countries, but the etiology of the disease is unknown. An aberrant immune response to some environmental triggers may play a role and involuntary exposure to tobacco smoke can alter immune functions. We thus prospectively examined the association between early childhood exposure to maternal smoking and the incidence of Kawasaki disease. We used a large, nationwide population-based longitudinal survey ongoing since 2010 and restricted participants to a total of 38,444 children for whom information on maternal smoking was available. Maternal smoking status was ascertained at 6months of age, and responses to questions about hospital admission for Kawasaki disease between the ages of 6 and 30months were used as outcome. We conducted binomial log-linear regression analyses adjusting for children's, parental, and residential factors with children of non-smoking mothers as our reference group. Maternal smoking increased the risk of admission, in particular for the period between 6 and 18months of age, in a dose-dependent manner. Compared with children of non-smoking mothers, the children of mothers who smoked had a risk ratio of 1.83 (95% confidence interval: 1.06, 3.35) for hospital admissions between 6 and 30months of age and a risk ratio of 2.69 (95% confidence interval: 1.56, 4.64) for hospital admissions between 6 and 18months of age. Early childhood exposure to maternal smoking may increase the risk of Kawasaki disease hospitalizations in childhood.

Acute Immune Hemolytic Anemia after administration of high dose IVIG in a child with Kawasaki disease

Background: Kawasaki disease is an acute febrile illness of unknown etiology, characterized by vasculitis of medium -sized arteries with a predilection for the coronary arteries. It is the leading cause of acquired heart disease in childhood with 20-25% of untreated children developing coronary artery abnormalities. The mainstays of therapy are intravenous Immunoglobulin (IVIG) and high dose aspirin to prevent or modify the most serious cardiac sequelae. Though rare, immune-mediated hemolysis is a recognized and potentially catastrophic side effect of administration. …

Ptosis as a complication of Kawasaki disease

Kawasaki disease is an acute febrile exanthematous disease that affects children younger than 5 years of age. It is regarded as the most common cause of childhood acquired heart disease,...

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.

Breastfeeding and Risk of Kawasaki Disease: A Nationwide Longitudinal Survey in Japan.

Kawasaki disease (KD) is the most common cause of childhood-acquired heart disease in developed countries. However, the etiology of KD is not known. Aberrant immune responses are considered to play key roles in disease initiation and breastfeeding can mature immune system in infants. We thus examined the association between breastfeeding and the development of KD. We used a nationwide population-based longitudinal survey ongoing since 2010 and restricted participants to a total of 37 630 children who had data on their feeding during infancy. Infant feeding practice was queried at 6 to 7 months of age, and responses to questions about hospital admission for KD during the period from 6 to 30 months of age were used as outcome. We conducted logistic regression analyses controlling for child and maternal factors with formula feeding without colostrum as our reference group. A total of 232 hospital admissions were observed. Children who were breastfed exclusively or partially were less likely to be hospitalized for KD compared with those who were formula fed without colostrum; odds ratios for hospitalization were 0.26 (95% confidence interval: 0.12-0.55) for exclusive breastfeeding and 0.27 (95% confidence interval: 0.13-0.55) for partial breastfeeding. Although the risk reduction was not statistically significant, feeding colostrum only also provided a protective effect. We observed protective effects of breastfeeding on the development of KD during the period from 6 to 30 months of age in a nationwide, population-based, longitudinal survey in Japan, the country in which KD is most common.

Echocardiographic pattern of rheumatic valvular disease in a contemporary sub-Saharan African pediatric population: an audit of a major cardiac ultrasound unit in Yaounde, Cameroon.

BackgroundRheumatic Heart Disease (RHD) remains a major cause of childhood acquired heart disease in developing countries. However reported echocardiographic features are limited to a few countries. This report is on the demographic and echocardiographic features of RHD in children using data from the largest referral hospital in Yaounde, the capital city of Cameroon.MethodsThe register of the cardiac ultrasound unit of the Yaounde General Hospital for the period 2003–2013 served as basis for data collection. RHD diagnosis was based on the World Heart Federation Criteria for the diagnosis of RHD. Demographic data, pattern of valve lesions and severity were analyzed.ResultsA total of 1130 first echocardiographic examinations were performed in children aged ≤ 18 years. Sixty-five (5.8 %) had a definite echocardiographic diagnosis of RHD with their mean age being 11.8 years (SD 3.6) and 31 (47.1 %) being boys. The commonest primary reasons for requesting an echocardiographic examination were a clinical diagnosis of RHD (24.6 %) without heart failure, a clinical diagnosis of heart failure (24.6 %), and heart murmurs (21.5 %). Isolated mitral regurgitation was the most common valve lesion (49.2 %) and was frequently associated with aortic regurgitation (35.4 %). Severe lesions were found in 63.3 % of participants. No right heart lesion was reported.ConclusionsA sizable proportion of children undergoing echocardiographic examination at this major referral hospital in Cameroon had RHD, with lesions found only on the left heart. These lesions predominated on the mitral valve, were commonly associated with aortic regurgitation, and more often severe.

Role of the PTEN/PI3K/VEGF pathway in the development of Kawasaki disease.

Kawasaki disease (KD) is a disease of unknown etiology and the leading cause of childhood acquired heart disease. In this study, the significance of the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/vascular endothelial growth factor (VEGF) pathway in the development of KD was investigated in a rabbit model. Rabbits were divided into the control group, which received saline injection, and the experimental group, which was treated with bovine serum albumin to induce arthritis and KD. After 1, 7 and 30 days the animals were sacrificed, and the white blood cell count, serum VEGF, and serum creatine kinase (CK) levels were measured. The coronary artery was examined histologically as well as immunohistochemically for PTEN and PI3K. After the induction of arthritis, coronary artery of the rabbits showed endothelial cell swelling, osteoporosis, necrosis and inflammatory cell infiltration. PTEN expression in these rabbits increased with the increasing number of modeling days. The expression of PI3K showed a decreasing trend. The number of white blood cells in rabbits after KD modeling were significantly higher than those in the controls. One day and 7 days after modeling the serum VEGF level in KD rabbits was significantly higher than that in the control group after 1 and 7 days followed by a decrease by 30 days. There was no significant change in serum CK on the day after the modeling, and the serum CK level was significantly higher after 7 and 30 days. In conclusion, the expression of PTEN/PI3K was altered at different stages of KD. PTEN expression gradually increased with the disease progression, while the expression of PI3K gradually decreased. Serum markers indicated that the PTEN/PI3K/VEGF signaling pathway is important in the vascular injury in KD.

Kawasaki disease: a comprehensive review of treatment options.

Kawasaki disease (KD) is an acute self-limiting systemic vasculitis with specific predilection for the coronary arteries that affects previously healthy young infants and children. It is the leading cause of childhood-acquired heart disease in the developed world. Although the stimulus for the cascade of inflammation in KD is unknown, prompt treatment within 10 days of symptom onset has been shown to improve clinical outcomes and reduce the risk of coronary artery complications. Standard initial therapy is intravenous immunoglobulin (IVIG) and aspirin. Non-responders to initial therapy remain a challenge. This present review summarizes the treatment options for initial and refractory KD, including the role of steroids and other immunosuppressive therapies. Literature search using PubMed database to identify pharmacologic studies in KD using the terms Kawasaki disease, intravenous immunoglobulin, refractory, corticosteroids, infliximab, cyclosporine, methotrexate, high risk from January 1988-May 2015 was performed. Bibliographies of selected references were also evaluated for relevant articles. Results were limited to those published in English. All articles identified from the PubMed searches were evaluated. Initial IVIG therapy results in rapid resolution of clinical symptoms in 80-90% of patients and has been shown to reduce the risk of coronary disease. Although concomitant aspirin remains the standard of care for the initial management of KD, the evidence to support its efficacy in improving coronary artery outcomes are lacking. Initial therapy with corticosteroids in addition to intravenous immunoglobulin and aspirin improves outcomes in patients in Japan. However, identifying patients at high risk who may benefit from additional corticosteroids in heterogeneous populations has been challenging. Therapeutic options for non-responders to initial therapy are also challenging given the paucity of data. Patients who fail to respond to the first dose of IVIG will most often receive a second dose. Patients who fail to respond to two doses of IVIG present a unique challenge as the appropriate treatment remains uncertain. Although their effectiveness remains unproven, treatment with infliximab, cyclosporine or methotrexate may be considered in those patients who fail multiple doses of IVIG and steroids. The role of steroids in high-risk non-Japanese patients is unclear, with the biggest challenge being early identification of patients at high risk of developing adverse coronary artery outcomes. Limited data evaluating other immunosuppressive agents are available and should be reserved for patients failing two doses of IVIG. Although recent advances in research have broadened our understanding of the epidemiology, genetic susceptibility and pathogenesis of KD, the aetiology of KD remains unclear. Ongoing research will help determine more precise pathogenesis and may assist in developing a diagnostic test as well as identifying new targets for more precise treatment interventions.